Acinetobacter baumannii 10 2 is worth treating. Acinetobacter infections: treatment, symptoms

A swab from the throat is taken for a standard bacteriological study to study the microbial composition and the quantitative ratio of the microflora of the nasopharynx. This is a laboratory diagnostic method that allows you to identify pathogens of infectious and inflammatory diseases of the upper respiratory tract. To determine the etiology of infection, it is necessary to conduct a bacteriological examination of the discharged nose and throat for microflora.

Specialists refer patients with chronic, and to the microbiological laboratory, where biomaterial is taken from the nose and throat with a sterile cotton swab and examined. Based on the results of the analysis, the specialist determines the causative agent of the pathology and its sensitivity to antibiotics.

Reasons and goals for taking a smear on the microflora from the throat and nose:

• Diagnosis caused by beta-hemolytic streptococcus and leading to the development of severe complications - glomerulonephritis, rheumatism, myocarditis.
• The presence of Staphylococcus aureus in the nasopharynx, which provokes the formation of boils on the skin.
• Bacteriological culture of clinical material in case of inflammation of the nasopharynx is carried out in order to exclude diphtheria infection.
• Suspicion of meningococcal or pertussis infection, as well as respiratory ailments.
• Diagnosis of stenotic, abscesses located near the tonsils, includes a single analysis.
• Persons in contact with an infectious patient, as well as children entering a kindergarten or school, undergo a preventive examination in order to detect bacterial carriage.
• A complete examination of pregnant women includes taking a swab from the pharynx for microflora.
• A prophylactic swab from the throat and nose for staphylococcus aureus is taken by all medical workers, kindergarten teachers, cooks and grocery store sellers.
• A swab from the throat to determine the cellular composition of the discharge. The studied material is applied to a special glass slide. Under a microscope, a laboratory assistant counts the number of eosinophils and other cells in the field of view. A study is underway to determine the allergic nature of the disease.

Patients are sent to the bacteriological laboratory to study the material from the nasopharynx in order to exclude or confirm a specific infection. In the direction indicate the microorganism, the presence of which must be confirmed or refuted.

Microflora of the nasopharynx

On the mucous membrane of the pharynx and nose, there are many microorganisms that make up the normal microflora of the nasopharynx. A study of the discharge of the throat and nose shows the qualitative and quantitative ratio of microbes living in this locus.

Types of microorganisms living on the nasopharyngeal mucosa in healthy people:

1. bacteroids,
2. veillonella,
3. Escherichia coli,
4. branhamella,
5. pseudomonas,
6. Streptococcus matans,
7. Neisseria meningitides,
8. Klebsiella pneumonia,
9. epidermal staphylococcus,
10. green streptococcus,
11. Non-disease-causing Neisseria
12. diphtheroids,
13. corynebacterium,
14. Candida spp.
15. Haemophilis spp.,
16. Actinomyces spp.

With pathology in a smear from the pharynx and nose, the following microorganisms can be detected:

• Beta-hemolytic group A,
• S. aureus
• Listeria,
• Branhamella catarrhalis,
• Acinetobacter baumannii,

Preparation for analysis

In order for the results of the analysis to be as reliable as possible, it is necessary to correctly select clinical material. For this you need to be prepared.

Two weeks before the material is taken, systemic antibiotics are stopped, and 5-7 days before, it is recommended to stop using antibacterial solutions, rinses, sprays and ointments for topical use. The analysis should be taken on an empty stomach. Before this, it is forbidden to brush your teeth, drink water and chew gum. Otherwise, the result of the analysis may be false.

A swab from the nose for eosinophils is also taken on an empty stomach. If a person has eaten, you must wait at least two hours.

Taking material

To properly take the material from the pharynx, patients tilt their heads back and open their mouths wide. Specially trained laboratory staff presses the tongue with a spatula and collects the pharyngeal discharge with a special tool - a sterile cotton swab. Then he removes it from the oral cavity and lowers it into a test tube. The tube contains a special solution that prevents the death of microbes during the transportation of the material. The tube must be delivered to the laboratory within two hours from the moment the material was taken. Taking a swab from the throat is a painless procedure, but unpleasant. Touching a cotton swab to the pharyngeal mucosa can provoke vomiting.

To take a swab from the nose, it is necessary to seat the patient opposite and tilt his head slightly. Before analysis, it is necessary to clear the nose of the existing mucus. The skin of the nostrils is treated with 70% alcohol. A sterile swab is introduced alternately first into one and then into the other nasal passage, turning the instrument and firmly touching its walls. The swab is quickly lowered into the test tube and the material is sent for microscopic and microbiological examination.

microscopic examination

The test material is applied to a glass slide, fixed in a burner flame, stained according to Gram and studied under a microscope with immersion oil. Gram-negative or gram-positive rods, cocci or coccobacilli are found in the smear, their morphological and tinctorial properties are studied.

Microscopic signs of bacteria are an important diagnostic landmark. If the smear contains gram-positive cocci, located in clusters resembling grapes, it is assumed that the causative agent of the pathology is staphylococcus aureus. If the cocci are positively Gram-stained and arranged in chains or pairs in the smear, these are probably streptococci; Gram-negative cocci - Neisseria; Gram-negative rods with rounded ends and a light capsule - Klebsiella, small Gram-negative rods - Escherichia,. Further microbiological research is continued taking into account microscopic signs.

Seeding of the test material

Each microorganism grows in its "native" environment, taking into account pH and humidity. The environments are differential-diagnostic, selective, universal. Their main purpose is to provide nutrition, respiration, growth and reproduction of bacterial cells.

Inoculation of the test material must be carried out in a sterile box or laminar flow cabinet. The health worker must be dressed in sterile clothes, gloves, a mask and shoe covers. This is necessary to maintain sterility in the work area. In boxing, one should work silently, carefully, ensuring personal safety, since any biological material is considered suspicious and obviously infectious.

A smear from the nasopharynx is inoculated on nutrient media and incubated in a thermostat. After a few days, colonies grow on the media, having a different shape, size and color.

There are special nutrient media that are selective for a particular microorganism.

The material is rubbed with a swab into the medium on a small area measuring 2 square meters. see, and then with the help of a bacteriological loop, they are sown with strokes over the entire surface of the Petri dish. Crops are incubated in a thermostat at a certain temperature. The next day, the crops are viewed, the number of grown colonies is taken into account and their character is described. Subculture individual colonies on selective nutrient media to isolate and accumulate a pure culture. Microscopic examination of a pure culture makes it possible to determine the size and shape of the bacterium, the presence of a capsule, flagella, spores, and the ratio of the microbe to staining. The isolated microorganisms are identified to the genus and species, if necessary, phage typing and serotyping are carried out.

Research result

The result of the study, microbiologists write out on a special form. To decipher the result of a swab from the throat, the values ​​\u200b\u200bof the indicators are required. The name of the microorganism consists of two Latin words denoting the genus and species of the microbe. Next to the name indicate the number of bacterial cells, expressed in special colony-forming units. After determining the concentration of the microorganism, they proceed to the designation of its pathogenicity - “conditionally pathogenic flora”.

In healthy people, bacteria that perform a protective function live on the mucous membrane of the nasopharynx. They do not cause discomfort and do not cause the development of inflammation. Under the influence of unfavorable endogenous and exogenous factors, the number of these microorganisms increases dramatically, which leads to the development of pathology.

Normally, the content of saprophytic and conditionally pathogenic microbes in the nasopharynx should not exceed 10 3 - 10 4 CFU / ml, and pathogenic bacteria should be absent. Only a doctor with special skills and knowledge can determine the pathogenicity of a microbe and decipher the analysis. The doctor will determine the appropriateness and necessity of prescribing anti-inflammatory and antibacterial drugs to the patient.

After identifying the causative agent of pathology and its identification to the genus and species, they proceed to determine its sensitivity to phages, antibiotics and antimicrobials. It is necessary to treat a disease of the throat or nose with the antibiotic to which the identified microbe is most sensitive.

throat swab results

Variants of the results of the study of a smear from the pharynx:

• Negative culture result- There are no causative agents of bacterial or fungal infection. In this case, the cause of the pathology is viruses, not bacteria or fungi.
• Positive microflora culture result- there is an increase in pathogenic or opportunistic bacteria that can cause acute pharyngitis, diphtheria, whooping cough and other bacterial infections. With the growth of fungal flora, oral candidiasis develops, the causative agent of which is biological agents of the 3rd pathogenicity group - yeast-like fungi of the genus Candida.

Microbiological examination of the separated pharynx and nose on the flora allows you to determine the type of microbes and their quantitative ratio. All pathogenic and opportunistic microorganisms are subject to full identification. The result of laboratory diagnostics allows the doctor to prescribe the right treatment.

Acinetobacter spp. refers to microorganisms that live freely in the environment (saprophytes), on various objects in medical institutions, in water, and food products. In addition, Acinetobacter spp. isolated from various biotopes (for example, from the skin, mucous membranes) of a person.

Presence Acinetobacter spp. in biomaterials from a patient in a hospital, it can be both a consequence of the colonization of the mucous membranes and skin, and the cause of infectious complications of various localization. Skin colonization occurs in 25% of adults, and upper respiratory tract colonization occurs in 7% of children. Acinetobacter spp., as well as P. aeruginosa, is able to stay in a viable state on various environmental objects for months.
In addition, Acinetobacter spp. resistant to many bactericidal solutions, for example to.

According to the CDC(NNIS), over the past 20 years, the importance of non-fermenting Gram-negative rods of the genus Acinetobacter as causative agents of NCI has grown significantly worldwide. During surgical interventions, Acinetobacter spp. isolated from purulent wounds in 2.1% of cases. The species A. baumannii accounts for 80% of all species of this genus responsible for ECI, and therefore the isolation of any other species of this genus suggests that there is a Coptam and nation of the studied biomaterial.

Reselection Acinetobacter spp. from any biomaterials is important to exclude contamination or colonization and, ultimately, for the correct interpretation of the results of microbiological studies. It should be noted that most often Acinetobacter spp. isolated in pneumonia (Acinetobacter spp. accounts for 6.9% of all pathogens in this localization), especially if it was preceded by colonization of the mucous membranes of the upper respiratory tract. Mortality in pneumonia caused by Acinetobacler spp. is 40-64%.

Along with others opportunistic microbes(such as S. maltophilia) Acinetobacter spp. is highly resistant to most antimicrobials, although there are significant differences in antibiotic resistance of strains in different countries and regions. Currently, according to various authors, most strains of A. baumannii are resistant to many classes of antimicrobial drugs. The fluoroquinolones, tigecycline, ceftazidime, trimethoprim/sulfamethoxazole, doxycycline, imipenem, meropenem, doripenem, polymyxin B, and colistin have until recently been considered active against nosocomial strains of A. baumannii.

Fast development A. baumannii resistance to most antibiotics (MDR-Acinetobacter) is registered worldwide. Sulbactam has a higher natural bactericidal activity against MDR-Acinetobacter in comparison with tazobactam and clavulanic acid, at the same time, there is an increase in resistance to sulbactam. The combination of imipenem with amikacin in in vitro studies has shown synergism against MDR strains, while in vivo the effect is less pronounced. The combination of fluoroquinolones with amikacin is acceptable when there is a low MIC of fluoroquinolones for hospital A baumannii strains.

When highlighting MDR-A strains. baumannii use a combination of polymyxip B with rifampicin (or with imipenem, or with azithromycin). There are few studies on the use of tigecycline for the treatment of infections caused by A. baumannii, but the use of this antibiotic is already associated with a gradual increase in resistance. According to data from Germany, resistance to tigecycline among A. baumannii is 6%, while resistance to coli is 2.8%.

According to SENTRY 2001-2004 (30 European countries), the proportion of strains of Acinetobacter spp. resistant to imipenem, meropenem, ampicillin / sulbactam and polymyxin B is 26.3, 29.6, 51.6 and 2.7%, respectively. It is important to note that even in countries with a low level of resistance, the phenomenon of the spread of MDR-, XDR- or PDR-strains of A. baumannii is not yet clear. One of the risk factors for MDR-A. baumannii is considered to be prescribed carbapenems and third-generation cephalosporins.
In addition, the risk is associated with artificial lung ventilation(IVL), prolonged stay in intensive care, surgery, contamination of surrounding objects.

Part 4. "Problem" gram-negative microorganisms: Pseudomonas aeruginosa and Acinetobacter
Synopsis of a clinician and microbiologist
Part 4. "Problem" gram-negative microorganisms: Pseudomonas aeruginosa and Acinetobacter">!}

There are a number of microorganisms (MO), which, due to the high level of acquired resistance, are usually called problematic. Among the causative agents of respiratory diseases, methicillin-resistant Staphylococcus aureus and some representatives of the gram-negative flora - Pseudomonas aeruginosa, P. aeruginosa, bacteria of the genus Acinetobacter (Acinetobacter spp.) and, in some cases, individual MOs of the family Enterobacteriaceae (E. coli, K . pneumoniae). This article will focus on P. aeruginosa and Acinetobacter spp.

