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Antimicrob Agents Chemother. 2013 Oct;57(10):5005-12. doi: 10.1128/AAC.00594-13. Epub 2013 Jul 29.

β-Lactam antibiotics targeting PBP1 selectively enhance daptomycin activity against methicillin-resistant Staphylococcus aureus.

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  • 1University of Wisconsin-Madison School of Pharmacy, Pharmacy Practice Division, Madison, Wisconsin, USA.


The activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal β-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different β-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different β-lactam antibiotics to determine if a specific PBP-binding profile is associated with the ability to enhance the anti-MRSA activity of DAP. We determined that both broad- and narrow-spectrum β-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas β-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by β-lactam antibiotics affects pathways of cell division in S. aureus that may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.

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