Clinical guidelines for pneumonia in the hospital. Clinical guidelines for the diagnosis, treatment and prevention of severe community-acquired pneumonia in adults
RUSSIAN RESPIRATORY SOCIETY
INTERREGIONAL ASSOCIATION FOR CLINICAL MICROBIOLOGY AND ANTIMICROBIAL CHEMOTHERAPY (IACMAC)
Community-acquired pneumonia in adults: practical recommendations for diagnosis, treatment and prevention
(Manual for doctors)
A.G. Chuchalin1, A.I. Sinopalnikov2, R.S. Kozlov3, I.E. Tyurin2, S.A. Rachina3
1 Research Institute of Pulmonology, Federal Medical and Biological Agency of Russia, Moscow
2 GBOU DPO "Russian Medical Academy of Postgraduate Education" of the Ministry of Health of Russia, Moscow
3 Research Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Ministry of Health of Russia
LIST OF ABBREVIATIONS USED
AMP - antimicrobial drug ABT - antibacterial drug VP - community-acquired pneumonia IHD - coronary heart disease IVL - artificial ventilation CI - clinical trial LS - drug LF - dosage form
NSAID - non-steroidal anti-inflammatory drug
ICU - intensive care unit
PRP - penicillin-resistant B. rpeiitotae
PPP - penicillin-sensitive B. rpeiitotae
ESR - erythrocyte sedimentation rate
COPD - chronic obstructive pulmonary disease
LIST OF ABBREVIATIONS OF MICROORGANISMS
B. cepacia - Burkholderia cepacia Candida spp. - genus Candida
C. pneumoniae - Chlamydophila pneumoniae Chlamydophila spp. - genus Chlamydophila Enterobacteriaceae - family Enterobacteriaceae Enterococcus spp. - genus Enterococcus
H. influenzae - Haemophilus influenzae
K. pneumoniae - Klebsiella pneumoniae
Klebsiella spp. - genus Klebsiella
L. pneumophila - Legionella pneumophila
Legionella spp. - genus Legionella
M. catarrhalis - Moraxella catarrhalis
M. pneumoniae - Mycoplasma pneumoniae
MSSA - methicillin-sensitive Staphylococcus aureus
MRSA - methicillin-resistant Staphylococcus aureus
Mycoplasma spp. - genus Mycoplasma
Neisseria spp. - genus Neisseria
P. aeruginosa - Pseudomonas aeruginosa
S. aureus - Staphylococcus aureus
Staphylococcus spp. - genus Staphylococcus
S. pneumoniae - Streptococcus pneumoniae
S. pyogenes - Streptococcus pyogenes
Community-acquired pneumonia (CAP) is one of the most common diseases in humans and is one of the leading causes of death from infectious diseases. To date, sufficient data have been accumulated to develop national recommendations for the management of patients with CAP. The main goal of clinical recommendations is to improve the diagnosis and quality of treatment of patients with CAP in outpatient practice and inpatient care.
The developed recommendations are addressed primarily to general practitioners and pulmonologists in clinics and hospitals, resuscitators, clinical pharmacologists, teachers of medical universities, and may also be of interest to doctors of other specialties. Clinical recommendations can serve as the basis for developing standards of medical care at the federal and regional levels.
Practical recommendations focus on the issues of diagnosis and antibacterial therapy of CAP in adults. At the same time, such important problems as CAP in patients with severe immune defects (HIV infection, cancer, etc.), restorative treatment and rehabilitation of patients who have suffered CAP, etc., which, according to the authors, were beyond the scope of the recommendations. should be the subject of a separate discussion.
The authors of the recommendations made an attempt to critically evaluate the validity of various approaches to the diagnosis and treatment of CAP from the standpoint of evidence-based medicine. For this purpose, all recommendations presented were classified according to the level of evidence. This approach seems strictly justified for developing an algorithm for diagnosing and examining patients with CAP. However, some problems have arisen with determining the levels of evidence for recommendations for antibiotic therapy. It is very difficult to correctly apply levels of evidence to the choice of antibiotics. This is due to the fact that most randomized clinical trials of antibiotics are conducted before they are administered.
limited use when the level of resistance to them is minimal. In addition, regional characteristics of resistance should be taken into account. Therefore, it is not always possible to extend research data conducted in other countries to Russia. The authors believe that recommendations on the choice of antibiotics should be based on expert opinion (category of evidence D), but take into account local data on the level of antibiotic resistance.
These recommendations are the result of a consensus opinion of experts, developed on the basis of a thorough analysis of all studies published over the past 15 years in this area in the domestic and foreign literature, including numerous foreign recommendations for the management of adult patients with CAP: recommendations of the British Thoracic Society (BTS, 2004, 2009 gg.), European Respiratory Society (ERS, 2005), consensus recommendations of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS, 2007).
The first edition of consensus national recommendations for the management of adult patients with CAP, prepared by experts from the Russian Respiratory Society, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC) and the Alliance of Clinical Chemotherapists and Microbiologists, was published in 2003. However, the authors of the recommendations were clearly aware that Due to rapidly changing ideas about CAP (deepening and expanding modern ideas about the epidemiology of respiratory infections, the emergence of new diagnostic methods, etc.), it is necessary to regularly review and update this document.
The second edition, published in 2006, included a more detailed description of Russian data on the epidemiology of CAP, new data on the resistance of key respiratory pathogens (Streptococcus pneumoniae and Haemophilus influenzae) in Russia, expanded and updated sections on the etiology, diagnosis and antibacterial therapy of CAP, and also new chapters devoted to the analysis of real practice in the treatment of CAP in the Russian Federation.
proof
A Randomized controlled trials Evidence is based on well-designed randomized trials conducted on a sufficient number of patients to obtain reliable results. Can be reasonably recommended for widespread use.
B Randomized controlled trials The evidence is based on randomized controlled trials, but the number of patients included is insufficient for reliable statistical analysis. Recommendations may be generalizable to a limited population.
C Non-randomized clinical trials Evidence is based on non-randomized clinical trials or studies performed on a limited number of patients.
D Expert opinion Evidence is based on consensus developed by a group of experts on a particular issue.
The presented third edition of the recommendations, in addition to the traditional update of sections on the epidemiology of CAP in the Russian Federation, antibiotic resistance of the most relevant pathogens and the practice of managing patients with CAP, includes the results of studies of the etiology of CAP in the Russian Federation in hospitalized patients. A new section has appeared dedicated to the X-ray diagnosis of VP.
I. EPIDEMIOLOGY
Community-acquired pneumonia is one of the most common acute infectious diseases. According to official statistics (Central Research Institute of Organization and Informatization of Health Care of Roszdrav), in 2006, 591,493 cases of the disease were registered in the Russian Federation, which amounted to 4.14%; in persons aged >18 years, the incidence was 3.44%. The highest incidence of pneumonia among adults was noted in the Siberian and Northwestern Federal Districts (4.18 and 3.69%, respectively), the lowest in the Central Federal District (3.07%).
It is obvious, however, that these figures do not reflect the true incidence of CAP in Russia, which, according to calculations, reaches 14-15%, and the total number of patients annually exceeds 1.5 million people. In certain categories, the incidence rate of CAP turns out to be significantly higher than all-Russian data. Thus, in particular, the incidence of CAP among conscripts in 2008 averaged 29.6%.
According to foreign epidemiological studies, the incidence of CAP in adults (>18 years) varies over a wide range: in young and middle-aged people it is 1-11.6%; in older age groups - 25-44%. During the year, the total number of adult patients (>18 years) with CAP in 5 European countries (Great Britain, France, Italy, Germany, Spain) exceeds 3 million people.
In the United States, more than 5 million cases of CAP are diagnosed annually, of which more than 1.2 million cases require hospitalization. Of the latter, more than 60 thousand people die directly from CAP. According to the Russian Ministry of Health, in 2006 in our country, among people aged >18 years, 38,970 people died from pneumonia, which amounted to 27.3 per 100 thousand population.
Mortality with CAP is the lowest (1-3%) in young and middle-aged people without concomitant diseases. On the contrary, in patients over 60 years of age with serious concomitant pathology (COPD, malignant neoplasms, alcoholism, diabetes mellitus, kidney and liver diseases, cardiovascular system, etc.), as well as in cases of severe CAP (multilobar infiltration, secondary bacteremia, frequency respiratory rate >30/min, hypotension, acute renal failure), this figure reaches 15-30%.
An analysis of Russian data in certain regions shows that the highest mortality from CAP is recorded among men of working age.
Risk factors for death in CAP, including data from anamnesis, physical and laboratory tests, are presented in Table. 1. One of the typical risk factors for death in our country is also the late presentation of patients for medical help.
Table 1. Probability of death in patients with CAP depending on medical history, physical examination and laboratory parameters
Investigated criterion Odds ratio
Demographics - male 1.3 (1.2-1.4)
History of present illness - hypothermia - change in mental status - shortness of breath 0.4 (0.2-0.7) 2.0 (1.7-2.3) 2.9 (1.9-3.8)
Concomitant diseases - chronic heart failure - immunodeficiency states - diabetes mellitus - coronary artery disease - oncological diseases - neurological diseases - kidney diseases 2.4 (2.2-2.5) 1.6 (1.3-1.8) 1.2 (1 .1-1.4) 1.5 (1.3-1.6) 2.7 (2.5-2.9) 4.4 (3.8-4.9) 2.7 (2.5-2.9 )
Physical examination - tachypnea (RR >28/min) - hypothermia (1 body<37 С) - гипотензия (СД <100 мм Н$ 2.5 (2,2-2,8) 2.6 (2,1-3,2) 5,4 (5,0-5,9)
Laboratory tests - blood urea nitrogen (>7.14 mmol/l) - leukopenia (<4х109/л) - лейкоцитоз (>10x109/l) - hypoxemia (Pa02<50 мм Нй) - наличие инфильтрации на рентгенограмме ОГК более чем в 1 доле 2,7 (2,3-3,0) 5,1 (3,8-6,4) 4.1 (3,5-4,8) 2.2 (1,8-2,7) 3,1 (1,9-5,1)
II. DEFINITION AND CLASSIFICATION
Pneumonia is a group of acute infectious (mainly bacterial) diseases, different in etiology, pathogenesis, and morphological characteristics, characterized by focal damage to the respiratory parts of the lungs with the obligatory presence of intra-alveolar exudation.
Since CAP is an acute infectious disease, the definition of “acute” before the diagnosis of “pneumonia” is unnecessary, especially since the diagnosis of “chronic pneumonia” is not pathogenetically justified, and the corresponding term is outdated.
In the International Classification of Diseases, Injuries and Causes of Death, Xth Revision (ICD-X, 1992), CAP is clearly separated from other focal inflammatory lung diseases of non-infectious origin. Thus, from the heading “Pneumonia”, diseases caused by physical (radiation pneumonitis) or chemical (“gasoline” pneumonia) factors, as well as those having an allergic (“eosinophilic pneumonia”) or vascular (pulmonary infarction due to thrombosis) are excluded.
Table 2. Classification of pneumonia in accordance with the International Classification of Diseases, Injuries and Causes of Death, X revision (1992)
J13 Pneumonia caused by Streptococcus pneumoniae
J14 Pneumonia caused by Haemophilus influenzae
J15 Bacterial pneumonia, not elsewhere classified (excludes: pneumonia caused by Chlamydia spp. - J16.0 and Legionnaires' disease - A48.1)
J15.0 Pneumonia caused by Klebsiella pneumoniae
J5.1 Pneumonia caused by Pseudomonas spp.
J15.2 Pneumonia caused by Staphylococcus spp.
J15.3 Pneumonia caused by group B streptococci
J15.4 Pneumonia caused by other streptococci
J15.5 Pneumonia caused by Escherichia coli
J15.6 Pneumonia caused by other aerobic gram-negative bacteria
J15.7 Pneumonia caused by Mycoplasma pneumoniae
J15.8 Other bacterial pneumonia
J15.9 Bacterial pneumonia of unspecified etiology
J16 Pneumonia caused by pathogens not classified elsewhere (excluded: psittacosis - A70, Pneumocystis pneumonia - B59)
J16.0 Pneumonia caused by Chlamydia spp.
J16.8 Pneumonia due to other identified pathogens
J17* Pneumonia in diseases classified elsewhere
J17.0* Pneumonia in diseases of a bacterial nature, classified in other headings (pneumonia in: actinomycosis - A42.0, anthrax - A22.1, gonorrhea - A54.8, nocardiosis - A43.0, salmonellosis - A022.2, tularemia - A721.2, typhoid - A031.0, whooping cough - A37.0)
J17.1* Pneumonia in viral diseases classified in other headings (pneumonia in: cytomegalovirus disease - B25.0, measles - B05.2, rubella - B06.8, chickenpox - B01.2)
J17.2* Pneumonia due to mycoses
J17.8* Pneumonia in diseases classified in other headings (pneumonia in: psittacosis - A70, Q fever - A78, acute rheumatic fever - A100, spirochitosis - A69.8)
J18 Pneumonia without specifying the pathogen
* Pneumonia is indicated for diseases classified in other headings and not included in the heading “Pneumonia”.
embolism of the branches of the pulmonary artery) origin. Inflammatory processes in the lungs in a number of highly contagious diseases caused by obligate pathogens of a bacterial or viral nature are considered within the framework of the corresponding nosological forms (Q fever, plague, typhoid fever, measles, rubella, influenza, etc.) and are also excluded from the heading “Pneumonia” .
There is no doubt that the classification that most fully reflects the characteristics of the course of pneumonia and makes it possible to justify etiotropic therapy should be built on an etiological principle. This principle forms the basis for the classification of pneumonia presented in ICD-X (Table 2).
However, insufficient information content and significant duration of traditional microbiological studies (absence of productive cough in 20-30% of patients, inability to isolate intracellular pathogens using standard diagnostic approaches, identification of the pathogen only 48-72 hours after receiving the material, difficulties in distinguishing the “witness microbe” " and "pathogen microbe", a common practice of taking antibacterial drugs before seeking medical help) are the reason for the lack of etiological diagnosis in 50-70% of patients, which makes it impossible to widely apply the etiological classification of CAP.
Currently, the most widespread classification is one that takes into account the conditions in which the disease developed; at the same time, it is also proposed to take into account the characteristics of infection of the lung tissue and the state of the immunological reactivity of the patient’s body (Table 3). This approach makes it possible to predict the etiology of the disease with a significant degree of probability.
From a practical point of view, the most significant is the division of pneumonia into community-acquired and nosocomial. It should be emphasized that such a division has nothing to do with the severity of the disease; the main criterion for differentiation is the environment in which the pneumonia developed.
Recently, pneumonia associated with the provision of medical care (healthcare-associated pneumonia) has become a separate group. This category, for example, includes pneumonia in people living in nursing homes or other long-term care facilities. According to the conditions of their occurrence, they can be considered community-acquired, but they, as a rule, differ from the latter in the structure of the pathogens and the profile of their antibiotic resistance.
CAP should be understood as an acute disease that arose in a community setting, i.e. out of hospital or later than 4 weeks after discharge from it, or diagnosed in the first 48 hours after hospitalization, or developed in a patient who was not in a nursing home/long-term care unit for >14 days, which is accompanied by symptoms of lower respiratory infection;
Table 3. Classification of pneumonia (R.G. Wunderink, G.M. Mutlu, 2006; as amended)
Community-acquired pneumonia Nosocomial Pneumonia associated with the provision of
pneumonia medical care
I. Typical (in patients with no pronounced I. Actually nosocomial- I. Pneumonia in residents of houses
immunity disorders): pneumonia in the elderly
A. bacterial; II. Fan-associated II. Other categories of patients:
b. viral; bathroom pneumonia a. antibacterial therapy
V. fungal; III. Nosocomial in the previous 3 months;
d. mycobacterial; pneumonia in patients b. hospitalization (for any reason) in those
II. In patients with severe immunological disorders: c. stay in other institutions
Niteta: a. in long-term care recipients;
A. acquired immunodeficiency syndrome of donor organs; d. chronic dialysis for >30 days;
(AIDS); b. in patients, d. treatment of the wound surface
b. other diseases/pathological conditions received at home;
III. Aspiration pneumonia/lung abscess cytostatic therapy e. immunodeficiency states/
diseases.
body pathways (fever, cough, sputum production, possibly purulent, chest pain, shortness of breath) and radiological signs of “fresh” focally infiltrative changes in the lungs in the absence of an obvious diagnostic alternative.
III. PATHOGENESIS
Anti-infective protection of the lower respiratory tract is carried out by mechanical factors (aerodynamic filtration, branching of the bronchi, epiglottis, coughing and sneezing, oscillatory movements of the cilia of the ciliated epithelium), as well as mechanisms of nonspecific and specific immunity. The reasons for the development of the inflammatory reaction can be either a decrease in the effectiveness of the protective mechanisms of the macroorganism, or a massive dose of microorganisms and/or their increased virulence.
There are 4 pathogenetic mechanisms that determine the development of CAP with different frequencies:
■ aspiration of oropharyngeal secretions;
■ inhalation of aerosol containing microorganisms;
■ hematogenous spread of microorganisms from an extrapulmonary source of infection (endocarditis with damage to the tricuspid valve, septic thrombophlebitis);
■ direct spread of infection from neighboring affected organs (for example, with a liver abscess) or as a result of infection from penetrating wounds of the chest.
It should be noted that the first two of the above mechanisms are the main ones.
Aspiration of oropharyngeal contents is the main route of infection of the respiratory parts of the lungs and the main pathogenetic mechanism for the development of CAP. Under normal conditions, a number of microorganisms, such as Streptococcus pneumoniae, can colonize the oropharynx, but the lower respiratory tract remains sterile. Microaspiration of oropharyngeal secretions is a physiological phenomenon observed in almost half of healthy individuals, mainly during sleep. However, the cough reflex, mucocili-
ary clearance, antibacterial activity of alveolar macrophages and secretory immunoglobulins ensure the elimination of infected secretions from the lower respiratory tract and their sterility.
When the mechanisms of “self-cleaning” of the tracheobronchial tree are damaged, for example, during a viral respiratory infection, when the function of the cilia of the bronchial epithelium is disrupted and the phagocytic activity of alveolar macrophages is reduced, favorable conditions are created for the development of CAP. In some cases, an independent pathogenetic factor may be the massive dose of microorganisms or the penetration of even single highly virulent microorganisms into the respiratory sections of the lungs.
Inhalation of microbial aerosol is a less commonly observed route of development of CAP. It plays a major role in infection of the lower respiratory tract with obligate pathogens, such as Legionella spp. Of even less importance (in terms of frequency of occurrence) is hematogenous (for example, Staphylococcus spp.) and direct spread of the pathogen from the source of infection.
Taking into account the described features of the pathogenesis of CAP, it is obvious that its etiology in the vast majority of cases is associated with the microflora of the upper respiratory tract, the composition of which depends on the external environment, the patient’s age and general health.
IV. ETIOLOGY
The etiology of CAP is directly related to the normal microflora that colonizes the upper respiratory tract. Of the numerous microorganisms, only a few that have increased virulence are capable of causing an inflammatory reaction when they enter the lower respiratory tract. These pathogens include, first of all, pneumococcus (Streptococcus pneumoniae) - 30-50% of cases.
The so-called atypical microorganisms, which in total account for 8 to 30% of cases of the disease, are of significant importance in the etiology of CAP:
Chlamydophila pneumoniae;
Mycoplasma pneumoniae;
Legionella pneumophila.
Rare (3-5%) pathogens of CAP include:
Haemophilus influenzae;
Staphylococcus aureus;
Klebsiella pneumoniae, and even more rarely - other enterobacteria.
In very rare cases, CAP can be caused by Pseudomonas aeruginosa (in patients with cystic fibrosis, in the presence of bronchiectasis).
It is important to emphasize that often mixed or co-infection is detected in adult patients with CAP. For example, in almost every second patient with pneumococcal etiology of the disease, it is possible to simultaneously detect serological signs of active mycoplasma or chlamydial infections.
Among other causative agents of CAP, respiratory viruses (influenza viruses type A and B, parainfluenza, adenovirus and respiratory syncytial virus) are often mentioned, but in reality they rarely cause direct damage to the respiratory parts of the lungs. Viral respiratory infections, and especially epidemic influenza, are certainly considered as a leading risk factor for pneumonia, being a kind of “conductor” of bacterial infection. However, pathological changes in lung tissue caused by viruses should not be called pneumonia and, moreover, must be clearly distinguished from it, since the approach to the treatment of these two conditions is fundamentally different. From this point of view, the common term “viral-bacterial pneumonia” does not seem entirely appropriate, since bacterial pneumonia itself is qualitatively different from the most often interstitial viral lung lesions.
It should be remembered that CAP may be associated with new, previously unknown pathogens that cause outbreaks of the disease. Causative agents of CAP identified in recent years include SARS-associated coronavirus, avian influenza virus, and metapneumovirus.
For some microorganisms, the development of bronchopulmonary inflammation is uncharacteristic. Their isolation from sputum most likely indicates contamination of the material by the flora of the upper respiratory tract, and not the etiological significance of these microbes. Such microorganisms include:
Streptococcus viridans;
Staphylococcus epidermidis and other coagulase-negative staphylococci;
Enterococcus spp.;
Neisseria spp.;
The etiological structure of CAP may vary depending on the age of the patients, the severity of the disease, and the presence of concomitant pathology. In patients hospitalized in the therapeutic department, pneumococci predominate in the etiology of CAP; M. pneumoniae and C. pneumoniae together account for about 25%. On the contrary, the latter are not essential in the ethio-
the history of severe CAP requiring treatment in the intensive care unit (ICU); at the same time, in this category of patients, the role of Legionella spp., as well as S. aureus and gram-negative enterobacteria, increases (Table 4).
Table 4. CAP etiology depending on the severity of the disease (in %)
Microorganisms Outpatients Hospitalized patients
to the therapeutic department in the ICU
S. pneumoniae 5 17.3 21
H. influenzae 2.3 6.6 -
S. aureus - 2.9 7.4
M. pneumoniae 24 13.7 -
C. pneumoniae 10.1 -
L. pneumophila - 1.3 5.8
Gram-negative aerobic bacteria 4.1 8.8
Etiology unknown 48 No data 35.6
The key causative agents of CAP in young patients without concomitant diseases (military personnel) with a mild course of the disease, according to one Russian study, are pneumococci, “atypical” microorganisms and their combinations (Fig. 1).
S. pneumoniae C. pneumoniae M. pneumoniae
C. pneumoniae + M. pneumoniae
S. pneumoniae + C. pneumoniae + M. pneumoniae
Rice. 1. Etiology of CAP in young patients
Other K. pneumoniae
H. influenzae + S. aureus
C. pneumoniae + H. influenzae + M. pneumoniae
L. pneumophila C. pneumoniae M. pneumoniae + H. influenzae S. pneumoniae + H. influenzae S. pneumoniae H. influenzae M. pneumoniae
Enterococcus spp. + K. pneumoniae
E. coli + P. pneumoniae
H. influenzae + S. pneumoniae + K. pneumoniae
5 10 15 20 25 30 35
Rice. 2. Structure of pathogens of non-severe CAP in adult hospitalized patients (%, n=109)
Rice. 3. Structure of pathogens causing severe CAP in adult hospitalized patients (%, n=17)
Another Russian study examined the structure of bacterial pathogens of CAP in adult patients hospitalized in multidisciplinary hospitals using standard bacteriological methods and PCR (to detect DNA of C. pneumoniae, M. pneumoniae and L. pneumophila). The material for the study was respiratory samples (sputum, BAL fluid), blood was additionally examined in patients with severe CAP, and autopsy material was used in fatal cases.
An etiological diagnosis was established in 42.7% of cases; M. pneumoniae, H. influenzae and S. pneumoniae were most often detected; they accounted for 77.9% of cases of pneumonia of established etiology (in the form of monoculture and associations). The structure of CAP pathogens, taking into account the degree of severity, is presented in Fig. 2 and 3.
Mortality in CAP depending on the pathogen is presented in Table. 5. The highest mortality rate is observed in CAP caused by S. pneumoniae, Legionella spp., S. aureus, K. pneumoniae.
During a pilot Russian study of the etiology of fatal CAP (autopsy material served as the material for the study), it was shown that the most frequently detected pathogens in this category of patients were K. pneumoniae, S. aureus, S. pneumoniae and H. influenzae (31.4; 28 .6; 12.9 and 11.4% of all isolated strains, respectively).
Table 5. Mortality in CAP
Pathogen Mortality, %
S. pneumoniae 12.3
H. influenzae 7.4
M. pneumoniae 1.4
Legionella spp. 14.7
K. pneumoniae 35.7
C. pneumoniae 9.8
From a practical point of view, it is advisable to identify groups of patients with CAP, taking into account concomitant pathology (COPD, diabetes mellitus, congestive heart failure, cerebrovascular diseases, diffuse diseases of the liver, kidneys with impaired function, chronic alcoholism, etc.), previous antibacterial therapy (taking systemic antibiotics in for >2 consecutive days in the last 3 months) and disease severity. Between these groups there may be differences not only in the etiological structure, the prevalence of drug-resistant strains of known types of pathogens, but also in the prognosis (Table 6).
