Neonatal infections remain one of the significant causes of infant mortality in the world. The change in the spectrum of pathogens, as well as their sensitivity to the main antibacterial drugs (ABDs), is a dynamically occurring process, characterized by a gradual increase in the proportion of the most dangerous pathogens, in particular, those belonging to the ESKAPE pathogen group. The study of the structure of pathogens and the parameters of their antibiotic resistance is the main tool for increasing the effectiveness of antibiotic therapy.

The aim. To analyze the structure of pathogens of nosocomial infections in patients of neonatal intensive care units (NICU) and assess the parameters of their antibiotic resistance.

Materials and methods. A retrospective epidemiological study of data from May 1, 2022 to May 1, 2024 of the laboratory information system LIS-Alice of the Kommunarka Center (Moscow, Russia) and medical documentation of patients with identified growth of microorganisms (MOs) in bacteriological cultures was carried out.

Results. The total number of crops was 5179, MOs growth was noted in 39.3% (n=2036) obtained from 734 patients, of which 87.1% were premature. Gram-positive pathogens were found in 59.6%. The top 5 identified MOs were: S. epidermidis (n=386 — 19%), S. haemolyticus (n=264 — 13%), S. aureus (n=218 — 10.7%), K. pneumoniae (n=210 - 10.3%) and E. coli (n=188 — 9.2%). The proportion of MOs belonging to the ESKAPE group was 28.6% (S. aureus — 10.7%; K. pneumoniae — 10.3%; Enterobacter spp. — 3.6%; P. aeruginosa — 2.3%; A. baumannii — 1.1%; E. faecium — 0.5%). Among Staphylococcus spp. — 71.2% were resistant to oxacillin, 53.9% — to gentamicin. At the same time, 100% sensitivity to any of the tested ABDs was not detected. The highest rates of resistance to oxacillin were observed in S. epidermidis (93.8%) and S. haemolyticus (86.7%). Also, 17% of S. aureus strains were resistant to oxacillin. Among K. pneumonia 48.8% were resistant to ceftazidime and 100% to ampicillin; E. coli 28.2% of strains were resistant to ceftazidime, 64.9% to ampicillin, 28.2% to sulfamethoxazole trimethoprim.

Conclusion. We found a high frequency of pathogen isolation (with a predominance of gram-positive pathogens) in newborns hospitalized in the ICU (mean gestational age <35 weeks). The results demonstrate alarming trends in relation to MOs resistance parameters and indicate the need for dynamic monitoring of the sensitivity of pathogens to the main ABDs used in the ICU.

The aim. To study the acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles.

Materials and methods. The study was performed on white laboratory female BALB/c mice (n=57) and male C57Bl/6 mice (n=66). Acute toxicity was assessed according to the interstate standard GOST 32644-2014 with histological evaluation of internal organs. Endothelial dysfunction was modeled by 7-day intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME). The studied small molecules were administered intragastrically using a probe. To assess the endothelial protective effect, the levels of systolic and diastolic blood pressure were evaluated, as well as the coefficient of endothelial dysfunction; for the cardioprotective effect, the results of stress tests on the myocardium were evaluated.

Results. The study of acute toxicity of the studied small molecules allowed us to classify them as class 4 and 5. The administration of compounds 1(a–d) and 2(a–c) to mice at a dose equal to 1/10 of LD50 led to changes in blood pressure and restoration of the dynamics of pharmacological tests in response to the administration of acetylcholine and sodium nitroprusside. Molecules 1b and 2c showed statistically significant endothelial protective activity in 3 doses (1/10, 1/50 and 1/100 of LD50). Also, these hit compounds demonstrated cardioprotective effects, recorded by the restoration of the functional capabilities of the myocardium in response to load and in the adrenoreactivity test, and to a lesser extent, during resistance exercise.

Conclusion. The studied compounds have low toxicity and have endothelial- and cardioprotective effects. This study may contribute to the formation of an idea about further directions in the study of the pharmacological activity of these molecules from the group of phenolic and thiophenolic derivatives of 2H-imidazoles.

The search for new antimicrobial medicines based on medicinal plant raw materials (MPRM) and its effective and safe use in modern pharmaceutical practice remains one of the most pressing issues in pharmacy. Today, the search for new biologically active compounds (BACs) with antimicrobial and antifungal activity is ongoing. Due to the content of the BACs complex, preparations based on MPRMs have a milder effect on the human body compared to synthetic analogues. According to the results of studying some foreign studies and publications on the topic of antimicrobial and antifungal activity, a promising source of BACs, namely the leaves of common myrtle (Myrtus communis L.), is of scientific interest.

The aim. Analysis and comparative study of the antibacterial activity of samples of extracts obtained using ethanol of various concentrations, and an infusion of common myrtle leaves (Myrtus communis L.) against clinical strains isolated from patients with cystic fibrosis.

Materials and methods. The objects of the study were water-alcohol extracts from common myrtle leaves, comparison preparations — ethanol with a concentration of 40, 70, 96% and eucalyptus tincture. 5 strains of pathogenic microorganisms isolated from the sputum of patients with cystic fibrosis were used as test cultures. The minimum inhibitory concentration was assessed using the method of double serial dilutions in broth.

