The study considered the possibility of using the membrane filtration method as a way of eliminating the antimicrobial effect upon determination of the microbial quality of antimicrobial medicines for oral administration. Azithromycin and amoxicillin powders for suspension, as well as levomycetin (chloramphenicol) and ciprofloxacin tablets were used as examples. The study demonstrated that in some cases the membrane filtration method precluded reliable results. In case of possible contamination of a medicinal product, suspended particles of the active ingredient deposited on a membrane filter may have an inhibitory effect on certain microorganisms due to the spectrum of action of the antimicrobial medicine. A supernatant facilitates filtration upon determination of the microbial quality; however, microorganisms may sediment on suspended particles of the test medicine in the process of suspension separation. The use of the membrane filtration method for the evaluation of the contamination of oral antimicrobial medicinal products should be based on the method validation, taking into account the solubility of the medicine, the composition of excipients, and experimental data on the absence of adhesion of microorganisms on the particles of excipients.

Escherichia coli isolates from various sources from 2018 to 2019 were included in the study. Mcr-1 genes were found in two of 105 animal strains (2%) and seven of 928 human strains (0.8%). All mcr-1-positive strains showed a low level of resistance to colistin (MIC ranged from 4 to 8 µg/ml). Both strains isolated from animals remained sensitive to betalactam antibiotics and did not contain beta-lactamase genes. Beta-lactamases were absent only in one of the strains isolated from humans. Four strains were resistant to cephalosporins with sensitivity to carbapenems and carried class A (blaCTX-M-15 or blaCTX-M-1) or class C (blaCMY-2) extended-spectrum beta-lactamases genes. One strain showed resistance to cephalosporins and meropenem and contained four beta-lactamase genes: blaNDM-1, blaCTX-M-15, blaTEM-1B, and blaCMY-6. Only one strain isolated from animals remained sensitive to ciprofloxacin, the rest showed high level of resistance, had amino acid substitutions in the DNA gyrase genes or mutations leading to overexpression of the mdfA gene. In terms of resistance to aminoglycosides, the strains varied widely and carried up to four aminoglycoside-modifying enzyme genes. One strain isolated from humans showed resistance to tigecycline, but no genes conferring resistance to this antibiotic were found. The data obtained substantiate the need for extended studies on the molecular epidemiology of associated resistance to polymyxins and beta-lactams.

The paper presents optimized methods for PCR and sequence typing of Streptococcus pneumoniae. The serotype composition of pneumococci isolated from children under 5 years of age with infections of the upper respiratory tract was analyzed using optimized methods. Between 2016 and 2021, there was a decrease in the frequency of serotypes included in the pneumococcal 13-valent conjugate vaccine (PCV13) from 94.1 to 25.8%, mainly due to the 6ABCD serogroup and the 19F serotype. The coverage of serotypes circulating in children with PCV15 and PCV20 vaccines was 28.1% and 41.6% in 2021, respectively. During the study period, the number of non-vaccine serogroups 11AD and 15AF, as well as serotypes that are not detected under this capsular PCR typing protocol, increased most significantly.

Background. The main factors reducing treatment effectiveness in patients with pulmonary tuberculosis are as follows: the growing drug resistance of mycobacteria, which necessitates the strengthening of chemotherapy regimens, the use of new antimicrobial drugs, as well as poor tolerability of treatment due to the high frequency of adverse drug reactions. Combinations of fluoroquinolones, bedaquiline, and linezolid with traditional anti-tuberculosis drugs are used in new regimens for the treatment of patients with multidrug- and extensively drug-resistant tuberculosis, but the safety of new regimens has yet to be sufficiently studied.

The aim was to study the features of toxic effect manifestations of the 5-component antimycobacterial drug complexes in an experiment on rats.

Methods. The study was carried out on 64 non-pedigree rats, old females, divided equally into 3 experimental groups and 1 control. Rats of the experimental groups received drug complexes at doses corresponding to therapeutic doses for humans. The complexes’ base components were: moxifloxacin, bedaquiline, linezolid, and capreomycin. The fifth drug in group 1 was prothionamide, in the 2nd — pyrazinamide, in the 3rd — cycloserine. After 14 and 28 days of administration, the clinical picture of intoxication, ECG results, behavioral reactions of rats in the open field test, biochemical blood and urine tests, as well as pathomorphological studies were analysed.

Results. Progressive damage to the gastrointestinal tract, liver, kidneys, and central nervous system was observed in rats of all experimental groups. The leading reason of polytoxicity is the nephrotoxic effect caused by capreomycin, to which rats have a high species sensitivity. In group 1, rats were treated with three drugs possessing potential cardiotoxicity; cardiotoxic effect was observed in the form of prolongation of the QT interval on the ECG after 14 days of administration. The most toxic combination of drugs was the one used in rats of the 3rd group, it was enhanced by the addition of neurotoxic cycloserine, which led to the death of more than a third of the animals by the end of the experiment.

Conclusion: the use of multicomponent combinations of antimycobacterial drugs, similar in safety profile, increases the risk of developing combined toxic reactions.

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.

The aim of the study was to assess the effect of Cytoflavin on the severity of neurocognitive parameters in patients with chronic cerebral ischemia, as well as vertebrobasilar insufficiency with symptoms of cerebral venous circulation. The study involved 60 patients who were divided into two groups. Cytoflavin was prescribed in the treatment group: once per day in the morning, slow intravenous drip of 10.0 ml per 200 ml of 0.9% sodium chloride solution, the duration of the infusion averaged 40–60 minutes for a course of 10 days with the transition to a tablet form — 2 tablets twice per day for 30 days against the background of standard basic therapy (acetylsalicylic acid and antihypertensive drugs). Patients in the comparison group received only basic therapy. The rating scales for headache (visual analogue scale) and asthenia (asthenic state scale) were used to assess the neurological status in addition to the standard clinical and labo ratory examination. It was revealed that the main clinical and neurological manifestations in patients with symptoms of cerebral venous discirculation are headaches (48 (80%) patients) and dizziness (53 (88.3%) patients). The incidence of dizziness increased with the progression of chronic cerebral ischemia, for example, at stage I dizziness occurred in 57% of cases, at stage II — in 78%, and at stage III — in 100%. When conducting a study of the headache severity dynamics on the VAS scale, a decrease in the intensity of headaches by 1.7 times (5.68±0.62 to 3.23±0.56 points, p[1]0.5) was noted in patients who received Cytoflavin, while only a slight decrease in the intensity of pain was noted in patients of the comparison group. In addition, the inclusion of the drug in the therapy regimens for patients with this pathology showed a significant decrease in the frequency of complaints, including specific «venous» complaints, the severity of cephalgic syndrome, as well as asthenic and autonomic disorders, which had a positive effect on the patients’ quality of life. The results obtained make it possible to recommend the inclusion of the drug in the therapy regimens for patients with symptoms of cerebral venous dysfunction.

The review presents the main directions of antibiotic therapy associated with rational pharmacotherapy of urinary tract infections (UTIs) in pediatric practice. As a serious pediatric problem, UTIs are often prone to recurrence, as well as may lead to the formation of more severe forms of urinary system diseases. Antibiotic therapy, timely and adequate in terms of etiological factors, drug and dosage choice, route of administration, as well as patient’s age, allows to avoid further progression of the disease, as well as development of disability in patients.