Broad In Vitro Activity Analysis of Tedizolid Compared with Other Agents against a Global Collection of Gram-Positive Isolates Causing Bloodstream Infections (2014–2016)

Abstract

Background

Tedizolid (TZD) is an oxazolidinone derivative with oral and intravenous formulations approved for the treatment of acute bacterial skin and skin structure infections in the US, European countries, and other regions. This study evaluated TZD’s and comparators’ activity against a collection of clinical isolates causing bloodstream infections (BSI).

Methods

A total of 7,284 gram-positive isolates collected during the Surveillance of Tedizolid Activity and Resistance (STAR) Program for 2014–2016 were included. Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility (S) testing was performed by CLSI methods, and interpretation used CLSI and EUCAST criteria.

Results

This Staphylococcus aureus collection contained 33.8% methicillin-resistant isolates. TZD was the most potent agent tested against all S. aureus (MIC_50/90, 0.12/0.12 µg/mL; 100.0%S) and the MRSA subset (Table). Other tested agents described in Table also had in vitro MRSA coverage. 15.6% of enterococci were vancomycin-resistant, which were mostly Enterococcus faecium (59.8%). Linezolid (LZD), ampicillin, daptomycin (DAP), and vancomycin (VAN) showed equivalent MIC₅₀ values (1 µg/mL) against E. faecalis, but these MIC₅₀ results were 8-fold higher than TZD (MIC₅₀, 0.12 µg/mL). Although LZD and DAP were highly active (98.9–99.4%S) against E. faecium, TZD MICs were 8- to 16-fold lower that LZD and DAP. Ceftaroline (CPT) showed the lowest MIC values against Streptococcus pneumoniae, whereas TZD and VAN were similarly active. TZD and CPT showed the lowest MIC₉₀ values against viridans group streptococci, while CPT, ceftriaxone, and penicillin had the lowest MIC₉₀ results against β-hemolytic streptococci.

Conclusion

TZD had potent activities against this global population of gram-positive clinical isolates that caused BSI. This in vitro potency and a favorable pharmacodynamic profile may suggest TZD is a promising candidate for treating BSI caused by gram-positive isolates, especially E. faecium.

Disclosures

R. E. Mendes, Merck: Research Contractor, Research grant; D. Shortridge, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant