Background. The spread of antibiotic resistance among pathogenic microorganisms is a global problem. One solution is the discovery of new, effective natural antibiotics. The aim of the study. To identify producers of these antibiotics, potential antibiotic-producing microorganisms were isolated and analyzed from natural sources with extreme environmental parameters that had not previously been studied in this regard. Twenty actinomycete isolates from the littoral zone of the Salt Lake Bolshoi Tambukan are described. Materials and Methods. Actinomycetes were identified using cultural and morphological characteristics and 16S rRNA gene analysis. Antimicrobial activity was determined in submerged cultures obtained on eight media of varying compositions. Thirteen collection microorganisms, including multidrug-resistant (MDR) bacteria, and 10 clinical MDR isolates of Klebsiella pneumoniae were used as test strains. Results. Of the 20 strains, 19 ex hibited antimicrobial properties, representing a high percentage of potential antibiotic producers (95%). In cases where multiple strains of a single species were isolated (2–3 strains each), intraspecific differences in antimicrobial spectra were observed in Micromonospora palomenae, Streptomyces badius, S. rubiginosohelvolus, and S. vastus, which contributes to the competitiveness and survival of the population as a whole. M. palomenae and S. xinghaiensis species, for which antibiotics have not previously been described, represent promising targets for chemical research. S. xinghaiensis INA 01375 and S. rubiginosohelvolus INA 01402 are of particular interest, as they are active against clinical isolates of MDR Klebsiella pneumoniae. Conclusion. The actinomycete flora of Lake Tambukan represents a promising target for the search for antibiotic producers capable of overcoming pathogen resistance.

Relevance. Microbicidal proteins are used to create natural antimicrobial drugs. It has been shown to date that ultrasound exposure of leukocytes results in complete cell destruction and the formation of new compounds — peptide complexes with immunobiological activity. The aim of the study was to update the parameters of ultrasound effect on the donor leukocytes to isolate individual polypeptides with biological activity. Materials and methods. New leukocyte protein-peptide complexes were obtained by ultrasonic treatment of donor leukocytes. Separation of peptide complexes was carried out on Superdex 200 increase chromatographic columns. HPLC and infrared spectroscopy methods were used to study them. The HPLC method was implemented on a Knauer chromatograph (Germany) using a spectrophotometric detector of analytical wavelengths of 280 nm and 293 nm. Results. It has been established that various ultrasound wave amplitudes and durations of their action contribute to the production of complex protein compounds. Under certain conditions (processing donor leukocytes with ultrasound for 90 sec., with an amplitude of 60%, a power of 50 W, and a frequency of 30 kHz), it is possible to obtain a complex of low-molecular peptides with a molecular weight of less than 6.5 kDa. Using Fourier transform infrared spectroscopy, it was determined that the composition of the obtained peptide complex includes amino acids such as Thr, Ser, Phe, Tyr, His, and Trp. It has been established that this complex has antibacterial activity. Conclusion. Ultrasound treatment of donor leukocytes produces a protein complex with antibacterial activity.

Background. Modern clinical practice often excludes the possibility of differential diagnostics for acute respiratory viral infection pathogens and identification of a specific viral pathogen. In this regard, it is important to search for drugs with a broad spectrum of activity against pathogens of acute respiratory viral infections. The aim of the study was to assess the antiviral activity of the drug Cytovir®-3 in vitro against the cytopathogenic effect of human adenovirus. Material and methods. The antiviral effect of the drug Cytovir®-3 in comparison with the drug Umifenovir against human adenovirus type 5 was studied on Vero cell culture. The drugs were administered 1 hour before (prophylactic regimen) and 1 hour after (therapeutic regimen) infection of the cell culture with the virus. The working concentration range for the studied drugs was determined based on the 50% cytotoxic concentration values, calculated based on the results of the microtetrazolium (MTT) assay. Results and discussion. The drug Cytovir®-3 in two application regimens (therapeutic or prophylactic) demonstrated antiviral efficacy in vitro against human adenovirus in the non-toxic range (0-631 µg/ml) regardless of the application scheme (therapeutic or prophylactic). Conclusion. The in vitro antiviral activity of the drug Cytovir®-3 against human adenovirus has been proven. Moreover, in all series of experiments, Cytovir®-3 had a selectivity index comparable to that of the reference drug Umifenovir.

