Disruption ofBiofilm by Bacteriophages inClinically Relevant Settings.

Abstract

Antibiotic-resistant bacteria are a growing threat to civilian and military health today. Although infections were once easily treatable by antibiotics and wound cleaning, the frequent mutation of bacteria has created strains impermeable to antibiotics and physical attack. Bacteria further their pathogenicity because of their ability to form biofilms on wounds, medical devices, and implant surfaces. Methods for treating biofilms in clinical settings are limited, and when formed by antibiotic-resistant bacteria, can generate chronic infections that are recalcitrant to available therapies. Bacteriophages are natural viral predators of bacteria, and their ability to rapidly destroy their host has led to increased attention in potential phage therapy applications. The present article sought to address a knowledge gap in the available literature pertaining to the usage of bacteriophage in clinically relevant settings and the resolution of infections particular to military concerns. PRISMA guidelines were followed for a systematic review of available literature that met the criteria for analysis and inclusion. The research completed for this review article originated from the U.S. Military Academy's library "Scout" search engine, which complies results from 254 available databases (including PubMed, Google Scholar, and SciFinder). The search criteria included original studies that employed bacteriophage use against biofilms, as well as successful phage therapy strategies for combating chronic bacterial infections. We specifically explored the use of bacteriophage against antibiotic- and treatment-resistant bacteria. A total of 80 studies were identified that met the inclusion criteria following PRISMA guidelines. The application of bacteriophage has been demonstrated to robustly disrupt biofilm growth in wounds and on implant surfaces. When traditional therapies have failed to disrupt biofilms and chronic infections, a combination of these treatments with phage has proven to be effective, often leading to complete wound healing without reinfection. This review article examines the available literature where bacteriophages have been utilized to treat biofilms in clinically relevant settings. Specific attention is paid to biofilms on implant medical devices, biofilms formed on wounds, and clinical outcomes, where phage treatment has been efficacious. In addition to the clinical benefit of phage therapies, the military relevance and treatment of combat-related infections is also examined. Phages offer the ability to expand available treatment options in austere environments with relatively low cost and effort, allowing the impacted warfighter to return to duty quicker and healthier.