STRUCTURE AND ANTIBIOTIC RESISTANCE OF BACTERIAL PATHOGENS IN A MULTIDISCIPLINARY HOSPITAL IN THE POSTCOVID PERIOD


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Abstract

Relevance. Antibacterial drugs are an integral component of the complex therapy of purulent-inflammatory diseases in therapeutic and surgical practice. Rational and reasonable use of antimicrobials in most cases affects the effectiveness of the treatment and often determines the outcome of therapy. The combination of factors such as the severity of the patients' condition, the inability in most cases to immediately isolate the pathogens of infection and determine their sensitivity to antibacterial agents makes it impossible to carry out etiotropic treatment at the initial stage. Errors in choosing the means of starting empirical antimicrobial therapy and dosage regimens increase the length of stay of patients in hospitals, aggravate the course of the disease, increase the risk of severe complications with a fatal outcome, lead to an increase in the cost of treatment, as well as an increase in antibiotic resistance.
Goal. To establish the dominant microorganisms in the BUZ VGKBSMP No. 1, to conduct a comparative assessment of antibiotic resistance indicators in the departments provided in 2020 and 2021 for the treatment of COVID-19 patients (2nd surgical, urological and pulmonological) and in the departments that were not directly involved in the treatment of patients with a new coronavirus infection.
Methods. The results of 2,810 bacteriological blood tests performed in 2019 (1,559 studies) and 2022 (1,251 studies) were retrospectively analyzed. The results were processed by the Statistica v.10.0 program.
Results. In the departments that have been repurposed to provide care to COVID-19 patients, there is a predominance of polyresistant flora (MDR), which has shown an increase in resistance to cephalosporins of the third generation, respiratory fluoroquinolones and aminoglycosides of the third generation, which is a negative trend. There is no similar increase in antibiotic resistance in departments that did not directly help patients with COVID-19.
Conclusion. Thus, the use of antibiotics significantly improves the prognosis of patients with purulent-inflammatory diseases, and on the other hand, negatively affects the life of society as a whole, brings huge social and economic losses associated with preventing the spread of infections caused by resistant microorganisms.

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Relevance
The annual increase in the resistance of microorganisms to antibacterial drugs leads to the need for local monitoring of the resistance of priority pathogens of purulent-septic diseases in multidisciplinary medical institutions in order to more appropriately prescribe antimicrobial agents. In addition to the growth of resistance and the appearance of more pathogenic strains of microorganisms, irrational pharmacotherapy with antibacterial drugs also leads to a violation of the intestinal biocenosis associated with a weakening of the enzymatic and immunological activity of the intestinal mucosa, the development of immediate hypersensitivity reactions [1, 2]. In addition, the increasing antibiotic resistance causes an increase in the economic burden on healthcare associated with the difficulties of treating infections caused by polyresistant strains of microorganisms [3]. During the pandemic of a new coronavirus infection, there was an unjustifiably widespread and uncontrolled use of antibacterial drugs among the population who were on outpatient treatment, which, in turn, played a role in the increase in antibiotic resistance of microorganisms. It has been documented that about 72% of patients with confirmed COVID-19 were treated with antimicrobials, whereas only 8% of these patients were diagnosed with bacterial or fungal concomitant infection [4, 5].

Purpose
To determine the bacteriological profile of the BUZ IN "VGKBSMP No. 1", to establish the dominant microorganisms, their sensitivity and resistance to antibacterial drugs, to identify changes in the spectrum of dominant types of resistant microorganisms, as well as changes in the profile of their antibiotic resistance in the departments repurposed to provide care to COVID-19 patients, in dynamics for 2019 and 2022.

