The battle against antibiotic-resistant bacteria with bacteriophages has until recently been an avenue looked at as an option. In the midst of Covid-19, it was observed that hospitalized patients placed on the ventilators, had developed pneumonia, serious cases of highly resistant bacterial infections that resulted in the patient’s death. Options against AMR have now no longer become a concern of the near future, but one to address in the present across several industries.
The Federal Service for the Oversight of Consumer Protection and Welfare in Russia has recently taken on a hands-on approach towards the urgent need of addressing the problem against antibiotic-resistant bacteria with bacteriophages. Russia is currently developing an intensive programme including;
- Prevention of food infections based on phages
- Designing phage-containing agents for decontamination of semi-finished food product
- Disinfection for processing instruments and premises of the medical prophylactic organization
- Set measures for bacteriophage prevention of infections associated with the provision of medical care
Programme against antibiotic-resistant bacteria with bacteriophages
Back in February 2018, on the basis of GN Gabrichevsky Institute for Epidemiology and Microbiology, the Federal Scientific and Methodological Center organized the study and identification of bacteriophages. Its main activity was to develop and introduce a new series of antimicrobial agents based on bacteriophages, regulations for their use in numerous fields across the health care system, veterinary health, plant health, food, and even the cosmetics industry. The aim was to also improve the methods for prevention and treatment of infection with the use of phages.
The development also required new algorithms for phage therapy and the use of phage as a means of prophylaxis in human infectious diseases. This initial study was on the topic of “Development of personalized therapy for patients suffering from infections associated with the provision of medical care”. It is currently being completed on the basis of two research centers: N.N. Burdenko National Medical Research Center for Neurosurgery and the Vorohobov’s City Clinical Hospital No. 67.
Individualized phage therapy for ICU patients
It was observed that there were several elements that were needed to result in the success of individualized bacteriophage therapy for ICU patients:
- Determination of the sensitivity of target bacteria that were isolated from the patient to individual strains of virulent phages.
- Evaluation of the level of neutralizing IgG antibodies in the patient’s serum to the phages that were selected for the therapy.
- Taking into account the localization of the infectious process and the pharmacokinetic properties of the selected phages, the selection of the route of administration and the corresponding dosage form, to ensure the optimum delivery of an effective amount of phages to the infection site.
As a result, the developed personalized algorithm for the selection of bacteriophages, the effectiveness of the therapy for antibiotic-resistant bacteria increased by 50%, averaging more than 80% in the clinics participating in the study.
Forms of bacteriophage products
Preliminary consultations with manufacturers of immunobiological preparations suggest the possibility of registering and subsequent serial production of new dosage forms of bacteriophage preparations develop at the center; suppositories, eye, and ear drops, metered aerosols for inhalation, gels, capsules (including those with liquid content).
A pilot programme is currently looking into the production of highly purified phage lysates with a high titer of bacteriophage particles, developed within the framework of the proposed cooperation. This will open new possibilities to modernize the technological cycle of the existing production lines towards an increase in the production of bacteriophage preparations with a reduction in cost.
Studies are also being looked at for rapid assessment of the sensitivity of target bacteria to the currently available bacteriophage preparations. This is aimed to speed up to the current testing system in order to deliver a faster result in the accuracy of in vitro selection of the bacteriophage preparation necessary for a patient, thereby, increasing the effectiveness of the phage therapy for the patient.
Monitoring and collection of phages
The Federal Scientific and Methodological Center has been monitoring the sensitivity of the strains of pathogenic microorganisms to the existing bacteriophage preparations. This assessment of phage sensitivity was carried out within the framework of more than 5000 complex analyses of the intestinal microflora and confirms the tendency for an increase in the percentage of lysed bacterial culture of opportunistic microflora of the gastrointestinal tract to the drug produced by various manufacturers.
Preliminary agreements have been made with a number of domestic and foreign manufacturers and research centers of the formation of a single collection of a starter culture of bacteriophages with the aim of subsequent creation on their basis of the World Bank of Phages. This museum’s deposit procedure has been developed at the institute, will provide all bacteriophages used for therapeutic purposes with the necessary phenotypic and molecular genetic characteristics. This will allow them to confirm their safety and guarantee patent protection for newly developed compounds.
Bacteriophages against antibiotic-resistant bacteria across various industries
The framework of the veterinary direction and crop production is associated primarily with the in vivo reorganization of farm animals and cultivated plants. The GN Gabrichevsky Institute for Epidemiology and Microbiology in cooperation with the Moscow State Academy of Veterinary Medicine and Biotechnology of K.I. Scriabin, P.A. Stolypin Ulyanovsk State Agrarian University and the Department of Bacteriology and Immunology-Immunobiology Research Program at the University of Helsinki in Finland has developed and passed clinical trials at agricultural enterprises and registered a number of bacteriophage compositions in the form of bio-disinfectants for veterinary use.
Amongst these is:
- A cocktail for poultry based on Salmonella (serotypes Infantis, Enteritidis, and Typhimurium), Escherichia coli and Campylobacterjejuni
- A polyvalent bacteriophage preparation for the vital rehabilitation of fish
- Two monovalent compositions (against MRSA strains) and Clostridium difficile in pig breeding
- For the prevention of developing potato bread disease, a bivalent bacteriophage preparation containing bacteriophages against Bacillus subtilis and Bacillus mesentericus has been developed
Innovative algorithms have been developed for the use of phages within the food industry, mainly aimed towards the decontamination and extension of product shelf life. The Federal Service for the Oversight of Consumer Protection and Welfare has developed and successfully tested at meat and fish processing plants, resulting in the reduction of the likelihood of acute intestinal and food toxic infections with the absence of chemicals and physical methods of processing semi-finished products.
Beyond industry use
The employees at the center are actively involved in developing specialized educational programmes for higher education and additional professional programmes, including a continuous medical and pharmaceutical education that was organized by G.N. Gabrichevsky Moscow Scientific Research Institute of Epidemiology and Microbiology and Moscow State University of Medicine and Dentistry A.I. Evdokimova, back in 2016 named as “Clinical Microbiology and Phage Therapy” under the guidance of Professor V.A. Alyoshkina. The topic on phage therapy, phage prophylaxis, clinical and laboratory diagnostics of infectious diseases using phages, covers a wide contingent of students from bacteriologists and medical doctors.
To contribute towards the raising of awareness of bacteriophages amongst the Russian specialists, more attention is being placed on international cooperation in the development of new antimicrobial agents based on bacteriophages. The Federal Service for the Oversight of Consumer Protection and Welfare holds a specialized scientific and practical conference, once every two years, with international participation; “Bacteriophages: theoretical and practical aspects of the application in medicine, veterinary and food industry “.