β-lactamase inhibitors enhance the synergy between β-lactam antibiotics and daptomycin against methicillin-resistant Staphylococcus aureus

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.