Table 6. Groups of patients with CAP and probable causative agents of the disease
Characteristics of patients Place of treatment Probable pathogens
Non-severe CAP in persons without concomitant diseases who have not taken antimicrobial agents in the last 3 months Possibility of treatment on an outpatient basis (from a medical point of view) S. pneumoniae M. pneumoniae C. pneumoniae
Non-severe CAP in persons with concomitant diseases and/or who have taken antimicrobial drugs in the last 3 months Possibility of treatment on an outpatient basis (from a medical point of view) S. pneumoniae H. influenzae C. pneumoniae S. aureus Enterobacteriaceae
Non-severe CAP Treatment in hospital: general hospital department S. pneumoniae H. influenzae C. pneumoniae M. pneumoniae S. aureus Enterobacteriaceae
Severe CAP Treatment in hospital: intensive care unit S. pneumoniae Legionella spp. S. aureus Enterobacteriaceae
Table 7. Dynamics of S. pneumoniae resistance to AMPs in the Russian Federation (according to the multicenter study PeGAS I-III, 1999-2009)
V. RESISTANCE OF MAIN PATHOGISTS TO AMP
An important problem currently is the spread of strains with reduced sensitivity to penicillin among pneumococci. In some countries, resistance of pneumococci to penicillin reaches 60%, and many of them are resistant to 3 classes of antibiotics or more. Such strains of pneumococci are called multidrug-resistant.
Resistance of pneumococci to penicillin is usually combined with resistance to cephalosporins of the first and second generations, tetracyclines, and co-trimoxazole. At the same time, III-IV generation cephalosporins (except ceftazidime), respiratory fluoroquinolones, vancomycin and linezolid remain active.
Data on monitoring the resistance of clinical strains of S. pneumoniae in the Russian Federation as part of the multicenter study PeGAS-III are presented in Table. 7. As the study shows, the level of resistance of pneumococci to penicillin in our country remains stable and does not exceed 10%, while in most cases moderately resistant strains are identified. All penicillin-resistant pneumococci (PRP) remain sensitive to amoxicillin and amoxicillin/clavulanate, resistance to ceftriaxone is 2.8%.
The resistance of S. pneumoniae to macrolides does not exceed 10%, however, over time there is a slight increase in the proportion of strains insensitive to macrolides
Antibiotic 1999- 2004- 2006-
2003 2005 2009
(n=791) (n=913) (n=715)
U/R, % R, % U/R, % R, % U/R, % R, %
Penicillin 7.8 1.9 6.9 1.2 9.1 2.1
Amoxicillin 0 0.1 0 0.3 0.4 0
Amoxicillin/clavulanate 0 0 0 0.3 0.4 0
Ceftriaxone/cefotaxime 1.4 0.4 0.9 1.1 0.4 0.6
Cefixime - - - - 2.2 4.6
Ceftibuten - - - - 6.2 6.7
Ertapenem - - - - 0 0
Erythromycin 0.1 8.1 0.2 6.4 1.0 3.6
Azithromycin 0.5 7.6 0.2 6.2 0.9 6.4
Clarithromycin 0.5 7.5 0.3 6.1 1.6 5.7
Josamycin - - - - 1.1 4.1
Midecamycin acetate 0.5 3.3 0.4 3.9 0.6 6.0
Spiramycin 1.0 1.0 0.9 3.6 1.0 5.3
Clindamycin 0.1 2.8 0 3.6 0.2 4.3
Levofloxacin 0 0 0 0.1 0 0
Moxifloxacin 0.3 0 0.1 0 0 0
Gemifloxacin - - - - 0 0
Ciprofloxacin - - - - 6.4 1.4
Tetracycline 2.4 24.9 4.8 24.8 3.1 21.5
Co-trimoxazole 26.3 5.4 29.1 11.8 22.4 16.6
Chloramphenicol 0 7.7 0 5.9 0 7.1
Vancomycin 0 0 0 0 0 0
Note. U/R - moderately resistant strains; R - resistant strains.
pneumococci, as well as an increase in their resistance to clindamycin, which may indicate a change in the predominant resistance phenotype in the Russian Federation in favor of a wider distribution of the mechanism of modification of the target of action - ribosome methylation (MLS phenotype).
Respiratory fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin), vancomycin, and ertapenem remain highly active against S. pneumoniae.
It should be noted that pneumococci remain at a high level of resistance to tetracycline and co-trimoxazole despite a significant reduction in their use for respiratory infections in outpatient practice.
The main mechanism of resistance of H. influenzae is associated with the production of ß-lactamases that hydrolyze aminopenicillins. However, as the PeGAS II study shows, the level of resistance to aminopenicillins among clinical strains of H. influenzae in the Russian Federation in 2003-2005. co-
Table 8. Resistance of H. influenzae to antimicrobial agents in the Russian Federation (n=258) (according to the multicenter study PeGAS II, 2004-2005)
Antibiotic U/R, % R, %
Ampicillin 4.6 0.8
Amoxicillin/clavulanate 0 0
Cefotaxime 0 0
Imipenem 0 0
Ciprofloxacin 0 0
Levofloxacin 0 0
Tetracycline 2.7 2.3
Co-trimoxazole 17.4 12.4
Chloramphenicol 4.3 0.4
Note. U/R - moderately resistant; R - resistant.
put 5.4%. No strains resistant to amoxicillin/clavulanate, third-generation cephalosporins (ceftriaxone), carbapenems, or fluoroquinolones were identified (Table 8). Resistance to tetracycline was 5.0%. The highest level of resistance of H. influenzae was observed to co-trimoxazole (29.8% of non-susceptible strains).
VI. CLINICAL AND RADIOLOGICAL SYMPTOMS AND SIGNS
Clinical diagnosis
In general, the key clinical signs and symptoms of CAP can be formulated as follows:
■ In most cases, based on an analysis of the clinical picture of the disease, it is not possible to speak with certainty about the probable etiology of CAP. In this regard, the division of CAP into “typical” (for example, pneumococcal) and “atypical” (mycoplasma or chlamydial) is of no particular clinical significance.
■ Signs of CAP such as onset with acute fever, chest pain, etc. may be absent, especially in weakened and elderly patients. Approximately 25% of patients over 65 years of age do not have fever, leukocytosis is observed only in 50-70%, and clinical symptoms can include fatigue, weakness, nausea, anorexia, abdominal pain, and impaired consciousness. Often, CAP “debuts” with symptoms of decompensation of concomitant diseases.
■ Late diagnosis and delay in starting antibacterial therapy (more than 4 hours) in hospitalized patients lead to a worse prognosis of the disease.
■ Pleural effusion (usually limited) complicates the course of CAP in 10-25% of cases and is not of particular importance in predicting the etiology of the disease.
0 10 20 30 40 50 60 70 80 90 100 Probability, %
Rice. 4. Probability of diagnosing CAP based on clinical examination data
Pneumonia should be suspected if the patient has a fever in combination with complaints of cough, shortness of breath, sputum production and/or chest pain. Patients suffering from pneumonia often complain of unmotivated weakness, fatigue, and severe sweating at night.
The information obtained from a physical examination of the patient depends on many factors, including the severity of the disease, the extent of pneumonic infiltration, age, and the presence of concomitant diseases.
Classic objective signs of VP are shortening (dullness) of percussion sound over the affected area of the lung, locally auscultated bronchial breathing, a focus of sonorous fine rales or crepitus, increased bronchophony and vocal tremors. However, in some patients, objective signs of CAP may differ from typical ones or be absent altogether (in approximately 20% of patients). The diagnostic value of history and physical examination data is presented in Fig. 4.
X-ray diagnostics
X-ray examination of patients with known or suspected pneumonia is aimed at identifying signs of an inflammatory process in the lungs and its possible complications, as well as assessing their dynamics under the influence of the chosen treatment. Of great importance is the differential diagnosis of changes detected in the lungs with other pathological processes that have clinical manifestations similar to pneumonia.
Radiation examination of patients with pneumonia should begin with a survey radiography of the chest organs in the anterior direct and lateral projections. If the localization of the inflammatory process is unknown, it is advisable to take a picture in the right lateral projection. In practical work, full-length film radiography is often replaced by large-frame fluorography or digital fluorography, which
in these cases it is performed in similar projections. Fluoroscopy is currently not mandatory, much less the primary method for X-ray examination of patients with pneumonia.
An X-ray examination is carried out at the onset of the disease and no earlier than 14 days after the start of antibacterial treatment. X-ray examination can be performed at an earlier date if complications occur or a significant change in the clinical picture of the disease
Detection of inflammatory changes in lung tissue depends on the type of X-ray examination technique used and the correctness of its implementation. The most informative technique is computed tomography (CT). Indications for its use are:
1. In a patient with obvious clinical symptoms of pneumonia, changes in the lungs on x-rays (fluorograms) are absent or are of an indirect nature (for example, a change in the pulmonary pattern).
2. An X-ray examination of a patient with clinically suspected pneumonia revealed changes atypical for this disease.
3. a) Recurrent pneumonia, in which infiltrative changes occur in the same lobe (segment) as in the previous episode of the disease, or b) prolonged pneumonia, in which the duration of existence of infiltrative changes in the lung tissue exceeds 1 month. In both cases, the cause of repeated occurrence or long-term persistence of changes in the lung tissue may be stenosis of a large bronchus, caused, among other things, by a malignant neoplasm, or another lung disease.
The main radiological sign of pneumonia is local compaction (shading, infiltration) of the lung tissue against the background of clinical symptoms of acute inflammatory lung disease. In the absence of a symptom of compaction of the lung tissue, an x-ray conclusion about the presence of pneumonia is invalid. Changes in the pulmonary pattern without infiltration of the lung tissue occur in other diseases, more often as a result of disturbances in the pulmonary circulation in response to intoxication and imbalance of extravascular fluid in the lung, but in themselves are not a sign of pneumonia, including interstitial pneumonia.
The main types of pneumonic changes during X-ray examination are: pleuropneumonia, bronchopneumonia, interstitial pneumonia. The X-ray picture of community-acquired pneumonia has no correlation with the etiology of pneumonia, the severity of its clinical course and does not allow determining the prognosis of the disease. Particular features of the X-ray picture of pneumonia should not be used to determine the etiology of pneumonia.
The most common complications of pneumonia detected by X-ray examination are
exudative pleurisy and abscess. In recognizing pleural effusion, polypositional fluoroscopy and ultrasound are of primary importance. To identify signs of suppuration, it is advisable to use CT or dynamic radiography.
The duration of recovery of pneumonia can vary widely, but is usually 3-6 weeks. X-ray manifestations of resolving pneumonia persist for a longer time than clinical symptoms and are not a reason to continue or discontinue treatment. If the clinical course of the disease is favorable, it is advisable to carry out a control X-ray examination no earlier than 2 weeks from the start of treatment. The purpose of radiography in these cases is to identify central cancer and pulmonary tuberculosis, occurring under the guise of pneumonia.
VII. LABORATORY DIAGNOSTICS AND ADDITIONAL RESEARCH METHODS
Data from a clinical blood test do not allow us to speak about the potential causative agent of CAP. However, leukocytosis more than 10-12x109/l indicates a high probability of bacterial infection; leukopenia below 3x109/l or leukocytosis above 25x109/l are unfavorable prognostic signs.
Biochemical blood tests (functional tests of the liver, kidneys, glycemia, etc.) do not provide any specific information, but detected deviations may indicate damage to a number of organs/systems, which has prognostic significance and also influences the choice of drugs and/or modes of their use.
In patients with symptoms of respiratory failure caused by widespread pneumonic infiltration, massive pleural effusion, development of CAP due to COPD and blood oxygen saturation<90% необходимо определение газов артериальной крови. Гипоксемия со снижением уровня РаО2 ниже 60 мм рт.ст. (при дыхании комнатным воздухом) является прогностически неблагоприятным признаком, указывает на необходимость помещения больного в ОИТ и является показанием к кислородотерапии. Распространенная в нашей стране практика исследования газов в капиллярной крови имеет относительную диагностическую ценность, плохую воспроизводимость и зачастую не соответствует результатам исследования артериальной крови.
The effectiveness of microbiological diagnostics largely depends on the timeliness and correctness of collection of clinical material. The most commonly tested material is sputum obtained by coughing. Rules for obtaining, storing and transporting freely separated sputum are presented in Appendix 1.
The first stage of microbiological examination is Gram staining of the sputum smear. If there is
If there are less than 25 polymorphonuclear leukocytes and more than 10 epithelial cells (when viewing at least 10 fields of view at a magnification of x100), cultural examination of the sample is inappropriate, since in this case the material being studied is most likely significantly contaminated with the contents of the oral cavity.
The detection in a smear of a large number of gram-positive or gram-negative microorganisms with a typical morphology (lanceolate gram-positive diplococci - S. pneumoniae; weakly stained gram-negative coccobacilli - H. influenzae) can serve as a guide for the choice of antibacterial therapy.
Interpretation of the results of bacterioscopy and cultural examination of sputum should be carried out taking into account clinical data.
Patients with severe CAP should obtain blood culture (2 venous blood samples from 2 different veins) before starting antibiotic therapy. General rules for obtaining blood for bacteriological testing are presented in Appendix 1.
However, despite the importance of obtaining laboratory material (sputum, blood) before prescribing antibiotics, microbiological testing should not be a reason for delaying antibacterial therapy. This primarily applies to patients with severe disease.
Serological diagnosis of infections caused by M. pneumoniae, C. pneumoniae and Legionella spp. is not considered among the mandatory research methods, since, taking into account the repeated collection of blood serum in the acute period of the disease and in the period of convalescence (several weeks from the onset of the disease ), this is not a clinical, but an epidemiological level of diagnosis. In addition, many commercial test systems available for diagnosing the above infections are characterized by low reproducibility of results.
Determination of antigens. Currently, immunochromatographic tests with the determination of S. pneumoniae and L. pneumophila antigens (serogroup I) in urine have become widespread. According to epidemiological studies, L. pneumophila serogroup I accounts for 80-95% of cases of community-acquired legionellosis. The sensitivity of the test varies from 70 to 90%, the specificity for detecting L. pneumophila serogroup I reaches 99%. Due to the lack of large-scale studies of the prevalence of L. pneumophila as a causative agent of CAP in the Russian Federation, the advisability of routine use of this rapid test in hospitalized patients with CAP remains unclear. Indications for its implementation may include severe disease, known risk factors for Legionella pneumonia (for example, recent travel), and ineffectiveness of initial ABT with ß-lactam antibiotics, provided they are adequately selected. It should be borne in mind that a negative test does not exclude the diagnosis of Legionella pneumonia, since
it is not validated for the detection of other L. pneumophila serogroups and other Legionella species.
The pneumococcal rapid test demonstrated acceptable sensitivity (50-80%) and fairly high specificity (>90%) for CAP in adults. Its use is most promising when it is impossible to obtain a high-quality sputum sample in patients already receiving systemic ABT, since previous use of antibiotics significantly reduces the informativeness of the culture test.
Legionella and pneumococcal rapid tests remain positive for several weeks after an episode of CAP, so they are of diagnostic value only in the presence of clinical manifestations of the disease.
Polymerase chain reaction (PCR). This method is promising for the diagnosis of bacterial pathogens of CAP such as C. pneumoniae, M. pneumoniae and L. pneumophila. However, the place of PCR in the etiological diagnosis of CAP has not been fully determined, since the available test systems require validation, and data on the impact of routine use of PCR in the etiological diagnosis of CAP on the outcome of treatment are limited.
In the presence of pleural effusion and conditions for safe pleural puncture (visualization on a laterogram of freely displaced fluid with a layer thickness of >1.0 cm), the study of pleural fluid should involve counting leukocytes with a leukocyte formula, determining pH, LDH activity, protein content, bacterioscopy of a stained smear Gram and other methods to identify mycobacteria, culture for aerobes, anaerobes and mycobacteria.
Invasive diagnostic methods. Fibrobronchoscopy with a quantitative assessment of microbial contamination of the obtained material (“protected” brush biopsy, bronchoalveolar lavage) or other invasive diagnostic methods (transtracheal aspiration, transthoracic biopsy, etc.) are recommended only if pulmonary tuberculosis is suspected in the absence of a productive cough, “obstructive pneumonia” due to bronchogenic carcinoma, aspirated bronchial foreign body, etc.
In recent years, in hospitalized patients, in order to differentiate CAP from other lower respiratory tract infections and determine the severity of the condition, the study of serum levels of C-reactive protein and procalcitonin has attracted increasing attention. It has been shown that the highest concentration of C-reactive protein is observed in patients with severe pneumococcal or Legionella pneumonia. The level of procalcitonin, according to various data, also correlates with the severity of the condition of patients with CAP and may be a predictor of the development of complications and unfavorable outcome. However, the question of the advisability of using the above tests in routine practice for CAP has not been completely resolved.
VIII. DIAGNOSIS CRITERIA
The diagnosis of CAP is definite (category of evidence A) if the patient has radiologically confirmed focal infiltration of the lung tissue and at least two clinical signs from the following: a) acute fever at the onset of the disease >38.0 °C); b) cough with sputum; c) physical signs (focus of crepitus and/or fine rales, harsh bronchial breathing, shortening of percussion sound); d) leukocytosis >10x109/l and/or stab shift (>10%). In this regard, one should, whenever possible, strive for clinical and radiological confirmation of the diagnosis of CAP. However, it is also necessary to take into account the likelihood of known syndrome-like diseases/pathological conditions.
The absence or unavailability of radiological confirmation of focal infiltration in the lungs (radiography or large-frame fluorography of the chest organs) makes the diagnosis of CAP inaccurate/uncertain (category of evidence A). In this case, the diagnosis of the disease is based on taking into account the epidemiological history, complaints and corresponding local symptoms.
If, when examining a patient with fever, complaints of cough, shortness of breath, sputum production and/or chest pain, an X-ray examination is not available, and there are no corresponding local symptoms (shortening/dullness of percussion sound over the affected area of the lung, locally auscultated bronchial breathing, focus of sonorous fine bubbling rales or inspiratory crepitus, increased bronchophony and vocal tremors), then the assumption of VP becomes unlikely (evidence category A).
Diagnosis of CAP, based on the results of physical and radiological examination, can only be equated to a syndromic diagnosis; it becomes nosological after determining the causative agent of the disease.
A thorough study of the epidemiological history (categories of evidence B and C) can provide some assistance in predicting the etiology of CAP (Table 9).
It is also necessary to take into account the features of the clinical course of CAP depending on its etiology (category of evidence B and C). Thus, pneumococcal CAP is characterized by an acute onset, high fever, and chest pain; for legionella - diarrhea, neurological symptoms, severe disease, liver dysfunction; for mycoplasma - muscle pain and headaches, symptoms of upper respiratory tract infection.
Despite the fact that in some cases there is a connection between the causative agent of CAP and its clinical and radiological manifestations, the features of the clinical and radiological course of CAP cannot be considered adequate predictors of the etiology of the disease.
Table 9. Epidemiology and risk factors for the development of CAP of known etiology
Conditions of occurrence Probable pathogens
Alcoholism S. pneumoniae, anaerobes, aerobic gram (-) bacteria (usually K. pneumoniae)
COPD/smoking S. pneumoniae, H. influenzae, M. catarrhalis, Legionella spp.
Decompensated diabetes mellitus S. pneumoniae, S. aureus
Staying in nursing homes S. pneumoniae, members of the family Enterobacteriaceae, H. influenzae, S. aureus, C. pneumoniae, anaerobes
Unsanitized oral cavity Anaerobes
Influenza epidemic S. pneumoniae, S. aureus, S. pyogenes, H. Influenzae
Suspected massive aspiration Anaerobes
Development of EP against the background of bronchiectasis, cystic fibrosis P. aeruginosa, B. cepacia, S. aureus
Intravenous Addicts S. aureus, anaerobes
Local bronchial obstruction (eg, bronchogenic carcinoma) Anaerobes
Contact with air conditioners, air humidifiers, water cooling systems L. pneumophila
Outbreak of disease in a closed, organized group (for example, schoolchildren, military personnel) S. pneumoniae, M. pneumoniae, C. pneumoniae
niya (category of evidence B). Moreover, specific clinical manifestations are more often associated not with the biology of the pathogen, but with such factors of the macroorganism as age, the presence or absence of concomitant diseases (category of evidence B). In this regard, the division of CAP into “typical” (caused primarily by S. pneumoniae) and “atypical” (caused by M. pneumoniae, C. pneumoniae, L. pneumophila) has no special clinical meaning.
To establish the etiology of CAP, bacterioscopy of a Gram-stained sputum smear and cultural examination of sputum are performed. Such a study is mandatory in a hospital setting and optional in an outpatient setting. However, due to the limited sensitivity of bacteriological research methods, the etiology of CAP cannot be established in 25-60% of cases (evidence categories B and C).
It should be remembered that no diagnostic tests should cause a delay in the initiation of antibiotic therapy (category of evidence B).
IX. CHARACTERISTICS OF MAIN CLASSES OF AMP
The natural activity of AMP against pathogens of CAP is presented in Table. 10.
ß-lactam antibiotics
ß-lactam antibiotics play an important role in the treatment of patients with CAP, which is due to their powerful bactericidal effect against a number of key pathogens of CAP (primarily S. Pneumonia), low toxicity, as well as many years of experience in their effective and safe use. Despite the increasing resistance of S. pneumoniae to penicillin, ß-lactams remain highly clinically effective in CAP caused by PRP. Most studies in patients without severe immunocompromise have not found an association between penicillin resistance and worse treatment outcomes for CAP.
Amoxicillin and its combinations with ß-lactamase inhibitors - amoxicillin/clavulanate, amoxicillin/sulbactam - are of greatest importance in the treatment of CAP in outpatients.
Amoxicillin has high activity against S. pneumoniae, acts on strains of H. influenzae that do not produce ß-lactamases, compared with ampicillin, it has significantly higher bioavailability when taken orally, independent of food intake, and is less likely to cause adverse reactions from the gastrointestinal tract. intestinal tract.
The advantage of inhibitor-protected amino-penicillins is their activity against ß-lactamase-producing strains of H. influenzae and M. catarrhalis, a number of gram-negative enterobacteria (K. pneumoniae, etc.), methicillin-sensitive strains of S. aureus and non-spore-forming anaerobes that produce ß-lactamase inhibitors sensitive.
Amoxicillin and amoxicillin/clavulanate, when dosed at 80-90 mg/kg/day for amoxicillin, retain activity against PRP. In 2010, a new dosage form of amoxicillin/clavulanate was registered in the Russian Federation, containing 1000 mg of amoxicillin and 62.5 mg of clavulanate in one tablet (recommended dosage regimen - 2 tablets 2 times a day), with a modified (immediate/gradual) release , which provides increased activity against PRP, allows the drug to be used 2 times a day and is characterized by better tolerability.
The key drugs for the treatment of hospitalized patients with CAP are third-generation cephalosporins - cefotaxime and ceftriaxone, which have high activity against S. pneumoniae, including PRP, H. influenzae, M. catarrhalis, as well as a number of gram-negative enterobacteria. An important pharmacokinetic advantage of ceftriaxone is its long half-life, allowing it to be administered once a day.
Benzylpenicillin remains highly active against S. pneumoniae (including PRP) and is recommended primarily for confirmed pneumococcal etiology of CAP.
Amoxicillin/clavulanate and amoxicillin/sulbactam can be used as step-down therapy for CAP in hospitalized patients.
The main disadvantage of all ß-lactam antibiotics is the lack of activity against “atypical” microorganisms (M. pneumoniae, C. pneumoniae, L. pneumophila).
Macrolides
The advantage of macrolides, along with their effect on S. pneumoniae, is their high activity against “atypical” microorganisms (M. pneumoniae, C. pneumoniae, L. pneumophila). Modern macrolides penetrate well into bronchial secretions and lung tissue, creating concentrations in them that are significantly higher than those in blood serum, are characterized by a favorable safety profile and the absence of cross-allergy with ß-lactam antibiotics.
Macrolides (erythromycin, clarithromycin, azithromycin, etc.) are the drugs of choice for the treatment of CAP caused by atypical microorganisms (mycoplasma, chlamydia), legionella pneumonia. Erythromycin, clarithromycin, spiramycin and azithromycin are available in both parenteral and oral dosage forms (DOF), which makes their use possible as part of stepwise therapy for CAP.
Currently, a new dosage form of azithromycin is available in the Russian Federation, which is a microcrystalline substance in the form of azithromycin dihydrate, which, when reduced in water, forms an alkaline suspension. This causes a slow release of the active substance in the stomach and duodenum. A single dose of the new azithromycin dosage form at a dose of 2.0 g, providing 100% compliance, allows for higher and more stable drug concentrations in plasma and is characterized by an effectiveness comparable to standard 3-5-day courses of therapy. According to the results of the clinical trial, a single dose of the new dosage form azithromycin for non-severe CAP was not inferior in effectiveness to 7-day therapy with clarithromycin and levofloxacin.
As a number of retrospective and prospective studies have shown, the use of macrolides in combination with ß-lactams compared with ß-lactam monotherapy in hospitalized patients with CAP is accompanied by a reduction in the length of hospital stay, a decrease in mortality, and a decrease in direct treatment costs.
There are reports of the ineffectiveness of macrolides when S. pneumoniae is resistant to them in vitro, which in most cases was observed in severe CAP accompanied by bacteremia. In addition, the low natural activity of macrolides against H. influenzae should be taken into account.
