Antibiotics and Chemotherapy

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ISSN : 0235-2990
Published by: Publishing House OKI (10.37489)
Total articles ≅ 2,923
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M. M. Baranova, N. V. Muravyeva, , M. V. Cherkasova, Zh. G. Verizhnikova,
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-39-44

Abstract:
Background. Immunosuppressive drugs are widely used for the treatment of patients with spondyloarthritis (SpA) to effectively control the activity of the disease. At the same time, the use of these drugs is associated with an increased risk of developing infections of the upper and lower respiratory tract, which can be prevented by vaccination. The aim of the study was to evaluate the immunogenicity, safety, and clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with SpA. Material and methods. The study included 54 patients with SpA: 39 with ankylosing spondylitis, and 15 with psoriatic arthritis. Most patients had a history of two or more cases of lower respiratory tract infections, 2 patients reported a monthly exacerbation of chronic sinusitis, one patient reported the development of otitis every 2–3 months. 72% of patients received immunosuppressive therapy at the time of inclusion in the study. PPV-23 was administered in the amount of 1 dose (0.5 ml) against the background of ongoing antirheumatic therapy. The level of antibodies to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clinical Diagnostics s.r.o., Czech Republic) at baseline, after 1, 3, and 12 months after vaccination. The tolerability of PPV-23, the effect of vaccination on SpA activity (according to the dynamics of the BASDAI index), and the incidence of upper and lower respiratory tract infections were assessed. Results. The concentration of antibodies to pneumococcal capsular polysaccharide was significantly higher 1, 3, and 12 months after vaccination compared to baseline. There was no negative effect of vaccination on the activity of SpA and the emergence of «new» autoimmune disorders. The vaccine was well tolerated by 76% of patients., Only one patient developed pneumonia during the observation period. Patients suffering from frequent sinusitis and otitis reported the absence of these infections after vaccination. Conclusions. Preliminary results of the study indicate sufficient immunogenicity, safety, and clinical efficacy of PPV-23 in patients with SpA.
B. G. Andryukov, N. N. Besednova, T. S. Zaporozhets
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-62-74

Abstract:
The emergence and spread of antibiotic-resistant pathogenic bacterial strains in recent decades is an alarming trend and a serious challenge for the future of mankind around the world. The horizontal transfer and spread of antibiotic resistance genes among microorganisms through mobile genetic elements (MGEs), an extremely diverse group of prokaryotic mobilomas capable of moving DNA molecules intra- or intercellularly, aggravate the situation. MGEs play a central role in the phenotypic adaptation of bacteria, providing resistance to antibiotics and physical parameters of the environment, acquiring pathogenicity factors, and transforming metabolic pathways. However, the importance of MGEs is often overlooked when planning the strategies to contain the spread of antimicrobial resistance in pathogens. The aim of this review is to briefly characterize the main types of MGEs (plasmids, transposons, bacteriophages, integrons, and introns) involved in the formation of antibiotic resistance in pathogenic bacteria, with an emphasis on the members of the Enterobacteriaceae family. In the final part of the review, promising modern strategies for combating antimicrobial resistance based on the use of antiplasmid approaches and CRISPR/Cas technologies are considered.
M. M. Fedotova, V. M. Malchuk, V. A. Churilin, A. A. Zapevalova, D. O. Yakovleva, D. D. Olenius, , S. V. Fedosenko,
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-45-52

Abstract:
Background. The growth of antibiotic resistance is an urgent problem of modern medicine associated with the irrational use of antibacterial drugs. The solution to this problem requires a comprehensive analysis of the situation not only from the patients’ standpoint, but also from that of medical specialists. Aim. To establish the level of awareness about the problem of antibiotic resistance and to study the practice of antibacterial drug use among senior students of a medical university. Material and methods. A one-time sociological study was conducted in the format of an online survey of the 5th–6th year students of the medical and pediatric faculties of the Siberian State Medical University of the Ministry of Health of the Russian Federation. Results. An invitation to the survey was sent to 406 5th–6th year students of the pediatric and medical faculties; 334 students voluntarily completed the questionnaire (return rate — 82.3%). Most students are aware of the problem of antibiotic resistance. 58.8% of the students took drugs as prescribed by a doctor, adhering to the prescribed duration of treatment. The most commonly used antibiotics were: amoxicillin/clavulanic acid — 57.6%, amoxicillin — 29%, azithromycin — 19.4%, ciprofloxacin — 13.4%, 3rd generation cephalosporins — 8.1%. It was found that 45.4% of students used antibiotics parenterally, of which half (50.4%) performed injections at home or in the dormitory. Up to 89.2% of respondents consider it necessary to use medications to restore the intestinal microflora against the back-ground of antibiotic therapy. Conclusions. Despite the high awareness of the problem of antibiotic resistance and adherence to medical recommendations regarding the use of antibiotics, it is necessary to increase the competence in the field of rational antibiotic therapy for both students and practitioners.
A. K.M. Alsowaidi, O. A. Karavaeva, O. I. Guliy
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-53-61

