Phage Therapy as an Alternative Strategy Against Pseudomonas aeruginosa: A Narrative Review of Preclinical and Clinical Evidence.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen and one of the main causes of nosocomial infections. This pathogen affects immunocompromised individuals such as patients with chronic wounds or cystic fibrosis. Its capacity to evade antimicrobial therapies through resistance mechanisms has resulted in widespread prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains. We searched three databases (PubMed/Medline, Scopus, and Web of Science) for articles evaluating the effects of phage administration in the management of P. aeruginosa infections in animals and humans. We analyzed the main characteristics of the interventions, the coverage of different bacterial strains, and discussed possible gaps in the evidence available in the last 10 years. Literature shows strong evidence that the use of phage therapy for several clinical conditions in humans and animal models is a safe and effective intervention for infections caused by MDR/XDR/PDR P. aeruginosa. Despite its therapeutic potential, phage therapy still faces several limitations such as lack of standardized dosing protocols, inconsistent endotoxin quantification, and limited regulatory frameworks. Future guidelines should focus on the regulation and validation of phage therapy in clinical practice, after overcoming the limitations currently identified. Further studies should ensure the standardization of phage production and the validation of delivery systems and routes of administration. Conducting multicenter clinical trials can contribute to the clinical implementation of phage therapy in countries where it is not yet regulated.