Delamanid is one of the key new drugs for the treatment of multidrug-resistant and, in particular, extensively drug-resistant tuberculosis. However, due to its relatively recent introduction into clinical practice, data on the frequencу of resistance detection to this drug remain limited. The aim of the study was to determine the phenotypic susceptibility of Mycobacterium tuberculosis, isolated from patients with pulmonary tuberculosis in the Russian Federation, to delamanid. Materials and methods. The study included a total of 271 M. tuberculosis isolates with different resistance pat terns, obtained from patients in the Russian Federation (2022–2025). Resistance to delamanid (pure substance, Otsuka Pharmaceutical Co., Ltd., Japan) was determined using a modified proportional assay in the BACTEC MGIT 960 system; the critical concentration for delamanid was 0.06 µg/mL. Results. Resistance to delamanid was detected in 14.39% (39/271) of cases in both M. tuberculosis isolates susceptible to other anti-tuberculosis drugs and M. tuberculosis isolates with resistance profiles including 1 to 10 drugs (excluding delamanid). The incidence of delamanid resistance in M. tuberculosis with retained susceptibility to rifampin and in M. tuberculosis with multidrug/extensive drug resistance did not differ significantly, amounting to 11.49% and 15.76%, respectively. Primary resistance to delamanid was detected in at least 3.69% (10/271) of the cases. Conclusion. The data obtained indicate a significant level of resistance to delamanid, including among isolates not exposed to the drug. Therefore, it is imperative to improve measures to control the spread of pathogens resistant to this antimicrobial agent.

The aim of the study was to compare the safety, tolerability, and pharmacokinetic profile of Grammidin® neo, lozenges, and Grammidin®, a metered-dose topical spray, manufactured by Valenta Pharm JSC, Russia, following single-dose administration in healthy volunteers. Material and methods. An open-label, randomized, two-period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic parameters of Grammidin® (metered-dose topical spray) compared to Grammidin® neo (lozenges). Healthy volunteers were randomized into two sequence groups according to the order of drug administration in periods I and II of the study. In group 1, subjects received 1 lozenge of Grammidin® neo during period I. In period II, the same volunteers received 4 sprays of Grammidin® to the oral and pharyngeal mucosa applied by the researcher. Group 2 subjects received the study medications in reverse order. The washout period between administrations of the study drugs was 7 days. Concentrations of the active pharmaceutical substances were determined in plasma using high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) with prior analyte extraction from the biological matrix. The study included ongoing monitoring of vital signs, as well as assessments of laboratory parameters (complete blood count, serum biochemistry, and urinalysis) and standard 12-lead ECG recordings. All subject-reported complaints, as well as any abnormalities or clinically significant deviations from reference ranges in general health status, laboratory findings, or ECG parameters were documented and categorized by the researcher as adverse events (AEs). Results. Of the 16 volunteers who received the study drugs in periods I and II, only 6 demonstrated plasma concentrations of gramicidin S and cetylpyridinium chloride above the lower limit of quantification (LLOQ) at isolated time points. Due to the insufficient number of measurable concentrations, pharmacokinetic parameters could not be reliably calculated. During the study, one mild adverse event (AE) was reported in a single volunteer — pain at the catheter insertion site. The relationship between this AE and study drug administration was assessed by the researcher as indeterminate. This AE resolved spontaneously without any therapeutic intervention. Conclusion. Topical administration of gramicidin S and cetylpyridinium chloride to the oropharyngeal mucosa resulted in minimal systemic exposure, making pharmacokinetic characterization unfeasible. The fixed-dose combination was safe and well tolerated in all participants, with no meaningful differences observed between the lozenge and spray formulations.

