Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug ResistanceKlebsiella pneumoniaein Mice

Abstract

Multidrug-resistant Klebsiella pneumoniae (MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growth in vitro with a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level of K. pneumoniae burden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effect in vitro and in vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistant K. pneumoniae.

Phages and Immunomodulation

“…In contrast, none of those cytokines were increased in mice fed with phage T7 [46]. Phages can also inhibit tissue expression of inflammatory cytokines, as reported by Cao et al They used a sublethal pneumonia model and discovered that phagetreated mice exhibited lower levels of inflammatory cytokines in their lungs [47]. It has been postulated that data suggesting cytokine-inducing ability of phage preparations in vitro and in vivo may be biased by endotoxin contamination of those preparations.…”

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

“…Even though systemic phage dissemination from the airways is probably not very efficient, phages were demonstrated to reach the lungs by inhalation and in most cases they were capable of controlling bacterial infections in the lungs. Inhalation with phages had a life‐saving effect in hemorrhagic pneumonia caused by Pseudomonas aeruginosa in a mink model, Acinetobacter baumannii ‐ or Klebsiella pneumoniae ‐induced pneumonia in mice, and fatal E. coli respiratory infection in chickens . Experimental pneumonia in mice was reduced by phage therapy in a time‐ and dose‐dependent manner .…”

Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

“…Due to their unique mechanism of antibacterial action phages are able to combat bacteria irrespectively to bacterial antibiotic resistance profiles (Chan et al, 2013, 2016; Cao et al, 2015; Oduor et al, 2016; Ozkan et al, 2016). Phages use specific receptors at the surface of bacterial cells to recognize targeted bacteria (Rakhuba et al, 2010).…”