Bacteriophage-Antibiotic Combination Strategy: an Alternative against Methicillin-Resistant Phenotypes of Staphylococcus aureus

Razieh Kebriaei; Katherine Lev; Taylor Morrisette; Kyle C Stamper; Jacinda C Abdul-Mutakabbir; Susan M Lehman; Sandra Morales; Michael J Rybak

doi:10.1128/AAC.00461-20

Bacteriophage-Antibiotic Combination Strategy: an Alternative against Methicillin-Resistant Phenotypes of Staphylococcus aureus

Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00461-20. doi: 10.1128/AAC.00461-20. Print 2020 Jun 23.

Authors

Razieh Kebriaei¹, Katherine Lev¹, Taylor Morrisette¹, Kyle C Stamper¹, Jacinda C Abdul-Mutakabbir¹, Susan M Lehman², Sandra Morales³, Michael J Rybak^{4

5}

Affiliations

¹ Anti-Infective Research Laboratory, College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
² Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
³ Phage Consulting, Sydney, New South Wales, Australia.
⁴ Anti-Infective Research Laboratory, College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA m.rybak@wayne.edu.
⁵ School of Medicine, Wayne State University, Detroit, Michigan, USA.

Abstract

Comparative time-kill experiments with Staphylococcus aureus bacteriophage (phage) Sb-1 alone and phage-antibiotic combinations (PACs) against two methicillin-resistant S. aureus (MRSA) strains have shown synergy with both daptomycin-phage and vancomycin-phage combinations. PACs prevented development of phage resistance and demonstrated bactericidal activity for all triple combinations. In addition, the extracellular membrane vesicle (MV) formation and the potential impact of phage on MV suppression were examined. Our results demonstrate the potential of PAC for combating MRSA infections.

Keywords: Staphylococcus aureus; bacteriophage therapy; combination therapy.

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacteriophages*
Humans
Methicillin Resistance
Methicillin-Resistant Staphylococcus aureus*
Microbial Sensitivity Tests
Phenotype
Staphylococcal Infections* / drug therapy
Staphylococcus aureus

Substances

Anti-Bacterial Agents