METHODS
Research design
The analysis of the nosological structure and antibiotic resistance of pathogenic bacteria isolated from patients of the BUZ VGKBSMP No. 1 of both therapeutic and surgical profiles, as well as three departments that provided care to patients with confirmed COVID-19 during 2020 and 2021 (pulmonological, urological, 2nd surgical) was carried out.
Compliance criteria
In 2019 and 2022, the data of bacteriological examination of biological material for pathogenic microflora in patients admitted to the BUZ HE "VGKBSMP No. 1" were analyzed. The inclusion criterion was the isolation of pathogenic microorganisms in patients with the main clinical symptoms of the purulent-inflammatory process: fever, neutrophilic leukocytosis with a shift of the leukocyte formula to young forms, high levels of C-reactive protein.
Conditions of the event
A retrospective analysis of the results of 2810 bacteriological studies of the biomaterial of hospitalized patients with the determination of sensitivity to various groups of antibacterial agents was carried out.
Duration of the study
The study was conducted from September 2022 to January 2023.
Description of medical intervention
The etiological structure of the pathogens of purulent-inflammatory diseases in patients hospitalized in the BUZ HE "VGKBSMP No. 1" in 2019 and 2022 was studied. The analysis of the data of the bacteriological study of biological material on the pathogenic microflora of patients admitted to the BUZ VGKBSMP No. 1 in 2019 and 2022 was carried out. The identification of bacteria was carried out by the culture method (bacteriological seeding) according to the regulatory documents regulating the work of bacteriological laboratories. Sensitivity to antimicrobial drugs was determined by the disco-diffusion method. The interpretation of the indicators was carried out in accordance with the methodological guidelines of EUCAST (Version 6.0, January 2017).
The main outcome of the study
Determination of local data on the resistance to antibacterial drugs of pathogenic microorganisms in patients.
Methods of registering outcomes
The source of information was the results of bacteriological blood tests with determination of resistance to various antimicrobial drugs.
Statistical analysis
The obtained data were analyzed using Statistica v.10.0 software packages, nonparametric statistical methods were used for statistical analysis.

Results
Analysis of the structure of purulent-inflammatory diseases in patients of the BUZ in "VGKBSMP No. 1" for 2019 and 2022 showed an increased level of patients with confirmed bacterial infection in therapeutic departments (pulmonological: 2019 100 cases of pathogenic microorganisms isolation for 275 studies (36.36%), 2022 76 cases of pathogenic microorganisms isolation for 145 studies (52.41%); therapeutic: 2019 9 cases of isolation of pathogenic microorganisms for 28 studies (32.14%), 2022 12 cases of isolation of pathogenic microorganisms for 32 studies (37.5%); neurological: 2019 4 cases of isolation of pathogenic microorganisms for 38 studies (10.52%), 2022 8 cases of isolation of pathogenic microorganisms for 24 studies (33.33%); 1st cardiological: 2019 9 cases of isolation of pathogenic microorganisms for 42 studies (20.93%), 2022 11 cases of isolation of pathogenic microorganisms for 28 studies (26.19%) and surgical profile (2nd surgical: 2019 50 cases of isolation of pathogenic microorganisms for 395 studies (12.6%), 2022 68 cases of isolation of pathogenic microorganisms for 327 studies (20.79%); urological: 2019 136 cases of isolation of pathogenic microorganisms for 612 studies (22.22%), 2022 175 cases of isolation of pathogenic microorganisms for 540 studies (32.4%); neurosurgical: 2019 15 cases of isolation of pathogenic microorganisms for 73 studies (20.54%), 2022 15 cases of isolation of pathogenic microorganisms for 45 studies (37.77%); traumatology: 2019 9 cases of isolation of pathogenic microorganisms for 95 studies (9.47%), 2022 12 cases of isolation of pathogenic microorganisms for 96 studies (12.5%).
In the structure of pathogens of bacterial purulent-septic diseases in therapeutic departments, the leaders are: Kl. pneumoniae (2019 – 36.92%, 2022 – 51.37%), Gr(-) non–fermenting sticks (2019 – 20%, 2022 – 22.33%), E. coli (2019 - 13.08%, 2022 – 17.12%), surgical profile: E. coli (2019 - 28.61%, 2022 – 33.67%), Ps. aeruginosa (2019 - 15.86%, 2022 – 16%), St. aureus (2019 - 8.5%, 2022 – 9%).
In the analysis of antibiotic resistance E. coli to ceftazidime (BLRS production marker – extended-spectrum beta-lactamase) in 2019 and 2022, in departments repurposed for the treatment of patients with confirmed COVID-19, there was an increase in resistance from 2 cases of resistance per 5 samples (40%) to 3 cases of resistance per 5 samples (60%) in the pulmonology department, p<0.05, from 41 cases of resistance per 74 samples (55.4%) to 52 cases of resistance per 86 samples (60.46%) in the urological, p<0.01, from 5 cases of resistance per 46 samples (10.86%) to 20 cases of resistance per 59 samples (20.33%) in the 2nd surgical, p<0.01, whereas in other departments, which did not function for the treatment of patients with COVID-19, such an increase is not observed and there is even a tendency to decrease from 8 resistant cases per 24 samples (33.33%) to 4 resistant cases per 30 samples (13.33%) in the trauma department, p<0.05; from 5 resistant cases per 21 samples (23.8%) up to 3 resistant cases per 26 samples (11.53%) in the therapeutic department, p<0.01.
A similar situation develops with fluoroquinolones (ciprofloxacin). There is an increase in antibiotic resistance in the departments repurposed for the treatment of patients with confirmed COVID-19, from 47 resistant cases per 101 samples (46.53%) to 56 resistant cases per 120 samples (55%) in the 2nd surgical department, p<0.01, from 15 resistant cases per 27 samples (55.56%) up to 22 resistant cases per 36 samples (61.11%) in the pulmonology department, p<0.01, while in the departments of the corresponding profile, but not functioning for the treatment of patients with COVID-19, such an increase is not observed. Thus, in the neurosurgical department, there was a decrease in resistance from 28 resistant cases per 39 samples (71.79%) to 17 resistant cases per 33 samples (51.56%), p<0.05, in the neurological department, the indicator of antibiotic resistance remained unchanged – 6 resistant cases per 12 samples (50%). At the same time, all isolated E. coli strains in the departments of both profiles were sensitive to imipenem/meropenem in 2019 and 2022. Based on this, it can be concluded that the E.coli strain belongs to the MDR - multidrug-resistant group (polyresistant strains).
When assessing the antibiotic resistance of Kl. pneumoniae, which is the most frequently detected in therapeutic profile departments, there is also an increase in the number of isolated BLRS producing strains from 6 resistant cases per 26 samples (23.07%) to 10 resistant cases per 32 samples (31.25%) in the pulmonology department, which was repurposed for the treatment of patients with COVID-19, p<0.05. At the same time, in other departments of the therapeutic profile that were not used for the treatment of patients with COVID-19, this indicator remained unchanged: in the therapeutic department 6 resistant cases per 50 samples (12%), in the neurological 2 resistant cases per 24 samples (8.33%), in the 1st cardiology 1 a resistant case for 28 samples (3.6%). There was also an increase in the resistance of Klebsiella to aminoglycosides of the third generation (amikacin). Thus, there was an increase in resistance from 14 resistant cases to 75 samples (18.67%) in 2019. up to 17 resistant cases per 79 samples (21.51%) - 2022, p<0.01 in the pulmonology department. At the same time, all isolated Klebsiella in the departments of both profiles were sensitive to imipenem/meropenem in 2019 and 2022, which makes it possible to attribute Kl. pneumoniae to the MDR - multidrug-resistant group (polyresistant strains).