The aim was to study the effectiveness of including remaxol in nutritional detoxification therapy in the perioperative period in patients with pancreatic diseases. Material and methods. The results of treatment of 55 patients were analyzed. In the nutritional detoxification therapy regimen in the perioperative period, Impact®Oral (orally, 3 sachets per day 5 days before surgery and 7 days after) were prescribed, and in the main group (N = 44) remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) was additionally prescribed: 400.0 ml intravenously by drip according to the regimen: 2 days before surgery daily and in the postoperative period — every other day, a course of 6 drips. Patients of the control group (N = 11) received a 5% glucose solution in comparable volumes in the infusion therapy regimen. The severity of pancreatitis was assessed using the M-ANNHEIM scoring system and the M-ANNHEIM severity index, while the severity of intoxication syndrome was assessed according to Chernov V. N. et al. The nutritional status was assessed using the NRS 2002 scale and the nutritional risk index was calculated. The levels of total protein, albumin, urea, creatinine, blood amylase, and transaminases, as well as the leukocyte intoxication index, were determined dynamically (before surgery and 9 days after it). Results. The inclusion of remaxol increased treatment effectiveness, which was manifested by more pronounced positive dynamics of clinical (ALS severity, improved well-being, and restoration of appetite) and laboratory data (reduced amylase and transaminase levels, LII), as well as correlated with a decrease in the severity of nutritional deficiency. No adverse events were detected during the use of the drug; all patients received full treatment. Conclusion. When planning therapy for patients with pancreatic diseases in the preoperative period, it is necessary to assess the degree of nutritional deficiency and perform its perioperative correction. The results obtained may serve as a basis for further research in this area.

Background. WHO experts emphasize that the use of bedaquiline in children is conditional, supported by limited evidence and a very low certainty of recommendations. The aim of the study was to evaluate the effectiveness of bedaquiline in chemotherapy regimens for drug-resistant tuberculosis in children depending on body weight. Methods. A retrospective study included 27 children (6–12 years) with confirmed or probable (reliable contact with a patient) MDR/pre-XDR tuberculosis. Group I included 11 children weighing  30 kg, Group II included 16 children weighing  30 kg. The bedaquiline dose was 200 mg daily for the first 2 weeks (saturation phase), then 100 mg 3 times a week for 22 weeks (maintenance phase). The following were assessed: the time to cessation of bacterial excretion and radiographic dynamics (closure of decay cavities; resorption of infiltrative, focal, and pleural changes). At the end of chemotherapy, the treatment outcomes were assessed; follow-up examinations were conducted after 6 months and after 1 year. Results. Within 3 months of chemotherapy, abacillation was achieved in all 3 patients with MBT. Lung cavity closure was achieved in 2 patients out of 4. Clinical cure was achieved in 100% of patients in the comparison groups (p  0.05). No recurrences were detected. Conclusion. This study, based on real-world clinical practice of using bedaquiline in children with tuberculosis aged 6–12 years, demonstrated the feasibility of effective use of the pediatric dosage of the drug in patients weighing 30 kg or more.

Breast cancer (BC) remains the leading cause of cancer-related death among women worldwide. Accumulated evidence reveals a complex relationship between thyroid dysfunction and BC, including an increased risk of development, progression, and worsening prognosis. This article provides a comprehensive review of the molecular mechanisms and pathophysiological aspects underlying this association. The article reviews the existing therapeutic strategies and emphasizes the need for an integrative approach to treating patients with breast cancer and comorbid thyroid conditions. Furthermore, the modern methods for early diagnosis and monitoring of breast cancer are described, taking into account its interactions with other body systems.

Background. Invasive mycoses pose a growing health threat, especially for patients with weakened immune systems, whose number is increasing due to advances in oncology, transplantation, and intensive care. The limitations of existing antimycotics are their toxicity, narrow spectrum of action, low bioavailability, and growing resistance of pathogens. The slow pace of development of new antifungal agents compared to antibacterial ones exacerbates the situation, which makes the search for new effective and safe drugs critical. The aim of this review was to summarize and systematize information on current trends in the development of antimycotics, covering both the evolution of approaches to «classical» targets (cell wall, cell membrane) and strategies aimed at overcoming the current limitations of antifungal therapy. Methods. A systematic analysis of scientific literature and clinical research data was carried out using Google Scholar, eLibrary, PubMed, Wally, and ClinicalTrials.gov databases. The main focus was on the publications of the last decade, taking into account the key earlier studies. Results. Over the past 10 years, only 4 new drugs have entered clinical practice. There are 9 molecules in active clinical trials, including Gwt1 inhibitors, dihydroorotate dehydrogenases, and inhaled triazoles. Compounds with new mechanisms of action are of particular interest, for example, mandimycin, which targets phospholipids, inhibitors of inositol-phosphoceramide synthase, which is absent in humans. Conclusion. Despite the challenges associated with the eukaryotic nature of fungi, the development of new antimycotics continues in several promising areas focused on improving the properties of representatives of existing classes, as well as searching for fundamentally new targets.