Results. All water-alcohol extracts from common myrtle leaves showed antimicrobial activity exceeding the control samples against 3 mucoid strains — Burkholderia cenocepacia, Stenotrophomonas maltophilia and Pseudomonas aeruginosa. No antimicrobial activity was detected for the remaining 2 strains. A pronounced antimicrobial effect was possessed by 70% tincture and aqueous infusion of leaves.

Conclusion. The data obtained during the study allow us to draw conclusions about the further prospects of studying 70% myrtle tincture and aqueous infusion for use in the therapy of patients with cystic fibrosis.

Drug sensitivity to, in particular to favipiravir, may vary among representatives of different ethnic groups. Studies have previously shown that carrying certain variants of the AOX1 and CYP1A2 genes may be associated with an increased incidence of adverse reactions with patients having COVID-19 and taking favipiravir. This work is devoted to studying the prevalence of mutant variants rs55754655 and rs10931910 of the AOX1 gene and rs762551 of the CYP1A2 gene in various ethnic groups of the North Caucasus.

The aim. To characterize the distribution structure of AOX1 (rs55754655 and rs10931910) and CYP1A2 (rs762551) variants among the peoples of the North Caucasus (Ossetians, Balkars, Kabardians, Avars, Dargins, Laks, Kumyks and Lezgins).

Materials and methods. The frequency of distribution of AOX1 and CYP1A2 gene variants was studied among 897 conditionally healthy volunteers (362 men — 40.4% and 535 women — 59.6%; average age — 34.6±6.3%), from 8 ethnic groups of the North Caucasus: Ossetians, Balkars, Kabardians, Avars, Dargins, Laks, Kumyks and Lezgins (n=100 for each), as well as 97 Russians (reference group).

Results. As a result of the analysis, a significant difference was found in the allele frequencies for the rs10931910 AOX1 genetic polymorphism between Balkars and Russians (p <0.05), Laks and Russians (p <0.05), and especially between Dargins and Russians (p <0.0001). No statistically significant differences in the allele frequencies of the CYP1A2 gene were found in the comparative analysis of ethnic groups with the comparison group.

Conclusion. Significant differences were revealed in the frequency of AOX1 polymorphisms (rs10931910, rs55754655) in the peoples of the North Caucasus relative to the Russian population. The largest deviations were recorded in Dargins: a decrease in the frequency of the minor allele rs10931910 to 28.5% (p <0.0001) and rs55754655 to 3.0% (p=0.0105). The results may be useful for optimizing therapy with medicines that are AOX1 substrates, which include favipiravir, used to treat patients with COVID-19.

The U.S. Food and Drug Administration (FDA), in particular the Center for Drug Evaluation and Research (CDER), plays a key role in ensuring the safety, efficacy, and innovation of medicines entering the U.S. market, and then the world. The annual review of new medicines approved by the FDA is an important tool for analyzing current trends in pharmacology and medicine, reflecting progress in the treatment of complex diseases, including cancers, orphan diseases, and infections. The review is compiled to familiarize medical specialists and pharmacologists with current trends in the registration of original medicines and in the therapy of malignant neoplasms, orphan diseases.

The aim. To summarize and systematize data on the newest medicines that entered the market in 2024, as well as to analyze the mechanisms of their action. The article aims to inform medical specialists and pharmacologists about current trends in the development and registration of innovative medicines in 2024.

Materials and methods. The presented data are taken from open sources and supplemented with the results of individual studies on new mechanisms and approaches in therapy. The main list of new drugs and introductory information about them are taken from the FDA report “Novel Drug Approvals for 2024”. Data on medicine prescriptions, as well as information on the mechanism of action, are taken from published summary of product characteristics (SmPC) published on this resource, as well as from the Drugs.com website. To describe previously registered medicines for which a new indication is presented, Drugs.com reports were also used. Structural formulas of drugs are taken from the PubChem resource. In case of the absence of structural formula, data from their SmPC or third-party resources, such as Drugbank, were used. The search for literature data on fundamental studies relating to the mechanisms of action of the presented medicines was carried out in the PubMed, ResearchGate, Google Scholar and elibrary.ru databases.

Results. A statistical analysis of registrations, the dynamics of changes in the shares of various types of medicines and basic data on new original drugs registered by CDER are presented. In 2024, the FDA registered 50 original medicines, among which 48% contain a “first-in-class” molecule as an active substance. Small molecules include active substances — 60%, and biopharmaceuticals — 34% (the remaining 6% are imaging agents). At the same time, monoclonal antibodies (mAb) of antitumor and anti-inflammatory action occupy a larger share among biopharmaceuticals.

Conclusion. The large proportion of biopharmaceuticals among those newly registered in 2024 emphasizes the dynamic development of the pharmaceutical industry and its focus on personalized medicine and biotechnology. Therapy based on mAbs interacting with receptors, as well as immunotherapy based on newly discovered mechanisms of antitumor immunity, occupies a separate part in the structure of registered original medicines. The search for new rational combinations of antibiotics remains relevant. Most of the original drug market is still made up of small molecules, among which there are medicines — ligands of new targets and oligonucleotide sequences.