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 emergence
of multidrug-resistant organisms in nosocomial infections is being highly associated with frequent causes
of morbidity and mortality in patients. In view of the growing threat of antibiotic resistance, the World
Health Organization has warned for a return into a pre-antibiotic era. The antibiotic crisis has rekindled the
interest in phage therapy approaches that were developed in Eastern Europe, one of the alternatives recently
regaining 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, Acinetobacter
baumannii, Pseudomonas aeruginosa, Enterobacter species pathogens” (ESKAPE) bacteria in humans
based on available studies.
Methods:
In this review, the study protocol was submitted for registration in PROSPERO and eligible studies
involved prospective interventional studies with patients infected with one or all the six pathogens and who
were treated with bacteriophages or a phage cocktail specific to the pathogen, regardless of the year of
publication up to December 2019. We searched the PubMed/Medline, Embase and Web of science
databases for articles on phage therapy. 14 studies were included in the review with six considered for metaanalysis
to 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 phage
administration. 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, I
2
= 96%). Most studies were pointing towards the overall effect size
with 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. Hence
more 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