Heterogeneity of genetic pathways toward daptomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics

Antimicrobial Agents and Chemotherapy
Andrew D BertiWarren E Rose

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 to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence of mprF mutation but did not prevent rpoBC mutation (P < 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not prevent mprF mutation. However, these same combinations prevented rpoBC mutation. Daptomycin alone or co...Continue Reading

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Citations

May 18, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·D I AnderssonJ Z Kubicek-Sutherland
May 3, 2018·The Journal of Antimicrobial Chemotherapy·Andrew D BertiWarren E Rose
Nov 7, 2018·Antimicrobial Agents and Chemotherapy·Elaine M BarrosMichael S Gilmore
Sep 1, 2018·Genome Medicine·Romain GuérillotBenjamin P Howden
Mar 21, 2019·Frontiers in Microbiology·Erica Lasek-NesselquistMeenakshi Malik
May 10, 2017·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Y IwataT Wada
Dec 30, 2020·Chemical Reviews·Jed F Fisher, Shahriar Mobashery
May 22, 2021·Journal of AOAC International·Jessica Freitas RichardiHérida Regina Nunes Salgado

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