The Safety and Efficacy of Phage Therapy for Bone and Joint Infections: A Systematic Review.

Alex Clarke,Joshua Jones,Steven De Soir

doi:10.3390/antibiotics9110795

Alex Clarke, Joshua Jones + Show 1 more

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https://doi.org/10.3390/antibiotics9110795

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Abstract

Bacterial resistance to antibiotics has catalysed interest in alternative antimicrobial strategies. Bacteriophages (phages) are viruses of bacteria with a long history of successful therapeutic use. Phage therapy is a promising antibacterial strategy for infections with a biofilm component, including recalcitrant bone and joint infections, which have significant social, financial and human impacts. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of bone and joint infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for bone and joint infections. Two authors independently assessed study eligibility and performed data extraction. Seventeen reports were eligible for inclusion in this review, representing the treatment of 277 patients. A cautionary, crude, efficacy estimate revealed that 93.1% (n = 258/277) achieved clinical resolution, 3.3% (n = 9/277) had improvement and 3.6% (n = 10/277) showed no improvement. Seven of the nine reports that directly commented on the safety of phage therapy did not express safety concerns. The adverse effects reported in the remaining two were not severe and were linked to the presence of contaminating endotoxins and pre-existing liver pathology in a patient treated with high-titre intravenous phage therapy. Three other reports, from 1940–1987, offered general comments on the safety of phage therapy and documented adverse effects consistent with endotoxin co-administration concomitant with the use of raw phage lysates. Together, the reports identified by this review suggest that appropriately purified phages represent a safe and highly efficacious treatment option for complex and intractable bone and joint infections.

Highlights

IntroductionIn his Nobel Lecture, 17 years after his serendipitous discovery of penicillin in 1928, Alexander
In his Nobel Lecture, 17 years after his serendipitous discovery of penicillin in 1928, AlexanderFleming warned that the misuse of penicillin could select for resistant bacteria [1]
Five were reports that described the use of phage therapy for a wide variety of conditions and the titles and abstracts of these records did not contain the specific search terms used [18,19,20,21,22]; three were from grey literature sources known to the authors not to be indexed or available online [23,24,25,31]; and the authors became aware of two further relevant records published after the systematic search date but that were included for completeness [26,27]

Summary

Introduction

In his Nobel Lecture, 17 years after his serendipitous discovery of penicillin in 1928, Alexander. Fleming warned that the misuse of penicillin could select for resistant bacteria [1]. Almost 100 years on, modern medicine is confronted with the ‘antimicrobial resistance crisis’. This crisis threatens, at great economic and human cost, to undermine substantial progress across medicine and surgery. Bacteriophages (phages) are viruses of bacteria whose discovery in 1915 and 1917 predates that of antibiotics [2]. The discovery of antibiotics catalysed the decline of phage therapy in the geopolitical West, where injudicious use, uncertainty about the nature of Antibiotics 2020, 9, 795; doi:10.3390/antibiotics9110795 www.mdpi.com/journal/antibiotics

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