ANALYSIS OF ANTIBIOTIC THERAPY IN PATIENTS WITH CORONAVIRUS INFECTION ON THE BACKGROUND OF TYPE II DIABETES MELLITUS

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Relevance. In the initial period of the development of the COVID-19 epidemic in Russia, the identification of the virus, diagnostic measures, and the choice of a treatment algorithm were a great difficulty. During the first wave of coronavirus infection, all medical services found themselves in a difficult situation due to the lack of etiotropic therapy. There is no available etiotropic treatment for coronavirus infection at the moment. To a greater extent, this complicates the treatment of patients with a chronic, multifactorial disease - type II diabetes mellitus. A high mortality rate from respiratory failure is recorded, and pneumonia prevention is necessary. Doctors are forced to use various combinations of drugs, including antibacterial, antiparasitic drugs. Currently, we are witnessing unreasonable antibiotic aggression in the vast majority of patients with COVID-19 with minimal evidence of bacterial coinfection [1]. Antibacterial therapy is prescribed if there are convincing signs of a bacterial infection (increase in procalcitonin more than 0.5 ng/ml, leukocytosis > 10*10⁹/l, purulent sputum) [2]. The choice of antibiotics and methods of their administration is carried out on the basis of the severity of the patient's condition, analysis of risk factors, encounters with resistant microorganisms (the presence of concomitant diseases, previous use of antibiotics, etc.), and the results of medical diagnostics [3]. An open question in the current situation is the lack of evidence for the effectiveness and safety of the drugs used. In the conditions of widespread use of antibiotic-resistant strains of microorganisms in hospitals, there is a regular decrease in the clinical efficacy of most AMPs in the treatment of nosocomial infections. In this regard, it is extremely important to strictly observe the strategic principles of the rational use of AMPs in a hospital, which consist in the development of rules (algorithms) for prescribing antibiotics and the implementation of measures aimed at reducing the irrational use of AMPs [3].

Objective: To analyze the frequency and structure of antibiotic therapy in patients with COVID -19 against the background of type II diabetes mellitus during the first wave of the pandemic.
Materials and methods: Study design - retrospective, descriptive and evaluative. We studied 112 epicrises of patients who were hospitalized at the Regional Clinical Hospital No. 1, among them 66 (58.93%) women and 46 (41.07%) men. 108 people had a history of type II diabetes, 4 people had type I diabetes. Among all patients, 26 (23.21%) are residents of the city of Voronezh and 86 (76.79%) are residents of the Voronezh region. Hospitalization time ranged from 8 to 39 days, with an average hospital stay of 18.75 ± 0.64 days. All patients were hospitalized with a diagnosis of bilateral pneumonia. Satisfactory condition was observed in 13 (11.61%) patients, 82 (73.21%) patients had a moderate condition, 17 (15.18%) were in a serious condition. The degree of lung damage according to computed tomography, laboratory parameters (general blood count, biochemical blood parameters, urinalysis), as well as prescribed antimicrobial therapy, were analyzed. The processing and analysis of the obtained material was carried out by a mathematical-statistical method using standard Microsoft Excel 2019 software packages, the mean and standard error were calculated. The significance of differences in relative indicators was determined using the χ2 method, p<0.05 was considered the level of significance.

