Analysis of MIC Relationship Between Tedizolid, Linezolid and Vancomycin Tested Against S. aureus and Enterococcal Clinical Isolates from USA and European Hospitals (2014 - 2015)

Background: Tedizolid (TZD) has demonstrated potent in vitro activity against Gram-positive organisms. This study evaluated the MIC relationships between TZD vs linezolid (LZD) and TZD vs vancomycin (VAN) against S. aureus and enterococci from USA and European hospitals.

Methods: 10,666 S. aureus and 2,449 enterococci (1,626 E. faecalis and 823 E. faecium) collected during The Surveillance of Tedizolid Activity and Resistance (STAR) Program for USA and Europe were included (2014 - 2015). Bacteria were identified by standard algorithms and MALDI-TOF. Susceptibility (S) testing was performed by CLSI methods (M07-A10); interpretation of MIC results used CLSI (2016) and EUCAST (2016) criteria.

Results: TZD (MIC₉₀, 0.12 µg/mL; 100.0% S) exhibited MIC₉₀ values 8-fold lower than linezolid (LZD; MIC₉₀, 1 µg/mL; 100.0% S) and vancomycin (MIC₉₀, 1 µg/mL; 100.0% S) against S. aureus and the MRSA subset. TZD had similar MIC₅₀ and MIC₉₀ values against E. faecalis (MIC_50/90, 0.12/0.25 µg/mL; 99.9% S) and E. faecium (MIC_50/90, 0.12/0.25 µg/mL; 99.8% S), as did LZD (MIC_50/90, 1/1 µg/mL for both; 99.8 - 99.9% S), while VAN was active against E. faecalis (MIC_50/90, 1/2 µg/mL; 97.9% S), limited activity was noted against E. faecium (MIC_50/90, 1/>16 µg/mL; 56.1% S). The TZD modal MIC and MIC₅₀ results obtained against S. aureus and enterococci increased as the LZD MIC values increased, a correlation observed regardless of methicillin or vancomycin resistance phenotype (i.e. MRSA and VRE; see Table). In contrast, the vast majority of TZD modal MIC and MIC₅₀ values remained at 0.12 µg/mL when analyzed against each vancomycin MIC result obtained against S. aureus, enterococci and their resistant subsets.

Conclusion: TZD and LZD showed potent activities against staphylococci and enterococci; however, TZD was 8-fold more potent than LZD. TDZ and LZD MIC results exhibited a monotonically increasing relationship against species tested, while no correlation was detected between TZD and VAN MIC values. The latter is likely due to distinct mechanisms of actions between oxazolidinone and glycopeptide classes.