Bacteriophage to overcome Nosocomial Infections Associated with Multidrug-Resistant Bacterial Pathogens: a Systematic Review and Meta-analysis
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Date
2020-06
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Addis Abeba University
Abstract
Background :Antibiotic-resistant pathogens constitute an important and growing threat to public health. The emergenceof multidrug-resistant organisms in nosocomial infections is being highly associated with frequent causesof morbidity and mortality in patients. In view of the growing threat of antibiotic resistance, the WorldHealth Organization has warned for a return into a pre-antibiotic era. The antibiotic crisis has rekindled theinterest in phage therapy approaches that were developed in Eastern Europe, one of thealternatives recentlyregaining interest, which was first introduced by Felix d’Herelle at the beginning of the 20th century.
Objectives: The main objective of this study was to quantify the pooled therapeutic efficacy and safety status of Bacteriophage for bio-control of nosocomial infections associated with but not limited to multidrugresistant“Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacterbaumannii, Pseudomonas aeruginosa, Enterobacter species pathogens” (ESKAPE) bacteria in humansbased on available studies.
Methods: In this review, the study protocol was submitted for registration in PROSPERO and eligible studiesinvolved prospective interventional studies with patients infected with one or all the six pathogens and whowere treated with bacteriophages or a phage cocktail specific to the pathogen, regardless of the year ofpublication up to December 2019. We searched the PubMed/Medline, Embase and Web of sciencedatabases for articles on phage therapy. 14 studies were included in the review with six considered for metaanalysisto quantify the therapeutic efficacy based on available studies on phages that may prevent and eradicate infections associated with but not limited to “Enterococcus faecium, Staphylococcus aureus,Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species pathogens” in humans for control of Nosocomial infections. In addition current gaps in the literature that would prompt further research on bacteriophage in the fight against antibiotic resistance were identified.
Results: Phage safety was sufficiently reported in that all studies showed no side effects related to phageadministration. A moderate pooled effect size was obtained with a high evidence of heterogeneity (SMD =0.52, (C.I. = -1.18, 2.22), P< 0.00001, I2= 96%). Most studies were pointing towards the overall effect sizewith one study regarded as an outlier. However, there was no significant treatment difference between the two 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. Hencemore streamlined phage clinical trials with large sample sizes are needed to detect sufficient effect sizes.
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Keywords
Antibiotic resistance, Multidrug resistance, Hospital acquired infections, Phage, Therapy, Clinical practice