Results
According to the results of the analysis, 100% of patients with COVID-19 on the background of diabetes mellitus received antibiotic therapy. Antibacterial drugs of the following groups were used: antiparasitic drugs (hydroxychloroquine, mefloquine) - 85 (75.89%) cases; protected penicillins (sultasin, amoxiclav, ampicillin sulbactam) - 70 (62.50%); macrolides (azithromycin) were prescribed in 58 (51.79%) cases. Approximately the same number of prescriptions was for protected cephalosporins (sulcef) - 31 (27.68%) and oxazolidinones (linezolid) - 28 (25.00%). Fluoroquinolone drugs (levofloxacin) were prescribed to 15 (13.39%) patients; carbapenems (meropenem, cilapenem) - in 9 (8.04%) cases; cephalosporins (ceftriaxone) - in 1 (0.89%) case.
Significantly more often in relation to the frequency of use of the rest, antiparasitic drugs were prescribed (hydroxychloroquine, mefloquine), (p≤0.021);
Most often, patients were prescribed several antimicrobial drugs, only 10.31% of patients received 1 antibiotic. Almost half of 48.45% during hospitalization were treated with 3 drugs, approximately the same number - with two and four drugs - respectively 19.59% and 17.53%. Significantly less often, patients received 5 drugs 4.12% (p ≤ 0.002).
The most commonly combined antiparasitic drugs, protected penicillins and cephalosporins, macrolides.
Differences in antibiotic treatment tactics were observed between patients with normal levels and elevated levels of one of the acute phase indicators - C-reactive protein (CRP). Significantly more often, a combination of two antibacterial drugs occurred in patients with normal CRP levels (p<0.0001). The three-drug combination was significantly more frequently prescribed in patients with elevated C-reactive protein levels (p<0.01). It is noteworthy that the appointment of 4 groups of antibiotics occurred equally often both with normal and with elevated levels of C-reactive protein - respectively in 15.38% and 17.86% of cases.
The structure of the used antimicrobial drugs was studied depending on the degree of lung damage according to computed tomography data (CT 1-4). Antiparasitic drugs and drugs of the group of protected penicillins (sultasin, amoxiclav, ampicillin sulbactam) were used most frequently, without significant differences between patients with varying degrees of pathology on CT (p=0.49). Reserve antibiotics – carbapenems – were used significantly more often in patients with lung injury degree CT 4, respectively, in 29.41% of cases at CT 4 versus 4.49% at CT 2-3 (p=0.009).

Discussion
It is hardly possible to imagine a discussion of the issues of modern medicine without touching on one of the most urgent health problems of the whole world - antibiotic resistance [4]. The study demonstrated that antibacterial agents of various classes were prescribed to all patients with diabetes mellitus and COVID-19, almost regardless of the presence of convincing signs of a bacterial infection. Most (76.79%) patients were from rural areas, they were transferred to the regional hospital from district hospitals, where they probably already received antibiotic therapy, in such a situation, the total number of antimicrobial drugs increases even more. In the initial period of the pandemic, when pneumonia with respiratory failure was the main cause of death, doctors were forced to use all the forces and means available to them to save people. Federal clinical guidelines also prescribe the use of antimicrobials in the management of patients with new infection. Nevertheless, foreign studies conducted as early as May 2020 reported the prevalence of associated infections with COVID-19, concomitant viral infections were more often observed [5]. It is noteworthy that protected penicillins and cephalosporins, reserve antibiotics (carbapenems) were used as drugs used in patients with COVID-19. As the severity of patients increases, the number of prescriptions for reserve antibiotics increases. The appointment of antibiotics in patients without such indications can contribute to the development of diseases of various organs and systems, inhibition of the natural microflora of the body. Broad-spectrum antibiotics are traditionally considered as a risk factor for the development of C. difficile infection and pseudomembranous colitis [6].
Conclusion
An analysis of the epicrises of 112 patients with COVID-19 against the background of diabetes showed that 100% received antimicrobial therapy. Most often, in the treatment of coronavirus infection in patients with diabetes mellitus, doctors used antiparasitic agents, protected penicillins and cephalosporins, and macrolides. The structure of the use of antimicrobial therapy was more often represented by a combination of 2-4 different agents. As the severity of lung damage increases, according to computed tomography, the number of prescriptions for reserve antibiotics increases.

About the authors

Anna Timashova

Author for correspondence.
Email: timashovaanya@gmail.com
ORCID iD: 0000-0002-4604-7934
SPIN-code: 4514-4969
ResearcherId: AAD-4426-2022

6th year student of the Faculty of Preventive Medicine

References