Table 10. Natural in vitro activity of AMPs against the main pathogens of CAP
Antibiotic S. pneumoniae (PPP) S. pneumo-niae (PRP) H. influenzae M. pneumo-niae, C. pneumo-niae Legionella spp. S. aureus (MSSA) S. aureus (MRSA) Klebsiella pneumoniae Pseudomonas aeruginosa
Benzylpenicillin1 +++ 0 + 0 0 0 0 0 0
Ampicillin ++ + ++ 0 0 0 0 0 0
Amoxicillin +++ +++ ++ 0 0 0 0 0 0
Amoxicillin/clavulanate, amoxicillin/sulbactam +++ +++ +++ 0 0 +++ 0 ++ 0
Cefazolin + 0 + 0 0 +++ 0 0 0
Cefuroxime ++ + ++ 0 0 ++ 0 ++ 0
Cefotaxime, ceftriaxone +++ ++ +++ 0 0 ++ 0 +++ 0
Ceftazidime 0 0 +++ 0 0 0 0 +++ +++
Cefepime +++ ++ +++ 0 0 +++ 0 +++ +++
Imipenem, meropenem2 +++ ++ +++ 0 0 +++ 0 +++ +++
Ertapenem ++ + +++ 0 0 ++ 0 +++ 0
Macrolides +++ ++ 0/+3 +++ +++ ++ 0 0 0
Doxycycline ++ ++ ++ +++ ++ ++ 0 0 0
Clindamycin, lincomycin4 +++ ++ 0 0 0 +++ + 0 0
Co-trimoxazole ++ + ++ 0 + ++ ++ + 0
Ciprofloxacin + + +++ ++ +++ + + +++ +++
Levofloxacin, moxifloxacin, gemifloxacin5 +++ +++ +++ +++ +++ ++ ++ +++ ++
Vancomycin +++ +++ 0 0 0 +++ +++ 0 0
Linezolid +++ +++ + 0 0 +++ +++ 0 0
Note. PPP - penicillin-sensitive strains of S. pneumonia; PRP - penicillin-resistant strains of S. pneumoniae; MSSA - methicillin-sensitive strains of S. aureus; MRSA - methicillin-resistant strains of S. aureus; +++ - high activity, confirmed by clinical data (AMP may be the drug of choice); ++ - good activity, confirmed by clinical data (AMP may be an alternative drug); + - low AMP activity; 0 - lack of clinically significant activity (in some cases with in vitro activity; 1, the prevalence of pneumococci insensitive to benzylpenicillin in the Russian Federation is 11.2% (of which -2.1% are strains with a high level of resistance - MIC >2 mg/l; 2 imipenem is slightly more active against gram-positive cocci; 3 azithromycin and clarithromycin have clinically significant activity against H. influenzae; 4 lincomycin is less active in vitro than clindamycin against most pathogens; 5 the activity of moxifloxacin against P. aeruginosa is lower than that of levofloxacin and has no clinical significance; levofloxacin is inferior in activity against S. pneumoniae to moxifloxacin and gemifloxacin.
Fluoroquinolones
Among the drugs in this group, the most important for CAP are the so-called respiratory fluoroquinolones - levofloxacin, moxifloxacin and gemifloxacin, which act on almost all possible causative agents of CAP, including PRP, ß-lactamase-producing strains of H. influenzae, and their activity against mycoplasmas and chlamydia and S.aureus is significantly higher compared to previous generation fluoroquinolones (ciprofloxacin, ofloxacin, etc.).
Good microbiological characteristics of the drugs are combined with favorable pharmacokinetics.
Chinese parameters (long half-life, allowing for once daily use, high concentrations in bronchial secretions and lung tissue).
The presence of oral and parenteral dosage forms for levofloxacin and moxifloxacin allows their use for stepwise therapy of CAP in hospitalized patients.
In numerous clinical trials, levofloxacin and moxifloxacin have demonstrated comparable or superior clinical efficacy compared to macrolides, β-lactams, and their combinations in outpatient and hospitalized patients with CAP.
Second generation fluoroquinolones (ciprofloxacin, ofloxacin, etc.) due to their low activity against S. pneumoniae and “atypical” pathogens (except for Legionella spp.) are not advisable to use in monotherapy for CAP.
Tetracyclines
Among tetracyclines, the most acceptable, taking into account pharmacokinetic characteristics, tolerability and ease of use, is doxycycline. It is characterized by good activity against “atypical” microorganisms (M. pneumoniae, C. pneumoniae, L. pneumophila) and a low level of secondary resistance of H. influenzae in the Russian Federation. Another advantage is the low cost and availability of the drug. However, the high frequency of isolation of tetracycline-resistant strains of S. pneumoniae in Russia does not allow us to consider it as a drug of choice for empirical treatment of CAP.
Drugs of other groups
The only oxazolidinone currently available in clinical practice that has demonstrated efficacy in CAP of proven or suspected pneumococcal etiology is linezolid. The main advantage of the drug is its high activity against multidrug-resistant gram-positive microorganisms, including PRP, methicillin-resistant S. aureus. Another advantage is the presence of oral and parenteral dosage forms with high bioavailability, which allows the drug to be used in hospitalized patients for step-down therapy.
Among the carbapenems, the most promising drug for the treatment of CAP is ertapenem. In terms of activity against most gram-positive and gram-negative microorganisms, it is similar to imipenem and meropenem, but does not have clinically significant activity against P. aeruginosa and Acinetobacter spp., which is an important advantage in CAP. The clinical and microbiological effectiveness of erta-penem has been proven in hospitalized patients with CAP. The advantage of the drug is the possibility of its single use per day.
Linezolid and ertapenem are not active against “atypical” pathogens (M. pneumoniae, C. pneumoniae, Legionella spp.).
X. ETIOTROPIC THERAPY OF CAP
This section presents the selection of AMPs for etiotropic therapy of the main causative agents of CAP, taking into account the natural activity of the drugs. However, in each specific situation it is necessary to take into account the prevalence and nature of secondary resistance of pathogens.
The drugs of choice for the treatment of pneumococcal CAP are ß-lactams - benzylpenicillin, amino-penicillins (amoxicillin - orally, ampicillin -
parenterally), including inhibitor-protected ones (amoxicillin/clavulanate, etc.) and third-generation cephalosporins (cefotaxime, ceftriaxone). Macrolide antibiotics are alternative drugs for allergies to ß-lactams. Respiratory fluoroquinolones (levofloxacin, moxifloxacin, hemifloxacin), vancomycin and linezolid are highly effective (including for CAP caused by PRP).
Aminoglycosides (gentamicin, etc.) do not have clinically significant activity against S. pneumoniae.
The drugs of choice for the treatment of CAP caused by H. influenzae are aminopenicillins (amoxicillin - orally, ampicillin - parenterally), amoxicillin/clavulanate, amoxicillin/sulbactam (active against strains producing ß-lactamases), II-III generation cephalosporins, fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gemifloxacin).
M. pneumoniae, C. pneumoniae
Macrolides, tetracyclines (doxycycline), and respiratory fluoroquinolones, which are the drugs of choice for CAP of mycoplasmal and chlamydial etiology, have the greatest natural activity against “atypical” pathogens. Reports of the presence of acquired resistance of the above microorganisms to macrolides, tetracyclines and fluoroquinolones remain isolated and do not have significant clinical significance.
The drugs of choice for the treatment of Legionella CAP are macrolides (erythromycin, clarithromycin, azithromycin). Fluoroquinolones (levofloxacin) have also demonstrated high efficacy in clinical studies. Doxycycline may be used as an alternative drug.
The advantages of combination therapy for confirmed legionella CAP, in particular the advisability of adding rifampicin to macrolides, are not so obvious today.
The drug of choice for staphylococcal pneumonia caused by MSSA is oxacillin; alternatives may include amoxicillin/clavulanate, amoxicillin/sulbactam, first generation cephalosporins, and lincosamides. If MRSA is detected, the use of vancomycin or linezolid is recommended, with the latter being preferred due to its more attractive pulmonary pharmacokinetics.
Enterobacteriaceae
Amoxicillin/clavulanate, amoxicillin/sulbactam, III-IV generation cephalosporins, carbapenems, and fluoroquinolones have high natural activity against these pathogens.
XI. CHOOSING A TREATMENT LOCATION
The choice of treatment site is a key issue for the doctor after confirming the diagnosis of CAP, as it determines the scope of treatment and diagnostic procedures and, thus, the cost of treatment. In accordance with modern principles of management of adult patients with CAP, a significant number of them can be treated at home. In this regard, the definition of criteria or indications for hospitalization is of particular importance. There are a number of clinical and laboratory scales that, based on the assessment of the prognosis of the disease, provide recommendations on the choice of place of treatment. The most widely used scale in the world is the PORT (Pneumonia Outcomes Research Team) scale, which involves determining 20 clinical and laboratory parameters, on the basis of which the so-called pneumonia severity index (PSI - Pneumonia Severity Index) is established, the risk of death is predicted and recommendations are formulated on the choice of place of treatment and priority areas of empirical antibacterial therapy (Appendix 2). However, to determine PSI, it is necessary to study a number of biochemical parameters, including urea, sodium, glucose, hematocrit, arterial blood pH, which is not available in outpatient clinics and many hospitals in the Russian Federation.
The CURB-65 and CRB-65 prognostic scales are simpler and more accessible for routine use. They are based on the modified British Thoracic Society scale, which involves the assessment of 5 and 4 parameters, respectively: age, impairment of consciousness, respiratory rate, systolic and diastolic blood pressure, urea nitrogen (the last parameter is not included in the CRB-65 scale). Based on the likelihood of death, patients are divided into 3 groups, for each of which a preferred place of treatment is recommended (outpatient, general hospital or ICU). The minimum number of points on this scale is 0, the maximum is 4 or 5 points. A detailed description of the CURB-65 and CRB-65 scales is presented in Appendix 2.
From a practical point of view, the CRB-65 scale is of greatest interest, the use of which is possible in outpatient settings, since it does not require the measurement of blood urea nitrogen.
Studies show that the predictive potential of the CURB-65/CRB-65 scales for patients at low risk of poor prognosis is not inferior to the PORT scale. At the same time, they are less studied than the PORT scale. In addition, to date there are no prospective controlled studies confirming the reduction in unnecessary hospitalizations when using the CURB-65 and CRB-65 scales in routine clinical practice.
Another scale, developed more recently by the Australian CAP Working Group, is based on assessing the severity of CAP, in particular identifying patients requiring intensive respiratory support and fluid resuscitation.
vasopressors to maintain adequate blood pressure levels. The SMART-COP scale provides a score for clinical, laboratory, physical and radiological signs to determine the probable need for the above intensive treatment methods. Its description is presented in Appendix 2. A modified version of the SMRT-C0 scale can be used in outpatient practice and hospital emergency departments, since it does not require the determination of parameters such as albumin level, PaO2 and arterial blood pH. Research by P.G.P. Charles et al. demonstrated a higher sensitivity of SMART-COP in identifying patients with severe CAP compared with the PORT and CURB-65 scales described above.
In the study by V.A. Rudnova et al., which included an analysis of observations of 300 cases of CAP in the ICU, showed comparable information content of the PORT, CURB-65, CRB-65 and SMRT-CO scales in predicting outcome in patients with severe CAP disease.
The introduction of the prognostic scales described above in CAP is certainly useful, as it allows to reduce the frequency of unreasonable hospitalizations among patients with a low risk of poor prognosis, as well as to identify the category of people in need of intensive care. However, their use is associated with a number of difficulties: they assess the severity of the patient's condition and / or prognosis in a specific period of time, while not taking into account the variability of the clinical picture of CAP and the possibility of a very rapid progression of the disease. Prognostic scales do not consider factors such as decompensation of concomitant chronic diseases, which are often the main reason for hospitalization of patients, as well as non-medical indications for hospitalization. Therefore, any of the prognostic scales can only be a guide in choosing the place of treatment, in each case this issue should be decided by the attending physician individually.
Hospitalization for a confirmed diagnosis of CAP is indicated if at least one of the following is present:
1. Physical examination data: respiratory rate >30/min; diastolic blood pressure<60 мм рт.ст.; систолическое артериальное давление <90 мм рт.ст.; частота сердечных сокращений >125/min; temperature<35,5 °С или >39.9 °C; disturbance of consciousness.
2. Laboratory and radiological data: the number of peripheral blood leukocytes<4,0х109/л или >20.0x109/l; SaO2<92% (по данным пульсоксиметрии), РаО2 <60 мм рт.ст. и/или РаСО2 >50 mmHg when breathing room air; serum creatinine >176.7 μmol/L or urea nitrogen >7.0 mmol/L (urea nitrogen = urea, mmol/L/2.14); pneumonic infiltration localized in more than one lobe; presence of decay cavity(s); pleural effusion; rapid progression of focal infiltrative changes in the lungs (increase in the size of infiltration >50% over the next 2 days); hematocrit<30% или
hemoglobin<90 г/л; внелегочные очаги инфекции (менингит, септический артрит и др.); сепсис или полиорганная недостаточность, проявляющаяся метаболическим ацидозом (рН <7,35), коагулопатией.
3. The inability to provide adequate care and follow all medical prescriptions at home.
The question of the preference for inpatient treatment of CAP may be considered in the following cases:
1. Age over 60 years.
2. The presence of concomitant diseases (chronic bronchitis/COPD, bronchiectasis, malignant neoplasms, diabetes mellitus, chronic renal failure, congestive heart failure, chronic alcoholism, drug addiction, severe body mass deficiency, cerebrovascular diseases).
3. Ineffectiveness of initial antibiotic therapy.
4. Pregnancy.
5. The wishes of the patient and/or his family members.
In cases where the patient has signs of severe CAP (tachypnea >30/min; systolic blood pressure<90 мм рт.ст.; двусторонняя или многодолевая пневмоническая инфильтрация; быстрое прогрессирование очагово-инфильтративных изменений в легких, септический шок или необходимость введения вазопрессоров >4 hours; acute renal failure), requiring urgent hospitalization in the ICU.
In addition to collecting anamnesis and physical examination, the diagnostic minimum should include studies to establish the diagnosis of CAP and decide on the severity of the course and the need for hospitalization of the patient. These include:
X-ray of the chest organs in 2 projections;
General blood analysis.
The diagnosis of CAP can be established only on the basis of the clinical picture of the disease and physical examination data without an X-ray examination. However, chest x-ray is useful in terms of assessing the severity of the disease, the presence of complications and deciding on hospitalization.
Routine microbiological diagnosis of CAP in outpatient practice is not informative enough and does not significantly influence the choice of an antibacterial drug (category of evidence B).
The characteristics of the activity of various classes of AMPs used for the treatment of CAP in relation to key pathogens are presented in Table. 10.
battle on the etiological structure and tactics of antibacterial therapy. The dosage regimen of antibacterial drugs is presented in table. 20.
Group 1 included patients without concomitant diseases and who had not taken systemic AMPs for >2 days in the last 3 months. In these patients, an adequate clinical effect can be obtained with the use of oral drugs (evidence category C). Amoxicillin (evidence category D) or macrolide antibiotics are recommended as the drugs of choice. Although in vitro aminopenicillins do not cover the entire spectrum of potential pathogens, clinical studies have not revealed differences in the effectiveness of these antibiotics, as well as individual members of the macrolide class or respiratory fluoroquinolones (category of evidence A).
Macrolides should be preferred if an "atypical" etiology of the disease (M. pneumoniae, C. pneumoniae) is suspected.
A meta-analysis of 13 randomized clinical trials, including 4314 outpatients aged >18 years, was devoted to the question of the comparative effectiveness of various antibacterial drugs in CAP. The meta-analysis compared the results of treatment with oral drugs from different classes, including those with (macrolides, fluoroquinolones) and those without (cephalosporins, aminopenicillins) activity against atypical pathogens. The study did not reveal statistically significant advantages of macrolides and fluoroquinolones over ß-lactams, as well as significant differences in treatment outcomes between individual classes of drugs, in particular macrolides and fluoroquinolones.
Table 11. Antibacterial therapy for community-acquired pneumonia in outpatients
Non-severe CAP in patients without concomitant diseases who have not taken AMPs for >2 days in the last 3 months
Most common pathogens
S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae
Mild CAP S. pneumoniae Amoxicillin/
in patients with H. influenzae clavulanate,
with concomitant C. pneumoniae amoxicillin/
diseases S. aureus sulbactam orally
and/or Entero- ± macrolide orally
have taken bacteriaceae or respiratory
for the latest fluoroquinolone
3 months AMP (levofloxacin,
>2 days moxifloxacin,
gemifloxacin) inside
Note. 1 Macrolides are the drugs of choice for suspected “atypical” etiology of CAP (C. pneumoniae, M. pneumoniae). Preference should be given to the most studied macrolides for CAP with improved pharmacokinetic properties (azithromycin, clarithromycin) or a favorable safety profile and minimal frequency of drug interactions (josamycin, spiramycin).
Drugs of choice
Amoxicillin orally or macrolide orally1
The 2nd group included CAP patients with concomitant diseases (COPD, diabetes mellitus, congestive heart failure, chronic renal failure, liver cirrhosis, chronic alcoholism, drug addiction, exhaustion) and/or who took AMP for >2 days in the last 3 months, which can influence the etiology and cause an unfavorable outcome of the disease.
In patients of this group, an adequate clinical effect can also be obtained by prescribing oral antibiotics. Since the likelihood of the etiological role of gram-negative microorganisms (including those with some resistance mechanisms) in these patients increases, amoxicillin / clavulanate or amoxicillin / sulbactam are recommended as the drug of choice. In patients of this category, it is possible to prescribe a combination of β-lactam and a macrolide due to the possible atypical etiology of CAP, however, to date, this strategy has not been proven to improve treatment outcomes. An alternative to combined therapy with β-lactams and macrolides can be the use of a respiratory fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin).
The widespread practice in some regions of the widespread use of aminoglycosides (gentamicin, etc.), cefazolin and ciprofloxacin in the treatment of CAP should be recognized as erroneous, since they are not active against key CAP pathogens.
Parenteral administration of antibiotics in outpatient settings
Parenteral antibiotics in the treatment of CAP on an outpatient basis have no proven advantages over oral ones. They can be used only in isolated cases (for example, when there is a suspected low compliance with oral medications, refusal or impossibility of timely hospitalization). In patients under the age of 60 years, in the absence of significant comorbidities, ceftriaxone or benzylpenicillin procaine can be used intramuscularly. In patients 60 years of age and older, intramuscular ceftriaxone is recommended. It is possible to combine the above drugs with macrolides or doxycycline (evidence category D).
An initial assessment of the effectiveness of therapy should be carried out 48-72 hours after the start of treatment (re-examination). It is advisable to have telephone contact with the patient the day after the start of therapy. The main criteria for effectiveness during this period are a decrease in temperature, a decrease in symptoms of intoxication, shortness of breath and other manifestations of respiratory failure. If the patient continues to have high fever and intoxication, or symptoms progress, then treatment should be considered ineffective. In this case, it is necessary to reconsider the tactics of antibacterial therapy and re-evaluate the advisability of
the patient's hospitalization. Recommendations for changing the antibacterial therapy regimen are given in Table. 12. If there is no adequate effect of amoxicillin therapy, it should be replaced with (or added to) a macrolide antibiotic (evidence category C).
Table 12. Choice of antibacterial drug if the initial treatment regimen for CAP is ineffective in an outpatient setting
Preparations for I Preparations for II Comments
stage of treatment stage of treatment
Amoxicillin Macrolide Possible “atypical” microorganisms (C. pneumoniae, M. pneumoniae)
Amoxicillin/clavulanate Amoxicillin/sulbactam Respiratory fluoroquinolone Macrolide Possible “atypical” microorganisms (C. pneumoniae, M. pneumoniae)
Macrolides Amoxicillin Amoxicillin/clavulanate Amoxicillin/sulbactam Respiratory fluoroquinolones A possible reason for the ineffectiveness of macrolides is resistant pneumococci or Gram(-) bacteria
Note. Macrolides can be prescribed either instead of or in addition to β-lactams.
To date, the optimal duration of treatment for patients with CAP remains a subject of debate. The key criterion for discontinuing ABT in non-severe CAP is persistent normalization of body temperature over 48-72 hours with positive dynamics of other symptoms and the absence of signs of clinical instability:
Temperature<37,8 °С;
Heart rate< 100/мин;
Breathing rate< 24 мин;
Systolic blood pressure >90 mmHg;
Saturation 02 >90% or Pa02 >60 mm Hg when breathing room air.
With this approach, the duration of treatment usually does not exceed 7 days (category of evidence C). Studies carried out in recent years indicate that in uncomplicated CAP, high clinical efficacy can be achieved with the use of shorter courses of antibacterial therapy. In particular, in the meta-analysis ¿.1. 1_1 et al. compared the effectiveness of short (<7 дней) и стандартного (>7 days) courses of antibiotic therapy in adults with mild CAP in randomized clinical trials (the short course group included drugs of different classes - p-lactams, fluoroquinolones, macrolides). According to such parameters as the frequency of clinical failures, mortality and microbiological effectiveness of the group
py did not differ significantly. Similar results were obtained in another meta-analysis by G. Dimopoulus et al., which included outpatient and hospitalized patients with non-severe CAP. Short courses of therapy (3-7 days) did not differ in clinical efficacy and safety from standard ones (7-10 days).
At the same time, it should be noted that a short course of antibiotic therapy can only be used in patients with uncomplicated CAP. Short courses may not be effective enough in elderly patients, with chronic concomitant diseases, with a slow clinical response to treatment, as well as in cases of CAP caused by pathogens such as S. aureus, P. aeruginosa.
Criteria for the adequacy of antibacterial therapy for CAP:
Temperature<37,5 °С;
No intoxication;
No purulent sputum;
<10х109/л, нейтрофи-лов <80%, юных форм <6%;
No negative dynamics on the radiograph. Retention of individual clinical, laboratory or
X-ray signs of CAP are not an absolute indication for continuation of antibacterial therapy or its modification (Table 13). In the overwhelming majority
Table 13. Clinical signs and conditions that are not indications for continuing antibiotic therapy or replacing antimicrobial agents
Clinical signs Explanation
Persistent low-grade fever (body temperature within 37.0-37.5 ° C) In the absence of other signs of bacterial infection, it can be a manifestation of non-infectious inflammation, post-infectious asthenia (autonomic dysfunction), drug fever
Persistence of residual changes on the radiograph (infiltration, increased pulmonary pattern) Can be observed within 1-2 months after CAP
Dry cough Can be observed for 1-2 months after CAP, especially in smokers and patients with COPD
Persistence of wheezing during auscultation Dry wheezing can be observed for 3-4 weeks or more after CAP and reflects the natural course of the disease (local pneumosclerosis at the site of the focus of inflammation)
An increase in ESR is a nonspecific indicator and is not a sign of a bacterial infection.
Continued weakness, sweating Manifestations of post-infectious asthenia
In most cases, their resolution occurs independently or under the influence of symptomatic therapy. Long-lasting low-grade fever is not a sign of a bacterial infection (category of evidence B).
X-ray manifestations of CAP resolve more slowly than clinical symptoms, so control chest X-ray cannot serve as a criterion for determining the duration of antibacterial therapy (evidence category B).
However, with long-lasting clinical, laboratory and radiological symptoms of CAP, it is necessary to carry out a differential diagnosis with diseases such as lung cancer, tuberculosis, congestive heart failure, etc. (see section XII).
HOSPITALIZED
PATIENTS
Diagnostic minimum examination
In addition to collecting anamnesis and physical examination, the diagnostic minimum should include studies to establish the diagnosis of CAP and decide on the severity of the course and the place of treatment of the patient (therapeutic department or ICU). These include (evidence categories B and C):
■ chest x-ray in 2 projections;
■ complete blood count;
■ biochemical blood test - urea, creati-
nin, electrolytes, liver enzymes;
■ microbiological diagnostics:
Microscopy of sputum smear, Gram-stained;
Bacteriological examination of sputum to isolate the pathogen and determine its sensitivity to antibiotics;
Bacteriological blood test (it is optimal to examine two samples of venous blood from different veins)*.
Pulse oximetry (BaO2) can be recommended as additional research methods in patients with non-severe CAP.<90% является критерием тяжелой ВП и показанием для проведения кислородотерапии) и электрокардиографическое исследование. При тяжелой ВП целесообразно исследовать газы артериальной крови (Р02, РС02) для уточнения потребности в проведении ИВЛ (категория доказательств А). В качестве дополнительного метода исследования могут быть рекомендованы экспресс-тесты на наличие пневмококковой и легионел-лезной антигенурии.
In the presence of pleural effusion, a pleural puncture is performed and a cytological, biochemical and microbiological examination of the pleural fluid is performed (categories of evidence C and B).
* The study is mandatory for severe CAP.
Criteria for severe CAP and the need for patient management in the ICU
When a patient with CAP is admitted to a hospital, it is necessary, first of all, to assess the severity of his condition and decide on the place of treatment (general department or ICU).
Severe CAP is a special form of the disease of various etiologies, manifested by severe respiratory failure and/or signs of severe sepsis, characterized by a poor prognosis and requiring intensive care (Table 14). The presence of each of these criteria significantly increases the risk of an unfavorable outcome of the disease (category of evidence A).
Table 14. Criteria for severe course of VP1
Clinical and instrumental laboratory criteria
criteria
Acute respiratory leukopenia (<4*109/л)
failure: Hypoxemia:
Respiration rate - Pa02<60 мм рт.ст. Гемоглобин <100 г/л
Ea02<90% Гематокрит <30%
Hypotension Acute renal
Systolic blood pressure failure (creatinine
<90 мм рт.ст. крови >176.7 µmol/l,
Diastolic blood pressure urea nitrogen >7.0 mmol/l)
<60 мм рт.ст.