T.A. Pertseva, Department of Faculty Therapy and Endocrinology, Dnepropetrovsk State Medical Academy, Ukraine; R.A. Bontsevich, Labytnangskaya Central City Multidisciplinary Hospital, Russia

Introduction

Pseudomonas aeruginosa was originally known to microbiologists as a pathogen of various plants, but later it turned out that it can also cause diseases in humans. In most cases, P. aeruginosa is an opportunistic pathogen for humans. It does not affect healthy, undamaged tissues. However, any tissue of the body can be infected with P. aeruginosa in case of damage or a general decrease in the protective functions of the macroorganism (immunodeficiency). Therefore, infections caused by P. aeruginosa are quite common, especially in nosocomial settings, when a significant part of these MOs quickly acquires multiresistance.

According to the American Center for Disease Control (CDC), the overall proportion of P. aeruginosa infections in US hospitals is about 0.4%. This MO, being the fourth most common among nosocomial pathogens, causes about 10.1% of all nosocomial infections. According to other data, P. aeruginosa is the cause of 28.7% of all hospital infections, 20-40% of all late nosocomial pneumonia. P. aeruginosa poses the greatest danger to oncological, burn and AIDS patients, in whom it can even cause bacteremia, in which mortality reaches 50%.

The natural habitat of Acinetobacter spp. are water and soil, they are often emitted from wastewater. These MOs are part of the microflora of the skin of healthy individuals (more often they colonize areas between the toes and in the inguinal region, especially in those living in a hot and humid climate), the gastrointestinal and urogenital tracts and belong to low pathogenic microorganisms, however, the presence of certain properties contributes to an increase in virulence. Acinetobacter spp. .

The most clinically significant MOs of the genus Acinetobacter spp. A. baumannii species are considered to be the causative agents of A. lwoffii diseases much less frequently. Therefore, when referring to Acinetobacter infection, A. baumannii is primarily meant.

In critically ill patients (intensive care units, intensive care units), A. baumannii can cause pneumonia, tracheobronchitis, bloodstream, urinary tract infections, catheter-associated and wound infections (Joly-Guillou, 2005). In intensive care units (ICUs) in the United States in 2003, Acinetobacter spp. caused 6.9% of all pneumonias, 2.4% of bloodstream infections, 2.1% of surgical site infections, and 1.6% of urinary tract infections. In tropical climates, Acinetobacter spp. may cause severe community-acquired pneumonia (Houang et al., 2001) . In addition, Acinetobacterium is capable of causing disease outbreaks during natural disasters.

Mortality in acinetobacter infection is usually very high and amounts to 20-60%, attributable mortality is about 10-20% (Joly-Guillou, 2005) .

The incidence of Acinetobacter infection is increasing. In the UK, Acinetobacter bacteremia increased by 6% between 2002 and 2003 to 1087 cases (Health Protection Agency, 2004). A serious problem is a significant increase in the frequency of bacteremia caused by multidrug-resistant strains of Acinetobacter spp. – more than 300% from 2002 to 2003 (7 and 22 cases respectively) (Health Protection Agency, 2004). In the US ICU, the rate of Acinetobacter pneumonia increased from 4% in 1986 to 7% in 2003 (Gaynes and Edwards, 2005) .

Currently, the greatest concern is the growth of multi-resistance of these microorganisms, there are strains that are resistant to all major antimicrobial drugs (AMPs). Because of this, MO has been figuratively dubbed "gram-negative MRSA".

In some regions, the problem of nosocomial Acinetobacter infection comes to the forefront. So, in Israel, according to the site antibiotic.ru, in the last decade Acinetobacter spp. became the leading cause of ventilator-associated pneumonia and bacteremia. The spread of this pathogen occurred at a rapid pace. Even 7-8 years ago, there were no cases of infections caused by Acinetobacter spp. in Israel, and today only in Tel Aviv about 500 cases are recorded annually, 50 of which are fatal. A retrospective cohort study of 236 patients found that infections caused by multidrug-resistant strains of A. baumannii had a less favorable outcome. In the group of patients in whom multidrug-resistant strains were isolated, mortality was 36%, while in case of infection with a non-multidrug-resistant strain it was 21% (p=0.02). Acinetobacteria are very difficult to eradicate. While efforts to eradicate MRSA and Clostridium difficile in Tel Aviv's medical facilities have been successful, Acinetobacter spp. failed. E. Harris (USA) in his report stated that today it is extremely necessary to search for preventive measures and new drugs for treatment. New antibiotics are needed that are active against gram-negative pathogens, although such drugs are not currently being developed.

Exciter characteristic

P. aeruginosa and Acinetobacter spp. are Gram-negative, non-fermenting bacteria.

P. aeruginosa (“Pseudomonas aeruginosa”) is a Gram-negative, motile rod-shaped bacterium, an obligate aerobe. It has dimensions of 0.5-0.8 microns in thickness and 1.5-3 microns in length. Belongs to the genus Pseudomonas (numbering more than 140 species of bacteria) of the family Pseudomonadaceae (pseudomonas). It is extremely resistant to most antibiotics due to the barrier created by the outer membrane liposaccharides, as well as the formation of a biofilm, which also plays a protective role. There are strains that are practically not affected by any of the known antibiotics.

The vast majority of MOs of the Pseudomonadaceae family, living in soil and water, are of little clinical significance (with the exception of B. mallei and B. pseudomallei, the causative agents of glanders and melioidosis, respectively). In domestic conditions, Pseudomonas aeruginosa is able to colonize the tile surface, clogging into the seams and forming a protective biofilm, which is why standard disinfectants have a bad effect on it.

In hospitals, P. aeruginosa can be found on the surfaces of various objects and equipment, as well as in fluid reservoirs. It is often carried with contaminated food or water, as well as in transit through bathrooms, sinks, water tap handles, objects, especially wet ones (for example, towels) that patients can share, through direct contact with a bacteriocarrier or indirectly through the hands of medical personnel, etc. .P. .

The high frequency of isolation and more pronounced pathogenicity of P. aeruginosa in comparison with other pseudomonads are associated with the presence of a number of virulence factors in this MO that promote colonization and infection of human tissues. Virulence determinants include adhesion, invasion, and cytotoxicity factors.

Phospholipase C, exotoxin A, exoenzyme S, elastase, leukocidin, pyocyanin pigment (which causes a blue-green color of the medium when growing a microorganism in culture or purulent discharge of infected wounds), lipopolysaccharide (an inducer of a systemic inflammatory reaction) have a local and systemic effect on the mammalian organism. capsular polysaccharide alginate (usually in patients with chronic infections, for example, with cystic fibrosis; alginate contributes to the formation of a film on the surface of the epithelium, which protects the pathogen from exposure to microorganism resistance factors and antibiotics).

P. aeruginosa is characterized by a variety of mechanisms for regulating the expression of virulence factors, which is aimed at the rapid adaptation of the microorganism to changing environmental conditions. When MO is in the external environment, virulence factors are not synthesized, but when it enters the internal environment of the mammalian body, an intensive synthesis of proteins begins, contributing to the development of the infectious process.

A number of scientists note that in addition to the regulation of the synthesis of virulence factors at the level of individual microbial cells, in P. aeruginosa, regulation also occurs at the population level. We are talking about the phenomenon of “cooperative sensitivity” or “quorum sensing” (quorum sensing), which consists in the accumulation of low molecular weight compounds (homoserine lactones) in the microbial population, which, when a certain concentration is reached, derepresses the synthesis of most virulence factors. Thus, the expression of virulence genes turns out to be dependent on the density of the microbial population. The biological meaning of the phenomenon is probably associated with the coordinated start of the synthesis of virulence factors only after the microbial population reaches a certain level of density. The expression of most virulence factors and secondary metabolites is subject to regulation at the level of cooperative sensitivity in P. aeruginosa.

The genus Acinetobacter combines gram-negative (sometimes poorly discolored with alcohol when stained according to Gram) immobile (movement in jerks can be observed due to polarly located fimbriae 10-15 microns long and 6 microns in diameter) coccobacilli. Strictly aerobic, oxidase-negative and catalase-positive.

A. baumannii is an aquatic organism that lives in various artificial and natural reservoirs. At the same time, these bacteria are able to survive on a dry surface for up to 1 month.

In hospital settings, A. baumannii often colonizes solutions for external, internal and parenteral multiple use. MO has low virulence. Often it can be isolated from the skin and sputum of patients, wounds, urine, which, as a rule, does not indicate infection, but colonization.

The development of acinetobacter infection is atypical, more typical for immunocompromised patients. The infection is more tropic to tissues and organs with a high fluid content (respiratory and urinary tracts, cerebrospinal fluid, blood, peritoneal fluid). Manifested in the form of nosocomial pneumonia, infections associated with prolonged peritoneal dialysis, catheter-associated infections.

The presence of MO in the respiratory secretions of intubated patients almost always indicates colonization. Pneumonia can be epidemiologically associated with the colonization of respiratory equipment or fluids, pleurisy with drainage systems, sepsis with catheters and other infusion equipment and solutions.

Characteristic features of colonization and incidence of Acinetobacter infection are presented in table 1.

Isolation of MO

In microbiological terms, Pseudomonas aeruginosa is undemanding, grows on various artificial media (ENDO, Kligler, Koda, Levin, etc.) under normal conditions, at temperatures up to 42 ° C (optimally - 37 ° C), does not ferment lactose and forms smooth round colonies of fluorescent greenish sweet smelling colors. In a smear prepared from a pure culture, rods can be arranged singly, in pairs, or form short chains. A specific property of P. aeruginosa is the phenomenon of "rainbow lysis", as well as the ability to intensely stain the medium (more often in blue-green colors). With the help of serological diagnostics, both the antigens of the infectious agent and the antibodies produced in response to antigenic stimulation of the immune system can be detected in a relatively short time.

There are MOs related to P. aeruginosa, such as S. maltophilia and B. cepacia, for which correct microbiological identification differential diagnosis is required. This is due to the fact that S. maltophilia has a natural resistance to carbapenems, B. cepacia to aminoglycosides, and P. aeruginosa has a natural sensitivity to them (although resistance may be acquired).

Acinetobacter is cultivated on conventional media in the temperature range of 20-30°C, with an optimal growth temperature of 33-35°C; these MOs do not need growth factors and are not capable of denitrification. Most strains grow on mineral media containing ethanol, acetate, pyruvate, lactate as the only source of carbon and energy, and ammonium salts or nitrates as a source of nitrogen.

Identification. In a practical laboratory, it is sufficient to use a minimal set of tests to identify bacteria of the genus Acinetobacter and differentiate them from other gram-negative MOs. In this case, the defining features are: the shape of the cells (cocci or small rods), the lack of mobility, the nature and ability of growth on MacConkey's medium (lactose-negative colonies of small and medium sizes), the absence of color changes of the indicator on Kligler's polycarbohydrate agar and alkalization of the medium, a negative cytochrome oxidase test. For differentiation of Acinetobacter spp. from other oxidase-negative non-fermenting bacteria, additional tests are used. Species identification of Acinetobacter is much more difficult and, as a rule, is not carried out in routine practice.

Resistance of P. aeruginosa to AMP

The main groups of antibiotics with clinically significant antipseudomonas activity include β-lactams, aminoglycosides, and fluoroquinolones. However, P. aeruginosa has multiple resistance mechanisms:

• to aminoglycosides - enzymatic inactivation, reduced permeability, modification of the target of action;
• to β-lactam AMPs - a change in the structure of the porin channel (decrease in permeability), hydrolysis by β-lactamases, active release with the participation of the OprM protein, modification of the target of PBP action, changes in the structure of the porin protein OprD;
• to fluoroquinolones - a change in the structure of the target of action (DNA gyrase), activation of the excretion system (MexA-MexB-OprM), a decrease in membrane permeability.

It is especially important that in 30-50% of patients P. aeruginosa polyresistance develops even with monotherapy.

Resistance to Acinetobacter spp. to AMP

MOs are resistant to many antibacterial drugs, depending on the source of isolation and species. Strains obtained from patients are more resistant to antibiotics than bacteria isolated from medical personnel or environmental objects, and the resistance of A. baumannii can be 10-20 times higher than the minimum inhibitory concentrations (MICs) of β-lactam antibiotics established for A. lwoffii. The vast majority of clinical isolates are resistant to penicillin at a dose of more than 100 U / ml, as well as to macrolides, lincosamides, chloramphenicol, cephalosporins of I-II generations. Hospital strains are becoming resistant to a wider range of antibacterial drugs, but remain relatively sensitive to carbapenems and amikacin.

Resistance to Acinetobacter spp. to β-lactam AMPs is associated with the production of plasmid and chromosomal β-lactamases, a decrease in the permeability of cell surface structures and a change in the structure of penicillin-binding proteins.

The resistance of Acinetobacter isolates to aminoglycosides is due to all three known groups of aminoglycoside-modifying enzymes: aminoacetyltransferases, adenyltransferases, and phosphorylases, which are controlled by genes localized on plasmids and transposons.

Resistance to fluoroquinolones occurs due to the modification of bacterial DNA gyrase, as a result of changes in the structure of the protein of the outer membrane and a decrease in the penetration of the drug into the cell.

