The aim of the study was to analyze the resistance to antibacterial drugs of Vibrio cholerae strains isolated from environmental water bodies on the territory of Russia in 2019.V.cholerae O1 El Tor (14) and V.cholerae nonO1/nonO139 strains were used in this work. Sensitivity/resistance to 11 antibacterial drugs was determined using the method of serial dilutions in a solid nutrient medium. The presence of drug resistance genes was determined using real-time PCR. Fluctuations in sensitivity/resistance of V.cholerae were found in various years. The phenotypic resistance of the strains to tetracycline and trimethoprim/sulfamethoxazole correlated with the presence of the tetR and dfrA1 genes in them. The presence of ICE was not detected in V.cholerae strains containing the tetR and qnrVC1 genes. The variability and wide spectrum of V.cholerae resistance require close attention to the problem of antibiotic resistance of cholera. The detection of ICE in the studied V.cholerae strains, as well as antibiotic resistance genes not associated with ICE elements, emphasize the need for molecular genetic monitoring of V.cholerae antibiotic resistance.

Relevance. The tendency to a decrease in sensitivity of bacterial agents to old antibiotics, as well as the slowdown in creation of new medications, dictate the need to develop effective approaches to combat bacterial resistance. Aim. Evaluation of the applicability of a pharmacokinetically-based approach to predicting anti-mutant effectiveness of combined therapy with doripenem and levofloxacin against gram-negative bacteria Pseudomonas aeruginosa. Material and methods. A collection strain of Pseudomonas aeruginosa was used in the study. The values of MPC (mutant prevention concentration) of the combination of doripenem and levofloxacin were evaluated at a ratio of their concentrations equal to therapeutic ratios of the area under the pharmacokinetic curve in the in vitro dynamic model. 5-day treatments with clinical doses of doripenem and levofloxacin individually and in combination were simulated. Bacteria-containing medium was sampled during the experiments and plated on agar media containing 2MIC of each antibiotic. Results. The MPCs of doripenem and levofloxacin decreased 4 times when used in combination compared to MPC values when used separately. P.aeruginosa population was enriched with resistant mutants during monotherapy with each medication; the number of the bacteria did not decrease or even increased by the end of observation period. The use of doripenem/levofloxacin combination completely prevented development of resistance to both drugs in P.aeruginosa. The observed anti-mutant effect of antibiotic combination was consistent with higher (compared to monotherapy) values of the time during which the concentration of the antibiotic exceeded MPC (T>MPC). Conclusion. The anti-mutant effectiveness of combined therapy with doripenem and levofloxacin increased with the decrease in the values of MPC of antibiotics when used simultaneously, which consequently led to the increase in the values of T>MPC. Obtained results confirm the applicability of a pharmacokinetically-based approach to the estimation of MPC of combined antibiotics for predicting anti-mutant effectiveness of combination therapy in the treatment of infections caused by gram-negative bacteria.

The aim of the work was to justify the algorithm of outpatient drug therapy in patients with COVID-19, based on the principle of «Multi-hit» Approach. The algorithm is based on the published results of clinical studies and observations, authors’ own practical experience in the use and management of more than 4 thousand patients diagnosed with COVID-19 of varying severity during the 2020 pandemic. The article substantiates a complex algorithm for the treatment of outpatients with COVID-19, which includes etiotropic, pathogenetic, and symptomatic components of therapy with different mechanisms of action. The described approach is the 1st stage (outpatient) of a complex algorithm for managing patients with COVID-19. It has been successfully implemented in the system of outpatient care for patients with novel coronavirus infections in several leading medical institutions in Russia. The authors believe that the developed algorithm for providing outpatient drug therapy for COVID-19, based on the principle of multiple exposure, may be useful in real clinical practice of managing patients with coronavirus infection.

Objective. To evaluate the effect of sodium meglumine succinate on the severity of the systemic inflammatory response syndrome when used in complex therapy in patients with severe COVID-19. Material and Methods. The clinical and laboratory data of 12 patients with the diagnosis «Novel coronavirus infection COVID-19 complicated by community-acquired bilateral polysegmental interstitial pneumonia» were analyzed. All patients underwent intensive therapy with a limited volume of water load in the intensive care unit in accordance with the recommendations of the Ministry of Health of the Russian Federation. Seven patients (observation group) received a polyelectrolyte solution containing meglumine sodium succinate (Reamberin) as part of the therapy at a daily dose of 5 ml/kg during the entire period of stay in the ICU (3–10 days). The control group included 5 patients who received a similar volume of a conventional polyelectrolyte solution containing no metabolically active substrates. The study was pilot in nature due to the small number of patients. The laboratory parameters of arterial and venous blood were measured at the following stages: 1) upon admission to the ICU; 2) 2–4 hours after the completion of Reamberin infusion; 3) 8–12 hours after drug administration; 4) 24 hours after the start of intensive care. Mortality rate and the incidence of thrombotic complications in the groups were assessed on the 28th day of observation. The presence of the therapeutic intervention effect was established using multivariate analysis of variance (MANOVA). Results. A positive effect of the study drug on the severity of systemic inflammatory response syndrome (SIRS) against the background of ongoing etiotropic therapy was noted. Efficiency criteria were the correction of hyperfibrinogenemia, normalization of the platelet count, decrease in the level of C-reactive protein, ferritin, and leukocytosis. A significant decrease in the frequency of thromboembolic events was observed within 28 days of treatment, as well as a reduction in the length of time the patients spent in the ICU. Conclusion. Based on the results of the pilot study, it can be assumed that the antihypoxic and antiradical effects of the drug contribute to the reduction of pulmonary and systemic endotheliitis, which is characteristic of severe forms of the disease and, as a result, inhibits the development of the systemic inflammatory response syndrome. The data obtained can serve as a basis for further in-depth studies.

Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, and has been produced in Russia since 2019. Cefepime has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms, sulbactam adds two clinically important pathogens to the antimicrobial spectrum of cefepime — Acinetobacter baumannii and Bacteroides fragilis. In addition, sulbactam protects cefepime from hydrolysis by class A broad- and extended-spectrum beta-lactamases, and cefepime itself is stable against class C chromosomal beta-lactamases and partially stable to OXA-type class D carbapenemases. In vitro studies have shown that most clinical strains of ESBL-producing Klebsiella pneumoniae, Escherichia coli, Proteus spp. are sensitive to cefepime/sulbactam, as well as some strains of K.pneumoniae and A.baumannii that are resistant to carbapenems as a result of the production of class D carbapenemases. The efficacy and safety of cefepime/sulbactam have been determined in three clinical studies. Clinical and bacteriological efficacy of the drug was 97.9% and 97.6% in patients with acute community-acquired pyelonephritis. In the MAXI-19 multicenter study, the clinical efficacy of cefepime/sulbactam in patients with intra-abdominal infections, nosocomial pneumonia, and ventilator-associated pneumonia was 78.4, 90.3, and 80.7%, respectively. A comparative study examined the efficacy of cefepime/sulbactam and carbapenems in severe nosocomial infections (84% of patients had sepsis or septic shock). Clinical efficacy of cefepime/sulbactam and carbapenems was high and did not significantly differ (71% vs. 62%), as well as the bacteriological efficacy — 87% vs. 73%, while typical hospital pathogens characterized by MDR or XDR were identified in the majority of patients (most often — K.pneumoniae, A.baumannii, E.coli). During treatment with carbapenems, carbapenem-resistant bacteria were detected significantly more often (74.5%, most often A.baumannii — 44.7%, K.pneumoniae — 38.3%), compared to cefepime/sulbactam (20.0%, P.aeruginosa and K.pneumoniae, both at 15.5%), P=0.0001. The risk of superinfection was also significantly higher with carbapenems than with cefepime/sulbactam (53.3% vs. 22.2%, P=0.001). For severe infections, cefepime/sulbactam was administered at a dose of 4 g (2 g + 2 g) every 12 hours or 2 g (1 g + 1 g) every 8 hours. Currently, cefepime/sulbactam should be considered as a reliable option for the treatment of severe infections in the hospital as a carbapenem-replacement strategy to reduce the risks of selection of carbapenem-resistant gram-negative bacteria.

The review presents the data of recent years concerning the most important modern problem — the search of the new inhibitors of coronaviruses’ reproduction. Polyphenolic compounds (phlorotannins) from terrestrial and marine plants, polyvalent bioregulators with multiple biological activity, are considered as promising compounds of this type. Polyphenols are able to interfere with different stages of coronaviruses’ life cycle. This fact characterizes polyphenols as multipurpose drugs that affect vital proteins of the pathogens. At the same time, the authors of the review draw attention to the fact that many difficulties must be overcome to develop medications based on plant polyphenols, since these compounds are characterized by complex structures, low bioavailability, as well as rapid excretion from the body. In addition, in vivo studies on animals, as well as in clinical trials, are required. Despite all the difficulties, plant polyphenols should eventually the source for creating antiviral medicines, biologically active food additives, and functional food products.

Relevance. If we reduce the treatment exclusively to the eradication of Helicobacter pylori (Hp), the question of monitoring the results of anti-Hp therapy is controversial, given the widely known data on the detection of Hp, including virulent strains of Hp, in most healthy individuals. The aim of the study: to track the dynamics of stomach colonization with various Hp strains in patients with gastric ulcer and duodenal ulcer (PUD) immediately after the use of standard three-component anti-Hp therapy (AHT) and 1.5–2 months after AHT. Methods. Genotyping of Hp strains was carried out by the VNTR method together with the determination of the cagA gene. Results. Assessment of the results of AHT in the form of «eradication of Hp — re-detection of Hp» (i. e., without taking the determination of Hp strains into account) showed less reliability in the differences than the «eradication — preservation of the strain or change of the strain» score in patients with PUD; in addition, the differences between the initial bacteriological picture and that observed immediately after AHT were on the verge of reliability, while the differences between the initial bacteriological picture and that observed after 1.5–2 months had a high degree of reliability. The number of eradications increased (eradication achieved immediately after AHT was not preserved, except for one) and the number of cagA-containing strains decreased (due to new eradication detected at late follow-up periods and due to a change in strains) in long-term follow-up in patients with PUD. Conclusion. Since all patients with PUD achieved clinical remission, which lasted for the next 1.5–2 months, the success of AHT should not be unambiguously associated with the eradication of Hp; the restoration of the organism's colonization resistance to Hp after a course of therapy is more likely.

