Experimental Research
Background. The search for new effective antibiotics is one of the main tasks in the field of medicine, which is due to the spread of antibiotic-resistant pathogens that are not amenable to traditional chemotherapy.
The aim of the study was the search for a microorganism that could potentially produce an antibiotic exhibiting antimicrobial activity against pathogenic bacteria with multiple drug resistance.
The object of the study was a bacterium isolated from a freshwater indoor aquarium, identified as Aquipseudomonas alcaligenes and deposited in the collection of NIINA under the number INA 01568.
Materials and methods. For the surface cultivation of A. alcaligenes, bacterial and fungal strains, universal medium No. 2 Gause was used. Submerged cultivation was carried out in 18 nutrient media of different compositions. An agar diffusion method was used to determine the antimicrobial activity. Thirteen collection test strains of bacteria and fungi were used as test strains. Species identification was carried out by morphological features and the 16S rRNA gene.
Results. When cultured under submerged conditions on 2 media out of 18, the A. alcaligenes INA 01568 strain demonstrated antimicrobial activity against 6 test strains, including bacteria from the ESKAPE group, namely MRSA, Pseudomonas aeruginosa, as well as the vancomycin-resistant strain Leuconostoc mesenteroides; activity against these strains has been described for the first time. Activity against fungi was not detected.
Conclusion. The A. alcaligenes strain INA 01568 is promising for chemical research.
Background. The search for new antimicrobial compounds remains critically important due to growing antibiotic resistance. Basidiomycetes represent an important resource for selecting producers of metabolites with targeted activity, as their metabolic profile is highly dependent on cultivation conditions. Stereum hirsutum is known for its ability to synthesize antimicrobial substances; however, the dependence of its biosynthetic activity on cultivation conditions has been insufficiently studied.
The aim of the work. To study the effect of the nutrient medium composition on the biomass growth and antimicrobial activity of culture liquid and mycelial extracts of the basidiomycete S. hirsutum.
Material and methods. Submerged cultivation of the S. hirsutum 1 strain on six media with different carbon (glucose, molasses, glycerol) and nitrogen (yeast extract, peptone) sources. Preparation of ethyl acetate extracts from the culture liquid and ethanol extracts from the mycelium. Preparation of ethyl acetate extracts from the culture liquid and ethanol extracts from the mycelium. Antibacterial activity was assessed using the broth microdilution method against Gram-positive and Gram-negative bacteria to determine the minimum inhibitory concentration (MIC). Antifungal activity was evaluated by the agar diffusion method.
Results. Medium composition significantly affected biomass accumulation (ranging from 3.6 to 15.45 g/L) and extract yields (ranging from 40.5 to 184.5 mg/L). The highest antibacterial activity was observed in the extract obtained on the medium with glucose and yeast extract, showing an MIC of 320 µg/mL against Staphylococcus haemolyticus 585. The extracts demonstrated antifungal activity against Candida albicans, Candida auris, Aspergillus brasiliensis, as well as other clinically significant pathogenic fungi.
Conclusion. The qualitative composition of the nutrient medium allows for the targeted regulation of the antimicrobial activity of S. hirsutum extracts. To obtain extracts with high antibacterial and antifungal activity, it is advisable to use glucose and yeast extract as the carbon and nitrogen sources, respectively. Media with molasses provide the highest yield of submerged biomass. The obtained results provide the basis for the development of biotechnology for producing antimicrobial preparations based on S. hirsutum metabolites.
Background. The work presents the results of a study of new phenylpyrazolotriazine derivatives in order to establish their potential use as anticancer agents, including for chemotherapy of metastatic breast cancer. The relevance of the work is due to the widespread prevalence of oncological diseases and high breast cancer mortality, which dictate the need for the continuous development of new antitumor drugs.
The aim of the study. Screening of the antitumor potential of four new phenylpyrazolotriazine derivatives by testing their cytotoxic (CTA) and cytostatic (CSA) activity on breast cancer cell cultures.
Materials and methods. The base methods used in this study are the culturing of MCF-7, MDAMB231, BT474, and MCF-10a cells, as well as determining the CTA and CSA activity of four new phenylpyrazolotriazine derivatives at concentrations from 0.25 to 10.0 mM/L.