Determination of sensitivity to AMP

First-line drugs in determining the antibiotic sensitivity of Pseudomonas spp. and Acinetobacter spp. are the means with the greatest natural activity.

Ceftazidime- one of the main AMPs used to treat infections caused by the considered group of microorganisms.

cefepime with a level of natural activity comparable to that of ceftazidime, in some cases it retains activity against MOs resistant to ceftazidime.

Gentamicin, amikacin. Aminoglycosides are not used for monotherapy of infections caused by this group of bacteria, but in many cases they are a necessary component of combined therapy regimens.

Ciprofloxacin among fluoroquinolones, it is considered the drug of choice in the treatment of this group of infections.

Meropenem, imipenem. Meropenem is characterized by the highest level of activity in relation to these MOs, imipenem is somewhat inferior to it. The expediency of including both carbapenems is explained by the absence of cross-resistance between them in some cases.

Additional drugs in terms of natural activity, as a rule, are inferior to first-line antibiotics, but in many cases, primarily for economic reasons, they can be used in therapy. In addition, it should be taken into account that non-fermenting bacteria differ significantly in the level of natural sensitivity to AMP.

Aztreonam, cefoperazone on the main properties are close to ceftazidime.

Cefoperazone/sulbactam, ticarcillin/clavulanate. Inhibitors used in therapy are not able to suppress the activity of most β-lactamases synthesized by P. aeruginosa, which is why combined preparations do not have significant advantages compared to the original antibiotics. At the same time, cefoperazone/sulbactam, as well as ampicillin/sulbactam, can be highly effective in the treatment of acinetobacter infections due to the intrinsic activity of sulbactam.

Carbenicillin. In view of the toxicity and high incidence of resistance, the use of carbenicillin for the treatment of infections caused by P. aeruginosa should be considered inappropriate.

Since severe infections caused by Pseudomonas are an indication for combination therapy, it is advisable to indicate the most effective combination of antibiotics from a microbiological point of view when issuing the results of microbiological studies to the clinic.

General requirements for material sampling and microbiological diagnostics are given in the article “Clinically significant pathogens of respiratory tract infections. Synopsis of a clinician and microbiologist. Part 1. Pneumococcus ”(see No. 3 (04), 2006) .

Risk factors and features of infection

Due to the presence of multiple virulence factors in P. aeruginosa, infections caused by this MO are potentially more virulent than those caused by other opportunistic pathogens.

The source of infection in the first place are patients with Pseudomonas aeruginosa, as well as attendants. A significant factor in the spread of Pseudomonas aeruginosa infection can be contaminated household items, solutions, hand creams, towels for the face, genitals, shaving brush, etc. Rare factors include the spread of infection through tools, devices and equipment that have been disinfected, which turned out to be ineffective.

Pseudomonas aeruginosa mainly affects people with weakened immune systems: hospitalized patients with concomitant diseases, the elderly and children. A number of conditions, such as cystic fibrosis, burns, leukemia, urolithiasis, being on artificial lung ventilation (ALV), are independent predisposing risk factors. The list of conditions predisposing to the development of infection is given in table 2.

The most serious nosocomial infections are ventilator-associated pneumonia. Risk factors for these P. aeruginosa pneumonias include previous therapy with third-generation cephalosporins, prolonged hospitalization, or obstructive pulmonary disease. Mortality in bacteriologically confirmed ventilator-associated pneumonia (contamination of the material obtained from the lower respiratory tract using special brushes, protected from contamination in the upper respiratory tract, more than 103 CFU / ml) is 73%, and with the colonization of the lower respiratory tract by P. aeruginosa (contamination of the material is less than 103 CFU / ml) - 19%.

With any localization of the primary focus of infection caused by P. aeruginosa, bacteremia may develop, which significantly worsens the prognosis of the disease. According to the multicentre European study SENTRY, the incidence of bacteremia caused by P. aeruginosa is 5%. At the same time, overall mortality rates are 40-75%, attributive - 34-48%.

The role of P. aeruginosa in the etiology of community-acquired infections is small.

Long-term hospitalization or antimicrobial therapy (especially AMPs with low activity against acinetobacteria), the presence of other patients colonized by this MO, and in the ICU conditions the use of invasive respiratory or catheter equipment predispose to the occurrence of acinetobacter colonization (and subsequently infection).

As noted above, Acinetobacter spp. affect immunocompromised patients. Most often, these MOs cause nosocomial infections. Many of them are relatively indolent, but they are extremely resistant to therapy.

Treatment

The problem of treating Pseudomonas aeruginosa and acinetobacter infections is becoming more and more urgent every year due to an increase in the frequency of occurrence, an increase in the resistance of MO and, accordingly, a decrease in the effectiveness of therapy. In pulmonology, the problem of eradication of MO data is more often associated with such nosologies as nosocomial pneumonia and cystic fibrosis, less often with chronic purulent bronchitis, pleurisy, and community-acquired pneumonia.

In recent years, work has been underway to create antipseudomonal vaccines, biofilm inhibitors, and "quorum sensing". Until recently, combinations of ciprofloxacin with ceftazidime or carbenicillin with gentamicin, often in combination with piperacillin, were the standard treatment for Pseudomonas aeruginosa infection. However, current data show a significant increase in resistance to the last two drugs mentioned, as well as to carbapenems. In view of the foregoing, the following treatment regimens may be most effective:

• ciprofloxacin + amikacin;
• ceftazidime + amikacin;
• ceftazidime + ciprofloxacin + amikacin.

In addition, be sure to remember the need for routine monitoring of local sensitivity and making appropriate adjustments to the treatment regimen.

The choice of antibiotics for the treatment of Acinetobacter spp. Hospital infections are also very limited and include imipenem, meropenem, amikacin in combination with an effective β-lactam or ciprofloxacin. For the treatment of mild infections, ampicillin/sulbactam may be effective, primarily due to the independent activity of sulbactam. However, the drug of choice in the treatment of severe and moderate infections is the combined antibiotic cefoperazone/sulbactam. Sulbactam quadruples the activity of cefoperazone and expands its spectrum of action, and the MIC of cefoperazone-resistant Acinetobacter strains (>128 g/l) is reduced to 12.5 g/l. Its clinical efficacy has been proven in a number of multicenter studies.

If necessary, the following combinations can be used:

• cefoperazone/sulbactam + amikacin;
• carbapenem + amikacin.

Drugs that also have antiacinetobacter activity, according to Go and Cunha (1999), are colistin, polymyxin B, rifampicin, mino- and tigecycline.

In the treatment of infections caused by P. aeruginosa and Acinetobacter spp., the possibility of using new fluoroquinolones has recently been actively considered. Levofloxacin has been the most extensively studied in this regard and has already been recommended in a number of standard regimens in different countries.

As an example, we present the treatment regimen for nosocomial pneumonia from our recent article and the treatment regimen for severe community-acquired pneumonia with a risk of Pseudomonas aeruginosa from the American Protocol for the Treatment of Community-Acquired Pneumonia ASCAP 1 -2005 (Table 3, ).

Conclusion

P. aeruginosa and Acinetobacter spp. are considered to be one of the most “problematic” pathogens. In pulmonological and therapeutic practice, they are significant in such severe conditions as nosocomial and ventilator-associated pneumonia, cystic fibrosis. These MOs are characterized by a significant breadth of natural resistance, but, most importantly, by a rapidly developing level of acquired resistance. At the same time, a number of strains show resistance to all major groups of AMP simultaneously (multi-resistance). In some cases, the doctor finds himself in an impasse due to lack of choice.

This reasonably causes great concern in the scientific medical community, requires a large and coordinated work to monitor the state of sensitivity, create formularies and standards for the use of AMPs, develop new antimicrobial agents, vaccines and drugs with other mechanisms of action that could solve the problem of multidrug-resistant gram-negative non-fermentative microorganisms, such as Pseudomonas aeruginosa and Acinetobacterium.

1 Antibiotic Selection and Outcome-Effective Management of Community-Acquired Pneumonia (ASCAP).

The list of references is in the editorial

Infections caused by Acinetobacter baumannii: risk factors, diagnosis, treatment, approaches to prevention /

Belarusian State Medical University Research Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Russian Federation

Gorbich U.L., Karpov I.A., Krechikova O.I.

Infections, induced byAcinetobacter baumannii: risk factors, diagnostics, treatment, prevention approaches

Nosocomial infections (lat. nosocomium hospital, Greek nosocmeo- hospital, care for the patient) - these are infections that developed in the patient at least 48 hours after hospitalization, provided that the infection did not exist and was not in the incubation period upon admission to the hospital; infections resulting from previous hospitalization, as well as infectious diseases of medical workers associated with their professional activities.

According to various authors, the number of patients who develop nosocomial infections ranges from 3 to 15% ?. Of these, 90% are of bacterial origin; viral, fungal pathogens and protozoa are much less common.

From the beginning of the era of antibiotics and until the 60s of the twentieth century. Approximately 65% ​​of nosocomial infections (HAIs) were staphylococcal in nature. With the advent of penicillinase-stable antibacterial drugs in the arsenal of doctors, they receded into the background, giving way to infections caused by gram-negative bacteria.

Currently, despite the slightly increased etiological role of gram-positive microorganisms and fungi as pathogens of nosocomial infections, strains of gram-negative microorganisms with multiple resistance to antibacterial drugs represent a serious problem in hospitals around the world. According to a number of authors, their frequency varies from 62 to 72% of all nosocomial infections. The most relevant pathogens of all nosocomial infections (except angiogenic) and sepsis are microorganisms of the family Enterobacteriaceae and non-fermenting bacteria, which include Pseudomonasaeruginosa And Acinetobacterspp. .

The most clinically significant species of the genus Acinetobacter is Acinetobacter baumannii(genomotype 2), which causes 2-10% of Gram-negative infections in Europe and the USA, up to 1% of all nosocomial infections.

Risk factors

As a common risk factor for infections caused by A. baumannii, allocate:

Male gender;

Elderly age;

The presence of concomitant diseases (malignant blood diseases, cardiovascular or respiratory failure, disseminated intravascular coagulation);

The duration of the use of invasive methods of treatment and monitoring (ventilation for more than 3 days; inhalation administration of drugs; the introduction of a nasogastric tube; tracheostomy; catheterization of the bladder, central vein, artery, surgery);

Prolonged stay in a hospital or intensive care unit (ICU);

Prior antibiotic therapy with cephalosporins, fluoroquinolones, or carbapenems.

Surgery prior to ICU admission increases the risk of infection by about 5 times.

As risk factors for infection with a carbapenem-resistant strain A. baumannii for adults, the following are described so far: the large size of the hospital (more than 500 beds); hospitalization in the ICU or hospitalization for emergency indications; long stay in the hospital; high density of patients with CRAB in the ward; male gender; immunosuppression; IVL, catheterization of the urinary tract or arteries, hemodialysis; recent surgery; pulse-lavage of wounds; prior use of meropenem, imipenem, or ceftazidime.

In the Republic of Belarus, as risk factors for colonization/infection with nosocomial isolates Acinetobacter baumannii resistant to carbapenem antibiotics, the previous use of "antipseudomonal" carbapenems, urinary tract catheterization, hospitalization in a non-therapeutic department, and age under 40 years were highlighted (Table 1).

Table 1 Risk factors for colonization/infection with a carbapenem-resistant strain A. baumannii in hospital healthcare organizations in Minsk(personal unpublished data)

* Odds ratio (OR) - defined as the ratio of the chances of an event in one to the chances of an event in another, or as the ratio of the chances that an event will occur to the chances that an event will not occur; ** meropenem, imipenem, doripenem.

Acinetobacter-associated

infections

A. baumannii in most cases causes disease in seriously ill immunocompromised patients. This microorganism can cause infections of the respiratory tract (sinusitis, tracheobronchitis, pneumonia), blood flow (sepsis, endocarditis of natural and artificial valves), urinary tract, wound and surgical infections, infections of the skin and soft tissues (including necrotizing fasciitis), nervous system (meningitis , ventriculitis, brain abscess), intra-abdominal (abscesses of various localization, peritonitis), musculoskeletal system (osteomyelitis, arthritis).

According to our own research conducted in 15 hospital healthcare organizations in Minsk, in the structure A. baumannii-associated infections are dominated by bloodstream infections, accounting for 39.4% of all infections caused by this pathogen. The second place is occupied by respiratory tract infections (35.4%), the third (19.7%) - infections of the skin and soft tissues (including infections of the surgical wound). Osteomyelitis was observed in 4.7% of cases, urinary tract infections - 0.8% of cases.

Bloodstream infections. Clinical manifestations of bloodstream infections caused by A. baumannii, range from transient bacteremia to extremely severe disease with a high mortality rate. The gates of infection are most often the respiratory tract, however, with the primary development of the septic process, the main role is played by intravascular catheters. Less commonly, the entrance gates are the urinary tract, skin and soft tissues, burn wounds, abdominal organs and the central nervous system. Nosocomial sepsis due to A. baumannii, in 73% of cases develops after the 15th day of hospitalization. Septic shock develops in about 30% of patients with Acinetobacter-associated sepsis. At the same time, patients with bacteremia associated with intravascular catheters have a better prognosis, presumably because the source of infection can be eliminated from the body when the catheter is removed.

