In vitro activity of radezolid against Enterococcus faecium and compared with linezolid

This study aims to explore the antimicrobial activity and resistance mechanism of radezolid against Enterococcus faecium, and to compare it with linezolid. A total of 232 E. faecium isolates were collected, and the minimal inhibitory concentrations of radezolid and linezolid were determined. The radezolid- or linezolid-nonsusceptible isolates were selected by passage in vitro under Antibiotic pressure. Oxazolidinone-resistant chromosomal genes and plasmid-borne genes cfr, optrA, and poxtA were detected by PCR and sequenced. Radezolid MIC₉₀ was 4 times lower than linezolid in the 232 E. faecium isolates, including the linezolid-nonsusceptible isolates. This study found that 6.5% (15/232) of the E. faecium isolates carried the plasmid-borne genes cfr and 9.5% (22/232) carried the optrA gene, but only one of these isolates had a linezolid MIC ≥ 4 mg l^-1. Among the 13 isolates with linezolid MIC ≥ 4 mg l^-1 or radezolid MIC ≥ 1 mg l^-1, genetic mutations in the V domain of 23S rRNA were only found in four isolates. The MICs of linezolid or radezolid against three E. faecium isolates increased to 4-16 times of the initial MICs after 140 days of daily passage in drug-containing medium. The radezolid MICs remained 8-16 times lower than linezolid in those linezolid-induced resistant isolates. Conversely, the radezolid MICs increased while the linezolid MICs remained unchanged in the most of the radezolid-induced resistant isolates. Radezolid exhibits excellent antimicrobial activity against E. faecium, and has minimal cross resistance with linezolid.