Background: Tedizolid (TZD) is approved for treatment of acute bacterial skin and skin structure infections in the United States (USA), European Union (EU), and Canada. The in vitro activity of TZD was tested against Gram-positive pathogens isolated collected from USA medical centers in 2014.
Methods: In 2014, 5,999 Gram-positive, non-duplicate, non-consecutive, single patient clinical isolates were collected from 29 medical centers across all nine USA census regions. Isolates were tested for antibacterial susceptibility (S) as per CLSI guidelines. MIC values for TZD and linezolid (LZD) were read both at (1) the first well where trailing begins (80% read; TZD80 and LZD80) as per CLSI M07-A10 and (2) at endpoint (100% growth inhibition; TZD100 and LZD100). USA-FDA, CLSI, and EUCAST breakpoints were used to determine %S.
Results: A total of 3,441 S. aureus strains were evaluated; 100% of strains were S to TZD. The MIC50/90 values for TZD80 (MIC50/90, 0.12/0.12 µg/mL) were one dilution lower than TZD100 (0.25/0.25 µg/mL) and four-fold lower than for LZD (LZD80, MIC50/90, 1/1 µg/mL; LZD100, MIC50/90, 1/2 µg/mL). Against 344 coagulase-negative staphylococci, TDZ80/100 (MIC50/90, 0.06-0.12/0.12-0.25 µg/mL) was four- to eight-fold more potent than LZD80/100 (MIC50/90, 0.5-1/0.5-1 µg/mL). TZD was active (80/100 MIC90, 0.25/0.5 µg/mL) against 524 Enterococcus spp. and 100.0% of 343 E. faecium isolates were S by USA-FDA breakpoint of ≤0.5 µg/mL (using TZD100). Against 563 beta-hemolytic streptococci, 100.0% of isolate were S to LZD100 (MIC50/90, 1/1 µg/mL) and TZD100 (MIC50/90, 0.12/0.25 µg/mL). Against 260 viridans group streptococci, 100.0% of isolate were S to LZD100 (MIC50/90, 0.5/1 µg/mL) and TZD100 was two- to four-fold more potent (MIC50/90, 0.12/0.25 µg/mL). TZD100 was also very active (MIC50/90, 0.25/0.25 µg/mL) against 867 pneumococcal isolates.
Conclusion: TZD demonstrated higher in vitro activity (two- to four-fold) than LZD when tested against Gram-positive pathogens isolated from patients in USA medical centers during 2014. MIC distributions and MIC50/90 values for TZD and LZD read without regard for pinpoint trailing colonies were one dilution lower than those read at 100% inhibition.
D. J. Farrell,
Merck & Co. Inc:
R. E. Mendes, Merck & Co. Inc: Research Contractor , Research support
R. N. Jones, Merck & Co. Inc: Research Contractor , Research support