Risk factors for developing bloodstream infections caused by A. baumannii, are emergency hospitalization, prolonged hospital stay, previous colonization with acinetobacteria, high rate of invasive procedures, mechanical ventilation, advanced age or age less than 7 days, weight less than 1500 g (for newborns), immunosuppression, malignant diseases, cardiovascular insufficiency, renal insufficiency, respiratory failure at the time of admission to the ICU, a history of an episode of sepsis that developed in the ICU, previous antibiotic therapy (especially ceftazidime or imipenem).

Respiratory tract infections. A. baumannii, along with Pseudomonas aeruginosa, Stenotrophomonasmaltophilia and MRSA, is the causative agent of late (developing later than 5 days after hospitalization) episodes of nosocomial pneumonia. In addition to the time of onset of infection, previous antibiotic therapy and hospitalization within the last 60 days are also important.

Nosocomial Acinetobacter-associated pneumonia is most often polysegmental. The formation of cavities in the lungs, pleural effusion, the formation of a bronchopleural fistula may be observed.

Independent risk factors for the development of VAP caused by A. baumannii are previous antibiotic therapy and the presence of acute respiratory distress syndrome. A previous episode of sepsis, use of antibacterial drugs before the development of infection (especially imipenem, fluoroquinolones and third-generation cephalosporins, piperacillin/tazobactam), duration of mechanical ventilation for more than 7 days, reintubation, length of hospital stay are identified as risk factors for the development of VAP caused by a multidrug-resistant strain A. baumannii .

A. baumannii is the third most common cause of nosocomial tracheobronchitis (NTB) in patients on mechanical ventilation, causing 13.6 and 26.5% of NTB cases in patients with surgical and therapeutic pathology, respectively. The development of NTP significantly led to an increase in the length of stay in the ICU and the duration of mechanical ventilation, even in cases where patients subsequently did not develop nosocomial pneumonia.

Skin and soft tissue infections. A.baumannii is a significant pathogen in traumatic injuries, burns, and also in relation to infectious complications of postoperative wounds. Skin and soft tissue infections caused by A. baumannii, in most cases are complicated by bacteremia.

Acinetobacteria are capable of causing infections of the subcutaneous fatty tissue at the site of the intravenous catheter, the resolution of which can be achieved only after its removal.

Infections of the nervous system. Acinetobacter baumannii can cause nosocomial meningitis, brain abscesses. Meningitis may develop acutely or have a gradual onset. A petechial rash may be observed on the skin (up to 30% of cases). Changes in the cerebrospinal fluid in meningitis caused by A. baumannii, do not differ from the corresponding changes in meningitis of another etiology and are represented by: pleocytosis with a predominance of neutrophils, an increase in protein and lactic acid levels, and a decrease in glucose levels.

Risk factors for the development of acinetobacter meningitis include: emergency neurosurgical intervention, external ventriculostomy (especially carried out for ³ 5 days), the presence of a cerebrospinal fistula, and the irrational use of antibacterial drugs in neurosurgical ICUs.

Urinary tract infections (UTIs). Despite frequent colonization of the lower urinary tract, Acinetobacterium is rarely the causative agent of UTI. Acinetobacter spp.. stand out in 1-4.6% of cases of nosocomial UTI.

Risk factors for Acinetobacter-associated UTIs are the presence of a catheter in the bladder and nephrolithiasis.

other infections. Acinetobacteria cause peritonitis in patients on long-term ambulatory peritoneal dialysis; as well as cholangitis against the background of transhepatic cholangiography or drainage of the biliary tract. Osteomyelitis and arthritis caused by A. baumannii associated with the introduction of artificial implants or trauma. Acinetobacter-associated eye lesions associated with contamination of soft contact lenses (corneal ulceration and perforation) have also been described. It is possible to develop other lesions of the organ of vision from conjunctivitis to endophthalmitis.

Diagnosis and definition

susceptibility to antimicrobials

In clinical practice, infections caused by A. baumannii, preceded by colonization of the skin, respiratory and urinary tract, gastrointestinal tract of patients. Significant distribution A. baumannii as a colonizing microorganism requires an objective assessment of the situation when isolating from the patient's biological material. At the same time, it should be noted that the selection Acinetobacterspp. as a colonizing microorganism is prognostically significant for determining the etiology of subsequent nosocomial infection (positive/negative predictive value - 94/73% for VAP, 43/100% for bloodstream infections, respectively).

Diagnosis of nosocomial infection, incl. A. baumannii-associated, from a clinical point of view, it is conventionally divided into 4 stages:

1. Collection and transportation of clinical material.

2. Identification of the pathogen.

3. Determination of the etiological significance of the isolated microorganism.

4. Determination of sensitivity to antimicrobial drugs and interpretation of the results.

Proper collection and transportation of clinical material can minimize the likelihood of inaccurate laboratory results, and therefore reduce the "inadequate" prescription of antimicrobials.

General rules for taking clinical material for microbiological examination (as amended):

1. The sampling, if possible, should be carried out before the start of antibiotic therapy. If the patient is already receiving antibiotic therapy, then the clinic The material should be taken immediately before the next administration of the drug.

2. Material for bacteriological examination must be taken directly from the source of infection. If not possible, use another clinically significant biological material.

3. Strictly observe the rules of asepsis, avoiding contamination of the material with foreign microflora.

4. To take discharge from the wound, smears from the mucous membranes, from the eye, ear, nose, pharynx, cervical canal, vagina, anus, use sterile cotton swabs. For blood, pus, cerebrospinal fluid and exudates - sterile syringes and specialized transport media; for sputum, urine, feces - sterile tightly closed containers.

5. The amount of material must be sufficient for the study.

6. Native material is delivered to the laboratory as soon as possible (no later than 1.5-2 hours after they are received). It is allowed to store the material in a refrigerator at 4 ° C (except for biological material obtained from normally sterile loci: cerebrospinal fluid, blood, intraarticular and pleural fluid). When using transport media, clinical material can be stored for 24-48 hours.

7. Liquid biological material can be transported directly in a syringe, on the tip of which a sterile cap or an angled needle is put on.

Identification of the causative agent. Genus Acinetobacter(family Moraxellaceae) consists of strict aerobic, immobile gram-negative lactose-non-fermenting oxidase-negative, catalase-positive coccobacteria 1-1.5 x 1.5-2.5 microns in size, oxidizing glucose to acid only in the presence of oxygen and capable of growing on ordinary nutrient media. On dense nutrient media, the colonies are smooth, opaque, somewhat smaller in size than representatives of enterobacteria.

These microorganisms have typical morphological forms in smears made from clinical material or from liquid nutrient media. When growing on dense media in the presence of antibiotics in smears, bacteria are rod-shaped. Some isolates of Acinetobacteria can retain crystal violet, discolour poorly on Gram stains, leading to their misinterpretation as Gram-positive bacteria.

Interpretation of results(with changes and additions). According to the deep conviction of the authors, a reliable criterion for infection associated with opportunistic nosocomial microflora, including Acinetobacter baumannii, is the isolation of culture from a sterile source.

Blood. The material for the study must be taken from at least two peripheral veins in different vials. Do not draw blood from a venous catheter unless a catheter-associated infection is suspected. When comparing cultures of two blood samples taken from a catheter and a peripheral vein and inoculated by a quantitative method, obtaining colony growth from the catheter that exceeds the number of identical colonies by 5-10 times the number of identical colonies from a venous blood culture indicates the presence of an infection associated with the catheter.

Liquor. Selection A. baumannii at low concentrations makes it difficult to interpret the results, especially in departments where this microorganism often colonizes the skin of patients. The likelihood of its etiological significance is significantly increased in the case of isolation of acinetobacteria from the cerebrospinal fluid in patients with an existing infection caused by A.baumannii, outside the central nervous system (the so-called secondary meningitis), after neurosurgical interventions, in patients with penetrating skull injuries, especially against the background of existing risk factors for acinetobacter-associated infections.

Interpretation of the clinical significance of acinetobacteria isolated from non-sterile loci is a multifactorial process that depends on the qualifications of the clinician, microbiologist, specialist who took the material, and the patient's condition. The following criteria are conditional to a certain extent, but at the same time, they increase the likelihood of an adequate interpretation of the isolated microorganism as a colonizing agent or infectious agent.

Sputum. Isolation of acinetobacteria in the amount of ³ 10 6 CFU / ml (from bronchial washings ³ 10 4 CFU / ml) is diagnostically significant, provided that the rules for sputum sampling are observed. However, these values ​​are not absolute, since against the background of antibiotic therapy, the number of causally significant bacteria in sputum decreases and, conversely, the concentration of colonizing microflora increases.

When examining sputum, its bacterioscopy is mandatory, as it allows you to judge the quality of the material taken. The presence of more than 10 epithelial cells and/or less than 25 polymorphonuclear leukocytes in one field of view at low magnification indicates contamination of the sample with saliva, so further study of this material is inappropriate. In this case, sputum should be taken again in compliance with all the rules of sampling.

Material for wound infection. Possible contamination of the test material with isolates should be excluded. A. baumannii from the surface of the skin, especially when using tampons. When isolating mixed cultures, preference should be given to microorganisms isolated in higher concentrations.

Urine. Diagnostically significant is the isolation of bacteria at a concentration of ³ 10 5 CFU / ml in the presence of symptoms of the disease. When taking urine directly from the bladder without catheterization of the urinary tract, the isolation of acinetobacteria in any titer is considered significant. The presence of three or more types of microorganisms in high concentrations indicates contamination during urine collection or improper storage.

An additional marker of etiological significance Acinetobacter baumannii is the positive dynamics of the general condition of the patient on the background of antiacinetobacter therapy.

Interpretation of the antibiogram(with changes and additions). After receiving the results of testing the pathogen for sensitivity to antibacterial drugs, etiotropic therapy should not be prescribed formally, relying only on the indications of the antibiogram. Sensitivity of the body to a particular antimicrobial drug in vitro does not always correlate with its activity in vivo. This may be due both to the individual characteristics of the pharmacokinetics and / or pharmacodynamics of the drug in this particular patient, and to errors in the research methodology, the quality of the materials used, etc.

When analyzing the antibiogram, attention should not be paid to any specific drug (s) to which the pathogen is sensitive / resistant, but to the whole picture as a whole. This makes it possible, by comparing the probable resistance phenotype of Acinetobacteria with the actual data, to correct the latter, thereby avoiding the prescription of ineffective drugs.

In particular, to identify strains that produce extended-spectrum beta-lactamase (ESBL), attention should be paid to the sensitivity of the pathogen to cefoxitin and aztreonam. If the isolate produces ESBL, cefoxitin remains active, but aztreonam does not. In this case, the isolate should be considered resistant to all I-IV generation cephalosporins and aztreonam, regardless of the actual results of the antibiogram. If the strain is resistant to cefoxitin but sensitive to aztreonam, it is a producer of chromosomal beta-lactamases. In this case, IV generation cephalosporins may retain their activity.

If sensitivity is determined only to one of the "antipseudomonal" carbapenems, the sensitivity of the others should not be assessed by analogy with it. Different representatives of carbapenems are unequally susceptible to the action of one or another mechanism of resistance. A. baumannii, resistant to, for example, meropenem, may remain susceptible to imipenem and/or doripenem, and vice versa.

If a strain resistant to colistin is found, this result should be treated with caution and susceptibility should be retested with parallel testing of control strains.

With regard to aminoglycosides, the interpretative assessment of the antibiotic profile is extremely difficult due to the large number of aminoglycoside-modifying enzymes and the variability of their substrate profile. Therefore, for aminoglycosides, a wide variety of susceptibility/resistance combinations within a class are acceptable.

Most clinical isolates A. baumannii resistant to fluoroquinolones and chloramphenicol, therefore, it is necessary to be careful when choosing these drugs as etiotropic drugs for the treatment of acinetobacter-associated infections, despite the results of determining sensitivity to antibiotics. In addition, assessing the sensitivity Acinetobacter baumannii to quinolones, one should take into account the fact that one mutation in the gene of either DNA gyrase (gyrA) or topoisomerase IV (parC) is sufficient for the formation of resistance to non-fluorinated quinolones. Mutations in both genes are required for the development of resistance to fluoroquinolones. Therefore, when obtaining the results of an antibiogram indicating the sensitivity of a strain to nalidixic or pipemidic acid with simultaneous resistance to fluorinated quinolones, one should be extremely skeptical about this antibiogram as a whole.

When interpreting antibiotic grams, it is also necessary to take into account that Acinetobacterspp. in general, they have natural resistance to cephalosporins of the I and II generation, natural and aminopenicillins, trimethoprim, fosfamycin.

