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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 69, No 1-2 (2024)
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ORIGINAL PAPERS

EXPERIMENTAL STUDIES

4-9 311
Abstract

The aim of this study was to screen the antimicrobial activity of a pyrimidine compound under the laboratory code VMA-21-01. Antimicrobial activity was studied in relation to: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis. The antimicrobial activity of 2,2-[6-Bromo-2,4-dioxoquinazoline- 1,3(2H)diyl]bis(N-carbamimidoylacetamide) was carried out in vitro by serial dilution and determination of its minimum inhibitory concentration. The sensitivity of microorganisms to the test substance was determined in a meat-peptone broth (visual assessment), followed by reinoculation on meat-peptone agar and colony count. DMSO tubes were used as a control. A 4% gentamicin solution was used as a comparison drug. In an in vitro experiment, it was found that the pyrimidine compound 2,2-[6-Bromo-2,4-dioxyquinazoline-1,3(2H)diyl]bis(N-carbamimidoylacetamide) under the laboratory cipher VMA21-01 has bactericidal activity against K. pneumonia comparable to the comparison drug gentamicin, as well as bacteriostatic activity against S. aureus, S. pneumoniae, E. coli, and P. mirabilis. 

10-14 1769
Abstract

Background. According to the International Center for Disease Control (CDC), 65–80% of all bacterial infections recorded in countries around the world are associated with the ability of their pathogens to form biofilms. To eliminate biofilms, various methods are being developed, including those involving the use of enzymes, proteins, plant extracts, and composite antibacterial coatings. Both antibiotic-resistant and sensitive strains have the ability to form biofilms, which confirms the relevance of the problem of biofilm formation by bacterial cells and the necessity of finding a solution to the treatment of infections caused by film-forming isolates.

The aim was to study the influence of the Wobenzym enzyme preparation on the formation of biofilms of clinical bacterial isolates and to determine the presence of a potentiating effect on the action of antibiotics.

Material and methods. A bacteriological method was used in the study. In this work, 20 strains that differed in their ability to form films were studied.

Results. The most pronounced film-forming ability was exhibited by Escherichia coli (OD=1.0) and Enterococcus faecalis (OD=0.649), isolated from the discharge of the cervical canal, as well as Enterobacter aerogenes (OD=0.406), isolated from the discharge of the pharynx of a newborn child. Cultivation of all studied strains in the presence of Wobenzym significantly reduces their film-forming ability (OD without the addition of enzyme — 0.255±0.005; with enzyme — 0.084±0.006, P=0.0009). Potentiation of the antibiotics ampicillin and amikacin by the Wobenzym enzyme preparation was confirmed by a more than two-fold decrease in CFU/µl.

Conclusion. Cultivation of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Enterobacter aerogenes strains in the presence of Wobenzym significantly reduces their ability to form biofilms, which can be used to prevent biofilm formation and eradicate strains of opportunistic microorganisms that cause infectious and inflammatory processes in normally non-sterile mucous membrane loci of the human body. The combined use of Wobenzym with antibacterial therapy has a direct potentiating effect of antibacterial drugs, as well as an indirect effect that increases the clinical effectiveness of antibacterial therapy by reducing the film-forming ability.

   
15-22 740
Abstract

Background. The growing number of multidrug-resistant bacterial strains causing intractable infectious diseases has become one of the serious problems of the 21st century. Therefore, new drugs that act against resistant microorganisms are urgently needed.

The aim of the study. Comparison of the ability to inhibit the growth and formation of biofilms of Gram-positive Bacillus subtilis and Gram-negative Pseudomonas aeruginosa, Escherichia coli bacteria with compounds containing one or two pharmacophore polyazaheterocycles.

Material and methods. The antibacterial activity of polyazaheterocycles was evaluated by serial dilution at a concentration of 31.25–1000 µg/ml against planktonic forms and biofilms of Pseudomonas aeruginosa PAO1, Escherichia coli AB1157, and Bacillus subtilis BKM B-407. The minimum inhibitory concentration (MIC₅₀) was defined as the concentration of the test compound that suppresses bacterial growth by 50% after 24 hours of incubation. Trifluoromethylbenzene derivatives containing benzimidazole and/or benzotriazole cycles were used as test compounds.

