Combinations of cefoxitin plus other β-lactams are synergistic in vitro against community associated methicillin-resistant Staphylococcus aureus

  • R. Banerjee
  • M. G. Fernandez
  • N. Enthaler
  • C. Graml
  • K. E. Greenwood-Quaintance
  • R. Patel
Article

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • R. Banerjee
    • 1
  • M. G. Fernandez
    • 2
  • N. Enthaler
    • 2
  • C. Graml
    • 2
  • K. E. Greenwood-Quaintance
    • 3
  • R. Patel
    • 3
  1. 1.Division of Pediatric Infectious DiseasesMayo ClinicRochesterUSA
  2. 2.Paracelsus Medical Private UniversitySalzburgAustria
  3. 3.Division of Clinical Microbiology, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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