To characterize resistance Acinetobacter baumannii It is recommended to use the following terms:

resistive ( resistant) Acinetobacterbaumannii- insensitive to one antimicrobial drug;

Multi-resistant ( multidrug- resistant - MDR) Acinetobacterbaumannii- insensitive to ³ 1 drug in ³ 3 classes listed in Table. 2;

Table 2. Antimicrobials used for classification Acinetobacter spp. according to the degree of resistance

Class	Antimicrobial
Aminoglycosides	Gentamicin
	Tobramycin
	Amikacin
	Netilmicin
"Antipseudomonal" carbapenems	Imipenem
	Meropenem
	Doripenem
"Antipseudomonal" fluoroquinolones	Ciprofloxacin
	Levofloxacin
"Antipseudomonal" penicillins + β-lactamase inhibitors	Piperacillin/Tazobactam
	Ticarcillin/clavo-lanate
Cephalosporins	Cefotaxime
	Ceftriaxone
	Ceftazidime
Folate Metabolism Inhibitors	Co-trimoxazole
Monobactams	Aztreonam
beta-lactams + sulbactam	Ampicillin-sul-
	Cefoperazone-sul-
Polymyxins	Colistin
	Polymyxin B
Tetracyclines	Tetracycline
	Doxycycline
	minocycline

Extensively resistant ( extensivelydrug- resistant - XDR) Acinetobacterbaumannii- insensitive to ³ 1 drug in ³ 8 classes listed in Table. 2;

Panresistant ( pandrug- resistant - PDR) Acinetobacterbaumannii- insensitive to all listed in the table. 2 antimicrobials.

When analyzing the antibiogram, no less important than the interpretation of the qualitative characteristics of resistance is the assessment of the minimum inhibitory concentration (MIC). In some cases, especially if the microorganism is intermediate-resistant (i.e., the MIC value exceeds the threshold of sensitivity, but does not reach the threshold value of resistance), based on the pharmacokinetic characteristics of the drug, it is possible to achieve a concentration of the drug that exceeds the MIC in the focus of infection, when prescribing the maximum dose and/or use of a prolonged regimen of administration. In particular, according to randomized controlled trials, the constant concentration of the drug, achieved in the serum with continuous administration, is 5.8 times higher than the minimum concentration, which is achieved with an intermittent regimen. And in the study by D. Wang, when comparing the use of meropenem at a dose of 1 g every 8 hours intravenously during a one-hour infusion and at a dose of 0.5 g every 6 hours during a three-hour infusion in the treatment of ventilator-associated pneumonia caused by multidrug-resistant strains A. baumannii, it was found that the concentration of the drug in the blood serum exceeded the MIC for 54 and 75.3% of the time between injections, respectively; the cost of antibiotic therapy was significantly 1.5 times lower in the second group. In table. 3 shows the criteria for interpretation of sensitivity according to the MIC and the corresponding zones of growth inhibition of microorganisms on a solid nutrient medium in accordance with the recommendations of the European Commission for the determination of sensitivity to antimicrobial drugs ( The European Committee on Antimicrobial Susceptibility Testing - EUCAST).

Table 3 Sensitivity Interpretation Criteria Acinetobacter spp.. to antimicrobials by MIC and zones of growth retardation (EUCAST)

Antimicrobiala drug	MIC (mg/l)		in disk (mcg)		Zone of stunting(mm)
Carbapenems
Doripenem
Imipenem
Meropenem
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Aminoglycosides
Amikacin
Gentamicin
Netilmicin
Tobramycin
Colistin*
Trimethoprim-sulfamethoxazole

* Diffuses poorly into solid nutrient media. Exclusively the definition of the IPC!

Treatment

Therapy for nosocomial infections caused by Acinetobacter baumannii, is carried out in accordance with the general rules for managing healthcare-associated infections (Fig. 1). The empirical prescription of antiacinetobacter therapy in case of suspected development of nosocomial infection is justified in those healthcare organizations or their structural divisions where A. baumannii is one of the leading causative agents of these infections, taking into account risk factors.

Evaluation of the effectiveness of ongoing therapy should be carried out 48-72 hours after its initiation, regardless of whether the therapy was prescribed empirically or after isolation of the pathogen. It should be based on the dynamics of the clinical picture and the results of microbiological studies (including repeated ones), and the clinical picture should serve as the prevailing factor for evaluation.

Despite a number of studies indicating the possibility of reducing the duration of antibiotic therapy, the duration of antimicrobial therapy should not be shortened for infections caused by A. baumannii. Thus, in a multicenter randomized study, it was found that a reduction in the duration of antibacterial therapy for VAP caused by non-fermenting gram-negative microorganisms from 15 to 8 days is associated with an increase in the frequency of relapses.

When choosing therapy, it should be taken into account that worldwide the most active antibacterial drugs in relation to A. baumannii are sulbactam, carbapenems, aminoglycosides, polymyxins, tigecycline and minocycline. However, the choice of a specific antimicrobial agent that can be used for empiric therapy A. baumannii-associated infections should be based on local data from the department or healthcare organization where the nosocomial infection developed.

In the event that antimicrobial therapy is prescribed after the isolation of acinetobacteria from pathological material, the choice of antibiotic should be based on the antibiogram, taking into account the interpretive analysis of its results (section "Diagnosis and determination of sensitivity to antimicrobial drugs").

Sulbactam. Sulbactam is currently the drug of choice for the treatment of Acinetobacter-associated infections. In the Republic of Belarus, 84.8% of hospital isolates are sensitive to this antimicrobial drug A. baumannii.

Sulbactam has intrinsic antimicrobial activity against A. baumannii, which is independent of the beta-lactam drug in combination with it.

In experimental animal studies, the efficacy of sulbactam was comparable to that of carbapenems against carbapenem-sensitive acinetobacteria. In clinical trials, the combination of sulbactam/beta-lactam showed similar efficacy compared to carbapenems in VAP and sepsis caused by multidrug-resistant isolates. A. baumannii. Treatment outcomes for multidrug-resistant sepsis A. baumannii, with the use of sulbactam did not differ from the outcomes observed with the treatment of other antibacterial drugs for sepsis caused by non-resistant A. baumannii .

With parenteral administration, the concentration of sulbactam in the blood serum is 20-60 mg / l, in the tissues - 2-16 mg / l. The optimal dosage regimen for sulbactam is 2 g as a 30-minute infusion after 6 hours or 1 g as a 3-hour infusion after 6-8 hours. When using high doses of sulbactam (3 g per injection), adverse drug reactions may develop in the form diarrhea, rashes, kidney damage.

As a result of a number of studies, a synergistic effect of sulbactam with meropenem, imipenem, rifampicin, cefpirome, and amikacin has been established.

Carbapenems. For the treatment of severe infections caused by A. baumannii, can be used with imipenem, meropenem and doripene. Ertapenem has no activity against Acinetobacterspp. generally .

Due to the increasing number of carbapenem-resistant strains A. bauma-nnii, including in the Republic of Belarus, the use of carbapenem antibiotics for the treatment of acinetobacter-associated infections in monotherapy is currently inappropriate. The exception is hospital healthcare organizations, where, according to local monitoring of antibiotic resistance of hospital pathogens, the vast majority of the latter remain sensitive to carbapenems.

In research in vitro a synergistic or additive effect of combinations of imipenem + amikacin + colistin, doripenem + amikacin, doripenem + colistin, meropenem + sulbactam, meropenem + colistin was established; in vivo- imipenem + tobramycin.

The use of a combination of carbapenem + beta-lactam/sulbactam for the treatment of bloodstream infections caused by multidrug-resistant A. baumannii is associated with better treatment outcomes than carbapenem monotherapy or carbapenem + amikacin combination. However, the combination of imipenem with sulbactam was associated with a lower survival rate in a mouse model of pneumonia compared with the combination of imipenem + rifampicin.

When choosing a drug from this class for the treatment of acinetobacter-associated infections, it should be taken into account that in the Republic of Belarus, imipenem has a slightly higher activity against nosocomial isolates. A. baumannii compared with meropenem (44.1 and 38.6% of susceptible strains, respectively). The activity of doripenem exceeds the activity of imipenem and meropenem only in relation to isolates A. baumannii having the OXA-58 gene, imipenem activity against OXA-23-producing strains A. baumannii. However, in the Republic of Belarus, OXA-40-producing strains of acinetobacteria prevail, which does not allow us to speak about the advantages of this drug over other representatives of the class in the treatment of infections caused by A. baumannii.

Aminoglycosides. Aminoglycosides are often used in the treatment of Gram-negative infections, but hospital isolates A. baumannii have a high level of resistance to this class of antibacterial drugs. In the Republic of Belarus, 64.4% are resistant to gentamicin, 89% of the studied strains are resistant to amikacin A. baumannii. The relatively low level of resistance to gentamicin is most likely due to the decline in the use of this antimicrobial drug in healthcare organizations over the past few years.

The appointment of this class of drugs is possible only in combination with antibiotics more active against acinetobacteria based on local data on the sensitivity of the pathogen.

Rifampicin. Given the sensitivity of hospital strains of acinetobacteria to rifampicin, this drug can be added to the treatment of infections caused by multidrug-resistant strains. A number of authors have shown the effectiveness of rifampicin in monotherapy, as well as in combination with imipenem or sulbactam. Synergism is also characteristic of the combination of rifampicin with colistin. Rifampicin and a combination of rifampicin and colistin have been shown to be effective in meningitis caused by an imipenem-resistant isolate. A. baumannii .

According to a number of studies, resistance to rifampicin develops during treatment, both when used alone and in combination with imipenem, however, when using the combination of rifampicin + colistin, no changes in the MIC of rifampicin were shown.

Tetracyclines. Tetracyclines (minocycline, doxycycline, tetracycline) in research invitro have activity against A. baumannii. The most active is minocycline (not registered in the Republic of Belarus), which is also active against isolates resistant to other tetracyclines. In general, experimental and clinical data characterizing the use of tetracyclines in infections caused by A. baumannii, are extremely few. Therefore, the appointment of drugs of this class is justified only on the basis of antibiogram data in the absence of another alternative.

Polymyxins. Of the five known drugs of this class (polymyxins A-E), only polymyxin B and polymyxin E (colistin) are currently available for clinical use. Colistin is used in two forms: colistin sulfate (for intestinal decontamination and for topical use in soft tissue infections; rarely for intravenous administration) and colistimethate sodium (for parenteral and inhalation administration). Sodium colistimethate (an inactive colistin precursor) has less toxicity and antibacterial activity compared to colistin sulfate.

Polymyxins are highly active against strains A. baumannii, including multi - resistant and carbapenem - resistant isolates . According to various studies, the level of clinical efficacy of colistin is 20-83%, microbiological 50-92%. According to pharmacokinetic studies, the concentration of colistin in the blood plasma after intravenous administration is in the range of 1-6 mg / l, in the cerebrospinal fluid - 25% of the serum concentration.

Due to poor penetration through the histohematic barriers in patients with lower respiratory tract infections, it is more preferable to prescribe polymyxins by inhalation, and in the treatment of infections of the central nervous system - intraventricularly or intrathecally, in combination with their parenteral administration or systemic use of other antimicrobials.

The incidence of nephrotoxicity with the use of polymyxins, according to modern studies, is comparable to other classes of antibacterial drugs and is 0-37%. The risk of developing nephrotoxicity with the use of polymyxins is dose-dependent. At the same time, the highest incidence of side effects from the kidneys was observed in patients with a previous violation of their function, however, developing renal failure was usually reversible.

According to research in vitro synergism of colistin with rifampicin, imipenem, minocycline and ceftazidime is noted; polymyxin B with imipenem, meropenem and rifampicin.

Currently, parenteral forms of polymyxins are not registered for use in the Republic of Belarus.

Tigecycline. Tigecycline has a bacteriostatic or bactericidal effect on A. baumannii, is not susceptible to resistance mechanisms characteristic of tetracyclines.

According to the results of a number of studies, tigecycline may retain activity against minocycline-resistant, imipenem-resistant, colistin-resistant, multidrug-resistant strains. A. baumannii .

Tigecycline has a large volume of distribution and creates high concentrations in the tissues of the body, including the lungs, however, according to some authors, the concentration of the drug in the blood and cerebrospinal fluid with the recommended mode of administration is suboptimal and does not provide sufficient antibacterial activity. Due to the low concentrations of the drug in the urine, it is not recommended to use tigecycline for UTI.

According to experts from the Food and Drug Administration (USA), tigecycline has been proven effective for the treatment of severe intra-abdominal infections caused by MSSA and VSE, severe skin and soft tissue infections caused by MSSA and MRSA, and community-acquired pneumonia. At the same time, the use of tigecycline for the treatment of nosocomial pneumonia (especially VAP) is associated with an increased risk of death in severely ill patients. The drug is not currently registered in the Republic of Belarus.

Table 4. Doses of antibacterial drugs and the frequency of their administration

during treatment A. baumannii-associated infections

A drug	Dose and frequency of administration
Ampicillin/sulbactam	in / in 12 g / day in 3-4 injections
Cefoperazone/sulbactam	in / in 8.0 g / day in 2 injections
Imipenem	IV drip for 30 minutes in 100 ml of 0.9% sodium chloride solution, 1.0 g every 6-8 hours
Meropenem	IV drip for 15-30 minutes in 100 ml of 0.9% sodium chloride solution, 2.0 g every 8 hours
Doripenem	in / in 1.5 g / day in 3 injections
Netilmicin	IV 4-6.5 mg/kg/day in 1-2 injections
Amikacin	IV 15-20 mg/kg/day in 1-2 injections
Tobramycin	IV 3-5 mg/kg/day in 1-2 injections
Rifampicin	IV 0.5 g/day in 2-4 doses
Tigecycline*	IV loading dose of 0.1 g followed by 50 mg every 12 hours
Colistin (sodium colistimethate*)	in / in 2.5-5 mg / kg / day in 2-4 injections; inhalation 1-3 million units every 12 hours

* The drug is not registered on the territory of the Republic of Belarus.

