Evaluation ofin vitrosusceptibility of Gram-positive pathogens from a tertiary care hospital in Singapore to a novel oxazolidinone, tedizolid, by a gradient diffusion method and broth microdilution

Abstract

We compared the in vitro antimicrobial activities of tedizolid and linezolid on the Sensititre broth microdilution system for Gram-positive cocci isolates (n=146) from skin and skin structure infections and bloodstream infections, bronchoalveolar lavage and sputum. These pathogens included 40 methicillin-resistant Staphylococcus aureus, 38 coagulase-negative staphylococci, 20 Enterococcus faecalis and 48 beta-haemolytic Streptococcus spp. Susceptibility was simultaneously determined for 48 vanA vancomycin-resistant enterococci isolates 2013–2016 from rectal swabs (23 E. faecalis and 25 E. faecium, of which 4 were linezolid-non-susceptible). MIC90s for tedizolid were fourfold to eightfold lower than linezolid on the Sensititre and ranged from 0.12 to 0.5 µg/mL for the different pathogen groups. All isolates were susceptible to tedizolid except two vanA E. faecium strains (MICs of 1 and 2 µg/mL, respectively). Categorical and essential agreement for tedizolid were 99.48% and 92%, respectively, between Liofilchem gradient diffusion and Sensititre methods. Overall, the drug exhibited excellent activity against the surveyed Gram-positive pathogens.

Pharmacokinetics and Pharmacodynamics of Tedizolid

“…Moreover, TDZ shows efficacy against VAN-resistant, daptomycin (DAP)-resistant, and some LNZresistant isolates and hence provides an alternative option to treat the less susceptible isolates of these antimicrobials [35,37,[43][44][45]. Other studies with further Gram-positive isolates mentioned earlier have almost similar findings [11,34,35,38,40,43,[46][47][48][49][50][51][52][53]. However, few isolates that were LNZ resistant (plasmid borne cfr multidrug resistance gene) showed a lower susceptibility (MIC > 0.5 mg/L) [54][55][56][57][58][59].…”

“…The non-susceptible isolates displayed an abundant plasmid-mediated ABC transporter optrA [ 50 , 121 ]. Choudhury et al also reported two clinical isolates (out of 48) of vanA E. faecium strains as ‘non-susceptible’ to TDZ (MIC 1–2 mg/L) [ 126 ]. In a recent study, two isolates of E. faecalis displayed TDZ MIC values of 2 mg/L (23S rRNA G2576T mutation).…”