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 multiresistant 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 10 8 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.

Identification and Characterization of New Bacteriophages to Control Multidrug-Resistant Pseudomonas aeruginosa Biofilm on Endotracheal Tubes

“…Bacteriophage-coated tubes could be attended to inhibit bacterial adhesion, whereas direct application may be useful in reducing microbial bioburden. Aleshkin et al (2016) reported the intragastric administration of a phage cocktail in patients on mechanical ventilation, aiming for the treatment of acute infections caused by nosocomial pathogens. The authors demonstrated an important reduction in bacterial counts after phage therapy, indicating it as an alternative purpose to antibiotics to treat healthcare-associated infections.…”

“…Recently, new lytic bacteriophages able to control multidrug-resistant P. aeruginosa planktonic cells and associated-biofilm forms were described ( Yuan et al, 2019 ; Adnan et al, 2020 ). Although promising, there are few reports on bacteriophage applicability to control biofilms associated with endotracheal tubes ( Aleshkin et al, 2016 ). Thus, we consider it essential to clarify whether newly isolated bacteriophages can be applied in order to control P. aeruginosa biofilms on the surface of endotracheal tubes.…”

Kaptive Web: user-friendly capsule and lipopolysaccharide serotype prediction forKlebsiellagenomes

“…Increasing rates of antimicrobial resistance, particularly against last-line drugs such as carbapenems, has led to a resurgence of interest in phage and monoclonal antibody therapies and vaccinations targeting K. pneumoniae (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). There is particular interest in targeting the globally distributed MDR clones including CG258 (21)(22)(23)26).…”

“…In particular, the emergence and global dissemination of extended-spectrum beta-lactamase (ESBL) and carbapenemase producing (CP) clones is a major concern and has led to the recognition of K. pneumoniae as an urgent public health threat (14,15). With the lack of new antimicrobial therapies, there has been a resurgence of interest in alternative strategies such as phage therapy (16)(17)(18)(19), monoclonal antibody therapy (20)(21)(22)(23) and vaccination (24)(25)(26). Several therapeutic targets have been suggested, and the polysaccharide capsule (K antigen) and lipopolysaccharide (O antigen) are among the most frequent.…”

Complete Nucleotide Sequence of Klebsiella pneumoniae Bacteriophage vB_KpnM_KpV477

“…In recent years, two clinical problems have been associated with K. pneumoniae , the spread of multidrug-resistant (MDR) strains ( 3 ) and the emergence of hypervirulent (hypermucoviscous) variants belonging mainly to K-1, K-2, K-57, and some other capsule serotypes ( 4 ). Lytic bacteriophages are considered the most accessible and acceptable alternative (additive) to antibiotics against K. pneumoniae infections ( 5 – 7 ).…”