Adjunct phage treatment enhances the effectiveness of low antibiotic concentration against Staphylococcus aureus biofilms in vitro

• Type of Material: Article
• Authors: James Dickey, Emory University; Veronique Perrot, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Dickey, Perrot.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0209390
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 14
• Issue: 1
• Start Page: e0209390
• End Page: e0209390
• Grant/Funding Information: This study was funded by NIH-NIGMS grant GM091875.; The Robert P. Apkarian Integrated Electron Microscopy Core is subsidized by the Emory College of Arts and Sciences and the Emory University School of Medicine and is one of the Emory Integrated Core Facilities, and the JEOL JEM-1400 120kV TEM is supported by NIH grant S10 RR025679.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: infection; experiment; antibiotic resistance; pretreatment; public health; bacterial biofilms; case study; staphylococcus aureus; phage therapy
• Research Categories: Biology, Virology; Health Sciences, Public Health; Health Sciences, Medicine and Surgery

Abstract

Phage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms of Staphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2×MIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10×MIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.