Prospects for the treatment of infections caused by A. baumannii. In research in vitro described the effectiveness of a new cephalosporin - ceftobiprol? against Acinetobacterspp., however, there are no data from clinical trials. The activity of ceftobiprol is superior to that of ceftazidime and cefepime in the absence or low expression of genes responsible for the synthesis of ADC-beta-lactamases. British authors in the study invitro showed the activity of the new monobactam BAL30072 in relation to 73% CRAB at a concentration of 1 mg/l and 89% at 8 mg/l.

In the study invivo modeling of burn lesions in mice shows the effectiveness of photodynamic therapy for the treatment of localized infections caused by multidrug-resistant A. baumannii .

Among the fundamentally new drugs under development with potential activity against A. baumannii possess efflux pump inhibitors, inhibitors of bacterial fatty acid biosynthesis enzymes (FabI- and FabK-inhibitors), inhibitors of peptide deformylase of metalloenzymes, antimicrobial peptides (buforin II, A3-APO), class D beta-lactamase inhibitors based on boronic acid. In the study invitro demonstrated the ability of an experimental drug NAB741 containing a cyclic polypeptide fragment identical to the analogous site of polymyxin B to increase sensitivity Acinetobacterbaumannii to drugs for which an intact outer membrane is an effective barrier. In a different invitro study showed that vancomycin was effective against A. baumannii using the technology of fusogenic liposomes for its delivery to the periplasmic space. The ability of biofilm-destroying substances (in particular, based on 2-aminoimidazole) to restore the sensitivity of multi-resistant isolates of acinetobacteria to antibiotics is described. The possibility of developing so-called "antigens" aimed at inhibiting the genes responsible for the formation of resistance mechanisms is discussed; active and passive immunization. A number of works have shown the activity of extracts and extracts from plants, animal secretions against multi-resistant acinetobacteria. In particular, oil helichrysumitalicum, tannic and ellagic acids significantly reduce the level of resistance A. baumannii to antibacterial drugs by inhibiting efflux.

Several studies have shown lysis of Acinetobacteria invitro, as well as the effectiveness of the use of bacteriophages in the treatment of experimental infections caused by Acinetobacter spp.., in animals.

Prevention

Given the high resistance Acinetobacterbaumannii to antimicrobials, as well as the ability of this microorganism to quickly develop resistance mechanisms, prevention is of great importance. A. baumannii-associated infections in the healthcare organization, which is based on the principles and norms of infection control.

A. baumannii are able to colonize normally sterile objects, survive both in dry and wet conditions of the hospital environment. Colonization is usually subject to objects surrounding the patient (feathers in pillows, mattresses, bed linen, curtains, beds, bedside tables and bedside tables, oxygen and water taps, water used in ventilators or for nasogastric administration), as well as those used to care for him , control of his condition, implementation of medical manipulations. Among the items used for the care and implementation of medical manipulations A. baumannii is released from ventilators and mechanical suction devices, objects associated with intravascular access (infusion pumps, pressure meters, systems for long-term hemofiltration, vascular catheters) can also be colonized. Among other colonization equipment, wheelchairs for transporting patients, medical gloves, gowns, tonometer cuffs, peak flow meters, pulse oximeters, laryngoscope blades, ventilation and air conditioning systems can be subjected to colonization. Due to the ability to exist in a humid environment A. baumannii contaminate a wide variety of solutions, including some disinfectants (furatsilin, rivanol). Objects in the hospital environment that are often in contact with the hands of staff (door handles, computer keyboards, medical records, tables at medical posts, sinks and even cleaning equipment), floor coverings also serve as an additional reservoir A. baumannii .

During nosocomial outbreaks of infections caused by A. baumannii, medical manipulations can also be associated with the spread of the pathogen, mainly due to the contamination of the materials used. Such manipulations can be hydrotherapy or pulse lavage of wounds, surgical interventions, catheterization, tracheostomy, spinal puncture.

For adequate implementation of infection control of nosocomial A. baumannii-associated infections, it is necessary to constantly maintain measures aimed at preventing the transmission of the pathogen from patient to patient (Fig. 2), since the main reservoir A. baumannii in the hospital are colonized/infected patients.

With the exception of the above measures, the introduction of strict indications for prescribing antimicrobials that are not included in the first line of antimicrobial therapy (for example, carbapenems, cephalosporins and IV generation fluoroquinolones, etc.) is of no small importance, which reduces the frequency of inadequate prescription of antibiotics in the hospital health organization in general and , as a result, the levels of resistance of hospital isolates, including A. baumannii.

In general, it should be said that Acinetobacter baumannii, is currently a "problem" causative agent of nosocomial infections, affecting mainly patients in severe clinical condition, well adapted to living in a hospital environment and highly resistant to most antiseptic and antimicrobial drugs. When prescribing antibiotic therapy for A. baumannii, it is necessary to take into account local data on its sensitivity in a particular healthcare organization, and more preferably in each specific department.

Medical news. - 2011. - No. 5. - S. 31-39.

Attention!The article is addressed to medical specialists. Reprinting this article or its fragments on the Internet without a hyperlink to the original source is considered a copyright infringement.

nosocomial infections. General characteristics. Research results.

Gorbich Yu.L., Karpov I.A., Krechikova O.I.

Belarusian State Medical University, Republic of Belarus.

Research Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Russian Federation.

Nosocomial infections (lat. nosocomium - hospital, Greek nosocmeo - hospital, care for the sick) are infections that have developed in a patient at least 48 hours after hospitalization, provided that there was no infection at admission to the hospital in the incubation period; infections resulting from previous hospitalization, as well as infectious diseases of medical workers associated with their professional activities.

According to various authors, the number of patients who develop nosocomial infections ranges from 3 to 15%. Of these, 90% are of bacterial origin; viral, fungal pathogens and protozoa are much less common.

From the beginning of the era of antibiotics and until the 60s of the twentieth century. Approximately 65% ​​of nosocomial infections (HAIs) were staphylococcal in nature. With the advent of penicillinase-stable antibacterial drugs in the arsenal of doctors, they receded into the background, giving way to infections caused by gram-negative bacteria.

Currently, despite the somewhat increased etiological role of gram-positive microorganisms and fungi as causative agents of nosocomial infections, strains of gram-negative microorganisms with multiple resistance to antibacterial drugs pose a serious problem in hospitals around the world. According to a number of authors, their frequency varies from 62 to 72% of all nosocomial infections. The most relevant pathogens of all nosocomial infections (except angiogenic ones) and sepsis are microorganisms of the Enterobacteriaceae family and non-fermentative bacteria, which include Pseudomonasaeruginosa and Acinetobacterspp. .

The most clinically significant species of the genus Acinetobacter is Acinetobacter baumannii (genome species 2), which causes 2–10% of Gram-negative infections in Europe and the USA, up to 1% of all nosocomial infections.

Risk factors

As common risk factors for infections caused by A. baumannii, there are:

•  male gender;

•  advanced age;

•  the presence of concomitant diseases (malignant blood diseases, cardiovascular or respiratory failure, disseminated intravascular coagulation);

•  the duration of the use of invasive methods of treatment and monitoring (ventilation for more than 3 days; inhalation administration of drugs; the introduction of a nasogastric tube; tracheostomy; catheterization of the bladder, central vein, artery, surgery);

•  long-term stay in hospital or intensive care unit (ICU);

•  previous antibiotic therapy with cephalosporins, fluoroquinolones, or carbapenems.

Prior hospitalization in the ICU, surgery increases the risk of infection by about 5 times.

As risk factors for infection with a carbapenem-resistant A. baumannii strain for adults, the following have been described so far: large size of the hospital (more than 500 beds); hospitalization in the ICU or hospitalization for emergency indications; long stay in

hospital; high density of patients with CRAB in the ward; male gender; immunosuppression; IVL, catheterization of the urinary tract or arteries, hemodialysis; recent surgery; pulse-lavage of wounds; previous use of meropenem, imipenem, or ceftazidime.

In the Republic of Belarus, the previous use of “antipseudomonal” carbapenems, urinary tract catheterization, hospitalization in a non-therapeutic department and age were identified as risk factors for colonization/infection with a nosocomial isolate of Acinetobacter baumannii resistant to carbapenem antibiotics. up to 40 years (Table 1).

Acinetobacter-associated infections

A. baumannii in most cases causes disease in seriously ill immunocompromised patients. This microorganism can cause infections of the respiratory tract (sinusitis, tracheobronchitis, pneumonia), blood flow (sepsis, endocarditis of natural and artificial valves), urinary tract, wound and surgical infections, infections of the skin and soft tissues (including necrotizing fasciitis), nervous system (meningitis, ventriculitis, brain abscess), intra-abdominal (abscesses of various localization, peritonitis), musculoskeletal system (osteomyelitis, arthritis).

According to our own studies conducted in 15 hospital healthcare organizations in Minsk, bloodstream infections prevail in the structure of A. baumannii-associated infections, accounting for 39.4% of all infections caused by this pathogen. The second place is occupied by respiratory tract infections (35.4%), the third (19.7%) - infections of the skin and soft tissues (including infections of the surgical wound). Osteomyelitis was observed in 4.7% of cases, urinary tract infections - in 0.8% of cases.

Bloodstream infections. Clinical manifestations of A. baumannii bloodstream infections range from transient bacteremia to extremely severe illness with a high mortality rate. The gates of infection are most often the respiratory tract, however, in the primary development of the septic process, the main role is played by intravascular catheters. Less commonly, the entrance gates are the urinary tract, skin and soft tissues, burn wounds, abdominal organs and the central nervous system. Hospital-acquired sepsis caused by A. baumannii develops in 73% of cases after the 15th day of hospitalization. Septic shock develops in about 30% of patients with Acinetobacter-associated sepsis. At the same time, patients with bacteremia associated with intravascular catheters

are characterized by a better prognosis, presumably because the source of infection can be eliminated from the body when the catheter is removed.

Risk factors for developing bloodstream infections caused by A. baumannii are emergency hospitalization, prolonged hospital stay, previous colonization with acinetobacteria, a high rate of invasive procedures, mechanical ventilation, advanced age or age less than 7 days, weight less than 1500 g (for newborns), immunosuppression, malignant diseases, cardiovascular insufficiency, renal failure, respiratory failure at the time of admission to the ICU, a history of an episode of sepsis that developed in the ICU, previous antibiotic therapy (especially ceftazidime or imipenem).

Respiratory tract infections. A. baumannii, along with Pseudomonas aeruginosa, Stenotrophomonasmaltophilia and MRSA, is the causative agent of late (developing later than 5 days after hospitalization) episodes of nosocomial pneumonia. In addition to the time of manifestation of the infection, previous antibiotic therapy and hospitalization within the last 60 days are also important.

Nosocomial Acinetobacter-associated pneumonia is most often polysegmental. The formation of cavities in the lungs, pleural effusion, the formation of a bronchopleural fistula may be observed.

Independent risk factors for the development of VAP caused by A. baumannii are previous antibiotic therapy and the presence of acute respiratory distress syndrome. A previous episode of sepsis, the use of antibacterial drugs before the development of infection (especially imipenem, fluoroquinolones and third-generation cephalosporins, piperacillin/tazobactam), the duration of mechanical ventilation for more than 7 days, reintubation, length of hospital stay are identified as risk factors for the development of VAP caused by multiresistant A. baumannii strain.

A. baumannii is the third most common cause of nosocomial tracheobronchitis (NTB) in ventilated patients, causing 13.6% and 26.5% of NTB cases in patients with surgical and therapeutic pathology, respectively. The development of NTP significantly led to an increase in the length of stay in the ICU and the duration of mechanical ventilation, even in cases where patients subsequently did not develop nosocomial pneumonia.

Skin and soft tissue infections. A. baumannii is a significant pathogen in traumatic injuries, burns, as well as in infectious complications of postoperative wounds. Skin and soft tissue infections caused by A. baumannii are in most cases complicated by bacteremia.

Acinetobacteria are capable of causing infections of the subcutaneous adipose tissue at the site of the intravenous catheter, the resolution of which can only be achieved after its removal.

Infections of the nervous system. Acinetobacter baumannii is capable of causing nosocomial meningitis, brain abscesses. Meningitis may develop acutely or have a gradual onset. A petechial rash may be observed on the skin (up to 30% of cases). Changes in the cerebrospinal fluid in meningitis caused by A. baumannii do not differ from the corresponding changes in meningitis of another etiology and are represented by: pleocytosis with a predominance of neutrophils, an increase in the level of protein and lactic acid, and a decrease in the level of glucose.

