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Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Phagebiotics in treatment and prophylaxis of healthcare-associated infections
A V Aleshkin1, O N Ershova2, N V Volozhantsev3
1G. N. Gabrichevsky Research Institute for Epidemiology and Microbiology, Moscow, Russia; Bphage LLC, Moscow, Russia.
Abstract:
We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute K. pneumoniae infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain K. pneumoniae. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 108 pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.
Insights
A novel phagebiotic composition effectively targets multi-drug resistant bacteria like Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. This new therapy shows promise as a safe and effective alternative to antibiotics for treating severe infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Healthcare-associated infections (HAIs) pose a significant threat, often caused by multi-drug resistant (MDR) bacteria.
- Antibiotic resistance necessitates the development of alternative therapeutic strategies.
- Bacteriophages offer a targeted approach to combating bacterial pathogens.
Purpose of the Study:
- To develop and evaluate a novel phagebiotic composition against key bacterial pathogens.
- To assess the safety and efficacy of the phagebiotic in preclinical and clinical settings.
- To explore phage therapy as an alternative to antibiotics for HAIs.
Main Methods:
- Development of a phagebiotic cocktail using 8 virulent bacteriophages targeting Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.
- Characterization of bacteriophages based on lytic activity, plaque morphology, genome sequencing, and DNA restriction profiles.
- Preclinical safety assessment in experimental animals.
- Efficacy evaluation in a murine model of Klebsiella pneumoniae infection.
- Small-scale clinical trial in an intensive care unit setting for HAIs.
Main Results:
- The phagebiotic composition demonstrated broad lytic activity against target pathogens and proved safe in animal studies.
- Significant therapeutic and prophylactic efficacy was observed in a Klebsiella pneumoniae infection model, comparable to ciprofloxacin.
- In a clinical trial, phage therapy reduced bacterial contamination in patients with HAIs from 79% to 21% within 3 days.
- The phagebiotic composition exhibited high therapeutic efficiency against multi-resistant strains.
Conclusions:
- A novel phagebiotic composition was successfully developed, targeting critical Gram-negative and Gram-positive pathogens.
- The phagebiotic is safe and effective, offering a promising alternative to conventional antibiotics for treating HAIs.
- This phage therapy represents a viable strategy to combat antibiotic resistance in clinical settings.
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