Double or multi-lobed
lung injury
Disturbance of consciousness
Extrapulmonary focus
infections (meningitis,
pericarditis, etc.)
Note. 1 If at least one criterion is present, CAP is regarded as severe.
In case of CAP, it is extremely important to quickly assess the severity of the patient's condition in order to identify signs of severe CAP requiring emergency treatment (category of evidence D), which should be carried out in the ICU.
The SMART-COP prognostic scale (Appendix 2) can be considered as a promising method for identifying a group of patients requiring intensive respiratory support and/or vasopressors.
Selection of initial antibiotic therapy
In hospitalized patients, a more severe course of CAP is expected, so it is advisable to begin therapy with parenteral antibiotics. After 2-4 days of treatment, when the temperature normalizes, intoxication and other symptoms of the disease decrease, it is possible to switch from parenteral to oral use of the antibiotic until the full course of therapy is completed (category of evidence B). In case of non-severe CAP in hospitalized patients, especially in case of hospitalization for non-medical reasons, immediate administration of oral antibiotics is allowed (evidence category B).
In hospitalized patients with mild CAP, parenteral use of benzylpenicillin, ampicillin, inhibitor-protected aminopenicillins (amoxicillin/clavulanate, amoxicillin/sulbactam), cephalosporins may be recommended.
Table 15. Antibacterial therapy for community-acquired pneumonia in hospitalized patients
Mild pneumonia1 S. pneumoniae H. influenzae C. pneumoniae S. aureus Enterobacteriaceae Benzylpenicillin IV, IM ± macrolide orally2 Ampicillin IV, IM ± macrolide orally2 Amoxicillin/clavulanate IV ± macrolide orally2 Amoxicillin/sulbactam IV, IM ± macrolide2 Cefotaxime IV, IM ± macrolide orally2 Ceftriaxone IV, IM ± macrolide orally2 Ertapenem IV, IM ± macrolide orally2 or Respiratory fluoroquinolone (levofloxacin, moxifloxacin) IV
Severe pneumonia3 S. pneumoniae Legionella spp. S. aureus Enterobacteriaceae Amoxicillin/clavulanate IV + macrolide IV Cefotaxime IV + macrolide IV Ceftriaxone IV + macrolide IV Ertapenem IV + macrolide IV or Respiratory fluoroquinolone (levofloxacin, moxifloxacin) IV + cefotaxime, ceftriaxone IV
Note. 1 Stepped therapy is preferred. If the patient’s condition is stable, oral administration of drugs is allowed immediately.
2 Preference should be given to the most studied macrolides for CAP with improved pharmacokinetic properties (azithromycin, clarithromycin) and/or a favorable safety profile and minimal frequency of drug interactions (josamycin, spiramycin).
3 If there are risk factors for P. aeruginosa infection (bronchiectasis, use of systemic glucocorticoids, broad-spectrum antibiotic therapy for more than 7 days in the last month, exhaustion), the drugs of choice are ceftazidime, cefepime, cefoperazone/sulbactam, ticarcillin/clavulanate piperacillin/tazobactam, carbapenems (meropenem, imipenem), ciprofloxacin. All of the above drugs can be used in monotherapy or combination with aminoglycosides of the II-III generation. If aspiration is suspected, it is advisable to use amoxicillin/clavulanate, cefoperazone/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam, carbapenems (meropenem, imipenem).
III generation (cefotaxime, ceftriaxone) or ertapenem. According to the results of a number of prospective and retrospective studies, the presence of an antibiotic active against atypical microorganisms in the initial treatment regimen improves the prognosis and reduces the length of patient stay in the hospital (evidence categories B and C). This circumstance makes the use of p-lactam in combination with a macrolide justified.
An alternative to combination therapy (P-lactam ± macrolide) may be monotherapy with a respiratory fluoroquinolone (moxifloxacin, levofloxacin).
In severe CAP, antibiotics should be prescribed urgently (category of evidence B); a delay in their administration of 4 hours or more significantly worsens the prognosis. The drugs of choice are third-generation intravenous cephalosporins, inhibitor-protected penicillins (amoxicillin/clavulanate) or carba-penems without antipseudomonal activity (ertapenem) in combination with macrolides for intravenous administration (erythromycin, clarithromycin, spiramycin, azithromycin). These combinations cover almost the entire spectrum of potential pathogens (both typical and "atypical") of severe CAP.
Early fluoroquinolones (ciprofloxacin, etc.) are characterized by weak antipneumococcal activity; cases of ineffective treatment of CAP caused by S. pneumoniae have been described.
Of the drugs in the fluoroquinolone group, preference should be given to respiratory fluoroquinolones (moxifloxacin, levofloxacin), which are administered intravenously. There are data from controlled clinical trials on the effectiveness of monotherapy with respiratory fluoroquinolones in severe CAP, comparable to the standard treatment regimen (a combination of a β-lactam antibiotic and a macrolide). However, such studies are few in number, so a combination of fluoroquinolones with third-generation cephalosporins (cefotaxime, ceftriaxone) is more reliable.
Criteria for the effectiveness of antibacterial therapy
The initial assessment of effectiveness should be carried out 48-72 hours after the start of treatment. The main criteria for effectiveness during these periods are a decrease in body temperature, intoxication and respiratory failure. If the patient continues to have high
fever and intoxication or the symptoms of the disease progress, then treatment should be considered ineffective. In this case, it is necessary to reconsider the tactics of antibacterial therapy. Recommendations for changing antibiotics are given in Table. 16. If therapy with β-lactam and macrolide is ineffective, it is advisable to prescribe respiratory fluoroquinolones - levofloxacin, moxifloxacin (evidence category C).
If antibacterial therapy is ineffective at stage II, it is necessary to examine the patient to clarify the diagnosis or identify possible complications of CAP (see sections XI-XII).
To assess the patient’s condition and the effectiveness of therapy, it is advisable, in addition to microbiological diagnostics, to carry out the following studies:
■ Complete blood count: upon admission, on the 2-3rd day and after the end of antibacterial therapy;
■ Biochemical blood test (ALT, AST, creatinine, urea, glucose, electrolytes): upon admission and after 1 week if there are changes in the first study or clinical deterioration;
■ Study of arterial blood gases (in severe cases): daily until the parameters normalize;
■ Chest X-ray: upon admission and 2-3 weeks after the start of treatment; if the condition worsens - at an earlier date.
Duration of antibacterial therapy
For mild CAP, antibacterial therapy can be completed once stable normalization of body temperature is achieved within 48-72 hours. With this approach, the duration of treatment is usually 7 days. For severe CAP of unspecified etiology, a 10-day course of antibiotic therapy is recommended (category of evidence D). Longer therapy (at least 14 days) is indicated for CAP of staphylococcal etiology or CAP caused by enterobacteria and P. aeruginosa (category of evidence C), and in the presence of extrapulmonary foci of infection, the duration of treatment is determined individually. For Legionella pneumonia, a 7-14-day course of therapy is usually sufficient, but for complicated cases, extrapulmonary foci of infection and a slow response, the duration of treatment is determined individually (category of evidence C).
Table 16. Choice of antibacterial drug if the initial treatment regimen is ineffective in hospitalized patients
Drugs at the first stage of treatment Drugs at the second stage of treatment Comments
Ampicillin Replace with (or add) a macrolide If the condition worsens, replace with third-generation cephalosporins, inhibitor-protected aminopenicillins + macrolide Possible “atypical” microorganisms (C. pneumoniae, M. pneumoniae, Legionella spp.), Gram (-) enterobacteria and S.aureus
Inhibitor-protected aminopenicillins Add macrolide Possible “atypical” microorganisms (C. pneumoniae, M. pneumoniae, Legionella spp.)
III generation cephalosporins Add a macrolide Possible “atypical” microorganisms (C. pneumoniae, M. pneumoniae, Legionella spp.)
Criteria for the sufficiency of antibacterial therapy for CAP:
Temperature<37,5 °С;
No intoxication;
Absence of respiratory failure (respiratory rate less than 20/min);
No purulent sputum;
White blood cell count<10х109/л, нейтрофи-лов <80%, юных форм <6%;
No negative dynamics on the radiograph. Preservation of individual clinical, laboratory
or radiological signs of CAP is not an absolute indication for continued antibiotic therapy or its modification (Table 13). In the vast majority of cases, their resolution occurs independently. Long-lasting low-grade fever is also not a sign of a bacterial infection.
Radiographic signs of pneumonia resolve more slowly than clinical symptoms; therefore, control radiography cannot serve as a criterion for discontinuing antibiotics, and persistent infiltration is an indication for continuing antibiotic therapy. However, with long-term clinical, laboratory and radiological symptoms of CAP, it is necessary to conduct a differential diagnosis with other diseases, primarily lung cancer and tuberculosis (see section XII).
Stepped antibacterial therapy for CAP
Stepwise antibiotic therapy involves a 2-stage use of antibiotics: the beginning of treatment with parenteral drugs, followed by the transition to their oral administration immediately after the stabilization of the patient's clinical condition. The main idea of stepwise therapy is to reduce the duration of parenteral antibiotic therapy, which provides a significant reduction in the cost of treatment and a reduction in the length of the patient's stay in the hospital while maintaining high clinical efficacy.
The best option for stepwise therapy is the sequential use of 2 dosage forms (for parenteral administration and oral administration) of the same antibiotic, which ensures the continuity of treatment. Perhaps the consistent use of drugs that are similar in their antimicrobial properties and with the same level of acquired resistance. Switching from a parenteral to an oral antibiotic should be done when the patient's condition stabilizes, the temperature normalizes and the clinical picture of CAP improves (category of evidence B). In this case, it is advisable to use the following criteria:
Normal body temperature (<37,5 °С) при двух измерениях с интервалом 8 ч;
Reduced shortness of breath;
No impairment of consciousness;
Positive dynamics of other symptoms of the disease;
No absorption disturbances in the gastrointestinal tract;
Consent (inclination) of patients to oral treatment.
In practice, the possibility of switching to the oral route of antibiotic administration appears on average 2-3 days after the start of treatment.
The following antibiotics are used for stepwise therapy: amoxicillin/clavulanate, levofloxacin, moxifloxacin, clarithromycin, azithromycin, spiramycin, erythromycin. For some antibiotics that do not have a dosage form for oral use, it is possible to replace them with drugs close in the antimicrobial spectrum (for example, ampicillin → amoxicillin; cefotaxime, ceftriaxone → amoxicillin/clavulanate).
Currently, there is no evidence of the advisability of prescribing biogenic stimulants, antihistamines, vitamins, immunomodulators (excluding granulocyte colony-stimulating factor and IgG for intravenous administration), as well as long-term use of NSAIDs and non-narcotic analgesics for CAP. The effectiveness and safety of these drugs have not been confirmed by the results of randomized controlled trials, which does not provide grounds for recommending them for the treatment of CAP.
At the same time, in severe CAP, antibiotic therapy should be accompanied by adequate respiratory support (the choice of method depends on the severity of respiratory failure), infusion therapy, if indicated, the use of vasopressors, and if CAP is complicated by refractory septic shock, hydrocortisone.
XIV. COMPLICATIONS OF EP
CAP complications include: a) pleural effusion (uncomplicated and complicated); b) pleural empyema; c) destruction/abscessation of lung tissue; d) acute respiratory distress syndrome; e) acute respiratory failure; f) septic shock; g) secondary bacteremia, sepsis, hematogenous dropout foci; h) pericarditis, myocarditis; i) nephritis, etc. At the same time, purulent-destructive complications of the disease are of particular importance (including from the point of view of the planned antibiotic therapy).
Lung abscess is characterized by the formation of a limited cavity in the lung tissue as a result of its necrosis and purulent fusion. The development of a lung abscess is associated primarily with anaerobic pathogens - x Bacteroides spp., F. nucleatum, Peptostreptococcus spp. and others - often in combination with enterobacteria or S. aureus. The antibiotics of choice are amoxicillin/clavulanate, ampicillin/sulbactam, cefoperazone/sulbactam, ticarcillin/clavulanate IV. Alternative drugs include: III-IV generation cephalosporins, ciprofloxacin or levofloxacin + metronidazole or carbapenems. The duration of therapy is determined individually, but, as a rule, is at least 3-4 weeks.
Pleural empyema (purulent pleurisy1) is characterized by the accumulation of pus in the pleural cavity. The main causative agents of pleural empyema are anaerobes, often in combination with gram-negative aerobic bacteria). In most cases, it is possible to carry out etiotropic antibiotic therapy, taking into account the data of a microbiological study of the contents of the pleural cavity.
If the purulent effusion turns out to be sterile, antibiotics (or a combination thereof) should be prescribed that have activity against likely pathogens - in cases of the so-called acute postpneumonic pleural empyema, this is primarily S. pneumoniae, S. pyogenes, S. aureus and H. influenzae . In this clinical situation, preference should be given to III-IV generation cephalosporins.
Less commonly, in the subacute/chronic course of empyema, anaerobic streptococci, bacteroides and gram-negative enterobacteria acquire etiological significance. In this regard, the drugs of choice are amoxicillin / clavulanate, ampicillin / sulbactam, cefoperazone / sulbactam, ticarcillin / clavulanate, and alternative drugs include III-IV generation cephalosporins, carbapenems. As a rule, along with antibacterial therapy, it is necessary to resort to thoracotomy drainage, and in rare cases, thoracoscopy and decortication.
XV. NON-RESOLVING (SLOWLY RESOLVING) PNEUMONIA
In most patients with CAP, by the end of 3-5 days after the start of potentially effective antibacterial therapy, body temperature normalizes and other clinical manifestations of the disease regress. In this case, radiological recovery, as a rule, lags behind the clinical one. In those cases when, against the background of an improvement in the clinical picture, by the end of the 4th week from the onset of the disease it is not possible to achieve complete radiological resolution of focal infiltrative changes in the lungs, one should speak of non-resolving (slowly resolving) or prolonged CAP.
In such a clinical situation, it is necessary, first of all, to establish possible risk factors for the protracted course of the disease: a) age over 55 years; b) alcoholism; c) the presence of concomitant disabling diseases of internal organs (COPD, congestive heart failure, renal failure, malignant neoplasms, diabetes mellitus, etc.); d) severe course of CAP; e) multilobar infiltration; f) highly virulent pathogens (L. pneumophila, S. aureus, gram-negative enterobacteria); g) smoking; h) clinical ineffectiveness of initial therapy (persistent leukocytosis and fever); i) secondary bacteremia.
1 Effusion with a leukocyte count >25,000/ml (with a predominance of polymorphonuclear forms) and/or with microorganisms and/or pH detected by bacterioscopy or culture<7,1.
Among the possible reasons for the slow resolution of CAP may be secondary resistance of pathogens to antibiotics. For example, risk factors for antibiotic resistance of S. pneumoniae are age >65 years, ß-lactam therapy for the previous 3 months, alcoholism, immunodeficiency diseases/conditions (including taking systemic glucocorticoids), multiple concomitant diseases of internal organs.
Particular attention should be paid to the correct choice of empirical antibiotic therapy, dosing regimen and patient compliance with medical recommendations. It is necessary to be sure that the prescribed therapy regimen creates the required concentration in the focus of infection, which means that “sequestered” foci of infection (for example, pleural empyema, lung abscess, extrathoracic “screenings”) should be excluded.
Of exceptional importance is the differential diagnosis of CAP of a protracted course with focal infiltrative pulmonary tuberculosis.
And, finally, one should keep in mind a wide range of non-communicable diseases, sometimes very reminiscent of pneumonia and in this regard creating known differential diagnostic difficulties (Table 17).
Table 17. Non-infectious causes of focal infiltrative changes in the lungs
Neoplasms
Primary lung cancer (especially so-called pneumonic
form of bronchioloalveolar cancer)
Endobronchial metastases
Bronchial adenoma
Lymphoma
Pulmonary embolism and pulmonary infarction
Immunopathological diseases
Systemic vasculitis
Lupus pneumonitis
Allergic bronchopulmonary aspergillosis
Bronchiolitis obliterans with organizing pneumonia
Idiopathic pulmonary fibrosis
Eosinophilic pneumonia
Bronchocentric granulomatosis
Other diseases/pathological conditions
Congestive heart failure
Drug-induced (toxic) pneumopathy
Foreign body aspiration
Sarcoidosis
Pulmonary alveolar proteinosis
Lipoid pneumonia
Round atelectasis
If risk factors for slow resolution of EAP are present, and at the same time clinical improvement is observed during the course of the disease, then it is advisable to conduct a follow-up X-ray examination of the chest organs after 4 weeks. If there is no clinical improvement and (or) the patient does not have risk factors for slow resolution of EP, then an additional examination is certainly indicated immediately (computed tomography of the chest organs, fibrobronchoscopy and other research methods) (Fig. 5).
Slowly resolving pneumonia^
There are risks of a protracted course of the disease
Control radiographic examination after 4 weeks
Resolution of pneumonic infiltration
Additional examination (CT, fibrobronchoscopy, etc.)
There are risks of a protracted course of the disease^
Rice. 5. Scheme of examination of a patient with slowly resolving (protracted) CAP syndrome
XVI. ANALYSIS OF REAL PRACTICE AND TYPICAL ERRORS IN THE TREATMENT OF CAP
In 2005-2006 In 29 multidisciplinary health care facilities in various regions of Russia, the practice of treating hospitalized patients with CAP was analyzed from the point of view of adherence to the following quality indicators (QI):
1. X-ray examination of the chest organs in the presence of clinical signs of CAP within 24 hours from the moment of hospitalization (if not performed on an outpatient basis);
2. bacteriological examination of sputum before prescribing antibiotics;
3. bacteriological blood test before prescribing antibiotics (in patients with severe CAP);
4. administration of the first dose of a systemic antibiotic in the first 8 hours from the moment of hospitalization;
5. compliance of the starting regimen of antibacterial therapy with national recommendations;
6. use of stepwise antibacterial therapy (for patients who required parenteral antibiotics);
The analysis included 3798 cases of CAP in patients aged 16 to 99 years (mean age - 49.5 ± 19.9 years), of which 58% were men. Severe CAP occurred in 29.5% of cases; complicated course of the disease - in 69.4% of patients.
The average level and spread of adherence indicators to various ICs are presented in Fig. 6. The highest level of adherence was typical for chest X-ray examination
100 90 80 70 60 50 40 30 20 10 0
Rice. 6. Adherence to IC in hospitalized patients with CAP in multidisciplinary healthcare facilities of the Russian Federation, 2005-2006. * The time of administration of the first dose of AMP was indicated in 61% of cases.
% 40 35 30 25 20 15 10 5
Rice. 7. Factors that are important for doctors when choosing AMPs in outpatients with CAP (%)
30 +27D 25 20 15 10 5 0
Rice. 8. Structure of AMPs used for initial monotherapy of CAP in outpatient settings in 2007.
cells (92%) and timely (<8 ч с момента госпитализации) начала антибактериальной терапии (77%).
The indicators with the lowest level of adherence included timeliness of bacteriological examination of blood (1%) and sputum (6%), availability of recommendations for vaccination against pneumococcal (14%) and influenza (16%) infections; stepwise antibiotic therapy was used in an average of 18% of cases.
Compliance of initial antibiotic therapy with recommendations was quite high for non-severe pneumonia (72%) and low for severe disease (15%); The main problems of antibacterial therapy for severe pneumonia were the unreasonable use of monotherapy, an inadequate route of administration of antibiotics and the use of their irrational combinations.
In a multicenter prospective pharmacoepidemiological study conducted in 2007 in outpatient clinics in 5 regions of Russia, factors determining the choice of antibacterial drugs by doctors, treatment tactics for outpatients with CAP, and the main sources of information about antibiotics were studied. The study involved 104 physicians, of whom 87% were district therapists.
The practice of treating 953 outpatients with CAP was analyzed.
The most significant factors when choosing antibiotics in patients with CAP in an outpatient setting from the point of view of doctors are presented in Fig. 7.
The structure of prescribed AMPs in different centers is shown in fig. 8. Along with amoxicillin, amoxicillin/clavulanate and macrolides, cefazolin and ciprofloxacin occupied a significant share in the structure of prescriptions; There was a high frequency of prescription of parenteral cephalosporins of the third generation - cefo-taxime and ceftriaxone.
In total, 57% of doctors in the treatment of CAP preferred the oral route of administration of AMPs, 6% - parenteral; the rest of the respondents did not express any preferences, since they usually use both oral and parenteral dosage forms of antibiotics.
As the most significant sources of information about AMPs, 85% of the surveyed doctors indicated conferences/round tables and materials from representatives of pharmaceutical companies, followed by periodical medical publications (57%), reference books on drugs (51%) and the Internet (20%).
XVII. ERRORS OF CAP ANTIBACTERIAL THERAPY IN ADULTS
Table 18. The most common mistakes in antibacterial therapy for CAP in adults _Purpose_\_Comment_
Choice of drug (non-severe CAP)
Gentamicin Lack of activity against pneumococcus and atypical pathogens
Ampicillin orally Poor drug bioavailability (40%) compared to amoxicillin (75-93%)
Cefazolin Poor anti-pneumococcal activity, no clinically significant activity against H. influenzae
Ciprofloxacin Poor activity against S. pneumoniae and M. pneumoniae
Doxycycline High resistance of S. pneumoniae in Russia
Respiratory quinolones It is not advisable to use them as drugs of choice in the absence of risk factors for therapeutic failure (comorbidities, previous use of antimicrobial drugs)
By choice of drug (severe CAP)
ß-lactams (including cefotaxime, ceftriaxone) as monotherapy Do not cover the spectrum of potential pathogens, in particular L. pneumophila
Carbapenems (imipenem, meropenem) Use as initial therapy is not economically justified; can only be used in cases of aspiration and suspected P. aeruginosa infection (except ertapenem)
Third generation antipseudomonas cephalosporins (ceftazidime, cefoperazone) Inferior to cefotaxime and ceftriaxone in activity against S. pneumoniae; use only if P. aeruginosa infection is suspected
Ampicillin Does not cover the spectrum of potential pathogens of severe CAP, in particular S. aureus and most enterobacteria
By choice of route of administration
Refusal of step therapy Step therapy can significantly reduce treatment costs without worsening the prognosis. In most cases, switching to oral antibiotics is possible on the 2-3rd day of therapy
Intramuscular administration of antibiotics in severe CAP is not advisable due to a possible decrease in the rate and degree of absorption of the drug into the systemic circulation
According to the start of therapy
Late initiation of antibacterial therapy Delay in prescribing antibiotics from the moment of hospitalization for 4 hours or more significantly worsens the prognosis
By duration of therapy
Frequent changes of AMPs during treatment, “explained” by the danger of developing resistance. Changing AMPs during treatment, except in cases of clinical ineffectiveness and/or intolerance, is inappropriate. Indications for replacing the antibiotic: clinical ineffectiveness, which can be judged after 48-72 hours of therapy; development of serious adverse events requiring discontinuation of the antibiotic; high potential toxicity of the antibiotic, limiting the duration of its use
Continuation of AB therapy until all clinical and laboratory indicators completely disappear. The main criterion for discontinuing the antibiotic is the reverse development of the clinical symptoms of CAP: normalization of body temperature; reduction of cough; decrease in volume and / or improvement in the nature of sputum, etc. Preservation of individual laboratory and / or radiological changes is not an absolute criterion for continuing antibiotic therapy
XVII. PREVENTION
Currently, pneumococcal and influenza vaccines are used to prevent CAP.
The feasibility of using the pneumococcal vaccine is explained primarily by the fact that even today S. pneumoniae remains the leading causative agent of CAP in adults and, despite the available effective antibacterial therapy, causes high morbidity and mortality. For the purpose of specific prevention of invasive pneumococcal infections, including pneumococcal CAP with secondary bacteremia, use
They are a 23-valent unconjugated vaccine containing purified capsular polysaccharide antigens of 23 S. pneumoniae serotypes (category A evidence).
Because patients who require pneumococcal vaccine often require influenza vaccine, it should be remembered that both vaccines can be administered simultaneously (in different arms) without increasing the incidence of adverse reactions or reducing the immune response (Evidence Category A).
Patients aged >65 years3 without immunocompromise A A second dose is recommended if the vaccine was received >5 years ago and the patient was<65 лет
Persons aged >2 and<65 лет с хроническими заболеваниями: сердечно-сосудистой системы (например, застойная сердечная недостаточность, кардиомиопатии) легких (например, ХОБЛ) сахарным диабетом алкоголизмом печени (цирроз) ликвореей А А А В В В Не рекомендуется
Persons aged >2 and<65 лет с функциональной или органической аспленией (например, с серповидно-клеточной анемией, после спленэктомии) А Если в возрасте >10 years, revaccination recommended 5 years after the previous dose
Persons aged >2 and<65 лет, живущие в определенных условиях окружающей среды или из особой социальной среды (например, аборигены Аляски и др.) С Не рекомендуется
Persons with immunodeficiency conditions aged >2 years, including patients with: HIV infection; Leukemia; Hodgkin's disease; multiple myeloma; generalized malignant neoplasms; on immunosuppressive therapy (including chemotherapy); chronic renal failure; nephrotic syndrome; organ failure or bone marrow transplant C Single booster dose if at least 5 years have passed since the first dose
Note. 1 A - reliable epidemiological data and significant clinical benefits of using the vaccine; B - moderate evidence of the effectiveness of the vaccine; C - the effectiveness of vaccination has not been proven, however, the high risk of developing the disease, the potential benefits and safety of the vaccine create the basis for immunization;
3 If immunization status is unknown, vaccination is recommended for patients in these groups.
The effectiveness of the influenza vaccine in preventing the development of influenza and its complications (including CAP) in healthy individuals younger than 50 years of age is estimated to be very high (category of evidence A). In people aged 65 years and older, vaccination appears to be moderately effective but may reduce episodes of upper respiratory tract infection, CAP, hospitalization, and death (Category of Evidence).
