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

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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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Acknowledgments

We thank Mark S. Rouse, Mayo Clinic, for helpful discussion and technical assistance, and are very grateful to Li Basuino, Binh Diep, and Henry Chambers of University of California, San Francisco, for providing strains and technical advice. M.G.F. was supported in part by funds from the German National Academic Foundation.

Funding

This work was supported by the Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.

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Authors and Affiliations

  1. Division of Pediatric Infectious Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    R. Banerjee

  2. Paracelsus Medical Private University, Strubergasse 21, 5020, Salzburg, Austria

    M. G. Fernandez, N. Enthaler & C. Graml

  3. Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    K. E. Greenwood-Quaintance & R. Patel

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  1. R. Banerjee
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Correspondence to R. Banerjee.

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Banerjee, R., Fernandez, M.G., Enthaler, N. et al. Combinations of cefoxitin plus other β-lactams are synergistic in vitro against community associated methicillin-resistant Staphylococcus aureus . Eur J Clin Microbiol Infect Dis 32, 827–833 (2013). https://doi.org/10.1007/s10096-013-1817-9

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