Risk factors for the development of acinetobacter meningitis include: emergency neurosurgical intervention, external ventriculostomy (especially carried out for ³5 days), the presence of a cerebrospinal fistula, and the irrational use of antibacterial drugs in neurosurgical ICUs.

Urinary tract infections (UTIs). Despite the frequent colonization of the lower urinary tract, acinetobacteria are rarely the etiological agent of UTI. Acinetobacter spp. stand out in 1–4.6% of cases of nosocomial UTI.

Risk factors for Acinetobacter-associated UTIs are the presence of a catheter in the bladder and nephrolithiasis.

other infections. Acinetobacteria cause peritonitis in patients on long-term ambulatory peritoneal dialysis; as well as cholangitis against the background of transhepatic cholangiography or drainage of the biliary tract. Osteomyelitis and arthritis caused by A. baumannii are associated with artificial implants or trauma. Acinetobacter-associated eye lesions associated with contamination of soft contact lenses (corneal ulceration and perforation) have also been described. It is possible to develop other lesions of the organ of vision from conjunctivitis to endophthalmitis.

Diagnosis and determination of sensitivity to antimicrobial drugs

In clinical practice, A. baumannii infection is preceded by colonization of the skin, respiratory and urinary tract, and gastrointestinal tract of patients. A significant spread of A. baumannii as a colonizing microorganism requires an objective assessment of the situation when isolating from the patient's biological material. At the same time, it should be noted that the isolation of Acinetobacterspp. as a colonizing microorganism is prognostically significant for determining the etiology of subsequent nosocomial infection (positive/negative predictive value - 94/73% for VAP, 43/100% for bloodstream infections, respectively).

Diagnosis of nosocomial infection, incl. A. baumannii-associated, from a clinical point of view, it is conventionally divided into 4 stages:

• 1. Collection and transportation of clinical material.

• 2. Identification of the pathogen.

• 3. Determination of the etiological significance of the isolated microorganism.

• 4. Determination of sensitivity to antimicrobial drugs and interpretation of the results.

Proper collection and transportation of clinical material can minimize the likelihood of inaccurate laboratory results, and therefore reduce the "inadequate" prescription of antimicrobial drugs.

General rules for taking clinical material for microbiological examination (as amended):

• 1. The sampling, if possible, should be carried out before the start of antibiotic therapy. If the patient is already receiving antibiotic therapy, then the clinical material should be taken immediately before the next administration of the drug.

• 2. Material for bacteriological examination must be taken directly from the source of infection. If it is impossible, use another clinically significant biological material.

• 3. Strictly follow the rules of asepsis, avoiding contamination of the material with foreign microflora.

• 4. To take discharge from the wound, smears from the mucous membranes, from the eye, ear, nose, pharynx, cervical canal, vagina, anus, use sterile cotton swabs. For blood, pus, cerebrospinal fluid and exudates - sterile syringes and specialized transport media; for sputum, urine, feces - sterile tightly closed containers.

• 5. The amount of material should be sufficient for the study.

• 6. Native material is delivered to the laboratory as soon as possible (no later than 1.5–2 hours after their receipt). It is allowed to store the material in a refrigerator at 4 °C (except for biological material obtained from normally sterile loci: cerebrospinal fluid, blood, intraarticular and pleural fluid). When transport media are used, clinical material can be stored for 24-48 hours.

• 7. Liquid biological material can be transported directly in a syringe, on the tip of which a sterile cap or an angled needle is put on.

Identification of the causative agent. The genus Acinetobacter (family Moraxellaceae) consists of strict aerobic, immobile, gram-negative, lacto-nonfermenting, oxidase-negative, catalase-positive coccobacteria 1–1.5 x 1.5–2.5 µm in size, oxidizing glucose to acid only in the presence of oxygen and capable of growing on conventional nutrient media. On dense nutrient media colonies

smooth, opaque, somewhat smaller than representatives of enterobacteria.

These microorganisms have typical morphological forms in smears made from clinical material or from liquid nutrient media. When growing on dense media in the presence of antibiotics in smears, bacteria are rod-shaped. Some isolates of Acinetobacteria can retain crystal violet, discolour poorly on Gram stains, leading to their misinterpretation as Gram-positive bacteria.

Interpretation of the results (with changes and additions). According to the deep conviction of the authors, a reliable criterion for infection associated with opportunistic nosocomial microflora, including Acinetobacter baumannii, is the isolation of a culture from a sterile source.

Blood. The material for the study must be taken from at least two peripheral veins in different vials. Do not draw blood from a venous catheter unless a catheter-associated infection is suspected. When comparing cultures of two blood samples taken from a catheter and a peripheral vein and inoculated by a quantitative method, obtaining colony growth from the catheter that exceeds the number of identical colonies by 5-10 times the number of identical colonies during culture of venous blood indicates the presence of infection associated with the catheter.

Liquor. The isolation of A. baumannii at low concentrations makes it difficult to interpret the results, especially in departments where this microorganism often colonizes the skin of patients. The probability of its etiological significance increases significantly in the case of isolation of acineto-bacteria from the liquor in patients with an existing infection caused by A. baumannii, outside the central nervous system (the so-called secondary meningitis), after neurosurgical interventions, in patients with penetrating damage to the skull, especially against the background of existing risk factors for Acinetobacter-associated infections.

Interpretation of the clinical significance of acinetobacteria isolated from non-sterile loci is a multifactorial process that depends on the qualifications of the clinician, microbiologist, specialist who took the material, and the patient's condition. The following criteria are conditional to a certain extent, but at the same time they allow to increase the probability of an adequate interpretation of the isolated microorganism as a colonizing agent or infectious agent.

Sputum. Isolation of acinetobacteria in the amount of ³106 CFU/ml (from bronchial washings ³104 CFU/ml) is diagnostically significant, provided that the rules for sputum sampling are observed. However, these values ​​are not absolute, since against the background of antibiotic therapy, the number of causally significant bacteria in sputum decreases and, conversely, the concentration of colonizing microflora increases.

When examining sputum, its bacterioscopy is mandatory, as it allows you to judge the quality of the material taken. The presence of more than 10 epithelial cells and/or less than 25 polymorphonuclear leukocytes in one field of view at a low magnification indicates contamination of the sample with saliva, so further study of this material is inappropriate. In this case, sputum should be taken again in compliance with all the rules for sampling.

Material for wound infection. Possible contamination of the test material with A. baumannii isolates from the skin surface should be excluded, especially when using tampons. When isolating mixed cultures, preference should be given to microorganisms isolated in higher concentrations.

Urine. Diagnostically significant is the isolation of bacteria at a concentration of ³105 CFU / ml in the presence of symptoms of the disease. When taking urine directly from the bladder without catheterization of the urinary tract, the isolation of acinetobacteria in any titer is considered significant. The presence of three or more types of microorganisms in high concentrations indicates contamination during urine collection or improper storage.

An additional marker of the etiological significance of Acinetobacter baumannii is the positive dynamics of the patient's general condition on the background of antiacinetobacter therapy.

Interpretation of the antibiogram (with changes and additions). After receiving

the results of testing the pathogen for sensitivity to antibacterial drugs, etiotropic therapy should not be prescribed formally, based only on the indications of the antibiotic gram. The sensitivity of the body to a particular antimicrobial drug in vitro does not always correlate with its activity in vivo. This may be due both to the individual characteristics of the pharmacokinetics and / or pharmacodynamics of the drug in this particular patient, and to errors in the research methodology, the quality of the materials used, etc.

When analyzing the antibiogram, attention should not be paid to any specific drug (s) to which the pathogen is sensitive / resistant, but to the whole picture as a whole. This allows, by comparing the probable resistance phenotype of Acinetobacteria with the actual data, to correct the latter, thereby avoiding the appointment of ineffective drugs.

In particular, to identify strains producing extended-spectrum beta-lactamase (ESBL), attention should be paid to the sensitivity of the pathogen to cefoxitin and aztreonam. If the isolate produces ESBL, cefoxitin remains active, but aztreonam does not. In this case, the isolate should be regarded as resistant to all I-IV generation cephalosporins and aztreonam, regardless of the actual results of the antibiogram. If the strain is resistant to cefoxitin, but sensitive to aztreonam, it is a producer of chromosomal beta-lactamases. In this case, IV generation cephalosporins may retain their activity.

If sensitivity is determined only to one of the "antipseudomonal" carbapenems, the sensitivity of the others should not be assessed by analogy with it. Various representatives of carbapenems are unequally susceptible to the action of one or another mechanism of resistance. A. baumannii resistant to, for example, meropenem may remain susceptible to imipenem and/or doripenem and vice versa.

If a strain resistant to colistin is found, it is necessary to treat this result with caution and re-determine the sensitivity with parallel testing of control strains.

With regard to aminoglycosides, the interpretive assessment of the antibiotic profile is extremely difficult due to the large number of aminoglycoside-modifying enzymes and the variability of their substrate profile. Therefore, for aminoglycosides, a wide variety of susceptibility/resistance combinations within the class are acceptable.

Most clinical isolates of A. baumannii are resistant to fluoroquinolones and chloramphenicol, so it is necessary to be careful when choosing these drugs as etiotropic drugs for the treatment of acinetobacter-associated infections, despite the results of determining sensitivity to antibiotics. In addition, when evaluating the sensitivity of Acinetobacter baumannii to quinolones, one should take into account the fact that one mutation in the gene of either DNA gyrase (gyrA) or topoisomerase IV (parC) is sufficient for the formation of resistance to non-fluorinated quinolones. Mutations in both genes are required for the development of resistance to fluoroquinolones. Therefore, when obtaining the results of an antibiogram indicating the sensitivity of a strain to nalidixic or pipemidic acid with simultaneous resistance to fluorinated quinolones, one should be extremely skeptical about this antibioticogram as a whole.

When interpreting antibiotic grams, it is also necessary to take into account that Acinetobacterspp. in general, they have natural resistance to cephalosporins of the 1st and 2nd generations, natural and aminopenicillins, trimethoprim, fosfamycin.

To characterize the resistance of Acinetobacter baumannii, it is recommended to use the following concepts:

•  resistant (resistant) Acinetobacterbaumannii - insensitive to one antimicrobial drug;

•  multidrug-resistant (MDR) Acinetobacterbaumannii - insensitive to ³1 drug in ³3 classes listed in Table. 2;

•  Extensively drug-resistant (XDR) Acinetobacterbaumannii - non-susceptible to ³1 drug in ³8 classes listed in Table. 2;

•  pandrug-resistant (PDR) Aci-netobacterbaumannii - insensitive to

• all listed in the table. 2 antimicrobial

• drugs.

When analyzing the antibiogram, no less important than the interpretation of the qualitative characteristics of resistance is the assessment of the minimum inhibitory concentration (MIC). In some cases, especially if the microorganism is intermediate-resistant (i.e., the MIC value exceeds the threshold of sensitivity, but does not reach the threshold value of resistance), based on the pharmacokinetic characteristics of the drug, it is possible to achieve a concentration of the drug that exceeds the MIC in the focus of infection, with the appointment of the maximum dose and / or the use of a prolonged regimen of administration. In particular, according to randomized controlled trials, the constant concentration of the drug, achieved in the serum with continuous administration, is 5.8 times higher than the minimum concentration, which is achieved with an intermittent regimen. And in the study by D. Wang, when comparing the use of meropenem at a dose of 1 g every 8 hours intravenously during a one-hour infusion and at a dose of 0.5 g every 6 hours during a three-hour infusion in the treatment of ventilator-associated pneumonia caused by multi- resistant strains of A. baumannii, it was found that the concentration of the drug in the blood serum exceeded the MIC during 54 and 75.3% of the time between injections, respectively; the cost of antibiotic therapy was significantly 1.5 times lower in the second group. In table. 3 shows the criteria for interpretation of MIC sensitivity and the corresponding zones of growth inhibition of microorganisms on a solid nutrient medium in accordance with the recommendations of the European Commission on Antimicrobial Susceptibility Testing (EUCAST) .

Therapy for nosocomial infections caused by Acinetobacter baumannii is carried out in accordance with the general rules for managing healthcare-associated infections (Fig. 1). The empirical prescription of antiacinetobacter therapy in case of suspected development of nosocomial infection is justified in those healthcare organizations or their structural divisions where A. baumannii is one of the leading causative agents of these infections, taking into account risk factors.

Evaluation of the effectiveness of ongoing therapy should be carried out 48–72 hours after its start, regardless of whether the therapy was prescribed em-

pyrically or after isolation of the pathogen. It should be based on the dynamics of the clinical picture and the results of microbiological studies (including repeated ones), and the clinical picture should serve as the prevailing factor for evaluation.

Despite a number of studies indicating the possibility of reducing the duration of antibiotic therapy, the duration of antimicrobial therapy should not be shortened for infections caused by A. baumannii. Thus, in a multicenter randomized study, it was found that the reduction in the duration of antibacterial therapy for VAP caused by non-fermenting Gram-negative microorganisms from 15 to 8 days is associated with an increase in the frequency of relapses.

