β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01564-16. doi: 10.1128/AAC.01564-16. Print 2017 Jan.

Abstract

The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam-β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide-β-lactam synergy.

Keywords: antibiotic combination; synergy; β-lactamase inhibitor; β-lactams.

MeSH terms

  • Ampicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Daptomycin / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Piperacillin / pharmacology
  • Sulbactam / pharmacology
  • Tazobactam
  • beta-Lactamase Inhibitors / pharmacology*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Ampicillin
  • Penicillanic Acid
  • Daptomycin
  • Sulbactam
  • Tazobactam
  • Piperacillin