A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans

Bacteriophages (phages) may constitute a natural, safe, and effective strategy to prevent and control multidrug-resistant organisms (MDROs), and ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens in particular. Few clinical studies have assessed the safety and efficacy of phages in patients infected with MDROs. This systematic review summarizes and critically evaluates published studies of phages in clinical practice and presents the appropriate phage selection criteria, as well as recommendations for clinicians and scientists for a successful therapy. Articles were identified through a search of the PubMed, Ovid, EMBASE, and Cochrane Library databases. Among 1102 articles and abstracts, 30 studies were selected and evaluated using selective inclusion criteria, phage criteria, and study characteristics. Most studies showed efficacy (87%) and safety (67%) of the tested phages, but few studies examined phage resistance (35%). Clinical studies and regulatory changes are needed to determine the safety and efficacy of phages and to advance their use in patients with MDRO infections.