Journal article

Heterogeneity of Genetic Pathways toward Daptomycin Nonsusceptibility in Staphylococcus aureus Determined by Adjunctive Antibiotics

Andrew D Berti, Sarah L Baines, Benjamin P Howden, George Sakoulas, Victor Nizet, Richard A Proctor, Warren E Rose

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | AMER SOC MICROBIOLOGY | Published : 2015

Abstract

Daptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistant Staphylococcus aureus (MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF, rpoBC, dltA, cls2, and yycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days of in vitro exposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared ..

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Grants

Awarded by National Health and Medical Research Council, Australia


Funding Acknowledgements

This work was supported by internal funding. A.D.B. is supported by a Pharmacy Practice research fellowship at the University of Wisconsin-Madison School of Pharmacy. This work was supported by the National Health and Medical Research Council, Australia (fellowship APP1023526).