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Eksperimental'naya i klinicheskaya urologiya

Possibilities for improving the therapeutic activity of bacteriophage preparations

Number №4, 2023 - page 156-163
DOI: 10.29188/2222-8543-2023-16-4-156-163
For citation: Perepanova T.S., Kazachenko A.V., Malova Yu.A., Khazan P.L., Nazirov M.R., Pseunova D.R., Apolikhin O.I., Kaprin A.D. Possibilities for improving the therapeutic activity of bacteriophage preparations. Experimental and Clinical Urology 2023;16(4):156-163; https://doi.org/10.29188/2222-8543-2023-16-4-156-163
Perepanova T.S. Kazachenko A.V. Malova Yu.A. Hazan P.L. Nazirov M.R. Pseunova D.R. Apolihin O.I. Kaprin A.D.
Information about authors:
  • Perepanova T.S. – Dr. Sci., professor, Head of the Department of infectious and inflammatory diseases and clinical pharmacology N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI Author ID 98934, https://orcid.org/0000‑0002‑2877‑0029
  • Kazachenko A.V. – Dr. Sci., Deputy Director for Medical Work of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation, professor of the Department of Urology and Operative Nephrology with a course of oncourology of RUDN University; Moscow, Russia; RSCI Author ID 334714, https://orcid.org/0000‑0003‑3198‑5933
  • Malova Yu.A. – specialist of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology; Moscow, Russia; RSCI Author ID 1023068
  • Khazan P.L. – PhD, Senior Researcher group of infectious and inflammatory diseases and clinical pharmacology, of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation; Moscow, Russia; RSCI Author ID 699146
  • Nazirov M.R. – Head of the Clinical Diagnostic Laboratory of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia; RSCI AuthorID 810306
  • Pseunova D.R. – doctor-bacteriologist of the clinical diagnostic laboratory of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia
  • Apolikhin O.I. – Dr. Sci., professor, сor.-member of RAS, director of N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation; Moscow, Russia; RSCI Author ID 683661; https://orcid.org/0000‑0003‑0206‑043X
  • Kaprin A.D. – Dr. Sci., professor, academician of RAS, general director of the National Medical Research Centre of Radiology of Ministry of health of Russian Federation, director of P.A. Herzen Institution, Head of Department of Oncology and Radiology named after V.P. Kharchenko of RUDN University; Moscow, Russia; RSCI Author ID 96775; https://orcid.org/0000‑0001‑8784‑8415
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Introduction. Growth of urological infection caused by antibiotic-resistant pathogens require the search for alternative antimicrobial treatments. Bacteriophage (phage) preparations are currently the only viable alternative to antibiotics. The therapeutic effect of bacteriophages is significantly different from antibiotics, making them active against multidrug-resistant bacteria. Bacteriophage therapy - creation of viral infection in bacteria. However, the effectiveness of treatment depends primarily on the quality of commercial bacteriophage preparations. The collections of bacteriophages is constantly updated in industrial production but in order to increase the lytic activity of bacteriophage preparations to the uropathogens of our clinic, it is necessary to constantly determine the sensitivity of the main pathogens of infection to commercial bacteriophage preparations and regularly update (adapting) commercial phage preparations.

Purpose. Improve the lytic activity of commercial bacteriophage preparations; adapt them to the pathogens of a particular hospital.

Materials and methods. From 2017 to the present, at the Research Institute of Urology and Interventional Radiology named after N.A. Lopatkin, a branch of the National Medical Research Center of Radiology of the Ministry of Health of Russia (hereinafter referred to as the Research Institute of Urology), regular work has been carried out to update (adapt) commercial bacteriophage preparations to the uropathogens. The most problematic multidrug-resistant microorganisms -pathogens of urological infection- were send for phage production. Wastewater from the clinical building of the Institute of Urology was also send to phage production.

Results. Analysis of data on antibiotic- and phage resistance of uropathogens for 2022 indicates multi-resistance of microorganisms in our clinic. Antibiotic resistance phenotypes of pathogens in the urine of outpatients and inpatients have been defined as a whole: extended-spectrum beta-lactamases (ESBLs): 5.3-1.6%, respectively (E.coli-38%; Klebsiella spp. 62%; Proteus mir. 38,5%; P. aeruginosa -61%) methicillin-resistant Staphylococcus aureus (MRSA) 9.9-8.4%; carbapenem-resistant enterobacteria (CRE) 1.7-4.5% (E.coli-1.9%; Klebsiella spp. 29%); Proteus mir. 5%; P. aeruginosa -47.7%) and bacteriophage resistance of uropathogens 4-16.3% . After adaptation of bacteriophage preparations, an increase in their lytic activity to specific microorganisms was obtained by an average of 14% (from 78% to 92%), and an increase in the lytic activity of Sextafag, a polyvalent piobacteriophage containing phagolysate filtrates of Staphylococcus spp., Streptococcus spp., Proteus (P. vulgaris, P. mirabilis), Pseudomonas aeruginosa, Klebsiella pneumonia, E. coli by 16% (48% to 64%)

Conclusions. To improve the lytic activity of bacteriophage preparations and improve the effectiveness of urological infection treatment, it is necessary to constantly update the composition of the cocktail of commercial bacteriophage preparations with phages from hospital wastewater and adapt them to freshly isolated microorganisms from urological patients.

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Keywords: antibiotic resistance; bacteriophage preparations; bacteriophage therapy of urological infection; improvement of the lytic activity of bacteriophage preparations