In vitro activity of radezolid against Enterococcus faecium and compared with linezolid.
J Antibiot (Tokyo). 2020 Jul 16;:
Authors: Xu Z, Wei Y, Wang Y, Xu G, Cheng H, Chen J, Yu Z, Chen Z, Zheng J
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.
PMID: 32678335 [PubMed - as supplied by publisher]