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

  • J Antibiot (Tokyo). 2020 Dec;73(12):845-851. doi: 10.1038/s41429-020-0345-y.
Zhichao Xu   #  1  2 ,  Ying Wei   #  3 ,  Yu Wang   #  1 ,  Guangjian Xu  1 ,  Hang Cheng  1  2 ,  Junwen Chen  1  2 ,  Zhijian Yu  1  2 ,  Zhong Chen  4  5 ,  Jinxin Zheng  6  7
Affiliations
  • 1. Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital, Shenzhen University of School Medicine, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China.
  • 2. Quality Control Center of Hospital Infection management of Shenzhen, Guang Dong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China.
  • 3. Heilongjiang Medical Service Management Evaluation Center, Harbin, Heilongjiang, 150031, China.
  • 4. Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital, Shenzhen University of School Medicine, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. [email protected].
  • 5. Quality Control Center of Hospital Infection management of Shenzhen, Guang Dong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. [email protected].
  • 6. Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital, Shenzhen University of School Medicine, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. [email protected].
  • 7. Quality Control Center of Hospital Infection management of Shenzhen, Guang Dong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. [email protected].
  • # Contributed equally.
PMID: 32678335 DOI: 10.1038/s41429-020-0345-y
Abstract

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.

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