The following target groups for vaccination are identified:
Persons over 50 years of age;
Persons living in long-term care homes for the elderly;
Patients with chronic bronchopulmonary (including bronchial asthma) and cardiovascular diseases;
Adults subject to ongoing medical supervision who were hospitalized in the previous year for metabolic disorders
disorders (including diabetes mellitus), kidney disease, hemoglobinopathies, immunodeficiency states (including HIV infection);
Women in the second and third trimesters of pregnancy.
Since vaccination of medical workers reduces the risk of death among patients in nursing departments, the indications for its implementation are expanding to include such groups as:
Doctors, nurses and other hospital and outpatient staff;
Long-term care staff;
Family members (including children) of persons at risk;
Medical workers providing home care for people at risk. The optimal time for vaccination is
October - first half of November. Vaccination is carried out annually, as the level of protective antibodies decreases throughout the year (evidence category A).
XIX. DOSING REGIME OF AMPS FOR EMPIRICAL THERAPY OF CAP IN ADULTS
Table 20. Dosage regimen of AMPs in adult patients with CAP Drugs Orally
Cefoperazone/sulbactam
Amikacin
Parenterally
Notes
Natural penicillins
Benzylpenicillin - 2 million units 4-6 times a day
Benzylpenicillin procaine - 1.2 million units 2 times a day
Aminopenicillins
Amoxicillin 0.5-1 g 3 times a day - Regardless of meals
Inhibitor-protected penicillins
Amoxicillin/clavulanate 0.625 g 3 times a day or 1-2 g 2 times a day 1.2 g 3-4 times a day With meals
Ampicillin/sulbactam 1.5 g 3-4 times a day
Amoxicillin/sulbactam 1 g 3 times a day or 2 g 2 times a day 1.5 g 3 times a day Regardless of meals
Ti carcillin/clavulanate - 3.2 g 3 times a day
Piperacillin/tazobactam - 4.5 g 3 times a day
III generation cephalosporins
Cefotaxime - 1-2 g 2-3 times a day
Ceftriaxone - 1-2 g 1 time per day
IV generation cephalosporins
1-2 g 2 times a day
Inhibitor-protected cephalosporins
2-4 g 2 times a day
Carbapenems
Imipenem - 0.5 g 3-4 times a day
Meropenem - 0.5 g 3-4 times a day
Ertapenem - 1 g 1 time per day
Macrolides
Azithromycin 0.251-0.5 g once a day or 2 g once a day2 0.5 g once a day 1 hour before meals
Clarithromycin 0.5 g 2 times a day 0.5 g 2 times a day Regardless of food intake
Clarithromycin SR 1 g once a day with meals
Josamycin 1 g 2 times a day or 0.5 g 3 times a day Regardless of meals
Spiramycin 3 million IU 2 times a day 1.5 million IU 3 times a day Regardless of food intake
Lincosamides
Clindamycin 0.3-0.45 g 4 times a day 0.3-0.9 g 3 times a day Before meals
Early fluoroquinolones
Ciprofloxacin 0.5-0.75 g 2 times a day 0.4 g 2 times a day Before meals. Simultaneous use of antacids, drugs M^, Ca, A1 impairs absorption
Respiratory fluoroquinolones
Levofloxacin 0.5 g once a day 0.5 g once a day Regardless of food intake. Simultaneous use of antacids, drugs M^, Ca, A1 impairs absorption
Moxifloxacin 0.4 g once a day 0.4 g once a day
Gemifloxacin 320 mg 1 time per day -
Aminoglycosides
15-20 mg/kg 1 time per day
Other drugs
Rifampicin 0.3-0.45 g 2 times a day 1 hour before meals
Metronidazole 0.5 g 3 times a day 0.5 g 3 times a day After meals
Linezolid 0.6 g 2 times a day 0.6 g 2 times a day Regardless of food intake
Note. 1 On the first day, a double dose is prescribed - 0.5 g; 2 dosage form of azithromycin prolonged action.
LITERATURE
1. Chuchalin A.G., Sinopalnikov A.I., Strachunsky L.S. and others. Community-acquired pneumonia in adults: practical recommendations for diagnosis, treatment and prevention in adults. - M.: Atmosphere, 2006.
2. Statistical materials “Morbidity rate of the Russian population in 2006.” Federal State Institution "Central Research Institute of Organization and Informatization of Health Care" of Roszdrav. Available from: http:// www.minzdravsoc.ru/docs/mzsr/letters/60.
3. Russian statistical yearbook - 2006. -M: Statistics of Russia, 2007.
4. Practical guide to anti-infective chemotherapy / Ed. L.S. Strachunsky, Yu.B. Belousova, S.N. Kozlova. - Smolensk: MAKMAKH, 2006.
5. Mandell L.M., Wunderink R.G., Anzueto A. et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults // Clin. Infect. Dis. - 2007. -Vol. 44. - Suppl. 2. - P. S27-72.
6. Guidelines for the management of adult lower respiratory tract infections // Eur. Respira. J. - 2005. - Vol. 26. - P. 1138-1180.
7. Mandell L.A., Marrie T.J., Grossman R.F. et al. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society // Clin. Infect. Dis. - 2000. - Vol. 31. - P. 383-421.
8. BTS Pneumonia Guidelines Committee. British Thoracic Society guidelines for the management of community-acquired pneumonia in adults - 2004 update. Available from: www.brit-thoracic.org.uk
9. Lim W.S., Baudouin S.V., George R.C. et al. British Thoracic Society guidelines for the management of community-acquired pneumonia in adults - update 2009 // Thorax. - 2009. -Vol. 64.-Suppl. III). - P. iii1-55.
10. Heffelfinger J.D., Dowell S.F., Jorgensen J.H. et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant S. pneumoniae Therapeutic Working Group // Arch. Intern. Med. - 2000. -Vol. 160. - P. 1399-1408.
11. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP) // Mortal. Morbid. Wkly Rep. - 1997. - Vol. 46(R-8).
12. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP) // Mortal. Morbid. Wkly Rep. Recomm. Rep. - 2005. - Vol. 54 (RR-8). - P. 1-40.
13. Low D.E. Trends and significance of antimicrobial resistance in respiratory pathogens // Curr. Opin. Infect. Dis. - 2000. - Vol. 13. - P. 145-153.
14. Metlay J.P. Update of community-acquired pneumonia: impact of antibiotic resistance on clinical outcomes // Curr. Opin. Infect. Dis. - 2002. - Vol. 15. - P. 163-167.
15. Andes D. Pharmacokinetic and pharmacodynamic properties of antimicrobials in the therapy of respiratory tract infectious // Curr. Opin. Infect. Dis. - 2001. - Vol. 14. - P. 165-172.
16. Metlay J.P., Fine M.J. Testing strategies in the initial management of patients with community-acquired pneumonia // Ann. Intern. Med. - 2003. - Vol. 138. - P. 109-118.
17. Fine M.J., Smith M.A., Carson C.A. et al. Prognosis and outcomes of patients with community-acquired pneumonia. A metaanalysis // JAMA. - 1996. - Vol. 275. - P. 134-141.
18. Lim W.S., van der Eerden M.M., Laing R. Et al. Determining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study // Thorax. - 2003. - Vol. 58. - P. 377-382.
19. Metersky M.L. Community-acquired pneumonia: process of care studies // Curr. Opin. Infect. Dis. - 2002. - Vol. 15. -P. 169-174.
20. Charles P. G. P., Wolfe R., Whitby M. et al. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia // Clin. Infect. Dis. - 2008. - Vol. 47. - P. 375-384.
21. Rudnov V.A., Fesenko A.A., Drozd A.V. Comparative analysis of the informational significance of scales for assessing the severity of the condition of patients with community-acquired pneumonia hospitalized in the ICU. Klin. microbiol. and antimicrobial. chemotherapy - 2007. - No. 9. - P. 330-336.
22. Dimopoulus G., Matthaiou D.K., Karageorgopoulos D.E. et al. Short versus Long-course antibacterial therapy for community-acquired pneumonia // Drugs. - 2008. - Vol. 68. -P. 1841-1854.
23. Li J.Z., Winston L.G., Moore D.H. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis // Am. J. Med. - 2007. - Vol. 120. - P. 783-790.
24. Maimon N., Nopmaneejumruslers C., Marras T.K. Antibacterial class is not obviously important in outpatient pneumonia: a meta-analysis // Eur. Respira. J. - 2008. - Vol. 31. -P. 1068-1076.
25. Robenshtok E., Shefet D., Gafter-Gvili A. et al. Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults // Cochrane Database Syst. Rev. - 2008: CD004418.
26. Ivanchik N.V., Kozlov S.N., Rachina S.A. et al. Etiology of fatal community-acquired pneumonia in adults // Pulmonology. - 2008. - No. 6. - P. 53-58.
27. Guchev I.A., Rakov A.L., Sinopalnikov A.I., et al. The influence of chemoprophylaxis on the incidence of pneumonia in an organized team // Military-med. magazine - 2003. - No. 3. - P. 54-61.
28. Sinopalnikov A.I., Kozlov R.S. Community-acquired respiratory tract infections: diagnosis and treatment. Guide for doctors. - M.: M-Vesti, 2008.
29. el Moussaoui R., de Borgie C.A.J.M., van den Broek P. et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomized double blind study // BMJ. -2006. - Vol. 332, N 7554. - P. 1355.
30. Rachina S.A., Kozlov R.S., Shal E.P. Evaluation of the adequacy of medical care for community-acquired pneumonia in hospitals in various regions of the Russian Federation: experience in the use of quality indicators // Pulmonology. - 2009. - No. 3. -S. 5-13.
31. Rachina S.A., Kozlov R.S., Shal E.P. Analysis of the practice of treating outpatients with community-acquired pneumonia: what factors determine physician preferences? // Ros. Honey. lead. - 2010. - No. 2 (accepted for publication).
32. Rachina S.A., Kozlov R.S., Shal E.P. and others. Structure of bacterial pathogens of community-acquired pneumonia in multidisciplinary hospitals in Smolensk // Pulmonology. -2010. - No. 2 (accepted for publication).
Rules for obtaining sputum for cultural examination
1. Sputum is collected as early as possible from the moment of hospitalization and before the start of ABT.
2. Before collecting sputum, you need to brush your teeth, the inside of your cheeks, and rinse your mouth thoroughly with water.
3. Patients should be instructed to cough deeply to obtain contents from the lower respiratory tract rather than the oropharynx or nasopharynx.
4. Sputum must be collected in sterile containers, which must be delivered to the microbiological laboratory no later than 2 hours from the moment the material is received.
Annex 1
Rules for obtaining blood for cultural examination
1. To obtain a blood culture, it is advisable to use commercial bottles with a nutrient medium.
2. The venipuncture site is treated first with 70% ethyl alcohol, then with 1-2% iodine solution.
3. After the antiseptic has dried, at least 10.0 ml of blood is taken from each vein (the optimal blood/medium ratio should be 1:5-1:10). The venipuncture site cannot be palpated after treatment with an antiseptic.
4. Transportation of samples to the laboratory is carried out at room temperature immediately after receiving them.
I. PORT scale
ALGORITHM FOR ASSESSING THE RISK OF ADVERSE OUTCOME IN CAP
Appendix 2
Age > 50 years?
Serious comorbidities?
Abnormal physical signs? (see table 1)
Score
demographic
related
diseases,
results
physical,
X-ray,
laboratory
examinations
(<70 баллов)
(71-90 points)
(91-130 points)
(>130 points)
INFECTIOUS DISEASES: news, opinions, training No. 2 2013
Table 1. Score of risk factors for CAP
Parameter Points
Demographic characteristics
Male age (years)
Female age (years) -10
Stay in a nursing home/long-term care facility + 10
Accompanying illnesses
Malignant neoplasm + 30
Liver diseases + 20
Congestive heart failure + 10
Cerebrovascular diseases + 10
Kidney diseases + 10
Physical signs
Impaired consciousness + 20
Respiratory rate > 30/min + 20
Systolic pressure<90 мм рт.ст. + 20
Temperature<35 °С или >40 °C + 15
Pulse >125/min + 10
Laboratory and radiographic data
Arterial blood pH<7,35 + 30
Blood urea >10.7 mmol/l + 20
Blood sodium<130 ммоль/л + 20
Blood glucose >14 mmol/l + 10
Hematocrit<30% + 10
RaO2<60 мм рт.ст. или Эа02 <90% + 10
Pleural effusion + 10
Note. The heading “Malignant neoplasms” takes into account cases of tumor diseases that manifest an “active” course or were diagnosed within the last year, excluding basal cell or squamous cell skin cancer. The heading “Liver diseases” takes into account cases of clinically and/or histologically diagnosed liver cirrhosis and chronic active hepatitis. The Congestive Heart Failure - CHF category includes cases of congestive heart failure due to left ventricular systolic or diastolic dysfunction documented by history, physical examination, chest x-ray, echocardiography, myocardial scintigraphy, or ventriculography.
The heading “Cerebrovascular diseases” takes into account cases of actual stroke, transient ischemic attack, or residual effects documented by CT or MRI of the brain after an acute cerebrovascular accident. In the “Kidney diseases” section, cases of anamnestic confirmed chronic kidney disease or an increase in the concentration of creatinine/residual urea nitrogen in the blood serum are taken into account. Easy-to-use scoring calculators for this scale are now available on the Internet (http://ursa.kcom.edu/CAPcalc/default.htm, http://ncemi.org, www.emedhomom.com/dbase.cfm) .
Table 2. Risk classes and clinical profile of patients with CAP
Risk class I II III IV V
Number of points -<70 71-90 91-130 >130
Mortality, % 0.1-0.4 0.6-0.7 0.9-2.8 8.5-9.3 27-31.1
Place of treatment Outpatient Outpatient Short-term hospitalization Hospital Hospital (ICU)
II. CURB/CRB-65 scale
ALGORITHM FOR ASSESSING THE RISK OF ADVERSE OUTCOME AND SELECTION OF TREATMENT LOCATION FOR CAP (CURB-65 SCALE)
Symptoms and signs:
Blood urea nitrogen > 7 mmol/l (Urea)
Respiratory rate >30/min
Systolic blood pressure< 90 или диастолическое АД < 60 мм рт.ст. (В1оос1 pressure)
У^» Age >65 years (65)__у
Group I (mortality 1.5%)
Group II (mortality 9.2%)
>3 points\
Group III (mortality 22%)
Ambulatory treatment
Hospitalization (short-term) or supervised outpatient treatment
Emergency hospitalization
ALGORITHM FOR ASSESSING THE RISK OF ADVERSE OUTCOME AND SELECTION OF TREATMENT LOCATION FOR CAP (CRB-65 SCALE)
fSymptoms and signs:
Confusion
Respiratory rate >30/min
Systolic blood pressure< 90 или диастолическое АД < 60 мм рт.ст. ^lood pressure)
Age >65 years (65)
Group I (mortality 1.2%)
Ambulatory treatment
Group II (mortality 8.15%)
Observation and assessment in hospital
>3 points\
Group III (mortality 31%)
Emergency hospitalization
III. SMART-COP scale A. Evaluated parameters
Indicator value Points
S Systolic blood pressure<90 мм рт.ст. 2
M Multilobar infiltration on the radiograph of OGK 1
R Respiratory rate >25/min at age<50 лет и >30/min at age >50 years 1
T Heart rate > 125/min 1
C Impaired consciousness 1
O Oxygenation: RaE02*< 70 мм рт.ст. или Эр02 < 94% или Ра02/РЮ2 <333 в возрасте <50 лет Ра02* < 60 мм рт. ст. или Эр02 <90% или Ра02/РЮ2 <250 в возрасте >50 years 2
P pH* arterial blood<7,35 2
B. Interpretation of SMART-COP
Points Requirement for respiratory support and vasopressors
0-2 Low risk
3-4 Medium risk (1 out of 8)
5-6 High risk (1 out of 3)
>7 B. Interp Score Very high risk (2 out of 3) retraction SMRT-CO Requirement for respiratory support and vasopressors
0 Very low risk
1 Low risk (1 in 20)
2 Medium risk(1 out of 10)
3 High risk (1 of 6)
>4 High risk (1 out of 3)
Total points
Note. * - not assessed on the SMRT-CO scale.
Appendix 3 Quality indicators of medical care for CAP in hospitalized patients*
Quality indicator Target level, %
X-ray examination of the chest organs in the presence of clinical signs of CAP within 24 hours from the moment of hospitalization (if not performed on an outpatient basis) 100
Bacteriological examination of sputum before prescribing antibiotics 50
Bacteriological blood test before prescribing antibiotics for severe CAP 100
Administration of the first dose of systemic AMP on time< 4 ч (при септическом шоке <60 мин) с момента госпитализации 100
Compliance of the starting regimen of antibacterial therapy with national or local recommendations/standards of therapy compiled on their basis 90
Use of stepped antibacterial therapy 80
Note. * - traditionally used parameters for assessing the quality of treatment of certain diseases (mortality, frequency of hospitalization in the ICU, length of hospital stay) are characterized by low sensitivity in CAP; their use as indicators is not recommended.
Appendix 4
List of international (generic) and proprietary (trade) names of the main antibacterial agents used to treat CAP (drugs from the main manufacturer are in bold)
Generic name (international nonproprietary name) Trade (proprietary) names
Azithromycin Sumamed
Hemomycin
Zetamax retard
Amoxicillin Flemoxin solutab
Hiconcil
Amoxicillin/clavulanate Augmentin
Amoxiclav
Flemoklav solutab
Amoxicillin/sulbactam Trifamox IBL
Ampicillin Pentrexil
Ampicillin/sulbactam Unazine
Gemifloxacin Factive
Josamycin Vilprafen Solutab
Doxycycline Vibramycin
Unidox Solutab
Imipenem/cilastatin Tienam
Clarithromycin Klacid
Klacid SR
Fromilid
Fromilid Uno
Clindamycin Dalacin C
Klimitsin
Levofloxacin Tavanic
Linezolid Zyvox
Meropenem Meronem
Metronidazole Flagyl
Metrogil
Trichopolum
Moxifloxacin Avelox
Piperacillin/tazobactam Tazocin
Rifampicin Rifadin
Benemicin
Rimactan
Spiramycin Rovamycin
Ticarcillin/clavulanate Timentin
Cefepime Maxipim
Cefoperazone/sulbactam Sulperazone
Cefotaxime Claforan
Cefantral
Ceftriaxone Rocephin
Lendatsin
Longacef
Cefuroxime Zinacef
Ciprofloxacin Ciprobay
Tsiprinol
Erythromycin Grunamycin
Erigexal
Ertapenem Invanz
The respiratory system performs one of the most important functions in our body. It provides cells, organs and tissues with uninterrupted respiration and the removal of harmful carbon dioxide from them. Inflammatory lung diseases greatly reduce respiratory function, and a pathology such as community-acquired pneumonia can lead to deep respiratory failure, oxygen starvation of the brain and severe complications.
Community-acquired pneumonia is pneumonia that strikes a person outside of a medical facility or within 48 hours of being admitted to the hospital.
Characteristic symptoms
Inflammation of the pulmonary structures begins acutely. There are several criteria that should alert those around a sick person and encourage him to come to the doctor:
- state of fever;
- cough;
- dyspnea;
- chest pain.
This set of symptoms should be a signal to contact a doctor at the clinic.
Fever is manifested by chills, headache, and a rise in temperature to high numbers. Possible nausea, vomiting after eating, dizziness. In severe cases, convulsive readiness, a state of confused consciousness.
The cough is dry and painful at first. After a few days, the sputum begins to disappear. It comes in different consistencies: from mucous to purulent with streaks of blood. Shortness of breath due to breathing pathologies of the expiratory (on exhalation) type. Painful sensations vary in intensity.
Very rarely, in old age there may be no fever. This happens after 60 years, in 25% of all pneumonias. The disease manifests itself with other symptoms. Chronic diseases come to the fore. Weakness and severe fatigue occur. Possible abdominal pain and nausea. Elderly people often lead a reclusive and sedentary lifestyle, which contributes to the development of congestion in the lungs and clinically atypical forms of pneumonia.
Main reasons
A healthy body is protected from most pathogenic microbes and pneumonia is not dangerous for it. But when unfavorable conditions arise, the risk of disease increases. The most common factors that can lead to pneumonia are:
- tobacco smoking;
- viral diseases of the upper respiratory tract;
- chronic pathologies of the heart, gastrointestinal tract, kidneys and liver;
- contacts with wild animals, birds, rodents;
- frequent changes of residence (travel to other countries);
- systematic or one-time severe hypothermia;
- younger and older people (unlike adults, children and old people get sick more often).
Predisposing factors often become the trigger of the disease, but community-acquired pneumonia occurs only if the pathogen has entered the lungs.
Classification of pathogen types in percentage terms
| Pathogen | % | Characteristic |
| Pneumococcus | 30–40 | The main causative agent of pneumonia. |
| Mycoplasma | 15–20 | Causes atypical inflammation in the lung tissue. |
| Haemophilus influenzae | 3–10 | Pneumonia caused by this bacterium is most prone to purulent complications. |
| Staphylococcus | 2–5 | Lives on the mucous membranes of most people and affects weakened organisms. |
| Influenza viruses | 7 | They cause specific viral inflammation of the lungs. |
| Chlamydia | 2–8 | It mainly causes diseases of the genital organs in humans, but is also transmitted by rodents and birds, so it can sometimes cause pneumonia. |
| Legionella | 2–10 | It is the causative agent of Legionnaires' disease and Pontiac fever, and sometimes causes pneumonia. It can live and reproduce peacefully in many environments. |
| Other flora | 2–10 | Klebsiella, Pseudomonas aeruginosa and Escherichia coli, Proteus, other microorganisms. |
Basically, the infection enters the body in three ways:
- Transbronchial, through the respiratory system, with air flow from the outside.
- Contact, that is, direct contact of the infected substrate with the lung tissue.
- Hematogenous, from the primary focus with blood flow through the vessels.
Diagnostics
When a patient is admitted with suspected pneumonia, the doctor begins the diagnosis with a survey of complaints and an initial examination with physical examination methods:
- palpation;
- tapping;
- listening.
When tapping, the sound is shortened over the affected part of the lung; the greater the dullness, the higher the risk of detecting complications. Auscultation reveals localized bronchial breathing, wheezing of various sizes, and possibly crepitus. Palpation of the chest reveals increased bronchophony and vocal tremor.
- chest x-ray;
- general blood analysis.
In the hospital, a biochemical blood test and sputum examination for the presence of microflora are performed. A general blood test shows signs of inflammation:
- leukocytosis, with a shift of the formula to the left;
- increased ESR;
- sometimes toxic granularity of erythrocytes and aneosinophilia.
On a radiograph, a sign of pneumonia is infiltrative darkening of the lung tissue, which can be of different sizes, from focal to total (right/left-sided) and bilateral. If there is an unusual picture on the x-ray (unclear changes or “nothing in the lungs”), computed tomography is prescribed for more complete visualization of the lesions.
Clinical recommendations for the diagnosis of community-acquired pneumonia indicate several clinical and laboratory signs for identifying severe pneumonia, in which the patient is indicated for hospitalization not in a specialized (therapeutic, pulmonological) hospital, but in the intensive care unit.
Signs of severe pneumonia
| Clinical | Laboratory |
| Acute respiratory failure (respiratory rate more than 30 per minute). | A decrease in leukocyte blood count below 4. |
| Blood pressure less than 90/60 (in the absence of blood loss). | Damage to several lobes of the lungs on an x-ray. |
| Reduced oxygen saturation below 90%. | Hemoglobin is below 100 g/l. |
| Partial pressure in arterial blood is below 60 mm. rt. Art. | |
| Confused state of consciousness not associated with other diseases. | |
| Symptoms of acute renal failure. |
Any of these signs is a significant signal for the doctor to decide to admit the patient to the emergency department and begin comprehensive therapy to restore the body.
Healing procedures
The general principles of inpatient treatment of community-acquired pneumonia are based on several important points:
- Gentle regimen for the patient.
- Complete drug therapy.
The regimen is chosen by the doctor depending on the clinical manifestations. During the feverish period - bed rest, with the head of the bed raised and frequent turns in bed. The patient is then allowed to walk a little.
Complex nutrition includes easily digestible carbohydrates, natural vitamins. Drinking large amounts of fluid is mandatory.
Drug treatment consists of 3 main points:
- etiotropic therapy aimed at suppressing the pathogen (antibiotics, specific serums, immunoglobulins);
- detoxification therapy, which is aimed at reducing fever and removing toxins from the body;
- symptomatic therapy.
Much attention is paid to the choice of antibiotic. Until the microflora is clarified, patients with pneumonia are treated empirically with antibiotics, based on the following data:
- conditions for the occurrence of pneumonia;
- patient's age;
- the presence of concomitant pathologies;
- severity of the disease.