When choosing therapy, it should be borne in mind that worldwide the most active antibacterial drugs against A. baumannii are sulbactam, carbapenems, aminoglycosides, polymyxins, tigecycline and minocycline. However, the choice of a specific antimicrobial drug that can be used for empirical therapy of A. baumannii-associated infections should be based on local data from the department or health care organization where the nosocomial infection developed.

In the event that antimicrobial therapy is prescribed after the isolation of acinetobacteria from pathological material, the choice of antibiotic should be based on the antibiogram, taking into account the interpretive analysis of its results (section "Diagnosis and determination of sensitivity to antimicrobial drugs").

Sulbactam. Sulbactam is currently the drug of choice for the treatment of acineto-bacter-associated infections. In the Republic of Belarus, 84.8% of hospital isolates of A. baumannii are sensitive to this antimicrobial drug.

Sulbactam has intrinsic antimicrobial activity against A. baumannii that is independent of the beta-lactam drug in combination with it.

In experimental animal studies, the efficacy of sulbactam was comparable to that of carbapenems against carbapenem-insensitive acinetobacteria. In clinical studies, the combination of sulbactam/beta-lactam showed similar efficacy compared to carbapenems in VAP and sepsis caused by multidrug-resistant A. baumannii isolates. The outcomes of treatment of sepsis caused by a multidrug-resistant A. baumannii strain using sulbactam did not differ from the outcomes observed in the treatment of sepsis caused by non-resistant A. baumannii with other antibacterial drugs.

When administered parenterally, the concentration of sul-bactam in the blood serum is 20-60 mg / l, in tissues - 2-16 mg / l. The optimal dosing regimen for sulbactam is 2 g as a 30-minute infusion after 6 hours or 1 g as a 3-hour infusion after 6–8 hours. development of unwanted drug reactions in the form of diarrhea, rash, kidney damage.

As a result of a number of studies, a synergistic effect of sulbactam with meropenem, imipenem, rifampicin, cefpirome, amikacin has been established.

Carbapenems. For the treatment of severe A. baumannii infections, imipenem, meropenem, and doripene may be used. Ertapenem has no activity against Acinetobacterspp. generally .

Due to the increase in the number of carbapenem-resistant strains of A. bauma-nnii, including in the Republic of Belarus, the use of carbapenem antibiotics for the treatment of acinetobacter-associated infections in monotherapy is currently inappropriate. The exception is hospital healthcare organizations, where, according to local monitoring of antibiotic resistance of hospital pathogens, the vast majority of the latter remain sensitive to carbapenems.

In vitro studies have established a synergistic or additive effect of combinations of imipenem + amikacin + colistin, doripenem + amikacin, doripenem + colistin, meropenem + sulbactam, meropenem + colistin; in vivo - imipenem + tobramycin.

The use of carbapenem + beta-lactam/sulbactam in the treatment of multidrug-resistant A. baumannii infections is associated with better treatment outcomes than carbapenem alone or carbapenem + amikacin. However, the combination of imipenem with sulbactam was associated with a lower survival rate in a mouse model of pneumonia compared with the combination of imipenem + rifampicin.

When choosing a drug from this class for the treatment of acinetobacter-associated infections, it should be taken into account that in the Republic of Belarus, imipenem has a slightly higher activity against nosocomial isolates of A. baumannii compared to meropenem (44.1 and 38.6% of susceptible strains, respectively). ). The activity of doripenem exceeds the activity of imipenem and meropenem only in relation to A. baumannii isolates with the OXA-58 gene, the activity of imipenem - in relation to OXA-23-producing strains of A. baumannii. However, OXA-40-producing strains of acinetobacteria prevail in the Republic of Belarus, which does not allow us to speak about the advantages of this drug over other representatives of the class in the treatment of infections caused by A. baumannii.

Aminoglycosides. Aminoglycosides are often used in the treatment of infections caused by gram-negative microorganisms, but hospital isolates of A. baumannii have a high level of resistance to this class of antibacterial drugs. In the Republic of Belarus, 64.4% are resistant to gentamicin, and 89% of the studied strains of A. baumannii are resistant to amikacin. The relatively low level of resistance to gentamicin is most likely associated with a decrease in the use of this antimicrobial drug in healthcare organizations over the past few years.

The appointment of this class of drugs is possible only in combination with antibiotics more active against acinetobacteria based on local data on the sensitivity of the pathogen.

Rifampicin. Given the sensitivity of hospital strains of acinetobacteria to rifampicin, this drug can be added to the treatment of infections caused by multidrug-resistant strains. A number of authors have shown the effectiveness of rifampicin alone, as well as in combination with imipenem or sulbactam. Synergism is also characteristic of the combination of rifampicin with coli-stin. Rifampicin and a combination of rifampicin and colistin have been shown to be effective in meningitis caused by an imipenem-resistant A. baumannii isolate.

According to a number of studies, resistance to rifampicin develops during treatment, both when used alone and in combination with imipenem, however, when using the combination of rifampicin + colistin, no changes in the MIC of rifampicin were shown.

Tetracyclines. Tetracyclines (minocycline, doxycycline, tetracycline) have been shown to be active against A. baumannii in in vitro studies. The greatest activity is shown by minocycline (not registered in the Republic of Belarus), which is also active against isolates resistant to other tetracyclines. In general, experimental and clinical data characterizing the use of tetracyclines in infections caused by A. baumannii are extremely few. Therefore, the appointment of drugs of this class is justified only on the basis of antibiogram data in the absence of another alternative.

Polymyxins. Of the five known drugs of this class (polymyxins A-E), only polymyxin B and polymyxin E (colistin) are currently available for clinical use. Colistin is used in two forms: colistin sulfate (for intestinal decontamination and for topical use in soft tissue infections; rarely for intravenous administration) and colistin methate sodium (for parenteral and inhalation administration). Sodium colistimethate (an inactive colistin precursor) has less toxicity and antibacterial activity compared to colistin sulfate.

Polymyxins are highly active against A. baumannii strains, including multi-resistant and carbapenem-resistant isolates. According to various studies, the level of clinical efficacy of colistin is 20–83%, microbiological 50–92%. According to pharmacokinetic studies

According to the results, the concentration of colistin in the blood plasma after intravenous administration is in the range of 1–6 mg / l, in the cerebrospinal fluid - 25% of the serum concentration.

Due to poor penetration through histohematic barriers in patients with infections of the lower respiratory tract, it is more preferable to prescribe polymyxins by inhalation, and in the treatment of infections of the central nervous system - intraventricularly or intrathecally, in combination with their parenteral administration or systemic use of other antimicrobial drugs. rats.

The incidence of nephrotoxicity with the use of polymyxins, according to modern studies, is comparable to other classes of antibacterial drugs and is 0–37%. The risk of developing nephrotoxicity with the use of polymyxins is dose-dependent. At the same time, the highest incidence of side effects from the kidneys was observed in patients with a previous violation of their function, however, developing renal failure was usually reversible.

According to in vitro studies, synergism of colistin with rifampicin, imipenem, minocycline and ceftazidime is noted; polymyxin B with imipenem, meropenem and rifampicin.

Currently, parenteral forms of polymyxins are not registered for use in the Republic of Belarus.

Tigecycline. Tigecycline has a bacteriostatic or bactericidal effect on A. baumannii, is not subject to resistance mechanisms characteristic of tetracyclines.

According to the results of a number of studies, tigecycline can retain activity against minocycline-resistant, imipenem-resistant, colistin-resistant, multidrug-resistant strains of A. baumannii.

Tigecycline has a large volume of distribution and creates high concentrations in the tissues of the body, including the lung, however, according to a number of authors, the concentration of the drug in the blood and cerebrospinal fluid with the recommended mode of administration is suboptimal and does not provide sufficient antibacterial activity . Due to the low concentrations of the drug in the urine, it is not recommended to use tigecycline for UTI.

According to experts from the Food and Drug Administration (USA), tigecycline has been proven effective for the treatment of severe intra-abdominal infections caused by MSSA and VSE, severe infections of the skin and soft tissues caused by MSSA and MRSA, and community-acquired pneumonia. At the same time, the use of tigecycline for the treatment of nosocomial pneumonia (especially VAP) is associated with an increased risk of death in severely ill patients. The drug is not currently registered in the Republic of Belarus.

Table 4. Doses of antibacterial drugs and the frequency of their administration in the treatment of A. baumannii-associated infections

Prospects for the treatment of infections caused by A. baumannii. In vitro studies describe the efficacy of a new cephalosporin, ceftobiprol? against Acinetobacterspp., however, there are no data from clinical studies. The activity of ceftobiprol is superior to that of ceftazidime and cefepime in the absence or low expression of genes responsible for the synthesis of ADC-beta-lactamase. British authors in an in vitro study showed the activity of the new monobactam BAL30072 in relation to 73% CRAB at a concentration of 1 mg/l and 89% at 8 mg/l.

An in vivo murine burn simulation study shows the effectiveness of photodynamic therapy for the treatment of localized infections caused by multidrug-resistant A. baumannii.

Among the fundamentally new drugs being developed, efflux pump inhibitors, inhibitors of bacterial fatty acid biosynthesis enzymes (FabI- and FabK-inhibitors), inhibitors of peptide deformylase of metalloenzymes, antimicrobial peptides (buforin II, A3-APO) have potential activity against A. baumannii , class D beta-lactamase inhibitors based on boronic acid. An in vitro study demonstrated the ability of the experimental preparation NAB741, which contains a cyclic polypeptide fragment identical to the analogous polymyxin B fragment, to increase the sensitivity of Acinetobacterbaumannii to drugs for which the intact outer membrane is an effective barrier. Another in vitro study demonstrated the efficacy of vancomycin against A. baumannii using fusogenic liposome technology to deliver it to the periplasmic space. The ability of biofilm-destroying substances (in particular, based on 2-aminoimidazole) to restore the sensitivity of multi-resistant isolates of acinetobacteria to antibiotics is described. The possibility of developing so-called "antigens" aimed at inhibiting genes responsible for the formation of resistance mechanisms is discussed; active and passive immunization. A number of works have shown the activity of extracts and extracts from plants, animal secrets in relation to multi-resistant acinetobacteria. In particular, Helichrysumitalicum oil, tannic and ellagic acids significantly reduce the level of A. baumannii resistance to antibacterial drugs by inhibiting efflux.

A number of studies have shown the lysis of Acinetobacteria in vitro, as well as the effectiveness of the use of bacteriophages in the treatment of experimental infections caused by Acinetobacter spp. in animals.

Prevention

Taking into account the high resistance of Acinetobacter baumannii to antimicrobial drugs, as well as the ability of this microorganism to quickly develop resistance mechanisms, the prevention of A. baumannii-associated infections in the healthcare organization, which is based on the principles and norms of infection control, is of great importance.

A. baumannii are able to colonize normally sterile objects and survive both dry and wet hospital environments. Objects surrounding the patient are usually colonized (feathers in pillows, mattresses, bed linen, curtains, beds, bedside tables and bedside tables, oxygen and water taps, water used in ventilators or for nasogastric administration), and also used to care for him, control his condition, and carry out medical manipulations. Among the items used for care and medical manipulations, A. baumannii is isolated from artificial lung ventilation devices and mechanical suction devices; objects associated with intravascular access (infusion pumps, pressure meters, systems for long-term hemofiltration) can also be colonized. , vascular catheters). Among the rest of the colonization equipment, wheelchairs for transporting patients, medical gloves, gowns, tonometer cuffs, peak flow meters, pulse oximeters, laryngoscope blades, ventilation and air conditioning systems can be subjected to colonization. Due to the ability to exist in a humid environment, A. baumannii contaminate a wide variety of solutions, including some disinfectants (furatsilin, rivanol). Items in the hospital environment that are often in contact with the hands of staff (doorknobs, computer keyboards, medical records, tables at medical posts, sinks and even cleaning equipment), floor coverings also serve as an additional reservoir of A. baumannii.

During nosocomial outbreaks of infections caused by A. baumannii, medical procedures can also be associated with the spread of the pathogen, mainly due to contamination of the materials used. Such manipulations can be hydrotherapy or pulse lavage of wounds, surgical interventions, catheterization, tracheostomy, spinal puncture.

For adequate infection control of nosocomial A. baumannii-associated infections, it is necessary to constantly maintain measures aimed at preventing the transmission of the pathogen from patient to patient (Fig. 2), since the main reservoir of A. baumannii in the hospital is colonized nye/infected patients.

With the exception of the above measures, the introduction of strict indications for prescribing antimicrobial drugs that are not included in the first line of antimicrobial therapy (for example, carbapenems, cephalosporins and IV generation fluoroquinolones, etc.) is of no small importance, which reduces the frequency of inadequate prescription of antibiotics in hospital organization of healthcare in general and, as a result, the levels of resistance of hospital isolates, including A. baumannii.

In general, it should be said that Acinetobacter baumannii is currently a “problematic” causative agent of nosocomial infections, affecting mainly patients in severe clinical condition, well adapted to living in a hospital environment and having a high resistance to most antiseptic and antimicrobial drugs. When prescribing antibacterial therapy aimed at A. baumannii, it is necessary to take into account local data on its sensitivity in a particular healthcare organization, and more preferably in each specific department.

This article is taken from the journal "Medical News", No. 5, 2011.