The present study focuses on the comparative assessment of the therapeutic efficacy of the antiviral drugs riamilovir and umifenovir in the treatment of patients diagnosed with influenza. The aim of the study was to compare the clinical efficacy and safety, as well as the incidence of complications, of the use of antiviral drugs riamilovir and umifenovir and the use of only symptomatic therapy in patients with a confirmed diagnosis of influenza. All patients were hospitalized at the Regional Clinical Hospital No. 2 in Vladivostok. The study included 150 patients, who were divided into 3 groups (50 patients in each group), comparable in gender, age, and admission to the hospital. Patients of the first group received riamilovir, the second group received uminofenovir, patients of the third group received only symptomatic therapy (control group). The duration of clinical manifestations of the disease, hematological disorders, as well as the content of cytokines TNF-α and IL-10 in blood serum were assessed. The incidence of complications in each group was taken into account. As a result of the study, it was found that the inclusion of the antiviral drugs riamilovir and umifenovir in the therapy of influenza decreases the amount of the pro-inflammatory cytokine TNF-α after 5 days of treatment; and in case of symptomatic therapy its level significantly exceeded the reference values. The level of anti-inflammatory cytokine IL-10 on the 5th day of treatment in the main group was three times lower than in the control group. Thus, riamilovir and umifenovir effectively relieve the main symptoms of the disease, reduce the incidence of complications, and reduce the severity of the inflammatory response by the 5th day of treatment.

Aim: To study cases of bacteremia caused by multidrug-resistant (MDR) and extremely-resistant (XDR) gram-negative bacteria in the departments of a multidisciplinary hospital. Material and Methods. Since 2017, a retrospective epidemiological study has been conducted to investigate cases of infections with bacteremia caused using gram-negative bacteria with multiple or extreme antibiotic resistance. The pathogens were identified using the MALDI-TOF MS method, the sensitivity to antibacterial drugs was determined using the automatic Phoenix system, the beta-lactamase genes were detected using real-time PCR on a GeneXpert analyzer. Results. In 2017, bacteremia caused by MDR and XDR pathogens was detected in 42 and 76 patients, in 2018 — in 57 and 81 patients, in 2019 — in 65 and 111 patients, respectively. During three years of observation, the most frequent XDR microorganisms were, in descending order, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa. In 2019, among 11 K.pneumoniae strains, class D carbapenemase (OXA-48) was detected in 5 cases (45.5%), 3 strains produced NDM metallo-carbapenemase, and 3 strains had a combination of NDM and OXA-48 enzymes. Infections caused by MDR and XDR pathogens were characterized by high mortality. Thus, the relative risk of death in patients with XDR infection was 1.33 times higher than in patients from the MDR group (95% CI 1.04-1.69, P<0.05) in 2019. The duration of hospital stay also increased: in the XDR group — up to 29.5 days, in the MDR group – up to 16.4 days, with an average length of hospitalization of 6.0 bed-days in 2019. Conclusions. K.pneumoniae and A.baumannii with extreme antibiotic resistance are the main causative agents of severe late nosocomial infections in immunosuppressed patients. Nosocomial infections with bacteremia caused by gram-negative bacteria with the XDR phenotype and resistant to carbapenems are characterized by a high mortality rate (from 72 to 80%), and increase the duration of hospitalization by more than 4 times.

The aim of the work was the search for materials from experimental and clinical studies reflecting the pathogenetic role of the possible use of succinates for the correction of hypoxia in COVID-19. Materials and methods. 79 foreign and domestic literature sources were analyzed concerning the pathogenesis of COVID-19 and the pathogenetic role of succinates in hypoxia under conditions of COVID-19, oxidative stress, and diaphragmatic dysfunction were analyzed. The literature search was carried out using Pubmed and ELIBRARY.ru databases. Results. As the analysis of the literature has shown, tissue hypoxia is the basis of COVID-19 pathogenesis, triggering the entire cascade of pathomorphological events leading to the development of multiple organ failure. A number of experimental and clinical studies (on a fairly large number of patients) reflect the positive effect of tissue hypoxia correction using succinates, both in adult patients and in children with a different spectrum of pathology associated with acute respiratory failure syndrome. Conclusion. Analysis of literature data allows to substantiate the prospect of using preparations containing succinate (reamberin, cytoflavin) in the complex therapy of severe cases of COVID-19.