Ann Lab Med 2020; 40(1): 57-62  https://doi.org/10.3343/alm.2020.40.1.57
Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus in Korea: High Rate of False Resistance to Linezolid by the VITEK 2 System
In Young Yoo, M.D.1, On-Kyun Kang, M.T.1, Hyang Jin Shim, M.T.2, Hee Jae Huh, M.D.1, and Nam Yong Lee, M.D.1
1Department of Laboratory Medicine and Genetics, and 2Center for Clinical Medicine, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Corresponding author: Hee Jae Huh, M.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-1836 Fax: +82-2-3410-2719 E-mail: pmhhj77@gmail.com

Nam Yong Lee, M.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-2706 Fax: +82-2-3410-2719 E-mail: micro.lee@samsung.com
Received: March 22, 2019; Revised: June 17, 2019; Accepted: July 26, 2019; Published online: January 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
As various linezolid resistance mechanisms have been identified in methicillin-resistant Staphylococcus aureus (MRSA), we investigated the molecular characteristics of MRSA with elevated linezolid minimum inhibitory concentrations (MICs), using the VITEK 2 system (bioMérieux, Marcy-l’Étoile, France). Twenty-seven MRSA isolates from 14 patients exhibiting linezolid MICs ≥8 µg/mL were examined by broth microdilution (BMD) test as well as by sequencing for mutations in the 23S rRNA gene or ribosomal proteins (L3, L4, and L22) and the presence of the optrA, cfr, and cfr(B) genes. Of the 27 isolates, four (14.8%) from one patient were confirmed as linezolid resistant by BMD and harbored a 23S rRNA T2500A mutation. The remaining 23 were confirmed as linezolid susceptible, indicating that the linezolid-resistant results were major errors generated by VITEK 2. The most commonly detected mutation (19/27, 70.4%), L3 Gly152Asp, was detected in only linezolid-susceptible isolates. No isolates contained optrA, cfr, or cfr(B) or any L4 or L22 protein alterations. Our results show that the 23S rRNA T2500A mutation was mainly associated with linezolid resistance, while the L3 Gly152Asp mutation was not related to linezolid resistance. A confirmatory test is recommended for VITEK 2 linezolid-resistant results owing to the high probability of false resistant results.
Keywords: Methicillin-resistant Staphylococcus aureus, Linezolid, Resistance, 23S ribosomal RNA, VITEK 2



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