Efficacy of Tedizolid against Enterococci and Staphylococci, Including cfr⁺ Strains, in a Mouse Peritonitis Model

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Emergence of antimicrobial resistance poses a significant threat to public health.
• Oxazolidinones, including tedizolid and linezolid, are crucial for treating infections caused by Gram-positive pathogens.
• Enterococcus faecium and Staphylococcus aureus are common causes of difficult-to-treat infections, often exhibiting resistance to multiple drugs.

Purpose of the Study:

• To evaluate the in vivo efficacy of tedizolid compared to linezolid and daptomycin.
• To assess the activity of tedizolid against specific Gram-positive bacterial strains, including those with cfr-mediated resistance.
• To investigate the comparative performance in a murine peritonitis model.

Main Methods:

• Utilized a mouse peritonitis model to simulate systemic bacterial infection.
• Tested tedizolid, linezolid, and daptomycin against Enterococcus faecium (including vancomycin and ampicillin-resistant strains), Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA).
• Included MRSA strains with and without the cfr gene, and Enterococcus faecium strains with cfr(B).

Main Results:

• Tedizolid demonstrated comparable efficacy to linezolid and daptomycin against vancomycin-resistant Enterococcus faecium, Enterococcus faecalis, and MRSA strains (with and without cfr).
• In vivo, tedizolid was found to be inferior to both linezolid and daptomycin when tested against a cfr(B)-positive Enterococcus faecium strain.
• This reduced efficacy occurred despite tedizolid exhibiting a lower minimum inhibitory concentration (MIC) in vitro against this specific strain.

Conclusions:

• Tedizolid exhibits broad in vivo activity against various resistant Gram-positive bacteria in a peritonitis model.
• The presence of cfr(B) in Enterococcus faecium significantly impacts tedizolid's in vivo effectiveness, rendering it inferior to linezolid and daptomycin.
• These findings highlight the importance of considering specific resistance mechanisms when selecting antibiotics for challenging Gram-positive infections.