Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: Low rate of 23s rRNA mutations in Enterococcus faecium

Purpose. To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Methodology. Enterococcal isolates exhibiting linezolid MICs ≥4mgl^–1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes. Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1% (34/87) of E. faecium and 18.8% (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70% (7/10) linezolid-resistant and 30% (3/10) linezolid-intermediate] and three E. faecium [33.3% (1/3) linezolid-resistant and 66.7% (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4% (10/14) linezolid-resistant and 28.6% (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6% (23/34) of linezolid-resistant E. faecium. Conclusion. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.