Results. The antibacterial and antibiofilm activity of N-aryl derivatives of benzimidazole, benzotriazole and hybrids based on them were studied. Compounds containing the benzimidazole cycle had a greater antibacterial effect compared to analogues with a benzotriazole fragment. New hybrid materials are capable of inhibiting bacterial pathogenicity factors, such as the ability to form biofilms. The presence of a methyl and trifluoromethyl substituent in the second position of benzimidazole enhanced the antibiofilm activity of the hybrid molecule.

Conclusion. The presence of a benzimidazole cycle in the compound is a prerequisite for the manifestation of high antimicrobial activity. The synergism of the action of two azaheterocycles — benzimidazole and benzotriazole — in a hybrid compound on bacterial biofilm formation, which is an important virulence determinant, was observed. The resulting hybrid substances are promising compounds for the development of new antibacterial drugs against resistant bacteria.

   
23-28 315
Abstract

Background. The study of the phylogeography of the tularemia microbe is not only practical, but also of scientific interest, as it allows us to evaluate the evolutionary processes of Francisella tularensis in modern conditions.

Aim. Phylogenetic analysis of strains of the causative agent of tularemia in the Rostov region and identification of erythromycin-sensitive genovariants.

Results. A representative collection of 122 cultures, isolated from various sources from 1945 to 2022, was studied. As it was established, all the studied strains of the causative agent of tularemia had typical cultural, morphological, and biological characteristics. The results of the study of bacteria antibiograms showed that all strains were resistant to β-lactams, polymyxin, clindamycin, and sensitive to aminoglycosides, rifampicin, and fluoroquinolones. In relation to erythromycin, only 2 erythromycin-sensitive strains were found. Phylogenetic analysis of 34 European and Russian strains of F. tularensis made it possible to determine whether these strains belong to subgroup B.7 of the main genetic group B.6.

Conclusion. For the first time, in the Tselinsky district of the Rostov region, the presence of «atypical» genovariants of the tularemia microbe belonging to subgroup B.7 of the main group B.6 of the subspecies holarctica was registered, according to the modern scheme of genetic typing of F. tularensis subsp. holarctica.

   
29-36 436
Abstract

Background. Progesterone receptors (PR) are regulators of cell proliferation and therefore can be considered as an aim for targeted medications in the treatment of oncological diseases. At the same time, a quantitative assessment of PR expression in the tissue of non-small cell lung cancer (NSCLC), which has not yet been carried out in other studies, will determine the possibility of using PR modulators for the treatment of this disease and identify the potential category of patients most susceptible to these drugs.

Purpose. To characterize NSCLC by quantitative indicators of PR expression and to determine the correlation of clinically significant characteristics of patients and clinical and morphological parameters of a NSCLC tumor with the PR expression to assess the possibility of using PR modulators in the treatment of this disease.

Methods. The PR expression in 130 surgical samples of NSCLC was quantified using an immunofluorescence method associated with flow cytometry. Primary antibodies to PR (NBP2-46388) and secondary antibodies conjugated with DyLight650 (ab98729) were used.

Results. The expression of progesterone receptors was detected in all the studied tumors; an abnormal distribution of the marker expression level was noted (P=0.01). The mean expression level was 55.3±16.2%, and the median was 57% with a range of 70%, which indicates heterogeneity of PR expression in tumors of different patients. There were no statistically significant differences in the level of PR expression depending on the histotype and stage of NSCLC, as well as on the sex of patients. At the same time, the level of expression and the frequency of overexpression of PR (>67%) in tumors in non-smoking patients are higher than in smokers (P⩽0.02).

Conclusion. The high frequency of occurrence and level of PR expression in NSCLC indicate the possible effectiveness of the use of their modulators in the treatment of this disease, especially in non-smoking patients.

GUIDELINES FOR PRACTITIONERS

37-43 440
Abstract

The aim of the study was to compare the clinical efficacy and safety of two antiviral therapy medications that suppress viral replication (viral RNA polymerase inhibitors) in the treatment of patients with COVID-19: favipiravir and riamilovir.

