Bacteriophage To Overcome Nosocomial Infections Associated With Multidrug-resistant Bacterial Pathogens A Systematic Review And Meta-analysis

Background :rnAntibiotic-resistant pathogens constitute an important and growing threat to public health. The emergencernof multidrug-resistant organisms in nosocomial infections is being highly associated with frequent causesrnof morbidity and mortality in patients. In view of the growing threat of antibiotic resistance, the WorldrnHealth Organization has warned for a return into a pre-antibiotic era. The antibiotic crisis has rekindled therninterest in phage therapy approaches that were developed in Eastern Europe, one of the alternatives recentlyrnregaining interest, which was first introduced by Felix d’Herelle at the beginning of the 20th century. rnObjectives: rnThe main objective of this study was to quantify the pooled therapeutic efficacy and safety status ofrnBacteriophage for bio-control of nosocomial infections associated with but not limited to multidrugresistantrnrn“Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacterrnbaumannii, Pseudomonas aeruginosa, Enterobacter species pathogens” (ESKAPE) bacteria in humansrnbased on available studies. rnMethods: rnIn this review, the study protocol was submitted for registration in PROSPERO and eligible studiesrninvolved prospective interventional studies with patients infected with one or all the six pathogens and whornwere treated with bacteriophages or a phage cocktail specific to the pathogen, regardless of the year ofrnpublication up to December 2019. We searched the PubMed/Medline, Embase and Web of sciencerndatabases for articles on phage therapy. 14 studies were included in the review with six considered for metaanalysisrnrnto quantify the therapeutic efficacy based on available studies on phages that may prevent andrneradicate infections associated with but not limited to “Enterococcus faecium, Staphylococcus aureus,rnKlebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter speciesrnpathogens” in humans for control of Nosocomial infections. In addition current gaps in the literature thatrnwould prompt further research on bacteriophage in the fight against antibiotic resistance were identified. rnResults: rnPhage safety was sufficiently reported in that all studies showed no side effects related to phagernadministration. A moderate pooled effect size was obtained with a high evidence of heterogeneity (SMD =rn0.52, (C.I. = -1.18, 2.22), P< 0.00001, Irn2rn = 96%). Most studies were pointing towards the overall effect sizernwith one study regarded as an outlier. However, there was no significant treatment difference between therntwo therapeutic arms as observed in the forest plots. Moreover, the therapeutic efficacy of bacteriophage is inconclusive due to the few available randomized phage studies found with even few sample sizes. Hencernmore streamlined phage clinical trials with large sample sizes are needed to detect sufficient effect sizes.

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