Abstract:
Antibacterial drugs are some of the most important medications used in health and veterinary medicine. The widespread use of antibiotics has led to significant pollution of the environment and water resources, in particular . In this regard, the problem of controlling antibiotic content in dosage forms, as well as their detection in liquids, food products, waste waters of pharmaceutical enterprises, and the other objects, is urgent. Microbiological, spectrophotometric, fluorimetric, chemiluminescent, chromatographic, as well as biodetection methods are used to identify antibiotics. The article provides a brief overview of methods and approaches for the detection of antibiotics. Progress in the development of biosensor systems for the analysis of antibiotics has been shown.
Ju. L. Lukyanova, , K. G. Shapovalov
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-32-38

Abstract:
COVID-19 is a global contemporary issue. Acute hypoxic respiratory failure and associated multiple organ dysfunction are the basics of the new disease pathogenesis. An important characteristic of COVID-19 is the damage to the central nervous system, which determines the peculiarities of the clinical course. In the case of vascular complications (ischemic stroke, encephalopathy, delirium) the prognosis of the disease is more severe. The article presents the experience of a large Russian monohospital in observation and treatment of patients with COVID-19 and neurological complications. It also shows the prospect of neuroprotective therapy in this category of patients.
, I. A. Zakharenkov, , , А. И. Синопальников, M. V. Archipenko, S. A. Gordeeva, M. S. Lebedeva, U. S. Portnyagina, N. V. Dyatlov
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-16-23

Abstract:
Community-acquired pneumonia (CAP) is a common cause of hospitalization and mortality worldwide. A timely start and an adequate choice of the initial antibiotic therapy (ABT) regimen are the key strategy for optimizing the prognosis in severe CAP.The aim was to study the practice of using systemic antimicrobial drugs (AMDs) in adults with severe CAP in multidisciplinary hospitals of the Russian Federation, as well as to assess compliance of initial ABT with current clinical guidelines.Methods. A prospective cohort study included adult patients with severe CAP hospitalized in multidisciplinary hospitals in 6 Russian cities during the period of 2014–2018. The adequacy criteria of the initial ABT for severe CAP were: the prescription of combination ABT, the compliance of the selected initial ABT regimen with Russian clinical guidelines, and the intravenous route of AMDs administration during the initial therapy. In addition, the frequency of using switch therapy and antimicrobial de-escalation was assessed.Results. A total of 109 patients (60.6% men; mean age 50.8±18.0 years) were included in the study. Hospital mortality was 22.9%. In all cases, AMDs were prescribed within 24 hours after admission, antiviral drugs were used in 2.8% of patients. Levofloxacin, ceftriaxone, azithromycin, amoxicillin/clavulanate were the most commonly used AMDs (prescribed in 14.4%, 12.5%, 11.9% and 10.7% of cases, respectively). Initial combination ABT was prescribed in 50.5% of patients; in 80.2% of the cases, the medications were administered intravenously. The duration of treatment was 13.9±11.2 days. Initial ABT regimens complied with Russian Clinical Guidelines in 37.6% of cases. Switch therapy and antimicrobial de-escalation was used in 11.9% and 3.6% of cases, respectively.Conclusion. Low adherence to Russian Clinical Recommendations regarding the regimens of initial ABT, as well as rare use of switch therapy and antimicrobial de-escalation were revealed.
O. A. Kolenchukova, V. D. Belenuk
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-4-8

Abstract:
The research focuses on the study of phagocyte activity of blood neutrophilic granulocytes, monocytes, and eosinophils under the exposure to methicillin-resistant strains of Staphylococcus aureus bacteria. The subjects of the research were represented by blood neutrophilic granulocytes, monocytes, and eosinophils, isolated from healthy people, as well as methicillin-resistant and methicillin-sensitive S.aureus bacteria strains (MRSA and MSSA). Phagocytosis functions (phagocytic number and phagocytic index) were estimated by FITC-labeled bacteria. The analysis of stained cells was performed using FC-500 flow cytofluorimeter (Beckman Coulter, USA) for whole peripheral blood. Phagocytosis research resulted in the following findings. In response to MRSA, the percentage of neutrophils involved in phagocytosis and average number of bacteria being present inside the cells increase as compared to those within sensitive strains. In response to MRSA exposure, the phagocytic index is higher in monocytes with CD14+CD16¯phenotype. At the same time, phagocytic number is higher in non-classic populations of monocytes CD14+CD16+and CD14lowCD16+. Moreover, it should be noted that the classical type of monocytes CD14+CD16¯tends to be activated faster in regard to MRSA, but phagocytosis efficiency is lowered. Blood eosinophils also actively respond to MRSA. Thus, changes in functional activity of neutrophilic granulocytes, monocytes, and eosinophils in peripheral blood were established during MRSA induction. The bacterial receptor apparatus changes due to the modification of cellular wall as a result of acquired resistance to antibiotics.
V. A. Ageevets, O. S. Sulian, A. A. Avdeeva, P. S. Chulkova, , I. V. Ageevets, , K. N. Alieva, D. P. Gladin,
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-9-15

