Fucoidans, sulfated polysaccharides extracted from brown algae (Phaeophyceae), have a wide spectrum of bioactivity. Studies of molecular structures of fucoidans and deciphering of molecular elements' impact on their biological activities are at their active stage. The article shows the role of sulfates and acetyl groups in fucoidan isolated from Fucus evanescens in proinflammatory cytokines production by human heparinized unfractionated peripheral blood cells. Material and Methods. The cells were incubated with native fucoidan (N) and its deacetylated (deA), partially desulfated (deS), and both deacetylated and partially desulfated (deAdeS) derivatives (100 μg/mL). Cytokine concentrations were determined in cell supernatants by ELISA in a 'sandwich' modification with commercial kits. Results. Incubation with N fucoidan led to an increase of IL-6, TNF-α, IL-8 levels in supernatants. Partial removal of sulfate groups cancelled or decreased stimulating effect for IL-6, TNF-α, cytokines, but not for IL-8. deAc fucoidan action was comparable with N polysaccharide. Native polysaccharide and its chemically modified derivatives did not change IFN-γ и IL-10 cytokine production. Conclusion. The obtained results suggest that sulfates have a significant role in cytokine-producing properties of fucoidan extracted from brown algae F.evanescens.

The growing threat of proliferation of biofilm-forming hospital strains of coagulase-negative staphylococci resistant to antibiotics determines the need for an urgent search for new effective antibacterial compounds, as well as the development of methods for the combined use of traditional and alternative antibiotics. The article presents the results of a study of the combined effect of the drug «SA» — a new synthetic derivative of the alkaloid isoquinoline and a low-molecular-weight cationic peptide of the lantibiotic family hominin, which inhibits the development of bacterial biofilms of the clinical strain of Staphylococcus haemolyticus and its vancomycin-resistant isolates. It was found that combinations of these compounds have a synergistic effect that suppresses the formation of biofilms of both studied strains of staphylococci at reduced concentrations of these antibacterial compounds.

The in vitro and in vivo activity of a phenylacetic acid derivative, diclofenac, was studied against V.cholerae O1 El Tor strains and biofilms formed by them. In the presence of a subinhibitory concentration of diclofenac (250 mg/l), a 4-fold decrease in the values of the minimum inhibitory concentrations of furazolidone and chloramphenicol was found in 30% and 100% of the strains resistant to these drugs, and a significant increase in the diameters of growth inhibition zones around discs with chloramphenicol. furazolidone, streptomycin (for all strains) and doxycycline (for two strains) in comparison with the control. Furazolidone, nalidixic acid, chloramphenicol, streptomycin, to which the infecting strain was resistant, were used in in vivo experiments in combination with diclofenac for the treatment of white mice; in the experimental group the number of surviving animals increased to 80% in comparison with monotherapy with these drugs (50% or less). The subinhibitory concentration of diclofenac did not have a pronounced effect on the antibiotic sensitivity of biofilms. The study using transmission electron microscopy method on the biofilm of the V.cholerae O1 El Tor 19667 strain after exposing it to diclofenac (250 mg/l) for 120 h revealed signs of destruction of the exopolysaccharide matrix. These results indicate the prospects for studying this group of drugs, as well as others in order to develop new ways to overcome bacterial resistance.

The article analyses the results of the study of 169 strains of microorganisms obtained from wound discharge from 132 patients with diabetes mellitus. Staphylococcus spp. bacteria held a leading place among Gram-positive pathogens. Gram-negative pathogens — Escherichia coli, Pseudomonas aeruginosa, etc. — were found less frequently. All isolated cultures were sensitive to levofloxacin and moxifloxacin, and only Acinetobacter spp. (n=2) remained intact (in vitro) after the use of levofloxacin. The intra-arterial route of administration of levofloxacin (500 mg/day) in combination with polyoxidonium (12 mg/day) through a port was used in 16 patients with diabetic foot. In all clinical cases, positive dynamics was noted: subsiding of the inflammatory process, cleansing of the wound from a purulent-necrotic substrate, and early epithelialization of the wound was observed in patients with diabetic foot.

Evaluation of the effectiveness of aminophthalhydroside in the complex treatment of patients with recurrent genital herpes was carried out. The efficacy of the drug was assessed by clinical, biochemical, and immunological criteria. The inclusion of aminophthalhydrazide in the complex therapy of patients with recurrent herpesvirus infection led to an earlier relief of clinical manifestations of the disease, an increase in the relapse period, a decrease in lipid peroxidation products in the blood plasma, an increase in the content of antioxidant defense components, and correction of immunological disorders.

