Phagebiotics in treatment and prophylaxis of healthcare-associated infections

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.

KEYWORDS:

• Acinetobacter baumannii
• healthcare-associated infections
• Klebsiella pneumoniae
• MRSA
• phagebiotics
• Pseudomonas aeruginosa

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Notes

* The whole-genome sequences of all 8 phages have been deposited in the NCBI nucleotide sequence database under the following GenBank assession numbers: AP22 - HE806280.1; AM24 - KY000079; KPV15 - KY000080; KPV811 - KY000081; PA5 - KY000082; PA10 - KY000083; SCH1 - KY000084; SCH111 - KY000085.