Abstract:
The rapid spread of gram-negative bacteria resistance to carbapenems due to the production of carbapenemases requires new treatment options. The activity of carbapenem antibiotic biapenem, recently registered in Russia, against producers of various carbapenemases was studied in comparison with other antibiotics of this group. Among NDM-type carbapenemase producers, 77.8% demonstrated clinical susceptibility to biapenem; 50.3% and 21.1% of isolates were susceptible to meropenem and imipenem, respectively. Among the producers of OXA-48-type carbapenemases, 82,6%, 60,9%, and 65,2% of isolates demonstrated susceptibility to biapenem, imipenem, and meropenem, respectively.Producers of KPC-type carbapenemases were 100% resistant to all carbapenems. The introduction of biapenem will significantly expand the possibilities of treating severe infections caused by carbapenemase producers.
, A. V. Aparkina, E. V. Grigoryeva, N. A. Magdeeva, N. M. Nikitina, N. D. Smirnova,
Antibiotics and Chemotherapy, Volume 67; https://doi.org/10.37489/0235-2990-2022-67-1-2-24-31

Abstract:
Although antibiotics (AB) are ineffective for the treatment of COVID-19, they are often prescribed to patients with the novel coronavirus infection (NCV) for a variety of reasons. They include the difficulty of excluding bacterial co-infection at the first contact with the patient, as well as the possibility of developing a secondary bacterial infection. The aim of the work is to assess the frequency and background of prescribing antibiotics to hospitalized patients with confirmed COVID-19. Material and methods. A retrospective analysis of 160 hospital records of patients with confirmed COVID-19, who were treated in various Infectious Diseases Departments during the period from September to October 2020, was carried out. The selection was done by the method of random sampling. The analysis did not include the records of patients admitted to the ICU for NCV. Results. Information about the appointment of antibacterial drugs before hospitalization was found in 109 patients, of which only 51 patients did not receive AB on an outpatient basis. The remaining 58 (53.2%) patients began taking ABs on their own or based on the recommendation of an outpatient doctor, including 31 patients who took two or more drugs (successively or simultaneously). The most commonly used antibiotics were: macrolides (37 patients), cephalosporins (24 patients), respiratory fluoroquinolones (12 patients), and aminopenicillins (5 patients). On admission, AB was prescribed for almost all patients, except for one. The most frequently prescribed antibiotics were: macrolides (61%), mainly azithromycin, and respiratory fluoroquinolones (54.1%), mainly levofloxacin. In most cases, these drugs were combined with 3rd or 4th generation cephalosporins. Most patients received more than one AB: two drugs were prescribed to 86 (54.1%) patients, three — to 34 (21.4%) patients. AB therapy was carried out for a long time: the maximum number of days for macrolide administration (excluding previous AB therapy at the outpatient stage) was 16 days, respiratory fluoroquinolones — 22 days,3rd generation cephalosporins — 19 days,4th generation cephalosporins — 17 days, carbapenems — 34 days. In almost 100% of cases, ABs were prescribed on the first day of admission of patients, and their therapy continued until the patient was discharged from the hospital. Conclusion. The appointment of antibiotics at the hospital stage was established for the vast majority of patients in the absence of clear indications for their appointment. Such a frequent prescription of antibiotics is accompanied by a number of problems: immediate – side effects of such therapy (for example, antibiotic-associated diarrhea), long-term — an increase in antibiotic resistance of microorganisms.
I. B. Bondareva, S. K. Zyryanov, M. S. Chenkurov
Antibiotics and Chemotherapy, Volume 66; https://doi.org/10.37489/0235-2990-2021-66-11-12-31-38

Abstract:
Meropenem is a carbapenem antibiotic widely used in treatment of severe infections in ICU. Critically ill patients’ pathophysiological features may cause changes in the pharmacokinetics of meropenem, such as augmented/impaired renal clearance, as well as an increase in the volume of distribution of the drug. Considerable variability in meropenem concentration for the same dosage regimen, severity of the diseases and the escalating antibiotic resistance support the need for an individualization of the dosing in critically ill patients. Estimation of meropenem pharmacokinetic (PK) parameters was performed using the NPAG (non-parametric adaptive grid) program from the Pmetrics package based on peak-trough TDM data. A one-compartment linear PK model with zero-order input and first-order elimination was used to analyze data of the 36 critically ill patients (66 measured meropenem concentrations totally) and to predict pharmacodynamic (PD) parameter values (%T>MIC) based on the time course of free meropenem concentration for empirically prescribed dosage regimens by MIC level. The estimated PK parameters of the meropenem model were in good agreement with those published in the literature earlier. A great interindividual variability for PK parameters from 44.5% up to 167% was revealed. Different regression lines between meropenem clearance and clearance creatinine (CLCr) were registered in patients with CLCr [1] 7 L/h versus > 7 L/h: statistically significant regression (n=30, p=0.015) versus no correlation (n=6, р=0.85), respectively. Bayesian feedback TDM-based meropenem dose personalization is the most practical approach to ensure adequate drug exposure in critically ill patients, especially in patients with augmented renal clearance.
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