The doctor chooses broad-spectrum antibiotics (penicillins, cephalosporins). If there is no effect of treatment within 2–4 days, the antibiotic is replaced with another or the dose is increased. And after identifying the pathogen, correction of etiotropic therapy is often carried out to increase efficiency.
The prognosis is favorable in the absence of severe pulmonary and other complications or concomitant chronic diseases. For effective recovery, timely contact with a specialist is important. For inpatient treatment, discharge home is usually given after 2 weeks in the hospital.
An early visit to a medical facility for consultation will allow the patient to receive outpatient treatment and take medications in a more comfortable home environment. However, when treating at home, it is necessary to observe a special regime for the patient (separate dishes, mask regime).
Prevention
Preventive measures aimed at reducing the risk of community-acquired pneumonia in the home should be carried out at different levels.
Prevention at the household level
Sanitary alertness in large groups
Enterprise management must take care of labor protection, improve work technologies and industrial sanitation.
Public prevention
Mass sports propaganda for a healthy lifestyle and giving up bad habits.
Prevention in medicine
Systematic timely vaccination of the population against influenza. The vaccine must match the strain of the virus that progresses during the season it is administered.
Personal prevention
Rational hardening, reducing the number of hypothermia (especially in the cold season), eliminating bad habits, daily exercise.
Any disease is easier to prevent than to treat.
In an attempt to strike a balance between responsible antibiotic therapy and the safe and effective treatment of certain nosocomial infections, new guidelines recommend antibiotic treatment durations of 7 days or less for both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), i.e. , for both categories, which are intended to replace the earlier umbrella term “healthcare-associated pneumonia.” This new document, jointly released by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), was published online July 14, 2016. in the journal Clinical Infectious Diseases. It replaces the previous version of the manual from 2005. Another important aspect of the new recommendations is the advice to develop your own antibiogram for each hospital. This should be a localized analysis of the bacterial strains that cause pneumonia, highlighting those pathogens that are cultured in intensive care units, as well as the antibiotics that have proven effective in treating these bacterial infections. As the paper's authors explained in a press release, if physicians are regularly informed about the causative agents of CAP and VAP in their institutions, as well as their susceptibility to specific antibiotics, they can make more effective treatment choices. These antibiograms also help to individualize treatment and ensure that the patient begins receiving the correct antibiotic as early as possible.
The new document was developed by a multidisciplinary team of experts who aimed to combat the development of antibiotic resistance without compromising patient safety, and relied on evidence from the latest systematic reviews and meta-analyses. However, the results of recent publications did not form the basis of any specific recommendations in the new guidelines, but rather guided experts in making decisions on a number of treatment recommendations.
Taken together, CAP and VAP account for 20–25% of hospital-acquired infections, and an estimated 10–15% of such cases result in patient death. When these categories are considered separately, VAP develops in approximately one in ten mechanically ventilated patients, and 13% of these infections are fatal.
Despite the understandable desire for more aggressive treatment of these conditions, scientific evidence has not shown that longer courses of antibiotic therapy have any advantage over shorter courses. However, longer treatment with antibiotics is associated with a higher incidence of side effects, in particular diarrhea, a higher risk of Clostridium difficile infection, increased treatment costs and the risk of antibiotic resistance.
Based on these considerations, experts recommend a 7-day duration of antibiotic treatment for both CAP and VAP, although they do caution that there are situations where a shorter or longer duration of antibiotic therapy may be indicated depending on the rate of clinical, radiological improvement and laboratory parameters. They also recommend reducing the intensity of antimicrobial therapy by using narrower-spectrum antibiotics instead of broad-spectrum drugs, and by starting monotherapy rather than combinations.
When deciding whether to discontinue an antibiotic in patients with CAP and VAP, the IDSA and ATS recommend looking at procalcitonin levels rather than just clinical indicators in addition to clinical criteria, although the authors acknowledge that this recommendation is based on relatively low-quality evidence.
Other recommendations focus on noninvasive methods for diagnosing VAP, which involve the use of purely clinical criteria for initiating antibiotic therapy, as well as empiric selection of treatment options in certain clinical circumstances. However, the evidence base for most of these recommendations is also not very strong.
In the section on developing antibiograms, the authors advise each institution to also make decisions regarding how often these antibiograms will be updated. Considerations such as the rate of change in the microbiological situation, institutional resources, and the amount of data available for analysis should be taken into account.
Finally, the guideline includes specific recommendations for initial empiric antibiotic therapy. Among other considerations, the choice of regimen depends on whether CAP or VAP is present, the risk of infection with methicillin-resistant Staphylococcus aureus strains, the risk of mortality, and the availability of antibiotics that are effective against Gram-positive or Gram-negative flora. In patients with suspected VAP, coverage of S. aureus, Pseudomonas aeruginosa, and other gram-negative organisms is recommended in all empirical antibiotic regimens. In patients who have already received empirical treatment for CAP, it is recommended to prescribe drugs that are active against S. aureus.
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1 Russian Respiratory Society (RRO) Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC) CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND PREVENTION OF SEVERE COMMUNITY-ACQUIRED PNEUMONIA IN ADULTS 2014
2 Team of authors Chuchalin Alexander Grigorievich Sinopalnikov Alexander Igorevich Kozlov Roman Sergeevich Director of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Chairman of the Board of the RRO, Chief freelance specialist pulmonologist of the Ministry of Health of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences. Head of the Department of Pulmonology, State Budgetary Educational Institution of Further Professional Education, Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Vice-President of IACMAH, Professor, Doctor of Medical Sciences. Director of the Research Institute of Antimicrobial Chemotherapy of the State Budgetary Educational Institution of Higher Professional Education "Smolensk State Medical Academy" of the Ministry of Health of the Russian Federation, President of IACMAH, Professor, Doctor of Medical Sciences. Avdeev Sergey Nikolaevich Deputy Director for Scientific Work, Head of the Clinical Department of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Professor, Doctor of Medical Sciences. Tyurin Igor Evgenievich Head of the Department of Radiation Diagnostics and Medical Physics, Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Chief Freelance Specialist in Radiation Diagnostics of the Ministry of Health of the Russian Federation, Professor, Doctor of Medical Sciences. Rudnov Vladimir Aleksandrovich Head of the Department of Anesthesiology and Reanimatology of the Ural State Medical Academy, Head of the Anesthesiology and Resuscitation Service of the Sverdlovsk Regional Oncology Center, Vice-President of MAKMAH, Professor, Doctor of Medical Sciences. Rachina Svetlana Aleksandrovna Senior researcher at the Research Institute of Antimicrobial Chemotherapy, Associate Professor of the Department of Clinical Pharmacology, Smolensk State Medical Academy of the Ministry of Health of the Russian Federation, Doctor of Medical Sciences. Fesenko Oksana Vadimovna Professor of the Department of Pulmonology, State Budgetary Educational Institution of Further Professional Education, Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Doctor of Medical Sciences. 2
3 Contents: 1 List of abbreviations 4 2 Synopsis 6 3 Introduction 12 4 Methodology 13 5 Epidemiology 16 6 Definition 17 7 Etiology 21 8 Resistance of pathogens to antimicrobial agents 25 9 Features of pathogenesis Diagnostics Differential diagnosis General recommendations for patient management Antimicrobial therapy Non-antimicrobial therapy Respiratory support Patients with TVP not responding to treatment Prevention References 72 Appendix 1. Scales and algorithms for assessing prognosis in CAP, determining criteria for admission to the ICU and identifying organ dysfunction Appendix 2. Rules for obtaining clinical material for microbiological research in severe CAP Appendix 3. Dosing regimens of antimicrobial agents for treatment of severe CAP in adults
4 1. List of abbreviations ABT AMP APS BAL ESBL EP GCS GCSF GMCSF IVL DN IG IL ITF CT LS MPC ON NLV NLR ARDS ICU MON PRP PPP PCR RCT RS virus MPU SVR SD SIVO SS TVP ultrasound TNF COPD ECMO antibacterial therapy antimicrobial drug activated protein C broncho-alveolar lavage extended spectrum beta-lactamases community-acquired pneumonia glucocorticosteroids granulocyte-colony-stimulating factor granulocyte-macrophage-colony-stimulating factor artificial ventilation respiratory failure immunoglobulin interleukin tissue factor inhibitor computed tomography drug minimal inhibitory concentration norepinephrine non-invasive ventilation adverse drug reaction acute respiratory distress res -syndrome intensive care unit multiple organ failure penicillin-resistant S.pneumoniae penicillin-sensitive S.pneumoniae polymerase chain reaction randomized clinical trial rhinosyncytial virus medical institution systemic inflammatory reaction diabetes mellitus systemic inflammatory response syndrome septic shock severe community-acquired pneumonia ultrasound examination tumor necrosis factor chronic obstructive lung disease extracorporeal membrane oxygenation 4
5 B.cepacia B.pertussis C.pneumoniae C.burnetii C.psittaci Candida spp CLSI E.coli Enterobacteriaceae Enterococcus spp. H. influenzae K. pneumoniae L. pneumophila Legionella spp. M.pneumoniae M.catarrhalis MRSA MSSA Neisseria spp P.aeruginosa PEEP S.aureus S.pneumoniae Staphylococcus spp. Burkholderia cepacia Bordetella pertussis Chlamydophila pneumoniae Coxiella burnetii Chlamydophila psittaci genus Candida Clinical and Laboratory Standards Institute of the United States Escherichia coli family Enterobacteriaceae genus Enterococcus Haemophilus influenzae Klebsiella pneumoniae Legionella pneumophila genus Legionella Mycoplasma pneumoniae Moraxella catarrhalis methicillin-resistant Staphyloc occus aureus methicillin-sensitive Staphylococcus aureus genus Neisseria Pseudomonas aeruginosa positive expiratory pressure Staphylococcus aureus Streptococcus pneumoniae genus Staphylococcus 5
6 2. Synopsis Severe community-acquired pneumonia (SCP) is a special form of the disease characterized by high mortality and medical care costs. Taking into account the high frequency of diagnostic errors in TVP in the Russian Federation and the widespread practice of irrational use of drugs, a list of recommendations has been developed for practitioners, following which will help improve the treatment outcomes of TVP in people aged 18 years and older. This document can be the basis for the creation of regional clinical recommendations/protocols for the management and standards of medical care for adult patients with TVP in various medical institutions in the Russian Federation. Diagnostics Diagnostic studies for TVP are aimed at confirming the diagnosis of pneumonia, establishing the etiology, assessing the prognosis, identifying exacerbation or decompensation of concomitant diseases, determining the indications for admission to the ICU and the need for respiratory support/vasopressors. In addition to a history and routine physical examination, all patients with TVP are recommended: Plain radiography of the chest organs in the anterior direct and lateral projections [B]. Pulse oximetry, and with SpO 2< 90% - исследование газов артериальной крови (PO 2, PCO 2, ph, бикарбонаты) [B]. Развернутый общий анализ крови с определением уровня эритроцитов, гематокрита, лейкоцитов, тромбоцитов, лейкоцитарной формулы [В]. Биохимический анализ крови (мочевина, креатинин, электролиты, печеночные ферменты, билирубин, глюкоза, альбумин) [С]. ЭКГ в стандартных отведениях [D]. Для оценки прогноза при ТВП целесообразно использовать шкалу CURB/CRB-65 или индекс тяжести пневмонии PSI/шкалу PORT; прогноз является неблагоприятным при наличии >3 points on the CURB/CRB-65 scale or belonging to risk class V according to the PSI pneumonia severity index/PORT scale [B]. It is recommended to use IDSA/ATS criteria to determine indications for ICU admission; in the presence of one “major” criterion: severe respiratory failure (RF), requiring mechanical ventilation or septic shock with the need for vasopressors, or three “minor” criteria: respiratory rate 30/min, PaO2/FiO2 250.6
7 multilobar infiltration, impaired consciousness, uremia (residual urea nitrogen 20 mg/dl), leukopenia (white blood cells< 4 х 10 9 /л), тромбоцитопения (тромбоциты < 100 х /л), гипотермия (<36 0 C), гипотензия, требующая интенсивной инфузионной терапии пациента необходимо госпитализировать в ОРИТ [В]. С целью этиологической диагностики ТВП целесообразно использовать следующие методы: Культуральное исследование двух образцов венозной крови [С]. Бактериологическое исследование респираторного образца - мокрота или трахеальный аспират (у пациентов, находящихся на ИВЛ) [В]. Экспресс-тесты по выявлению пневмококковой и легионеллезной антигенурии [В]. Исследование респираторного образца (мокрота, мазок из носоглотки и задней стенки глотки) на грипп методом полимеразной цепной реакции (ПЦР) во время эпидемии в регионе, наличии клинических и/или эпидемиологических данных, свидетельствующих о вероятном инфицировании вирусом гриппа [D]. По показаниям пациентам с ТВП проводятся дополнительные лабораторные и инструментальные исследования, в том числе исследование свертывающей способности крови и определение биомаркеров воспаления, компьютерная томография (КТ), фибробронхоскопия, ультразвуковые исследования, плевральная пункция с цитологическим, биохимическим и микробиологическим исследованием плевральной жидкости [D]. Лечение Всем пациентам с ТВП показано назначение системных антимикробных препаратов (АМП) и адекватная инфузионная терапия, по показаниям используются неантибактериальные ЛС и респираторная поддержка. С целью профилактики системных тромбоэмболий при ТВП показано назначение низкомолекулярных гепаринов или нефракционированного гепарина [A]; для профилактика стрессовых язв используются антисекреторные препараты [B]; рекомендуется ранняя иммобилизация [В] и ранний перевод пациентов на энтеральное питание [С]. Антибактериальная терапия Системную антибактериальную терапию (АБТ) ТВП целесообразно начинать в как можно более короткие сроки с момента постановки диагноза; задержка с введением первой дозы АМП на 4 ч и более (при развитии септического шока на 1 ч и более) ухудшает прогноз [С]. 7
8 Starting ABT TVP involves intravenous administration of AMPs [C]. In the future, as clinical stabilization occurs, it will be possible to transfer the patient to oral administration of AMPs within the framework of the concept of step therapy. The choice of empiric AMT TVP regimen depends on the presence of risk factors for P. aeruginosa infection, suspected/documented aspiration, clinical and/or epidemiological data indicating infection with influenza viruses. In individuals without risk factors for P. aeruginosa infection and aspiration, the drugs of choice are third-generation cephalosporins without antipseudomonas activity, cefepime, inhibitor-protected aminopenicillins, or ertapenem in combination with an intravenous macrolide [B]. An alternative regimen is a combination of moxifloxacin or levofloxacin with a third-generation cephalosporin without antipseudomonal activity [B]. In the presence of risk factors for P.aeruginosa infection, the drugs of choice are β-lactam AMPs with antipseudomonal activity (piperacillin/tazobactam, cefepime, meropenem, imipenem) in combination with ciprofloxacin or levofloxacin at a high dose [C]; it is possible to prescribe a β-lactam with antipseudomonal activity in combination with aminoglycosides of the II-III generation and macrolides, or respiratory fluoroquinolones [C]. For documented/suspected aspiration, the drugs of choice are inhibitor-protected β-lactams, carbapenems, or a combination of a third-generation cephalosporin without antipseudomonal activity with clindamycin or metronidazole [C]. In patients with clinical and/or epidemiological data suggesting infection with influenza viruses, oseltamivir or zanamivir is recommended in addition to antibiotics [D]. The effectiveness of the initial ABT regimen should be assessed within an hour from the start of treatment. If the initial ABT is ineffective, it is necessary to conduct an additional examination of the patient to clarify the diagnosis, identify possible complications of TVP and adjust the ABT regimen taking into account the results of microbiological studies [D]. If the dynamics are positive, the possibility of transferring the patient to oral ABPs as part of step-down therapy should be considered. The transition from parenteral to oral ABT is carried out when hemodynamic parameters are stabilized, body temperature is normalized and clinical symptoms and signs of TVP improve [B]. 8
9 The duration of ABT for TVP is determined individually, taking into account age, concomitant diseases, the state of the immune system, the presence of complications, the speed of response to the initial ABT, the characteristics of the prescribed antibacterial drug (ABP), and the pathogens identified. For TVP of unspecified etiology, the duration of ABT should be 10 days [C]. Longer courses of ABT (14-21 days) are recommended for the development of complications (empyema, abscess), the presence of extrapulmonary foci of infection, infection with S.aureus, Legionella spp., non-fermenting microorganisms [D]. Non-antibacterial (adjuvant) therapy Among the drugs related to adjuvant therapy, the most promising in patients with TVP is the use of systemic glucocorticosteroids (GCS) if there are appropriate indications. The use of systemic corticosteroids for TVP is recommended in the following cases: duration of septic shock (SS)< 1 сут., рефрактерный СШ или необходимость использования норадреналина (НА) в дозе, превышающей 0,5 мкг/кг/мин [D]. Препаратом выбора является гидрокортизон в дозе мг/сутки. Через 2 сут. необходимо оценить эффект от включения ГКС в схему терапии ТВП; длительность их назначения не должна превышать 7 дней [D]. Рутинное использование системных ГКС у пациентов с острым респираторным дистресс-синдромом (ОРДС) без СШ, их назначене другим категориям больных ТВП не рекомендуется. Рутинное применение внутривенных ИГ пациентам с ТВП, осложненной сепсисом нецелесообразно ввиду ограниченной доказательной базы и гетерогенности исследуемой популяции больных [B]. Для успешного выбора кандидатов к проведению иммуностимуляции с помощью гранулоцит-колониестимулирующего фактора (ГКСФ) и гранулоцит-макрофаг-колониестимулирующего фактора (ГМКСФ) необходимо знание фенотипа воспалительного ответа; их использование у пациентов с ТВП на основании клинических критериев сепсиса нецелесообразно [D]. Доказательств, позволяющих рекомендовать рутинное использование статинов при ТВП, в настоящее время недостаточно [C]. Респираторная поддержка Пациентам с ТВП респираторная поддержка показана при РаО 2 < 55 мм рт.ст. или Sр(a)O 2 < 88% (при дыхании воздухом). Оптимальным является поддержание Sa(р)O 2 в пределах 88-95% или PaO 2 в пределах мм рт ст. [D]. 9
10 In case of moderate hypoxemia (SpO%), provided that the patient has sufficient respiratory effort, preserved consciousness and rapid reverse dynamics of the infectious process, hypoxemia should be corrected with oxygen inhalation using a simple nasal mask (FiO%) or a mask with a dispensing bag (FiO%) [ C]. If, against the background of oxygen therapy, the “target” parameters of oxygenation are not achieved or their achievement is accompanied by an increase in respiratory acidosis and pronounced work of breathing for the patient, the issue of ventilation should be considered. Absolute indications for mechanical ventilation in TVP are: respiratory arrest, impaired consciousness (stupor, coma), psychomotor agitation, unstable hemodynamics, relative - respiratory rate >35/min, PaO 2 / FiO 2< 150 мм рт. ст, повышение РаСО 2 >20% of baseline, change in mental status [D]. In persons with TVP without pronounced asymmetry between the lungs, protective mechanical ventilation tactics are used (using small V T and the “open lung” approach); this can significantly reduce the risk of ventilator-associated lung injury [A]. Carrying out mechanical ventilation against the background of asymmetrical (unilateral) lung damage in TVP requires special caution due to the high risk of barotrauma; to improve oxygenation, the use of pharmacological drugs (inhaled nitric oxide) has been proposed [D]; periodically placing the patient on the healthy side (decubitus lateralis) [D]; separate ventilation of the lungs, taking into account different compliance and different needs for positive expiratory pressure (PEEP) in a healthy and “sick” lung [C]. An alternative to traditional respiratory support for TVP is non-invasive pulmonary ventilation (NVL), it is indicated for severe shortness of breath at rest, respiratory rate > 30/min, PaO 2 / FiO 2< 250 мм рт.ст., РаСО 2 >50 mmHg or rn< 7,3. НВЛ позволяет избежать развития многих инфекционных и механических осложнений ИВЛ. Для проведения НВЛ при ТВП необходим строгий отбор больных, основными критериями являются сохранение сознания, кооперативность больного и стабильная гемодинамика. Применение НВЛ при ТВП наиболее обосновано у больных с хронической обструктивной болезнью легких (ХОБЛ), при условии хорошего дренирования дыхательных путей и на ранних этапах развития острой ДН [C]. НВЛ может быть использована для отлучения больных от респиратора после длительной ИВЛ [C]. 10
11 Extremely severe cases of acute DN with severe CAP may require extracorporeal membrane oxygenation (ECMO) [C]. ECMO should be performed in departments and centers with experience in using this technology. Prevention For secondary prevention of CAP, the use of pneumococcal (23-valent polysaccharide and 13-valent conjugate) and influenza vaccines is recommended. Vaccination with pneumococcal vaccine is recommended for groups of people at high risk of developing invasive pneumococcal infections: age > 65 years; persons with concomitant chronic diseases of the bronchopulmonary, cardiovascular systems, diabetes mellitus (DM), chronic liver diseases, chronic renal failure, nephrotic syndrome, alcoholism, cochlear implants, liquorrhea, functional or organic asplenia; patients with immunodeficiency, residents of nursing homes and other closed institutions, smokers [B]. If vaccination with polysaccharide pneumococcal vaccine was carried out before 65 years of age, at the age of 65 years (not< 5 лет с момента введения первой дозы вакцины) рекомендуется ревакцинация [С]. Иммунокомпрометированные пациенты >50 years of age should be vaccinated initially with a single dose of conjugate vaccine and then (>8 weeks) with polysaccharide pneumococcal vaccine. Administration of the influenza vaccine is recommended if there is a high risk of complicated influenza: age > 65 years, concomitant chronic diseases of the bronchopulmonary, cardiovascular system, diabetes, kidney disease, hemoglobinopathies, residents of nursing homes and other closed institutions, 2-3 trimester of pregnancy (in period of seasonal increase in incidence) [B]. Vaccination is also recommended for health care workers treating and caring for individuals at high risk of complications from influenza [C]. Vaccination with influenza vaccine is carried out annually [B]. eleven
12 3. Introduction Community-acquired pneumonia (CAP) is a widespread disease in adults, occupying a leading place in the structure of morbidity and mortality from infectious diseases in developed countries. It should be noted that the greatest problem for doctors is presented by patients with TVP, because, despite the available diagnostic and treatment methods, including modern antimicrobial agents, the mortality rate in this category of patients remains high, and treatment is complex and expensive. Analysis of the practice of treating hospitalized patients with CAP in various regions of the Russian Federation in the years. showed that the most serious problems with the choice of antimicrobial therapy and the quality of etiological diagnosis were observed in patients with severe disease: compliance of the starting ABT regimen with national recommendations was noted in 15% of cases, only 44% of patients received combined ABT, of which 72% of combinations were irrational. Bacteriological blood testing was performed in 8% of patients, and sputum was examined in 35% of cases, and in most cases, clinical material was collected after the start of ABT, which significantly reduced the information content of this research method. The identified problems in the provision of medical care, as well as the growing medical and socio-economic significance of severe CAP, led to the preparation of separate national clinical recommendations for the management of this group of patients. The developed recommendations are addressed, first of all, to general practitioners, pulmonologists, resuscitators of multidisciplinary healthcare institutions of the Russian Federation, students, interns, residents and teachers of medical universities; they may also be of interest to doctors of other specialties. The recommendations are the result of a consensus opinion of experts from different specialties, developed on the basis of a critical assessment of studies carried out in recent years on severe CAP in the domestic and foreign literature, as well as an analysis of the most authoritative foreign clinical recommendations. This document is a logical continuation and addition to the practical recommendations for the diagnosis, treatment and prevention of CAP in adults published in 2010 by RRO and IACMAH. These recommendations focus on the issues of diagnosing TVP in immunocompetent patients, assessing the severity of CAP and prognosis, choosing the optimal strategy for empirical and etiotropic ABT, respiratory support and other treatment methods, and modern possibilities for secondary prevention of CAP. 12
13 4. Methodology Methods used to collect/select evidence: electronic database searches and additional manual searches in specialized Russian journals. Description of the methods used to collect/select evidence: the evidence base for recommendations are publications included in the Cochrane Library, the EMBASE and MEDLINE databases, and Russian specialized journals. The search depth was 10 years. Methods used to evaluate the quality and strength of evidence: expert consensus; assessment of significance in accordance with the rating scheme (Table 1). Table 1 Rating scheme for the strength of recommendations Levels of evidence Description 1++ High quality meta-analyses, systematic reviews of randomized controlled clinical trials (RCTs) or RCTs with very low risk of bias 1+ Well-conducted meta-analyses, systematic reviews or RCTs with low risk of bias 1- Meta-analyses, systematic, or RCTs with high risk of bias 2++ High-quality systematic reviews of case-control or cohort studies. High-quality reviews of case-control or cohort studies with very low risk of confounding effects or biases and moderate likelihood of causation 2+ Well-conducted case-control or cohort studies with moderate risk of confounding effects or biases and moderate likelihood of causation associations 2- Case-control or cohort studies with high risk of confounding effects or biases and moderate likelihood of causation 3 Non-analytical studies (e.g. case reports, case series) 4 Expert opinion Methods used to analyze the evidence: reviews of published metadata -analyses; systematic reviews with evidence tables. 13
14 Evidence tables: Evidence tables were completed by members of the working group. Methods used to formulate recommendations: expert consensus. Table 2. Rating scheme for assessing the strength of recommendations Strength Description A At least one meta-analysis, systematic review or RCT rated 1++, directly applicable to the target population and demonstrating robustness of the results, or Body of evidence including results from studies rated as 1+, directly applicable to the target population and demonstrating general robustness of the results B Group of evidence including results from studies rated 2++, directly applicable to the target population and demonstrating general robustness of the results, or extrapolated evidence from studies rated 1++ or 1 + C A body of evidence that includes results from studies rated 2+, directly applicable to the target population, and demonstrating overall robustness of the results; or extrapolated evidence from studies rated 2++ D Level 3 or 4 evidence; or extrapolated evidence from studies rated 2+ Economic analysis: No cost analysis was performed and pharmacoeconomics publications were not reviewed. Consultation and Peer Review: Recent changes to these guidelines were presented for discussion in a draft version at the 2014 Congress. The preliminary version was put up for wide discussion on the RPO and IACMAH website, so that persons not participating in the congress had the opportunity to take part in the discussion and improvement of the recommendations. The draft recommendations were also reviewed by independent experts, who were asked to comment, first of all, on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations. 14
15 Working group: For final revision and quality control, the recommendations were re-analyzed by members of the working group, who concluded that all comments and comments from experts were taken into account, and the risk of systematic errors in the development of recommendations was minimized. Key Recommendations: Strength of Recommendations (A-D) is given to outline the key points in the text of the recommendations. 15
16 5. Epidemiology According to official statistics of the Russian Federation (Central Research Institute of Organization and Informatization of Health Care of the Ministry of Health of the Russian Federation), in 2012, cases of CAP were registered in the Russian Federation, which amounted to 4.59; in persons aged >18 years, the incidence was 3.74. However, these figures do not reflect the true incidence of CAP in the Russian Federation, which, according to calculations, reaches 14-15, and the total number of patients annually exceeds 1.5 million people. In the United States, 5-6 million cases of CAP are registered annually, of which about 1 million people require hospitalization. According to rough estimates, for every 100 cases of CAP, about 20 patients require hospital treatment, of which 10-36% are in intensive care units (ICU). Among hospitalized patients in Europe and the USA, the proportion of patients with TVP ranges from 6.6 to 16.7%. Despite the advances made in antibiotic therapy, respiratory support and sepsis therapy, mortality among patients with severe CAP ranges from 21 to 58%. According to US statistics, among all causes of mortality, CAP ranks 8th, and the total share of deaths from CAP among all deaths in 2004 was 0.3%. The main cause of death in patients with TVP is refractory hypoxemia, SS and multiple organ failure (MOF). In prospective studies, the main factors associated with an unfavorable prognosis of patients with severe CAP were: age > 70 years, mechanical ventilation, bilateral localization of pneumonia, sepsis and P. aeruginosa infection. An analysis of the causes of death in 523 patients with TVP, carried out in health care facilities in Yekaterinburg, showed that significant aggravating factors were alcoholism and delays in seeking medical help. Patients with severe CAP require long-term hospital treatment and require quite expensive therapy. For example, in the USA, patients with severe CAP in the ICU, compared to CAP patients hospitalized in general wards, usually spend 23 days in hospital (versus 6 days), and the cost of their treatment amounted to US dollars (versus 7500 US dollars, respectively) . According to the results of recent observational studies, in recent years in developed countries there has been an increase in the number of hospitalizations for severe CAP, which is associated with an increase in the proportion of older people in the general population. Among the elderly, there was also an increase in the number of ICU hospitalizations and mortality from CAP. 16
