ß-Lactam antibiotics targeting PBP1 selectively enhance daptomycin activity against methicillin-resistant Staphylococcus aureus.
Antimicrob Agents Chemother
; 57(10): 5005-12, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23896478
ABSTRACT
The activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal ß-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different ß-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different ß-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 ß-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas ß-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by ß-lactam antibiotics affects pathways of cell division in S. aureus that may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Daptomicina
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Beta-Lactamas
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Proteínas de Ligação às Penicilinas
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article