Evaluation of Bacteriophage-Antibiotic Combination Therapy for Biofilm-Embedded MDR Enterococcus faecium

Katherine Lev, Ashlan J.Kunz Coyne, Razieh Kebriaei, Taylor Morrisette, Kyle Stamper, Dana J. Holger, Gregory S. Canfield, Breck A. Duerkop, Cesar A. Arias, Michael J. Rybak

Research output: Contribution to journalArticlepeer-review

Abstract

Multidrug-resistant (MDR) Enterococcus faecium is a challenging pathogen known to cause biofilm-mediated infections with limited effective therapeutic options. Lytic bacteriophages target, infect, and lyse specific bacterial cells and have anti-biofilm activity, making them a possible treatment option. Here, we examine two biofilm-producing clinical E. faecium strains, daptomycin (DAP)-resistant R497 and DAP-susceptible dose-dependent (SDD) HOU503, with initial susceptibility to E. faecium bacteriophage 113 (ATCC 19950-B1). An initial synergy screening was performed with modified checkerboard MIC assays developed by our laboratory to efficiently screen for antibiotic and phage synergy, including at very low phage multiplicity of infection (MOI). The data were compared by one-way ANOVA and Tukey (HSD) tests. In 24 h time kill analyses (TKA), combinations with phage-DAP-ampicillin (AMP), phage-DAP-ceftaroline (CPT), and phage-DAP-ertapenem (ERT) were synergistic and bactericidal compared to any single agent (ANOVA range of mean differences 3.34 to 3.84 log10 CFU/mL; p < 0.001). Furthermore, phage-DAP-AMP and phage-DAP-CPT prevented the emergence of DAP and phage resistance. With HOU503, the combination of phage-DAP-AMP showed the best killing effect, followed closely by phage-DAP-CPT; both showed bactericidal and synergistic effects compared to any single agent (ANOVA range of mean differences 3.99 to 4.08 log10 CFU/mL; p < 0.001).

Original languageEnglish (US)
Article number392
JournalAntibiotics
Volume11
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • antimicrobial
  • bacteriophage
  • biofilm
  • Enterococcus faecium
  • frequency of resistance
  • nontraditional antibacterial
  • phage sensitivity
  • phage therapy
  • resistance management

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Evaluation of Bacteriophage-Antibiotic Combination Therapy for Biofilm-Embedded MDR Enterococcus faecium'. Together they form a unique fingerprint.

Cite this