β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus.
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.
Division of Infectious Diseases, Wayne State University and Detroit Medical Center, Detroit, Michigan, USA.
Karl Evans R
KE
Henson
Anti-infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Juwon
J
Yim
Anti-infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Jordan R
JR
Smith
University of California San Diego School of Medicine, San Diego, California, USA.
George
G
Sakoulas
Anti-infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA aa1592@wayne.edu.|Wayne State University School of Medicine, Detroit, Michigan, USA.
Michael J
MJ
Rybak
D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D013407:Sulbactam / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D000667:Ampicillin; D010397:Penicillanic Acid; D017576:Daptomycin; D013407:Sulbactam; D000078142:Tazobactam; D010878:Piperacillin
antibiotic combination; synergy; β-lactamase inhibitor; β-lactams