Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

Abstract

Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued.

Keywords

• phage therapy
• effects on the immune system
• activated t lymphocytes
• nk cells
• ifnγ
• ifnα
• antibiotic-resistant pneumonia