Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics.

The work is devoted to the organization of postcovid rehabilitation by developing a strategy of adative phage therapy, which is the production and application of a complex of bacteriophages for a specific medical institution/department based on an up-to-date collection of hospital bacterial strains isolated from the biomaterial of patients of the same institution. Bacteriophages were actively used in the world in the 20-40s of the twentieth century in various fields of medicine, but the rapid development of phage resistance in each individual case limited their use. The use of complex preparations of bacteriophages from the collection pure lines of bacteriophages of the SPC "MikroMir" a set of various phages aimed at restoring the human microbiome after a covid infection allowed to sharply reduce the number of antibiotics used in intensive care units and reduce antibiotic resistance with proven safety of phage therapy.