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Eur J Clin Microbiol Infect Dis ; 32(6): 827-33, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23340864

ABSTRACT

In vitro studies demonstrate that oxacillin minimal inhibitory concentrations (MICs) of methicillin-resistant S. aureus (MRSA) strains USA300 and 400 decrease in the presence of cefoxitin. The aim of this study was to characterize the activity of cefoxitin plus ß-lactams against a collection of MRSA isolates. We assessed the in vitro antimicrobial activity of a selection of ß-lactams alone and together with subinhibitory concentrations of cefoxitin against a collection of MRSA, methicillin-susceptible S. aureus (MSSA), and vancomycin-intermediate S. aureus (VISA) isolates using MICs and time kill assays. For community-associated (CA) MRSA strains USA300 and USA400, MICs of nafcillin, cefazolin, cephalexin, cefuroxime, ceftriaxone and cefotaxime decreased by 8- to 64-times in the presence of 10 µg/ml cefoxitin. In contrast, for hospital-associated (HA) strains COLn, N315, and Mu50, there was no change in any ß-lactam MIC in the presence of cefoxitin. When combined with cefoxitin, the cephalexin MIC decreased for eight CA-MRSA and five MSSA sequence types but did not change for seven HA-MRSA sequence types. ß-lactam/cefoxitin combinations were synergistic against CA- but not HA-MRSA strains in time kill assays. Cefoxitin combined with a variety of ß-lactams enhances their activity against CA-MRSA strains in vitro. Further studies of combination ß-lactam therapy may provide insight into ß-lactam biology, penicillin binding protein cooperativity, and novel therapeutic strategies against MRSA.


Subject(s)
Cefoxitin/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/microbiology , beta-Lactams/pharmacology , Community-Acquired Infections , Cross Infection , Drug Synergism , Humans , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests
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