Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)

Abstract

BackgroundTedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens causing community (CA)-acquired and HA infections in the US.MethodsDuring the Surveillance of Tedizolid Activity and Resistance (STAR) Program, 10,091 GP isolates were recovered from patients in 31 US hospitals. Isolates were identified by standard biochemical algorithms and MALDI-TOF MS. Susceptibility (S) testing followed CLSI methods and CLSI/EUCAST interpretation. CA and HA infections were defined based on CDC criteria.ResultsTZD (MIC50/90, 0.12/0.12 µg/mL; 100.0%S) showed equivalent MIC50 and MIC90 values against MSSA and MRSA, regardless of infection type or origin of isolate (Table). Linezolid (LZD; MIC50/90, 0.5–1/1 µg/mL; 100.0%S), daptomycin (DAP; MIC50/90, 0.25/0.5 µg/mL; 99.5–100.0%S), vancomycin (VAN; MIC50/90, 0.5–1/1 µg/mL; 100.0%S) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/≤0.5 µg/mL; 93.0–99.5%S) were also active throughout against MSSA and MRSA, while MICs for other agents varied. TZD (MIC50/90, 0.12/0.25 µg/mL; 100.0%S) activities were consistent against E. faecalis causing various infections from different origins, as were LZD (MIC50/90, 1/1 µg/mL; 100.0%S), ampicillin (MIC50/90, 1/1–2 µg/mL; 100.0%S), DAP (MIC50/90, 1/1–2 µg/mL; 100.0%S), and VAN (MIC50/90, 1/2 µg/mL; 94.9–97.0%S), although these agents had MIC50 and MIC90 values 4- to 8-fold higher than TZD. TZD (MIC50/90, 0.12/0.25 µg/mL), LZD (MIC50/90, 1/1–2 µg/mL; 97.6–100.0%S) and DAP (MIC50/90, 1/2–4 µg/mL; 97.4–100.0%S) were active in vitro against E. faecium, regardless of infection type. S. pneumoniae isolates were S to several drugs tested, and ceftaroline showed the lowest MICs (MIC50/90, ≤0.015/0.06 µg/mL; 100.0%S).ConclusionTZD had potent in vitro activity against GP isolates causing CA and HA infections in US hospitals, regardless of infection site or bacterial species. The TZD in vitro potency was also generally higher than clinically available comparator agents.Disclosures R. E. Mendes, Merck: Research Contractor, Research grant; D. Shortridge, Merck: Research Contractor, Research grant; S. J. R. Arends, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; M. Castanheira, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant