title: Combinations of cefoxitin plus other β-lactams are synergistic in vitro against community associated methicillin-resistant Staphylococcus aureus.
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 β-lactams against a collection of MRSA isolates. We assessed the in vitro antimicrobial activity of a selection of β-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 β-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. β-lactam/cefoxitin combinations were synergistic against CA- but not HA-MRSA strains in time kill assays. Cefoxitin combined with a variety of β-lactams enhances their activity against CA-MRSA strains in vitro. Further studies of combination β-lactam therapy may provide insight into β-lactam biology, penicillin binding protein cooperativity, and novel therapeutic strategies against MRSA.
authors: Division of Pediatric Infectious Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Banerjee.ritu@mayo.edu
authors: R
authors: R
authors: Banerjee
authors: M G
authors: MG
authors: Fernandez
authors: N
authors: N
authors: Enthaler
authors: C
authors: C
authors: Graml
authors: K E
authors: KE
authors: Greenwood-Quaintance
authors: R
authors: R
authors: Patel
mesh_terms: D002440:Cefoxitin / Q000494:pharmacology*; D017714:Community-Acquired Infections; D003428:Cross Infection; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000382:microbiology*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D047090:beta-Lactams; D002440:Cefoxitin