Results. For the MCF-7 culture, the maximum cell viability inhibition of the comparison drug temozolomide was equal to 2.44 and the concentration causing 50% cell death (IC₅₀) was 6.81 mM/L; for other cultures, CTA indicators were lower. Phenylpyrazolotriazine 3 demonstrated lower activity compared to temozolomide, IC₅₀ was not achieved in most cases. This derivative has been classified as a compound with low CTA and moderate CSA. Phenylpyrazolotriazines 1 and 4 showed higher activity than the comparison drug and were classified as compounds with low or moderate CTA and moderate CSA. Finally, phenylpyrazolotriazine 2 with a maximum cell viability inhibition of 3.70 and IC₅₀ of 1.66 mM/L showed the highest values of CTA and CSA.
Conclusion. According to the results of the in vitro study, four new phenylpyrazolotriazine derivatives can be evaluated in ascending order of the CTA and CSA combination: phenylpyrazolotriazine 3 ˂ temozolomide ˂ phenylpyrazolotriazines 1 and 4 ˂ phenylpyrazolotriazine 2. Thus, 3-(3'-Phenyl-4'methoxycarbonyl-isoxazolyl)-7-(p-tolyl)-pyrazolo[5,1-c][1,2,4]triazine (phenylpyrazolotriazine 2) is the undisputed leader in the tested series of new imidazotriazine derivatives and is recommended for further preclinical trials.
The aim was to study the inhibitory and bactericidal activity against bacteria of different systematic groups in vitro, as well as the anti-inflammatory activity of the leukocyte peptide complex in a model experiment of carrageenan edema.
Material and Methods. Leukocyte protein-peptide complex was obtained by ultrasound treatment of healthy donors' blood leukocytes with subsequent fractionation via high-performance liquid chromatography. Antibacterial activity of the isolated fraction was determined using the twofold dilution method. Anti-inflammatory activity was studied on the model of acute carrageenin edema caused by subplantar injection of carrageenin solution into the hind paw of white nonlinear rats.
Results. The leukocyte peptide complex consisting of peptides with molar mass less than 6.5 kDa demonstrated a pronounced antibacterial activity against Escherichia coli, Mycolicibacterium smegmatis, and Staphylococcus aureus. The minimum inhibitory concentrations of the complex were 0.5, 0.25, and 0.125 mg/mL, respectively. Intraperitoneal administration of leukocyte protein-peptide complex compared to the reference drug (nimesulide) provides a statistically significant inhibition of the inflammatory response, reaching 62.3%. The anti-inflammatory efficacy of the leukocyte protein-peptide complex exceeded that of nimesulide by more than 13%.
Conclusion. The possibility of creating an anti-inflammatory drug with pronounced antibacterial activity based on a peptide complex isolated from human blood leukocytes using a simple, fast, and effective method of ultrasound exposure has been shown.
GUIDELINES FOR PRACTITIONERS
The aim was to study the characteristics of the gut microbiota (GM) in urinary stone disease (urolithiasis) in comparison with healthy volunteers (HV), to identify bacteria whose content changes affect the risk of developing urolithiasis, as well as to establish threshold values for these indicators.
Material and methods. The composition of GM in 35 patients with urolithiasis and 31 healthy volunteers was conducted using the method of gas chromatography-mass spectrometry (GCMS) of fecal samples; subsequent statistical analysis of the obtained results was performed to identify the bacteria whose changes in abundance are associated with the risk of urolithiasis.
Results. In the group of patients with urolithiasis, an increase in the numbers of the following bacteria was noted: Alcaligenes spp. / Klebsiella spp., C. hystolyticum / S. pneumonia, Bacillus cereus, Clostridium perfringens, Clostridium difficile. The GM composition in patients with urolithiasis differed depending on the type of urinary stones: in case of oxalate urolithiasis, there was an increase of opportunistic bacteria Peptostreptococcus anaerobius 18623 and Clostridium perfringens, while in uric acid urolithiasis, a decrease in healthy microbiota representatives Propionibacterium jensenii and Clostridium propionicum was observed. An increase in the number of Peptostreptococcus anaerobius 18623 over 37996×105 cells/g and/or a decrease in the number of Clostridium propionicum to fewer than 2178×105 cells/g were associated with increased risk of urolithiasis. Conclusions. The GM of patients with urolithiasis significantly differs from the GM of healthy volunteers. The composition of GM varies depending on the type of urinary stones. An increase in the amount of Peptostreptococcus anaerobius 18623 and/or a decrease in the amount of Clostridium propionicum in GM can be considered as potential risk factors of urolithiasis.