Discussion

Thus, when conducting a comparative analysis of the results of bacteriological monitoring in the departments of the BUZ VGKBSMP No. 1, which were repurposed to provide care to COVID-19 patients in 2020-2021, a statistically significant increase in the number of resistant strains of gram-negative microorganisms of the Enterobacterales family – producers of BLRS was established. In addition to the production of BLRS, these strains of microorganisms have also demonstrated insensitivity to fluoroquinolones and aminoglycosides of the third generation. Thus, we can talk about an increase in the number of strains of polyresistant microorganisms (MDR). In the departments that did not provide direct assistance in the treatment of patients with a new coronavirus infection, there was no similar increase in antibiotic resistance. The results obtained can be attributed to the irrational use of antimicrobials by patients at the outpatient stage without a doctor's appointment, as well as the widespread use of antibacterial drugs in hospital settings [6].

Conclusion
Resistance to antibacterial drugs is an urgent global problem and is considered by the World Health Organization to be one of the biggest threats to global health [7]. The pandemic of the new coronavirus infection COVID-19 and the related problem of the widespread, often uncontrolled use of antimicrobials, had an additional negative contribution to the spread of the problem of antibiotic resistance. The results of this study confirm this thesis. Tightening control over the administration and release of antibacterial agents, informing about the growing problem of antibiotic resistance of microorganisms, increasing the level of knowledge of medical workers and patients in the rational use of drugs of this group will optimize the therapy of infectious diseases and preserve the effectiveness of antimicrobial therapy currently available in the arsenal of medicine for years to come.

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About the authors

Angelina Araikovna Abramyan

Voronezh State medical university named after N.N. Burdenko

Author for correspondence.
Email: linamia2000@gmail.com
ORCID iD: 0000-0002-9616-4362
SPIN-code: 5881-2587

5th course student of faculty of General Medicine

Russian Federation, 10 Studentskaya str., Voronezh, 394036, Russia

Anton Vadimovich Silkin

Voronezh State medical university named after N.N. Burdenko

Email: anton.silkin.99@mail.ru
ORCID iD: 0000-0002-2238-5808
SPIN-code: 4207-6665

5th course student of faculty of General Medicine

Russian Federation, 10 Studentskaya str., Voronezh, 394036, Russia

Andrey Andreevich Klyukin

Voronezh State medical university named after N.N. Burdenko

Email: flowye@mail.ru
ORCID iD: 0000-0003-2257-3216
SPIN-code: 4657-7314

5th course student of faculty of General Medicine

Russian Federation, 10 Studentskaya str., Voronezh, 394036, Russia

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