17 6. Definition CAP should be understood as an acute illness that occurred in a community setting (that is, outside the hospital or later than 4 weeks after discharge from it, or diagnosed within the first 48 hours from hospitalization), accompanied by symptoms of lower respiratory tract infection (fever, cough, sputum production, possibly purulent, chest pain, shortness of breath) and radiological signs of “fresh” focal infiltrative changes in the lungs in the absence of an obvious diagnostic alternative. TVP is a special form of pneumonia characterized by severe DN, usually in combination with signs of sepsis and organ dysfunction. From a clinical point of view, the concept of TVP is contextual in nature, so there is no single definition. CAP can be considered severe if there is a high risk of death, the need for hospitalization of the patient in the ICU, decompensation (or its high probability) of concomitant pathology, as well as the patient’s unfavorable social status. Assessing the prognosis of TVP is most often associated with a disease characterized by an extremely unfavorable prognosis. High mortality rates and a serious prognosis combine TVP with such an urgent disease that requires intensive care as acute myocardial infarction. To assess the risk of an unfavorable outcome in CAP, a variety of criteria and scales can be used, of which the most common currently are the Pneumonia Severity Index (PSI) or the PORT (Pneumonia Outcomes Research Team) scale, as well as the CURB/CRB-65 scale. PSI/PORT scale Contains 20 clinical, laboratory and radiological signs of CAP. The risk class is determined by stratifying the patient into one of five groups. For this purpose, a complex 2-stage scoring system is used, which is based on the analysis of demographic, clinical, laboratory and radiological signs that are significant from the point of view of prognosis (Appendix 1). During the development and further validation of the scale, researchers found that the mortality rates were: for class I 0.1 0.4%; Class II 0.6 0.7%; III class 0.9 2.8%; IV class 8.2 9.3%. The maximum (27.0 - 31.1%) are the mortality rates for patients with CAP belonging to risk class V. 17
18 The PSI/PORT score is widely used to assess the risk of death in patients with CAP in North America. Limitations of the scale: Labor intensive, requires the use of a number of biochemical parameters that are not routinely determined in all healthcare facilities in the Russian Federation. It does not always accurately determine the indications for sending a patient to the ICU. Overdiagnosis of TVP in elderly patients and underdiagnosis in young people who do not suffer from concomitant pathology are typical. It does not take into account social factors and a number of significant concomitant diseases, for example, the presence of chronic obstructive pulmonary disease (COPD) or some immune disorders. CURB/CRB-65 scale The CURB-65 scale is a simpler approach to assessing the risk of an unfavorable outcome in CAP, which suggests analyzing only 5 signs: 1) impaired consciousness caused by pneumonia; 2) increase in the level of urea nitrogen > 7 mmol/l; 3) tachypnea 30/min; 4) decrease in systolic blood pressure< 90 мм рт.ст. или диастолического 60 мм рт.ст.; 5) возраст больного 65 лет. Наличие каждого признака оценивается в 1 балл, общая сумма может варьировать от 0 до 5 баллов, причем риск летального исхода возрастает по мере увеличения общей суммы баллов (Приложение 1). CRB-65 отличается отсутствием в критериях оценки лабораторного параметра - азота мочевины, что упрощает использование данной шкалы у амбулаторных больных/в приемном отделении ЛПУ. CURB/CRB-65 наиболее популярны при оценке риска летального исхода и выбора места лечения пациентов с ВП в странах Европы. Ограничения шкал: Не учитывают важные показатели, характеризующие ДН (например, уровень оксигенации). Не позволяют оценить необходимость госпитализации в ОРИТ. Не учитывают декомпенсацию сопутствующей патологии вследствие ВП. Не учитывают социальные факторы и сопутствующие заболевания. Невысокая информативность при определении прогноза у пациентов пожилого возраста. 18
19 The need for admission to the ICU The most effective tool for developing indications for referral to the ICU are the IDSA/ATS (American Thoracic Society and Infectious Diseases Society of America) recommendations, as well as the SMART-COP scale, which take into account the manifestations of sepsis-induced organ dysfunction and respiratory disorders as much as possible. IDSA/ATS criteria Based on the use of two “major” and nine “minor” TVP criteria, Table 3. The presence of one “major” or three “minor” criteria is an indication for hospitalization of the patient in the ICU. Table 3. IDSA/ATS criteria for severe CAP “Major” criteria: Severe DN requiring mechanical ventilation Septic shock (need for vasopressors) “Minor” criteria 1: RR 30/min PaO 2 /FiO Multilobar infiltration Impaired consciousness Uremia (residual urea nitrogen 2 20 mg/dl) Leukopenia (white blood cells< 4 х 10 9 /л) Тромбоцитопения (тромбоциты < 100 х /л) Гипотермия (<36 0 C) Гипотензия, требующая интенсивной инфузионной терапии 1 Могут учитываться дополнителельные критерии гипогликемия (у пациентов без сахарного диабета), гипонатриемия, необъяснимы другими причинами метаболический ацидоз/повышение уровня лактата, цирроз, аспления, передозировка/резкое прекращение приема алкоголя у зависимых пациентов 2 остаточный азот мочевины = мочевина, ммоль/л/2,14 Шкала SMART-COP Данная шкала разработана Австралийской рабочей группой по ВП, основана на оценке тяжести ВП путем выявления пациентов, нуждающихся в интенсивной респираторной поддержке и инфузии вазопрессоров с целью поддержания адекватного уровня АД. Шкала SMART-COP предусматривает балльную оценку клинических, лабораторных, физических и рентгенологических признаков с определением вероятностной потребности в указанных выше интенсивных методах лечения. 19
20 A description of the SMART-COP scale is presented in Appendix 1. In accordance with this scale, CAP is defined as severe with a score of 5 or more, while 92% of patients with a score >3 require mechanical ventilation. There is a modified version of the SMRT-CO scale, which does not require the determination of parameters such as albumin level, PaO 2 and arterial blood pH. The SMART-COP scale when assessing the need to refer patients to the ICU is not inferior to the IDSA/ATS criteria. Other scales, such as SCAP, CORB or REA-ICU, use various variations of minor ATS criteria and/or additional indicators such as low arterial pH, albumin, tachycardia or hyponatremia. These scales allow diagnosing TVP with the same accuracy as the IDSA/ATS criteria, but are less studied and require additional validation. Decompensation (or high risk of decompensation) of concomitant pathology A significant contribution to the high mortality rates in CAP is made by exacerbation or progression of concomitant diseases. Although the PSI scale contains indications for a number of diseases, most guidelines do not consider comorbidity as a prognostic factor for TVP. This results in a large gap between existing scales and actual clinical practice. Concomitant diseases of the kidneys, liver, heart, central nervous system, malignant neoplasms and diabetes mellitus (DM) have an independent negative impact on the prognosis of TVP. This is based on the provocation of acute systemic inflammation by TVP and the intensification of hypercoagulation processes. Decompensation of extrapulmonary chronic pathology is observed in 40% of cases of pneumonia requiring hospitalization, and in half of the patients signs of organ dysfunction are observed already on the first day of the disease. Acute cardiac disorders are more often observed in patients with chronic cardiovascular pathology (relative risk 4.3), and the risk of their occurrence correlates with the class of the PSI scale (37-43% for classes IV-V). The maximum risk of cardiovascular events is observed in the first 24 hours after hospitalization. Thus, the routine approach to a patient with CAP should include a rigorous assessment of comorbidities, and the detection of exacerbation (decompensation) should be considered as a marker of TVP requiring intensive monitoring. Burdened social status Despite the unanimity of most experts about the need to take into account social factors when choosing a place of treatment for a patient with CAP, only a few works 20
21 are devoted to the study of this complex problem. Low socioeconomic status increases the likelihood of hospitalization for CAP by more than 50 times, even among patients formally considered to be at low risk of death (<5%). Несколько исследований, недавно проведенных в Европе, показали, что плохой прогноз ТВП у больных, проживающих в домах престарелых, обусловлен низкими показателями функционального статуса вследствие тяжелых, а иногда и сочетанных заболеваний. Поэтому неэффективность лечения чаще обусловлена очевидными или скрытыми ограничениями к проведению интенсивной терапии, чем присутствием полирезистентного или редкого возбудителя. Для выделения этой важной группы больных должна использоваться оценка функционального статуса, предпочтительно с помощью валидированных шкал, таких как оценка повседневной активности или оценка общего состояния по критериям ВОЗ. 7. Этиология Описано более ста микроорганизмов (бактерии, вирусы, грибы, простейшие), которые при определенных условиях могут являться возбудителями ВП. Однако большинство случаев заболевания ассоциируется с относительно небольшим кругом патогенов. К числу наиболее актуальных типичных бактериальных возбудителей тяжелой ВП относятся Streptococcus pneumoniae (S.pneumoniae), энтеробактерии - Klebsiella pneumoniae (K.pneumoniae) и др., Staphylococcus aureus (S.aureus), Haemophilus influenzae (H.influenzae). У некоторых категорий пациентов - недавний прием системных АМП, длительная терапия системными ГКС в фармакодинамических дозах, муковисцидоз, вторичные бронхоэктазы - в этиологии тяжелой ВП существенно возрастает актуальность Pseudomonas aeruginosa (P.aeruginosa). Среди атипичных возбудителей при тяжелом течении ВП наиболее часто выявляется Legionella pneumophila (L.pneumophila), меньшую актуальность представляют Mycoplasma pneumoniae (M.pneumoniae) и Chlamydophila pneumoniae (С.pneumoniae). Значимость анаэробов, колонизующих полость рта и верхние дыхательные пути в этиологии ТВП до настоящего времени окончательно не определена, что в первую очередь обусловлено ограничениями традиционных культуральных методов исследования респираторных образцов. Вероятность инфицирования анаэробами может возрастать у лиц с доказанной или предполагаемой аспирацией, обусловленной эпизодами нарушения сознания при судорогах, некоторых неврологических заболеваниях (например, инсульт), дисфагии, заболеваниях, сопровождающихся нарушением моторики пищевода. 21
22 The frequency of occurrence of other bacterial pathogens - Chlamydophila psittaci (C.psittaci), Streptococcus pyogenes, Bordetella pertussis (B.pertussis), etc. usually does not exceed 2-3%, and lung lesions caused by endemic micromycetes (Histoplasma capsulatum, Coccidioides immitis and etc.) are extremely rare in the Russian Federation. TVP can be caused by respiratory viruses, most often influenza viruses, coronaviruses, rhinosyncytial virus (RS virus), human metapneumovirus, human bocavirus. In most cases, infections caused by a group of respiratory viruses are characterized by a mild course and are self-limiting, but in elderly and senile people, in the presence of concomitant bronchopulmonary, cardiovascular diseases or secondary immunodeficiency, they can be associated with the development of severe, life-threatening complications. The growing relevance of viral pneumonia in recent years is due to the emergence and spread of the pandemic influenza virus A/H1N1pdm2009 in the population, which can cause primary damage to lung tissue and the development of rapidly progressing DN. There are primary viral pneumonia (develops as a result of direct viral damage to the lungs, characterized by a rapidly progressive course with the development of severe DN) and secondary bacterial pneumonia, which can be combined with primary viral damage to the lungs or be an independent late complication of influenza. The most common causes of secondary bacterial pneumonia in patients with influenza are S.aureus and S.pneumoniae. The frequency of detection of respiratory viruses in patients with CAP is strongly seasonal and increases in the cold season. With CAP, co-infection with two or more pathogens can be detected; it can be caused either by the association of various bacterial pathogens or by their combination with respiratory viruses. The incidence of CAP caused by pathogen associations varies from 3 to 40%; According to a number of studies, CAP caused by an association of pathogens tends to be more severe and have a worse prognosis. It should be noted that the frequency of occurrence of various pathogens of severe CAP can vary significantly depending on the geographical location, season and patient profile. In addition, the likelihood of infection with a particular pathogen is determined by the presence of relevant risk factors (Table 22
23 4), as well as research methods used for microbiological diagnostics. The frequency of detection of various CAP pathogens among patients hospitalized in the ICU based on the results of studies in European countries is presented in Table 5. Russian data on the etiology of severe CAP remain scarce. However, in general, they confirm the patterns identified in foreign studies. In a small study carried out in Smolensk, the most common bacterial pathogen of CAP in people with severe disease was S. pneumoniae, followed by Enterobacteriaceae (Fig. 1). In a study of the etiology of fatal CAP (autopsy material was examined), the most common bacterial pathogens were K. pneumoniae, S.aureus and S.pneumoniae - 31.4%, 28.6%, 12.9% of all isolated isolates, respectively. Table 4. Frequency of detection of various CAP pathogens in patients admitted to the ICU (according to studies in Europe) Pathogen Detection frequency, % S. pneumoniae 28 Legionella spp. 12 Enterobacteriaceae 9 S. aureus 9 H. influenzae 7 C. burnetii 7 P. aeruginosa 4 C. pneumoniae 4 Respiratory viruses 3 M. pneumoniae 2 Not established 45 For some microorganisms (Streptococcus viridans, Staphylococcus epidermidis and other coagulase-negative staphylococci, Enterococcus spp. , Neisseria spp., Candida spp.) development of bronchopulmonary inflammation is uncharacteristic. Their isolation from sputum in patients without severe immunodeficiency indicates with a high degree of probability that the material is contaminated by the microflora of the upper respiratory tract. It should be noted that, despite the expansion of opportunities for microbiological diagnosis, in about half of patients with severe CAP, the etiological diagnosis remains unidentified. 23
24 Table 5. Comorbidities/risk factors associated with certain CAP pathogens Disease/risk factor COPD/smoking Decompensated diabetes mellitus Influenza epidemic Alcoholism Confirmed or suspected aspiration Bronchiectasis, cystic fibrosis Intravenous drug use Contact with air conditioners, humidifiers, water cooling systems, recent (<2 нед) морское путешествие/проживание в гостинице Тесный контакт с птицами Тесный контакт с домашними животными (работа на ферме) Коклюшеподобный кашель >2 weeks Local bronchial obstruction (eg, bronchogenic carcinoma) Stay in nursing homes Outbreak of disease in an organized group Probable pathogens H. influenzae, S. pneumoniae, M. catarrhalis, Legionella spp., P. aeruginosa (severe COPD) S. pneumoniae, S aureus, enterobacteria Influenza virus, S. pneumoniae, S. aureus, H. influenzae S. pneumoniae, anaerobes, enterobacteria (usually K. pneumoniae) Enterobacteria, anaerobes P. aeruginosa, B. cepacia, S. aureus S. aureus, anaerobes , S. pneumoniae Legionella spp. C. psittaci C. burnetii B. pertussis Anaerobes, S. pneumoniae, H. influenzae, S. aureus S. pneumoniae, enterobacteria, H. influenzae, S. aureus, C. pneumoniae, anaerobes S. pneumoniae, M. pneumoniae, C pneumoniae, influenza virus M.pneumoniae 41.2 S.pneumoniae L.pneumophila 11.8 H.influenzae+S.pneumoniae+K.pneumoniae K.pneumoniae E.coli E.coli+K.pneumoniae K.pneumoniae+Enterococcus spp. Rice. 1. Structure of bacterial pathogens of severe CAP in adult patients (%, Smolensk) 24
25 8. Resistance of pathogens to antimicrobial agents From the point of view of the choice of regimens of empirical antimicrobial therapy (AMT) for TVP, local monitoring of antibiotic resistance of S. pneumoniae and H. influenzae is of greatest clinical importance. S. pneumoniae An urgent problem in the world is the spread of isolates among pneumococci with reduced sensitivity to β-lactam AMPs (primarily penicillins) and the increase in resistance to macrolides. A distinctive feature of the Russian Federation is the high level of resistance of S. pneumoniae to tetracyclines and co-trimoxazole, which may be due to the unreasonably high frequency of their use for the treatment of respiratory infections in the 20th and early 21st centuries. Monitoring data for the sensitivity of clinical strains of S. pneumoniae in the Russian Federation isolated from patients with community-acquired respiratory infections as part of the multicenter studies Cerberus and PeGAS are presented in Table 6. Since 2008, the recommendations of the Clinical and Laboratory Standards Institute (CLSI) of the United States have revised the control values of the minimum suppressive concentrations (MIC) of penicillin G for pneumococcus, which, when administered parenterally to non-meningeal isolates, are 2 (sensitive), 4 (moderately resistant) and 8 (resistant) mg/l, respectively. The change in the sensitivity criteria of S. pneumoniae to penicillin is due to the results of pharmacodynamic and clinical studies demonstrating the high effectiveness of the drug when administered intravenously at a dose of 12 million units per day against S. pneumoniae with an MIC of 2 mg/l, as well as maintaining effectiveness against moderately resistant isolates (MIC 4 mg/l) when using high doses (18-24 million units per day). As the Cerberus multicenter study shows, the level of resistance of pneumococci to penicillin and aminopenicillins in the Russian Federation remains low (2.0 and 1.4% of non-susceptible isolates, respectively). The detection rate of S.pneumoniae resistant to ceftriaxone is 1.8%, and the proportion of moderately resistant ones is 0.9%. All pneumococci, including penicillin-resistant (PRP), remained sensitive to ceftaroline, which showed the highest activity against this pathogen in vitro (Table 6. Resistance of S. pneumoniae to erythromycin was 8.4%; most macrolide-resistant S. pneumoniae showed resistance to clindamycin, 25
26 which may indicate the predominance in the Russian Federation of the MLSB resistance phenotype, which is caused by modification of the target and determines the resistance of S. pneumoniae to all macrolides, including 16-membered ones, and a significant increase in MIC values. Linezolid and respiratory fluoroquinolones showed high activity against S. pneumoniae. The level of resistance of pneumococci to tetracycline, despite a significant reduction in the use of this group of antimicrobial agents in the Russian Federation in recent years, remains high (33.1% of non-susceptible isolates). Table 6. Sensitivity of clinical isolates of S. pneumoniae to AMPs in the Russian Federation (according to the Cerberus multicenter study, n=706) Name of AMPs Distribution of isolates by MIC category, mg/l H UR R 50% 90% Benzylpenicillin 98.0% 1.7% 0.3% 0.03 0.25 Amoxicillin 98.6% 1.3% 0.1% 0.03 0.125 Ceftriaxone 97.3% 0.9% 1.8% 0.015 0.25 Ceftaroline 100 .0% 0 0 0.008 0.03 Erythromycin 90.8% 0.8% 8.4% 0.03 0.25 Clindamycin 93.2% 0.1% 6.7% 0.03 0.06 Levofloxacin 100, 0% 0 0 0.50 1.0 Tetracycline 66.9% 3.1% 30.0% 0.25 16.0 Linezolid 100.0% 0 0 0.50 0.5 Note: H sensitive, UR moderately resistant , P resistant (CLSI criteria, 2013) H. influenzae The greatest clinical significance in the world is the increase in resistance of H. influenzae to aminopenicillins, which is most often caused by the production of β-lactamases that hydrolyze this group of AMPs. As the PeGAS III study shows, the level of resistance to aminopenicillins among clinical strains of H. influenzae isolated in the Russian Federation from patients with community-acquired respiratory infections remains low (2.8% of non-susceptible isolates); no strains resistant to inhibitor-protected aminopenicillins have been identified (Table 7). 26
27 Third generation cephalosporins retain high activity against H. influenzae; no isolates resistant to fluoroquinolones were identified Table 7. The highest level of resistance of H. influenzae was registered to co-trimoxazole (32.8% of non-susceptible isolates). Table 7. Sensitivity of clinical isolates of H. influenzae to AMPs in the Russian Federation (according to the multicenter study PeGAS III, n=433) Name of AMPs Distribution of isolates by MIC category, mg/l H UR R 50% 90% Amoxicillin 97.2% 1.6% 1.2% 0.25 1.0 Amoxicillin/clavulanate 100.0% 0 0 0.25 0.5 Ceftriaxone 100.0% 0 0 0.03 0.03 Levofloxacin 100.0% 0 0 0 .03 0.03 Moxifloxacin 100.0% 0 0 0.015 0.03 Azithromycin 100.0% 0 0 0.5 1.0 Clarithromycin 99.5% 0.5% 0 4.0 8.0 Tetracycline 96.2% 0.5% 3.3% 0.25 0.5 Co-trimoxazole 67.2% 8.7% 24.1% 0.125 16.0 Note: H sensitive, UR moderately resistant, P resistant (CLSI criteria, 2013 .); Despite the general trends, the resistance profile of respiratory pathogens may differ in individual regions, therefore, when choosing drugs, it is most advisable to be guided by local data on the resistance of microorganisms to AMPs. In addition, it is necessary to take into account individual risk factors for the detection of antibiotic-resistant pathogens. Risk factors for detecting PRP are age over 65 years, recent (<3 мес.) терапия β-лактамными АМП, серьезные хронические сопутствующие заболевания, алкоголизм, иммунодецифит или иммуносупрессивная терапия, тесный контакт с детьми, посещающими дошкольные учреждения. Частота встречаемости ПРП увеличивается при недавнем использовании макролидов и ко-тримоксазола. Вероятность инфицирования макролидорезистентными S.pneumoniae возрастает у пожилых пациентов, при применении данной группы АМП в ближайшие 3 месяца, 27
28 recent use of penicillins or co-trimoxazole, HIV infection, close contact with persons colonized with resistant isolates. A key risk factor for the detection of fluoroquinolone-resistant S. pneumoniae is a history of repeated fluoroquinolone use. A potential issue that may influence the strategy of empirical antibiotic therapy for severe CAP is the spread of methicillin-resistant S. aureus (MRSA) in the community. For some countries, the so-called community-acquired MRSA (CA-MRSA), which is characterized by high virulence due, in particular, to the production of Panton-Valentine leukocidin, is relevant. CA-MRSA infection is often recorded in young, previously healthy individuals and is characterized by the development of severe necrotizing pneumonia, serious complications (pneumothorax, abscesses, pleural empyema, leukopenia, etc.) and high mortality. CA-MRSA are resistant to β-lactam AMPs, but, as a rule, remain sensitive to other classes of AMPs (lincosamides, fluoroquinolones, cotrimoxazole). The relevance of the CA-MRSA problem for the Russian Federation is currently unclear. Studies of the molecular epidemiology of S.aureus indicate that the Russian Federation is characterized by the spread in community settings not of CA-MRSA, but of typical nosocomial strains of MRSA. The prevalence of MRSA among adults with severe CAP in the Russian Federation does not appear to be high, although this issue requires further study. Risk factors for MRSA infection include colonization or a history of infection with this pathogen, recent surgery, hospitalization or stay in a nursing home, the presence of an indwelling intravenous catheter, dialysis, and previous antibacterial therapy. Another potential threat is due to the possible spread in community settings among members of the Enterobacteriaceae family of isolates that produce extended spectrum β-lactamases (ESBLs), which determines their insensitivity to III-IV generation cephalosporins, as well as the increased resistance of enterobacteria to inhibitor-protected aminopenicillins and fluoroquinolones, which are first-line drugs for empirical treatment of TVP. This trend in the Russian Federation can be seen in relation to pathogens of community-acquired urinary tract infections, but has not yet been studied in patients with CAP. 28
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Russian Respiratory Society (RRO)
Interregional Association for Clinical Microbiology
and antimicrobial chemotherapy (MACMAC)
Clinical guidelines for the diagnosis, treatment and prevention of severe community-acquired pneumonia in adults
2014
|
Chuchalin Alexander Grigorievich |
Director of the Federal State Budgetary Institution "Research Institute of Pulmonology" of the FMBA of Russia, Chairman of the Board of the RRO, Chief Freelance Specialist Therapist-Pulmonologist of the Ministry of Health of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences |
|
Sinopalnikov Alexander Igrevich |
Head of the Department of Pulmonology, SBEE DPO “Russian Medical Academy of Postgraduate Education” of the Ministry of Health of the Russian Federation, Vice-President of IACMAC, Professor, MD |
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Kozlov Roman Sergeevich |
Director of the Research Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy of the Ministry of Health of the Russian Federation, President of IACMAC, Professor, MD |
|
Avdeev Sergey Nikolaevich |
Deputy Director for Research, Head of the Clinical Department of the Federal State Budgetary Institution "Research Institute of Pulmonology" of the Federal Medical and Biological Agency of Russia, Professor, MD |
|
Tyurin Igor Evgenievich |
Head of the Department of Radiation Diagnostics and Medical Physics of the Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Chief Freelance Specialist in Radiation Diagnostics of the Ministry of Health of the Russian Federation, Professor, MD |
|
Rudnov Vladimir Alexandrovich |
Head of the Department of Anesthesiology and Resuscitation of the Ural State Medical Academy, Head of the Anesthesiology and Resuscitation Service of the Sverdlovsk Regional Oncology Center, Vice-President of IACMAH, Professor, MD |
|
Rachina Svetlana Alexandrovna |
Senior Researcher of the Research Institute of Antimicrobial Chemotherapy, Associate Professor of the Department of Clinical Pharmacology, Smolensk State Medical Academy of the Ministry of Health of the Russian Federation, MD |
|
Fesenko Oksana Vadimovna |
Professor of the Department of Pulmonology, State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Postgraduate Education” of the Ministry of Health of the Russian Federation, Doctor of Medical Sciences. |
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List of abbreviations | ||
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Synopsis | ||
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Introduction | ||
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Methodology | ||
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Epidemiology | ||
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Definition | ||
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Etiology | ||
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Resistance of pathogens to AMPs | ||
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Features of pathogenesis | ||
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Diagnostics | ||
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Differential diagnosis | ||
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Antimicrobial therapy | ||
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Non-antimicrobial therapy | ||
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Respiratory support | ||
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Patients with TVP not responding to treatment | ||
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Prevention | ||
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Bibliography | ||
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Appendix 1. Scales and algorithms for assessing prognosis for CAP, determining criteria for admission to the ICU and identifying organ dysfunction | ||
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Appendix 2. Rules for obtaining clinical material for microbiological research in severe CAP | ||
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Appendix 3. Dosing regimens of antimicrobial agents for the treatment of severe CAP in adults | ||
List of abbreviations
ABT antibacterial therapy
AMP antimicrobial drug
APS activated protein C
BAL broncho-alveolar lavage
Extended spectrum beta-lactamase ESBLs
CAP community-acquired pneumonia
GCS glucocorticosteroids GCSF granulocyte-colony-stimulating factor
GM-CSF granulocyte-macrophage-colony-stimulating factor
IVL artificial ventilation of the lungs
DN respiratory failure
IG immunoglobulin
IL interleukin
ITF tissue factor inhibitor
CT computed tomography
medicinal product
MIC minimum inhibitory concentration
ON norepinephrine
NIV non-invasive ventilation
ADR adverse drug reaction
ARDS acute respiratory distress syndrome
ICU intensive care unit
MOF multiple organ failure
PRP penicillin-resistant S. pneumoniae PPP penicillin-sensitive S. pneumoniae
PCR polymerase chain reaction
RCT randomized clinical trial
MS virus rhinosyncytial virus health care facility treatment and prophylactic institution
SVR systemic inflammatory response
diabetes mellitus
SIRS systemic inflammatory response syndrome
SS septic shock
TVP severe community-acquired pneumonia
Ultrasound ultrasound examination
TNF tumor necrosis factor
COPD chronic obstructive pulmonary disease
ECMO extracorporeal membrane oxygenation
B.cepacia Burkholderia cepacia
B.pertussis Bordetella pertussis
C. pneumoniae Chlamydophila pneumoniae
S. burnetii Coxiellaburnetii
C.psittaci Chlamydophila psittaci
Candida spp genus Candida
CLSI US Clinical and Laboratory Standards Institute
E.coli Escherichia coli
Enterobacteriaceae family Enterobacteriaceae
Enterococcus spp. genus Enterococcus
H.influenzae Haemophilus influenzae
K. pneumoniae Klebsiella pneumoniae
L.pneumophila Legionella pneumophila
Legionella spp. genus Legionella
M. pneumoniae Mycoplasma pneumoniae
M. catarrhalis Moraxella catarrhalis
MRSA methicillin-resistant Staphylococcus aureus
MSSA methicillin-sensitive Staphylococcus aureus
Neisseria spp genus Neisseria
P. aeruginosa Pseudomonas aeruginosa
PEEP positive expiratory pressure
S. aureus Staphylococcus aureus
S. pneumoniae Streptococcus pneumoniae
Staphylococcus spp. genus Staphylococcus
Synopsis
Severe community-acquired pneumonia (CAP) is a special form of the disease characterized by high mortality and medical costs. Taking into account the high frequency of diagnostic errors in TVP in the Russian Federation and the widespread practice of irrational use of drugs, a list of recommendations has been developed for practitioners, following which will help improve the treatment outcomes of TVP in people aged 18 years and older. This document can be the basis for the creation of regional clinical recommendations/protocols for the management and standards of medical care for adult patients with TVP in various medical institutions in the Russian Federation.