The aim of the study was to evaluate the effectiveness of including the drug cytoflavin in the complex rehabilitation of patients after radiofrequency catheter ablation.
Material and methods. The results of outpatient treatment of 112 patients after radiofrequency ablation associated with paroxysmal atrial fibrillation were analyzed. The subjects were randomized into two groups: in group 1 (main, N=59), in addition to standard therapy, the drug Cytoflavin (inosine+nicotinamide+riboflavin+succinic acid) was prescribed according to a two-step regimen: 20.0 ml intravenously by drip in 200 ml of 0.9% sodium chloride solution for 10 days, then 2 tablets 2 times a day for 20 days. In the 2nd group (comparison, N=53), in addition to standard therapy, patients received a ten-day course of daily intravenous drip infusions of 10 ml of placebo diluted in 200.0 ml of 0.9% sodium chloride solution, followed by eleutherococcus extract 100 mg, 2 tablets 2 times a day before meals, and combination preparations of B vitamins in the dosage recommended by the manufacturer. The psychoemotional state of patients (using the Hospital Anxiety and Depression Scale (HADS)) and quality of life with a point assessment of subjective characteristics (using the multi-purpose MOS SF-36 questionnaire) were studied dynamically (before and after rehabilitation).
Results. The inclusion of cytoflavin in the regimens contributed to a more significant reduction in the severity of anxiety compared to the patients in the control group — 5.3 times, while in the control group the reduction amounted to only 1.75 times (P˂0.05), and signs of depression — 2 and 1.5 times, respectively (P˂0.05). The effectiveness of the presented outpatient treatment regimen was confirmed by the positive dynamics of patients' quality of life indicators on all SF-36 scales: the initial level of physical health of patients in group 1 increased from 69.8±13.2 to 85.6±4.2 (P˂0.05), and mental health — from 62.3±8.4 to 78.4±3.2 (P˂0.05), while in the comparison group — from 68.7±13.4 to 81.2±3.2 (P˂0.05) and from 61.4±7.3 to 71.3±2.2 (P˂0.05), respectively.
Conclusion. The study showns the effectiveness of using Cytoflavin in the early restorative treatment of patients after radiofrequency catheter ablation, which is manifested by a more pronounced improvement in the psychoemotional state and quality of life of these patients.
GUIDELINES FOR PRACTITIONERS
Relevance. Hospital-acquired pneumonia (HAP), particularly ventilator-associated pneumonia (VAP), remains one of the leading infectious complications in intensive care units in the context of increasing antimicrobial resistance and is associated with high mortality rates. The aim of the study was to present current approaches to the diagnosis of HAP with emphasis on clinical, laboratory, radiological, and ultrasound methods, as well as integrated scoring systems and rapid diagnostic tests.
Methods. The study analyzes Russian and international clinical guidelines, original studies, and systematic reviews published between 1991 and 2025, focusing on the epidemiology, diagnosis, and differential diagnosis of HAP. Special attention was given to imaging methods (chest X-ray, computed tomography, lung ultrasound), biomarkers, and molecular technologies for rapid pathogen identification.
Results. HAP diagnosis is based on a combination of clinical and laboratory findings and imaging methods, but their sensitivity and specificity remain limited. The CPIS score is still the most widely used, yet it lacks sufficient accuracy. New integrated scores (CEPPIS, VPLUS) and ultrasound-based protocols improve diagnostic reliability, while molecular rapid tests enable early detection of pathogens, their resistance mechanisms, and timely initiation of adequate etiotropic antibiotic therapy.