Background. Vancomycin is still widely used for the treatment of severe infections caused by Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA). The aim of antibiotic therapy is optimal efficacy with minimal potential toxicity. This is especially important for medications with narrow therapeutic ranges, including vancomycin, as well as for special patient populations, in particular neonates and preterm neonates, who have high levels of inter-individual pharmacokinetic (PK) and pharmacodynamic (PD) variability. In these populations, therapeutic drug monitoring (TDM) is recommended in vancomycin for dosage optimization. Aim. The primary objective of the study was to descriptively analyze the features of population PK/PD modeling of vancomycin in neonates and preterm neonates. Methods. A literature search was conducted in the PubMed® (MEDLINE) database for the period from 1981 through August 2024. Results. The study describes the main approaches to personalizing vancomycin dosage regimens, as well as methods for calculating the currently recommended target PK/PD index based on TDM data for optimizing therapy in clinical practice, including the Bayesian AUC-guided dosing approach using computer software. The results of the systematic review of published population PK models of vancomycin are presented; model structures, as well as the identified factors that influence PK variability in the preterm neonate population, are described. In the selected studies (N = 31), that included preterm infants, vancomycin clearance and volume of distribution were estimated over a wide range (0.01–0.22 L/h/kg and 0.47–1.5 L/kg, respectively) with estimated high inter-individual variability in PK parameters reaching up to 50%. In the majority of these studies, current body weight, renal function, and/or age were significant predictors of vancomycin clearance, and body weight was an important predictor of vancomycin volume of distribution. Conclusion. In the newborn population, the observed significant inter-individual vancomycin PK/PD variability led to a high risk of underdosing or overdosing with standard dosage regimens, which demonstrated the need for TDM for delivery of optimal vancomycin therapy. Identification of the factors that contribute to vancomycin PK variability and the use of calculated population PK models can help in choosing the initial vancomycin dosing regimen. However, the magnitude of the residual unexplained variability usually remaining in these final regression models demonstrates the need for TDM to personalize vancomycin dosage regimens. AUC-guided therapeutic dosing and monitoring, preferably with a Bayesian approach, may be considered as the best way to achieve the target vancomycin exposure likely to be required for a successful outcome of treatment for an MRSA infection for neonates and to avoid the development of microbial resistance. 

Glucocorticoids (GCs) are widespread anti-inflammatory drugs used in medical practice. The immunosuppressive effect of systemic GCs and increased susceptibility to infections are well known. Randomized controlled trials of the use of GCs in low doses and in short periods, as a rule, did not reveal an increased risk of comorbid infections (CI) or even showed its absence. However, observational studies in real clinical practice consistently demonstrate a dose-dependent increase in the risk of serious CI, including opportunistic ones (pneumocystis pneumonia, shingles, and tuberculosis). The review presents the main immunological effects of GCs that increase susceptibility to CI. The risks of CI in patients with immune-mediated inflammatory rheumatic diseases (IIRDs) receiving GCs were analyzed, taking into account the effect of doses, the duration of their use in combination with biological factors of the macro-organism, as well as concomitant immunosuppressive therapy. Physicians should actively evaluate the benefit-risk ratio of systemic GCs in patients with IIRD and take preventive measures to prevent infectious complications.

There is some controversy regarding the impact of water hardness on the risk of stone formation. Therefore, this article presents a review of studies examining the impact of drinking water hardness on the development of urolithiasis. The role of hard or soft water in the development of urolithiasis remains controversial. When characterizing water, calcium, magnesium, and bicarbonate levels should be considered. According to modern literature, the prevalence of urolithiasis depends on regional climate conditions, environmental factors, the quality and quantity of water used, as well as the diet, lifestyle, gender, and age of the population.