Material and methods. Clinical efficacy and safety were assessed based on a retrospective study of 1071 patients, including 561 patients who received favipiravir and 510 patients who received riamilovir.

Results. A statistically significant reduction in the duration of symptoms and average hospital days was recorded among patients who received ramilovir in both moderate and severe forms of the disease compared with the group that received favipiravir. Inflammatory markers (CRP, fibrinogen) decreased faster in the riamilovir group.

Conclusion. Riamilovir has demonstrated higher levels of clinical efficacy and safety in the treatment of COVID-19 compared to favipiravir.

   
44-50 278
Abstract

The aim of the study was to identify the dynamics on the incidence of major socially significant infectious diseases (SIDs) before, during, and after the COVID-19 pandemic in penitentiary populations. The effectiveness of accompanying therapy was assessed using the example of clinical observation of comorbid widespread destructive pulmonary tuberculosis.

Material and methods. Statistical reporting data on the administrative unit of the Federal Penitentiary Service of one of the constituent entities of the Russian Federation was analyzed. Verification of diagnosis and treatment was carried out using generally accepted methods in accordance with regulatory documentation and standards of therapy. At the first stage, the dynamics of incidence for the periods 2000–2019 (before the COVID-19 pandemic) and 2020–2022 (against the background and after the COVID-19 pandemic) was analyzed . The second stage of the study was the analysis of data on tuberculosis (TB): features of the clinical course, etiotropic treatment, and the possibility of increasing efficiency through accompanying therapy.

Results. At the first stage of epidemiological data analysis, it was revealed that in the pre-pandemic period, the incidence of SIDs in the Federal Penitentiary Facilities decreased. HIV infection was the exception, the incidence of which increased by 3.8 times during this period. The COVID-19 pandemic did not have a significant impact on the formation of the epidemiological situation. However a change in the structure of the pathology was noted: multidirectional dynamics were recorded in parasitic infections — a 1.8-fold increase (from 38.7 to 69.5 per 100 thousand people) in scabies and a 2.8-fold decrease (from 290.4 to 104.2 per 100 thousand) in head lice (P>0.05). Moreover, all cases were detected in pre-trial detention centers when detainees were admitted to them; these diseases were not recorded in correctional facilities. The same pattern of incidence was noted for the main sexually transmitted infections: against the background of a 4.5-fold increase in trichomoniasis (from 58.1 to 260.6 per 100 thousand) a 4.4-fold decrease in the incidence of syphilis (from 154.9 to 34 .7 per 100 thousand), (P>0.05) was recorded. At the same time, the incidence of TB and HIV infection has almost halved. A further decrease in the incidence of the main SIDs was recorded in the post-Covid period (2020–2022). The exceptions were gonorrhea (a 1.8-fold increase — from 18.2 to 32.7 per 100 thousand) and tuberculosis (a 1.5-fold increase — from 364.8 to 552.1 per 100 thousand), P>0.05. At the second stage, it was noted that TB/HIV comorbidity in combination with viral hepatitis remains a problem in correctional facilities. In this regard, accompaniment therapy becomes an important element of treatment — in the event of the adverse events development in response to the main (etiotropic) therapy, in particular. The presented clinical case describes the positive effect of including remaxol, a polyionic infusion hepatotropic drug, in the treatment regimen for comorbid common destructive TB/HIV and poor tolerability of anti-tuberculosis drugs, which helped reduce the severity of hepatotoxicity and made it possible not to introduce changes to the main treatment regimen.

   
51-58 1527
Abstract

Digestive diseases, chronic gastritis with erosions being one of them, are common in elderly patients. Helicobacter pylori infection is one of the etiopathogenetic factors of chronic gastritis. Eradication therapy is currently considered one of the main treatments and prophylaxis of H. pylori infection. However, the increase in the duration of eradication therapy leads to an increase in the frequency of side effects, especially in the gastrointestinal tract, as well as the risk of cardiotoxicity which results in a decrease in the patient's compliance with therapy.