Conclusion. Improving diagnostic accuracy of HAP is possible through integration of clinical data, instrumental methods, and modern rapid tests. Lung ultrasound combined with biomarkers and molecular techniques represents a promising direction for a personalized approach to disease management.
DRUG STANDARDIZATION AND QUALITY CONTROL
Background. Capreomycin is a multicomponent natural antibiotic and is a mixture of 4 related compounds (capreomycins IA, IB, IIA, and IIB). Quality control of capreomycin medicinal preparations by active substance is carried out according to the «capreomycin I» indicator, not taking into account the individual contributions of capreomycins IA and IB. With this approach, no correlation is observed between the total content of capreomycin IA and IB components determined by chromatographic methods and capreomycin activity determined by microbiological methods. WHO recommended studying the feasibility of introducing the ratio between capreomycin IA and IB in the specifications for capreomycin preparations.
The aim of the study was to develop a technique for quantitative estimation of the capreomycin IA and IB content ratio in the drug preparation Capreomycin sulphate using NMR spectroscopy.
Objects of the study. Capreomycin sulphate standard samples, pharmaceutical preparations Capreomycin, powder for preparation of solutions for intravenous and intramuscular administration from various manufacturers. Material and methods: NMR spectroscopy, HPLC.
Results. Structural interpretation of 1H and 13C spectra of capreomycin sulfate in D₂O solution was performed. 13C spectra revealed characteristic signals of capreomycin IA and IB, which did not overlap with the signals of minor capreomycin components and related impurities. On the basis of normalized integral intensities, the ratio of mole fractions of capreomycin IA and IB (IA/IB) was calculated. The results of IA/IB measurement using 13C NMR and HPLC practically coincide when the chromatographic conditions allow separating the signals of the major and impurity components of capreomycin on the chromatogram.
REVIEWS
Antibiotics, which evolved as a chemical weapon of some bacteria against others, are primarily known for their microbicidal and/or bacteriostatic effects; however, they also have numerous pleiotropic effects: anti-amyloid, anti-inflammatory, antioxidant, and anti-apoptotic. This review considers antibiotics with a translation-inhibiting mechanism of action, primarily tetracyclines, in the context of their non-antibiotic biological aspect, namely, the possibilities of supportive therapy for neurodegenerative diseases, as well as their antimitochondrial action and the mediated effect of aging cancellation.
Lyme disease (LD), or tick-borne borreliosis, annually affects thousands of people in different parts of the world, primarily the United States and Europe. At the same time, the issues of rational antimicrobial therapy of LD, which is aimed at achieving the desired effect while minimizing toxicity and adverse events, are becoming increasingly relevant. This review analyzes the literature data on the possibility of conducting short courses of antibiotic therapy for LD. The urgency of the problem under consideration necessitates further studies aimed at assessing treatment duration, with sufficient sample sizes and clearly defined treatment outcomes.
Cephalosporins are important agents in the treatment of a wide range of bacterial infections. Since the isolation of their first representative in 1945, they have become widespread both in local treatment of infections and in complex treatment in hospitals. A special place among cephalosporins is occupied by a representative of their third generation, cefixime. It is not only the first semi-synthetic, orally active, and effective antibiotic, but it also demonstrates remarkable antibacterial activity against a wide range of bacterial strains. The choice of dosage form for oral administration of cefixime remains relevant to this day. A rather modest range of cephalosporin antibiotics in capsule form and cefixime in oral forms is sold on the Russian market in 2025. Despite the potential material costs in production, capsules containing cefixime as an active pharmaceutical substance may be eligible candidates for the treatment of a wide range of bacterial infections due to a number of advantages of this particular dosage form. The review presents brief information about cephalosporins (history of discovery, classification, spectrum of action, scheme of semi-synthetic synthesis, etc.), as well as advantages and disadvantages of oral capsule dosage form. Also, the state of the Russian pharmaceutical market regarding registered capsule dosage forms based on cephalosporins and, in general, oral dosage forms based on a representative of class 3 cephalosporins, cefixime, had been analyzed.














































