Topically applied bacteriophage to control multi-drug resistant Pseudomonas aeruginosa-infected wounds in a New Zealand rabbit model

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a widespread, gram-negative, pathogenic bacterium that causes serious internal and external infections in humans and other animals. The increasing antibiotic resistance has complicated bacterial infection treatment, and current antibiotic therapies cannot cure all infections. Owing to this, bacteriophages (phages) have regained attention as potential therapeutics for bacterial infections. In this study, the phage “PaVOA” was isolated from hospital sewage and characterized. Next, a New Zealand rabbit skin infection model was used to determine the therapeutic efficacy of PaVOA as compared to a phage cocktail or the cephalosporin antibiotic ceftriaxone. Characterization results demonstrated that phage PaVOA belongs to the Myoviridae family, has a double-stranded DNA genome, is resistant to low temperatures (−20°C), is most optimal at 40°C, has good acid–base tolerance, and remains stable for 30 min under 20 W ultraviolet (UV) intensity. The optimal multiplicity of infection of PaVOA was 0.1, and a one-step growth curve showed a short latency period (10 min), thus demonstrating its ability to rapidly kill bacteria. Furthermore, the addition of calcium (Ca) and magnesium (Mg) ions significantly increased the PaVOA titer. An in vivo phage kinetic curve showed that PaVOA was rapidly inactivated within the blood of New Zealand rabbits (undetectable after 12 h), and no animals died due to phage treatment. Wound healing studies showed that the phage cocktail induced a high healing rate and an acceleration of the skin remodeling process, and was more efficacious than ceftriaxone. Therefore, phage cocktail therapy represents a novel therapeutic approach in the treatment of traumatic skin infections caused by multi-drug resistant P. aeruginosa.

The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice

“…Several studies have evaluated the efficacy of topical bacteriophages in treating burn wounds, and the results have been promising [ [42] , [43] , [44] ]. There is also a study showed that the topically applied bacteriophage cocktail could reduce the bacterial load significantly in multi-drug resistant P. aeruginosa (MDR-PA) infected wounds in the New Zealand rabbit model, resulting in improved wound healing outcomes [ 45 ]. Following this, we isolated the lytic bacteriophages of P. aeruginosa and used them topically against this pathogenic bacterium.…”

Bioprospecting the Skin Microbiome: Advances in Therapeutics and Personal Care Products

“…Multiple bacteriophages are reportedly being explored for phage therapy for various manifestations of skin-associated pathogens. Support for clinical research comes from phage therapy success for skin infections of Mycobacterium chelonae and multiple-drug resistant (MDR) Pseudomonas aeruginosa [ 104 , 105 ]. Topical bacteriophage therapy targeting C. acnes has advanced to phase I clinical trials after displaying efficacy in reducing C. acnes abundance without significant safety concerns [ 106 ].…”

Characterization and genomic analysis of a broad-spectrum lytic phage HZ2201 and its antibiofilm efficacy against Pseudomonas aeruginosa

“…Wang et al. constructed a New Zealand rabbit skin infection model and treated it with a Pseudomonas aeruginosa phage, and found that phage treatment of skin infections was significantly more effective than antibiotic treatment, indicating that phages have great potential in treating skin infections ( Wang et al., 2022 ). In another clinical study, the authors combined phages with antibiotics to successfully treat MDR-PA infections caused after liver transplantation in young children, which provides new insights for the treatment of post-surgical bacterial infections ( Van Nieuwenhuyse et al., 2022 ).…”