The aim of the study was to evaluate the effectiveness of H. pylori eradication in the treatment of chronic gastritis with erosions using azithromycin and amoxicillin.

Material and methods. A clinical and endoscopic examination of 134 patients with chronic gastritis with erosions associated with H. pylori was carried out. Depending on the treatment regimen, all patients were divided into 2 groups. The first group consisted of patients who received azithromycin for 5 days and amoxicillin for 10 days, omeprazole 2 times a day for 14 days, then once daily for 4 weeks, De-Nol for 28 days. In the second group, patients received clarithromycin and amoxicillin for 14 days, omeprazole 2 times a day for 14 days, then once daily for 4 weeks, De-Nol for 28 days. Control studies were conducted 6 weeks after the end of drug administration.

Results. Abdominal and sternal pain, dysphagia, nausea, heartburn, vomiting, bloating, stool disorders — diarrhea or constipation — were the predominant complaints in the elderly patients. Assessment of the local effectiveness of the applied eradication regimens allows the select of the most effective and safe therapyregimens.

Conclusion. Given the short course of administration of azithromycin (5 days) and  (10 days), these drugs can be used in patients with low adherence to treatment, as well as for prevention of complications caused by antibiotics in elderly patients who are constantly taking medications for other diseases.

   
59-64 592
Abstract

Background. Inflammatory bowel diseases (IBD) (ulcerative colitis and Crohn's disease) are an unresolved problem in gastroenterology due to increasing incidence, progressive course, severe complications, and expensive treatment.

The aim of the study was to analyze data on patients with IBD in the Kabardino-Balkarian Republic (KBR), including clinical and demographic characteristics, frequency of use of different classes of medications, and response to treatment.

Material and methods. An analysis of the socio-demographic and clinical characteristics of patients with IBD who were treated in gastroenterological hospitals for the period of 2020–2022 was carried out. The analysis included data from 143 patients with ulcerative colitis and Crohn's disease.

Results. Analysis of gender characteristics of the prevalence of IBD over time showed an increase in the proportion of female patients. During the study period, there was a tendency for the incidence of IBD to increase in younger age groups (20–29 and 30–39 years old). Moreover, CD was more common in young age groups than UC. IBD onset peaked between ages 20–29 years, with a slight downward trend. There was a high frequency of severe and moderate forms of IBD (78.8%) in the KBR due, in the authors’ opinion, to late diagnosis and not to the characteristics of the patient population. Extraintestinal manifestations were recorded in 37.5%, i. e. more than according to statistical data for the Russian Federation. The vast majority of patients with UC (84.8%) and CD (42.9%) received therapy with oral 5-aminosalicylic acid. Glucocorticoids were used in the treatment of 69.7% of patients with UC and 39.0% of patients with CD. 16.7% of patients with UC and 24.7% of patients with CD received immunosuppressants. In the first 2 years of the study, GEBDs were prescribed to a small number of IBD patients. GEBDs were more often used in the treatment of CD, with Infliximab being the most frequently used drug. The results of the study indicate that over the 3 years of the study, the treatment of patients became more consistent with the recommended approaches.

Conclusion. The study of regional features of the course and treatment of IBD will help improve the quality and efficiency of medical care for patients both at the inpatient and outpatient stages. Creation of a regional registry of patients with IBD in the KBR will be the first step to improving the situation.

   

REVIEWS

65-73 386
Abstract

In modern conditions, patients with immuno-inflammatory rheumatic diseases (IIRD) are at significant risk of influenza, pneumococcal and herpes viral infections, as well as COVID-19, in some cases fatal. The most effective way to prevent infectious diseases and reduce mortality from them is vaccination, which is recommended in the inactive phase of IIRD. However, a number of patients with IIRD have a refractory course of the disease, and achieving remission in them turns out to be a difficult task, and therefore the problem of vaccination of such patients against the background of an active inflammatory process is very relevant. The review analyzes data on the use of vaccine prophylaxis for the above infections in the active phase of IIRD. In the vast majority of cases, vaccination was safe and did not lead to an exacerbation of IIRD or the development of new autoimmune phenomena.

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