Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens

Abstract

Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy's efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages as a treatment option for Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis infection models. It also illustrates appropriate phage selection criteria, as well as recommendations for successful therapy. Published studies included in this review were identified through EMBASE, PubMed, and Web of Science databases and were published in the years between 2010 to 2020. Among 1082 identified articles, 29 studies were selected using specific inclusion and exclusion criteria and evaluated. Most studies (93.1%) showed high efficacy and safety for the tested phages, and a few studies also examined the effect of phage therapy combined with antibiotics (17.2%) and resistance development (27.6%). Further clinical studies, phage host identification, and regulatory processes are required to evaluate phage therapy's safety and efficacy and advance their clinical use.

Keywords: E. faecalis; K. pneumoniae; P. aeruginosa; S. aureus; combination therapy; phage therapy.

Figure 1

Flow diagram of search process. The diagram is divided into three steps; identification, screening, and articles included. Search terms and date range were identified in the computer search box. Eligible studies included in vivo, and in vitro models infected with one of the four selected pathogens and were treated with bacteriophage specific to the pathogen. All clinical trials were excluded. Abbreviations; n: number of studies.

Figure 2

Schematic illustration of selected bacteriophage targets available in the literature. The figure is divided into four columns and five rows. The column headings represent the pathogens, while the rows heading represent targets in/on bacteria required for phage activity, effect of these targets of phage therapy, available methods to improve target to prevent/overcome phage resistance development, the outcome observed if the improved method is used, and citation. Abbreviations: WAT GlcNac: wall teichoic acid N-acetylglucosamine; WcaJ enzyme: undecaprenyl-phosphate glycosyltransferase; Epa: enterococcal polysaccharide antigen. See Refs. [55,56,57,58].