In Vitro Activities of Tedizolid and Linezolid against Gram-Positive Cocci Associated with Acute Bacterial Skin and Skin Structure Infections and Pneumonia

Abstract

Tedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptible Staphylococcus aureus (MSSA) (n ‫؍‬ 100), methicillin-resistant Staphylococcus aureus (MRSA) (n ‫؍‬ 100), Streptococcus pyogenes (n ‫؍‬ 50), Streptococcus agalactiae (n ‫؍‬ 50), Streptococcus anginosus group (n ‫؍‬ 75), Enterococcus faecalis (n ‫؍‬ 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n ‫؍‬ 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited better in vitro activities than linezolid against MSSA (MIC 90 s, 0.5 versus 2 g/ml), MRSA (MIC 90 s, 0.5 versus 2 g/ml), S. pyogenes (MIC 90 s, 0.5 versus 2 g/ml), S. agalactiae (MIC 90 s, 0.5 versus 2 g/ml), Streptococcus anginosus group (MIC 90 s, 0.5 versus 2 g/ml), E. faecalis (MIC 90 s, 0.5 versus 2 g/ml), and VRE (MIC 90 s, 0.5 versus 2 g/ml). The tedizolid MICs against E. faecalis (n ‫؍‬ 3) and VRE (n ‫؍‬ 2) intermediate to linezolid (MICs, 4 g/ml) were 1 g/ml and 0.5 g/ml, respectively. The tedizolid MIC 90 s against S. anginosus, S. constellatus, and S. intermedius were 0.5, 1, and 0.5 g/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2-to 4-fold better in vitro activities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates of S. anginosus and S. constellatus than against those of S. intermedius in Taiwan were noted.

Comparative Efficacies of Tedizolid Phosphate, Linezolid, and Vancomycin in a Murine Model of Subcutaneous Catheter-Related Biofilm Infection Due to Methicillin-Susceptible and -Resistant Staphylococcus aureus

“…In addition to these MIC data, in vitro time-kill studies showed that tedizolid had better anti-S. aureus activity than linezolid in that it prevented regrowth at 24 h of incubation. The in vitro findings in this study mirror those in previously published investigations of tedizolid and linezolid activity against S. aureus (9,26). In the present study, we further evaluated the impact of tedizolid versus that of linezolid and vancomycin on biofilm formation in S. aureus and found that exposure of these antibiotics at the MIC to 10ϫ MIC significantly decreased S. aureus biofilm formation.…”

“…It exerts bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of the bacteria. It has been reported that tedizolid is more active against staphylococci and enterococci than linezolid is in vitro (9,10).…”

Activities of Tedizolid and Linezolid Determined by the Reference Broth Microdilution Method against 3,032 Gram-Positive Bacterial Isolates Collected in Asia-Pacific, Eastern Europe, and Latin American Countries in 2014

“…The study of Chen et al (9) differed from previous studies of tedizolid in the use of an agar dilution method rather than the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) method (11) to determine the susceptibility of tested isolates to tedizolid and linezolid. Furthermore, Chen et al (9) did not provide methodological details concerning the inoculum concentration, the duration of incubation, or the criteria used for MIC endpoint determination.…”

“…Surprisingly, the Taiwanese isolates of the S. anginosus group were uniformly susceptible to linezolid despite only 38.7% susceptibility to tedizolid (9). Notably, a linezolid-susceptible and tedizolid-resistant phenotype had not been reported in previous in vitro surveillance surveys (1,2,5,8,10).…”

“…Whereas the vast majority of in vitro studies of tedizolid confirm the activity and spectrum of the agent against pathogens associated with ABSSSI (2,5,7,8), a recent study from Taiwan has raised concern about increased resistance to tedizolid among isolates of the Streptococcus anginosus group (including S. anginosus, Streptococcus intermedius, and Streptococcus constellatus) collected from January 2013 to October 2014 (9). Surprisingly, the Taiwanese isolates of the S. anginosus group were uniformly susceptible to linezolid despite only 38.7% susceptibility to tedizolid (9).…”