Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Vancomycin-resistant enterococci (VRE) pose a significant threat, especially in vulnerable patients.
• Limited therapeutic options exist for VRE infections, with linezolid being a common choice.
• Emergence of linezolid-resistant VRE (LR-VRE) necessitates alternative treatment strategies.

Purpose of the Study:

• To evaluate the in vitro activity of tedizolid against a collection of LR-VRE isolates.
• To investigate the resistance mechanisms present in LR-VRE strains.

Main Methods:

• Tested tedizolid activity against 30 LR-VRE isolates using MIC determination.
• Employed pulsed field gel electrophoresis (PFGE) for clonal typing.
• Utilized PCR to screen for known resistance genes (cfr, cfr(B), optrA) and analyzed 23S rDNA for mutations.

Main Results:

• Tedizolid MICs ranged from 2-32 mg/l, lower than linezolid but above the FDA breakpoint.
• No cfr, cfr(B), or optrA genes were detected in the LR-VRE isolates.
• All isolates harbored mutations in the 23S rDNA, identified as the predominant resistance mechanism.

Conclusions:

• Tedizolid has limited clinical value for treating most LR-VRE infections due to prevalent 23S rDNA mutations.
• Resistance mechanisms other than cfr genes are responsible for linezolid resistance in these VRE strains.
• Tedizolid may be an option for a small subset of LR-VRE isolates, but not broadly effective.