Diagnostics
Diagnostic studies in TP are aimed at confirming the diagnosis of pneumonia, establishing the etiology, assessing the prognosis, identifying exacerbation or decompensation of concomitant diseases, determining indications for hospitalization in the ICU and the need for respiratory support / prescribing vasopressors.
In addition to taking a history and routine physical examination, it is recommended that all patients with CVD:
Plain radiography of the organs of the chest cavity in the anterior direct and lateral projections [B].
Pulse oximetry, and with SpO 2< 90% - исследование газов артериальной крови (PO 2 ,PCO 2, pH, бикарбонаты) [B].
A detailed general blood test with the determination of the level of erythrocytes, hematocrit, leukocytes, platelets, leukocyte formula [B].
Biochemical blood test (urea, creatinine, electrolytes, liver enzymes, bilirubin, glucose, albumin) [C].
ECG in standard leads [D].
To assess the prognosis for TVS, it is advisable to use the CURB / CRB-65 scale or the PSI severity index / PORT scale; the prognosis is unfavorable if there is > 3 points on the CURB / CRB-65 scale or belonging to risk class V according to the PSI severity index / PORT [B] scale.
It is recommended to use IDSA/ATS criteria to determine indications for ICU admission; in the presence of one "major" criterion: severe respiratory failure (DN), requiring mechanical ventilation or septic shock with the need for the introduction of vasopressors, or three "minor" criteria: respiratory rate ³30 / min, PaO2 / FiO2 ≤ 250, multilobar infiltration, impaired consciousness, uremia (residual urea nitrogen ≥ 20 mg/dl), leukopenia (white blood cells< 4 х 10 9 /л), тромбоцитопения (тромбоциты < 100 х 10 12 /л), гипотермия (<36 0 C), гипотензия, требующая интенсивной инфузионной терапии пациента необходимо госпитализировать в ОРИТ [В].
For the purpose of etiological diagnosis of TVP, it is advisable to use the following methods:
Culture of two venous blood samples [C].
Bacteriological examination of a respiratory specimen - sputum or tracheal aspirate (in ventilated patients) [B].
Rapid tests to detect pneumococcal and legionella antigenuria [B].
Investigation of a respiratory sample (sputum, nasopharyngeal and posterior pharyngeal swab) for influenza by polymerase chain reaction (PCR) during an epidemic in the region, there are clinical and/or epidemiological data indicating a probable infection with influenza virus [D].
According to indications, patients with TVP undergo additional laboratory and instrumental studies, including a study of blood coagulation and determination of biomarkers of inflammation, computed tomography (CT), fibrobronchoscopy, ultrasound, pleural puncture with cytological, biochemical and microbiological examination of pleural fluid [D].
Treatment
All patients with TVP are prescribed systemic antimicrobial drugs (AMPs) and adequate infusion therapy; non-antibacterial drugs and respiratory support are used when indicated.
To prevent systemic thromboembolism in TVP, the administration of low molecular weight heparins or unfractionated heparin is indicated [A]; Antisecretory drugs are used to prevent stress ulcers [B]; Early immobilization [B] and early transfer of patients to enteral nutrition are recommended [C].
Antibacterial therapy
It is advisable to start systemic antibacterial therapy (ABT) for TVP as soon as possible from the moment of diagnosis; a delay in administering the first dose of AMPs for 4 hours or more (with the development of septic shock for 1 hour or more) worsens the prognosis [C].
The starting ABT TVP involves intravenous administration of AMPs [C]. In the future, as clinical stabilization occurs, it will be possible to transfer the patient to oral administration of AMPs within the framework of the concept of step therapy.
The choice of empirical AMT TVP regimen depends on the presence of risk factors for infection P. aeruginosa, suspected/documented aspiration, clinical and/or epidemiological evidence of infection with influenza viruses.
In persons without risk factors for infection P. aeruginosa and aspiration, the drugs of choice are third-generation cephalosporins without antipseudomonal activity, cefepime, inhibitor-protected aminopenicillins or ertapenem in combination with a macrolide for intravenous administration [B]. An alternative regimen is a combination of moxifloxacin or levofloxacin with a third-generation cephalosporin without antipseudomonal activity [B].
If there are risk factors for infection P. aeruginosa the drugs of choice are β-lactam AMPs with antipseudomonal activity (piperacillin/tazobactam, cefepime, meropenem, imipenem) in combination with high-dose ciprofloxacin or levofloxacin [C]; it is possible to prescribe a β-lactam with antipseudomonal activity in combination with aminoglycosides of the II-III generation and macrolides, or respiratory fluoroquinolones [C].
For documented/suspected aspiration, the drugs of choice are inhibitor-protected β-lactams, carbapenems, or a combination of a third-generation cephalosporin without antipseudomonal activity with clindamycin or metronidazole [C].
In patients with clinical and/or epidemiological data suggesting infection with influenza viruses, oseltamivir or zanamivir is recommended in addition to antibiotics [D].
Evaluation of the effectiveness of the starting ABT regimen should be carried out 48-72 hours after the start of treatment. If the initial ABT is ineffective, it is necessary to conduct an additional examination of the patient to clarify the diagnosis, identify possible complications of TVS, and adjust the ABT regimen taking into account the results of microbiological studies [D].
If the dynamics are positive, the possibility of transferring the patient to oral ABPs as part of step-down therapy should be considered. The transition from parenteral to oral ABT is carried out when hemodynamic parameters are stabilized, body temperature is normalized and clinical symptoms and signs of TVP improve [B].
The duration of ABT in TVS is determined individually, taking into account age, concomitant diseases, the state of the immune system, the presence of complications, the speed of the “response” to the starting ABT, the characteristics of the prescribed antibacterial drug (ABD), and pathogens detected. For TVP of unspecified etiology, the duration of ABT should be 10 days [C]. Longer courses of ABT (14-21 days) are recommended for the development of complications (empyema, abscess), the presence of extrapulmonary foci of infection, infection S. aureus,Legionella spp., non-fermenting microorganisms [D].
Non-antibacterial (adjuvant) therapy
Among drugs related to adjuvant therapy, the most promising in patients with TVP is the use of systemic glucocorticosteroids (GCS) in the presence of appropriate indications.
The use of systemic corticosteroids for TVP is recommended in the following cases: duration of septic shock (SS)< 1 сут., рефрактерный СШ или необходимость использования норадреналина (НА) в дозе, превышающей 0,5 мкг/кг/мин [D]. Препаратом выбора является гидрокортизон в дозе 200-300 мг/сутки. Через 2 сут. необходимо оценить эффект от включения ГКС в схему терапии ТВП; длительность их назначения не должна превышать 7 дней [D]. Рутинное использование системных ГКС у пациентов с острым респираторным дистресс-синдромом (ОРДС) без СШ, их назначене другим категориям больных ТВП не рекомендуется.
Routine use of intravenous IGs in patients with TPK complicated by sepsis is not reasonable due to the limited evidence base and the heterogeneity of the studied patient population [B].
Successful selection of candidates for immunostimulation with granulocyte-colony-stimulating factor (GCSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) requires knowledge of the inflammatory response phenotype; their use in patients with TVP based on clinical criteria for sepsis is inappropriate [D].
Respiratory support
For patients with TVP, respiratory support is indicated at PaO 2< 55 мм рт.ст. или Sр(a)O 2 < 88% (при дыхании воздухом). Оптимальным является поддержаниеSa(р)O 2 в пределах 88-95% илиPaO 2 – в пределах 55-80 мм рт ст. [D].
In the case of moderate hypoxemia (SpO 2 80-88%), subject to sufficient respiratory effort of the patient, preserved consciousness and rapid reverse dynamics of the infectious process, hypoxemia should be corrected by inhalation of oxygen using a simple nasal mask (FiO 2 45-50%) or a mask with consumable bag (FiO 2 75-90%) [C].
If, against the background of oxygen therapy, the “target” parameters of oxygenation are not achieved or their achievement is accompanied by an increase in respiratory acidosis and pronounced work of breathing for the patient, the issue of ventilation should be considered. Absolute indications for mechanical ventilation in TVP are: respiratory arrest, impaired consciousness (stupor, coma), psychomotor agitation, unstable hemodynamics, relative - respiratory rate >35/min, PaO 2 / FiO 2< 150 мм рт. ст, повышение РаСО 2 >20% of baseline, change in mental status [D].
In persons with TVP without pronounced asymmetry between the lungs, protective mechanical ventilation tactics are used (using small V T and the “open lung” approach); this can significantly reduce the risk of ventilator-associated lung injury [A].
Carrying out mechanical ventilation against the background of asymmetrical (unilateral) lung damage in TVP requires special caution due to the high risk of barotrauma; to improve oxygenation, the use of pharmacological drugs (inhaled nitric oxide) has been proposed [D]; periodically placing the patient on the healthy side (decubitus lateralis) [D]; separate ventilation of the lungs, taking into account different compliance and different needs for positive expiratory pressure (PEEP) in a healthy and “sick” lung [C].
An alternative to traditional respiratory support for TVP is non-invasive pulmonary ventilation (NVL), it is indicated for severe shortness of breath at rest, respiratory rate > 30/min, PaO 2 / FiO 2< 250 мм рт.ст., РаСО 2 >50 mmHg or pH< 7,3. НВЛ позволяет избежать развития многих инфекционных и механических осложнений ИВЛ. Для проведения НВЛ при ТВП необходим строгий отбор больных, основными критериями являются сохранение сознания, кооперативность больного и стабильная гемодинамика. Применение НВЛ при ТВП наиболее обосновано у больных с хронической обструктивной болезнью легких (ХОБЛ), при условии хорошего дренирования дыхательных путей и на ранних этапах развития острой ДН [C]. НВЛ может быть использована для отлучения больных от респиратора после длительной ИВЛ [C].
Extremely severe cases of acute DN in severe CAP may require extracorporeal membrane oxygenation (ECMO) [C]. ECMO should be performed in departments and centers with experience in using this technology.
Prevention
Vaccination with pneumococcal vaccine is recommended for groups of people at high risk of developing invasive pneumococcal infections: age > 65 years old; persons with concomitant chronic diseases of the bronchopulmonary, cardiovascular systems, diabetes mellitus (DM), chronic liver diseases, chronic renal failure, nephrotic syndrome, alcoholism, cochlear implants, liquorrhea, functional or organic asplenia; patients with immunodeficiency, residents of nursing homes and other closed institutions, smokers [B].
If vaccination with polysaccharide pneumococcal vaccine was carried out before 65 years of age, at the age of 65 years (not< 5 лет с момента введения первой дозы вакцины) рекомендуется ревакцинация [С]. Иммунокомпрометированные пациенты >50 years of age should be initially vaccinated once conjugated, and then ( > 8 weeks) polysaccharide pneumococcal vaccine.
The introduction of influenza vaccine is recommended in the presence of a high risk of complicated course of influenza: age > 65 years old, concomitant chronic diseases of the bronchopulmonary, cardiovascular system, diabetes, kidney disease, hemoglobinopathies, residents of nursing homes and other institutions of a closed type, 2-3 trimester of pregnancy (during the seasonal rise in incidence) [B]. Vaccination is also recommended for health care workers treating and caring for individuals at high risk of complications from influenza [C]. Vaccination with influenza vaccine is carried out annually [B].
Introduction
Community-acquired pneumonia (CAP) is a widespread disease in adults, which occupies a leading place in the structure of morbidity and mortality from infectious diseases in developed countries. It should be noted that the greatest problem for doctors is presented by patients with TVP, because, despite the available diagnostic and treatment methods, including modern antimicrobial agents, the mortality rate in this category of patients remains high, and treatment is complex and expensive.
A analysis of the practice of treating hospitalized patients with CAP in various regions of the Russian Federation in 2005-2006. showed that the most serious problems with the choice of antimicrobial therapy and the quality of etiological diagnosis were observed in patients with severe disease: compliance of the starting ABT regimen with national recommendations was noted in 15% of cases, only 44% of patients received combined ABT, of which 72% of combinations were irrational. Bacteriological blood testing was performed in 8% of patients, and sputum was examined in 35% of cases, and in most cases, clinical material was collected after the start of ABT, which significantly reduced the information content of this research method.
The identified problems in the provision of medical care, as well as the growing medical and socio-economic significance of severe CAP, led to the preparation of separate national clinical recommendations for the management of this group of patients.
The developed recommendations are addressed, first of all, to general practitioners, pulmonologists, resuscitators of multidisciplinary healthcare institutions of the Russian Federation, students, interns, residents and teachers of medical universities; they may also be of interest to doctors of other specialties. The recommendations are the result of a consensus opinion of experts from different specialties, developed on the basis of a critical assessment of studies carried out in recent years on severe CAP in the domestic and foreign literature, as well as an analysis of the most authoritative foreign clinical recommendations.
This document is a logical continuation and addition to the practical recommendations for the diagnosis, treatment and prevention of CAP in adults published in 2010 by RRO and IACMAH. These recommendations focus on the issues of diagnosing TVP in immunocompetent patients, assessing the severity of CAP and prognosis, choosing the optimal strategy for empirical and etiotropic ABT, respiratory support and other treatment methods, and modern possibilities for secondary prevention of CAP.
Methodology
Methods used to collect/select evidence: search in electronic databases and additional manual search in specialized Russian journals.
Description of methods used to collect/select evidence: the evidence base for recommendations is publications included in the Cochrane Library, EMBASE and MEDLINE databases, and Russian specialized journals. The search depth was 10 years.
Methods used to assess the quality and strength of evidence:
expert consensus;
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Levels of Evidence |
Description |
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High quality meta-analyses, systematic reviews of randomized controlled clinical trials (RCTs) or RCTs with very low risk of bias |
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High-quality meta-analyses, systematic reviews or RCTs with low risk of bias |
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Meta-analyses, systematic, or RCTs with a high risk of bias |
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High-quality systematic reviews of case-control or cohort studies. High-quality reviews of case-control or cohort studies with very low risk of confounding effects or bias and moderate probability of causality |
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Well-conducted case-control or cohort studies with a moderate risk of confounding effects or bias and a moderate probability of causality |
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Case-control or cohort studies with a high risk of confounding effects or bias and a moderate probability of causality |
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Non-analytic studies (for example: case reports, case series) |
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Expert opinion |
Methods used to analyze evidence:
systematic reviews with tables of evidence.
Evidence tables: the evidence tables were filled in by members of the working group.
Methods used to formulate recommendations: expert consensus.
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Description |
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At least one meta-analysis, systematic review or RCT rated 1++, directly applicable to the target population and demonstrating robustness of the results A body of evidence that includes study results rated 1+, directly applicable to the target population, and demonstrating overall robustness of the results |
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A body of evidence that includes study results rated 2++, directly applicable to the target population and demonstrating overall robustness of the results extrapolated evidence from studies rated 1++ or 1+ |
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A body of evidence that includes findings from studies rated 2+, directly applicable to the target population, and demonstrating overall robustness of the results; extrapolated evidence from studies rated 2++ |
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Level 3 or 4 evidence; extrapolated evidence from studies rated 2+ |
Economic analysis: no cost analysis was performed and pharmacoeconomics publications were not reviewed.
Consultation and expert assessment:
Recent changes to these guidelines were presented for discussion in a draft version at the 2014 ____________ Congress. The preliminary version was put up for wide discussion on the RPO and IACMAH website, so that persons not participating in the congress had the opportunity to take part in the discussion and improvement of the recommendations.
Working group:
For final revision and quality control, the recommendations were re-analyzed by members of the working group, who concluded that all comments and comments from experts were taken into account, and the risk of systematic errors in the development of recommendations was minimized.
Epidemiology
According to official statistics of the Russian Federation (Central Research Institute for Organization and Informatization of Health Care of the Ministry of Health of the Russian Federation), in 2012, 657,643 cases of CAP were registered in the Russian Federation, which amounted to 4.59‰; in older people > At the age of 18, the incidence was 3.74‰. However, these figures do not reflect the true incidence of CAP in the Russian Federation, which, according to calculations, reaches 14-15‰, and the total number of patients annually exceeds 1.5 million people.
In the United States, 5-6 million cases of CAP are registered annually, of which about 1 million people require hospitalization. According to rough estimates, for every 100 cases of CAP, about 20 patients require hospital treatment, of which 10-36% are in intensive care units (ICU). Among hospitalized patients in Europe and the USA, the proportion of patients with TVP ranges from 6.6 to 16.7%.
Despite the advances made in antibiotic therapy, respiratory support and sepsis therapy, mortality among patients with severe CAP ranges from 21 to 58%. According to US statistics, among all causes of mortality, CAP ranks 8th, and the total share of deaths from CAP among all deaths in 2004 was 0.3%.
The main cause of death in patients with TVP is refractory hypoxemia, SS and multiple organ failure (MOF). In prospective studies, the main factors associated with an unfavorable prognosis of patients with severe CAP were: age > 70 years, mechanical ventilation, bilateral localization of pneumonia, sepsis and infection P. aeruginosa.
An analysis of the causes of death in 523 patients with TVP, carried out in health care facilities in Yekaterinburg, showed that significant aggravating factors were alcoholism and delays in seeking medical help.
Patients with severe CAP require long-term hospital treatment and require quite expensive therapy. For example, in the United States, patients with severe CAP in the ICU, compared with CAP patients hospitalized in general wards, usually spent 23 days in hospital (vs. 6 days), and the cost of their treatment was 21,144 US dollars (vs. 7,500 US dollars, respectively). ).
According to the results of recent observational studies, in recent years in developed countries there has been an increase in the number of hospitalizations for severe CAP, which is associated with an increase in the proportion of older people in the general population. Among the elderly, there was also an increase in the number of ICU hospitalizations and mortality from CAP.
Definition
CAP should be understood as an acute illness that occurred in a community setting (that is, outside the hospital or later than 4 weeks after discharge from it, or diagnosed in the first 48 hours after hospitalization), accompanied by symptoms of lower respiratory tract infection (fever, cough, sputum production , possibly purulent, chest pain, shortness of breath) and radiological signs of “fresh” focal infiltrative changes in the lungs in the absence of an obvious diagnostic alternative.
TVP is a special form of pneumonia characterized by severe DN, usually in combination with signs of sepsis and organ dysfunction. From a clinical point of view, the concept of TVP is contextual in nature, so there is no single definition. CAP can be considered severe if there is a high risk of death, the need for hospitalization of the patient in the ICU, decompensation (or its high probability) of concomitant pathology, as well as the patient’s unfavorable social status.