The aim of the work is to study the immunogenicity, tolerability, and clinical efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Material and methods. The study included 61 patients with a confirmed diagnosis of SLE, including 53 women, 8 men, aged 19 to 68 years. The disease activity at the time of vaccination: in 9 patients — high, in 13 — medium, in 34 — low, in 5 — remission. Therapy outline: 59 patients received glucocorticoids (GC) 5–30 mg/day in terms of prednisolone, 45 — hydroxychloroquine (GC), 33 — cytostatics (CS), 22 — genetically engineered biological drugs (GEBD): 11 — rituximab (RTM), 10 — belimumab (BLM). 23-valent polysaccharide pneumococcal vaccine in an amount of 0.5 ml (1 dose) was injected subcutaneously. Follow-up period: 9 patients — 3 months, 52 — 1 year after the vaccination. Patients were examined before vaccination, as well as in 1, 3, and 12 months after the vaccination. Results and discussion. After a year of observation, the number of «responders» to vaccination was 61.5%, «non-responders» — 38.5%. There was a decreased response to vaccine in patients receiving GEBD compared with patients who did not receive GEBD (40% and 75%, respectively), p=0.02. No differences were found against the background of RTM and BLM therapy. Administering GC in a dose exceeding 10 mg/day did not lead to a more significant decrease in response to vaccine compared to other patients. Standard local vaccination reactions of mild to moderate severity were noted in 50.8% of the patients, general reaction of mild severity — in 1 patient (1.6%), hyperergic Arthus-like reaction — in 1 patient (1.6%), the symptoms of which were relieved in 7 days. During the observation period (1 year), not a single case of exacerbation of SLE, reliably associated with the vaccination, was registered, and no new autoimmune phenomena were identified. Clinically positive dynamics was noted in the form of a decrease in the number of episodes of pneumonia, as well as acute and exacerbated chronic bronchitis, sinusitis. Conclusion. Sufficient immunogenicity, good tolerance, and clinical effectiveness of PPV-23 in patients with SLE, incl. those, who received combined immunosuppressive therapy. Further studies are needed in large groups of patients with long follow-up periods.

The resistance of Enterobacterales to carbapenems can be realized by different mechanisms, but the most common one is enzymatic, associated with the production of carbapenemases. Carbapenemases of enterobacteria are characterized by a wide variety; they are represented in three classes of beta-lactamases. The most well-known carbapenemases belong to classes A (KPC, GES enzymes), D (OXA-48), and B (metalloenzymes — NDM, VIM, IMP). Detailed clinical and microbiological characteristics of carbapenemases are given, as well as recommendations for their detection. Carbapenemases are widespread, and the paper discusses the geographical distribution of carbapenemases in different regions of the world; OXA-48 and NDM are the most widely distributed enzymes in Russia. The clinical significance of carbapenemases and risk factors for these infections are discussed, including the following: 1) previous carbapenem therapy; 2) high levels of carbapenemases in the Department; 3) colonization of the intestine with carbapenemase-producing enterobacteria; 4) traveling to regions with a high prevalence of carbapenemases (4th and 5th epidemiological levels). The possibilities of antibacterial therapy of infections caused by carbapenem-resistant enterobacteria are discussed, the clinical and pharmacological characteristics of different antibiotics (ceftazidime/avibactam, aztreonam, carbapenems, polymyxins, tigecycline, fosfomycin), their effectiveness and treatment options are analyzed in detail. Current clinical data showing the effectiveness of ceftazidime/avibactam monotherapy for infections caused by carbapenemase producers OXA-48 and KPC are presented. Practical issues of management of such patients are discussed. Algorithms for empirical and targeted therapy of infections caused by carbapenem-resistant enterobacteria are presented.

The review discusses modern ideas concerning the biofilms of microorganisms. The development phases, structure and components of biofilms are considered as possible antibiotic resistance factors (ARF). Examples of various types of ADB in biofilm bacteria are given. The process of collective regulation through coordination of gene expression in a bacterial population that mediates the specific behavior of cells is considered. Various approaches that affect the components of biofilms have been evaluated in order to reduce their resistance/integrity using a combination of antibacterial drugs and enzymes of various origins. Promising methods for influencing matrix components, signaling molecules, and adhesion factors are recognized. A promising way to increase the effectiveness of the effect of antibiotics on biofilms is the use of hydrolytic enzymes.

The literature data on the frequency and manifestations of neurotoxic effects of a number of antimicrobial drugs on the central and peripheral nervous system are analyzed. The predisposing factors for the development of neurotoxicity and risk groups are identified. The mechanisms of the neurotoxic action of fluoroquinolones, aminoglycosides, oxazolidinones, and a number of anti-tuberculosis drugs are described. Particular attention is paid to anti-tuberculosis drugs due to the need for the complex use of several drugs with a similar safety profile. The necessity of early detection of neurotoxicity of drugs and complex regimens for minimization of side effects, timely correction, and full treatment of patients has been substantiated.