Emergence of optrA-Mediated Linezolid-Nonsusceptible Enterococcus faecalis in a Tertiary Care Hospital

Abstract

This study investigated resistance mechanisms and epidemiology of emerging linezolidnonsusceptible Enterococcus faecalis (LNSEF) in a tertiary care hospital. LNSEF isolated from clinical samples were collected from November 2017 to June 2019. The isolates were investigated for linezolid resistance and the associated molecular mechanisms, including mutations of 23S rRNA domain V and acquisition of the cfr or optrA resistance gene. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing for the molecular typing of the isolates. Among 4,318 E. faecalis isolates, 10 (0.23%) were linezolid-nonsusceptible. All LNSEF isolates were optrA-positive and cfr-negative. Of these isolates, five were sequence type (ST) 476, two ST585, one ST16, one ST16-like, and one ST480. Six LNSEF isolates obtained in the first year clustered to three types in the PFGE analysis: two ST476 isolates of type A, two ST585 isolates of type B, and two ST16 or ST16-like isolates of type C. Seven cases were of community-onset and three were hospital acquired, but total of eight were healthcare-associated including five community-onset. None of the patients had a history of linezolid treatment, and in one patient, we detected linezolid-susceptible E. faecalis one month before LNSEF detection. In conclusion, heterogenous clones of optrA-positive LNSEF emerged in the hospital mainly via communityonset. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://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.

Drug Resistance Determinants in Clinical Isolates of Enterococcus faecalis in Bangladesh: Identification of Oxazolidinone Resistance Gene optrA in ST59 and ST902 Lineages

“…The present detection rate of optrA in E. faecalis in Bangladesh (2.4%) may be comparable to those reported in China, implying relatively high prevalence among clinical isolates in this country, and may suggest also the potential distribution among the healthy population since LZD has been rarely used. The occurrence of optrA-positive E. faecalis was reported also in patients having no history of LZD treatment in Korea [48]. Because the five LZD-non-susceptible isolates in our study exhibited resistance to multiple drugs including NIT, it is possible that these isolates might have occurred by selection with ordinary antimicrobial treatment.…”

Synergistic Combination of Linezolid and Fosfomycin Closing Each Other’s Mutant Selection Window to Prevent Enterococcal Resistance

“…The common mechanisms of Enterococcus resistance to linezolid include point mutations in chromosome 23S rRNA genes or genes encoding L3, L4, and L22 ribosomal proteins ( Mendes et al, 2014 ; Wang et al, 2014 ). Other important mechanisms include plasmid-mediated chloramphenicol-florfenicol resistance cfr gene or ribosome protection gene optrA and poxtA ( Wang et al, 2014 ; Park et al, 2020 ; Ruiz-Ripa et al, 2020 ). Correspondingly, several mechanisms have been proposed to be related to fosfomycin resistance including fosfomycin forming an inactive adduct ( Falagas et al, 2018 ), fosfomycin modification enzyme ( Cassir et al, 2014 ), mutations in the chromosomal genes encoding fosfomycin transporters ( Fu et al, 2016 ; Xu et al, 2017 ) and mutations in the target enzyme MurA ( Falagas et al, 2016 ).…”

Prevalence and Characteristics of Phenicol-Oxazolidinone Resistance Genes in Enterococcus Faecalis and Enterococcus Faecium Isolated from Food-Producing Animals and Meat in Korea

“…ST16 was identified in three optrA -positive E. faecalis ; two isolates cocarried fexA, and one isolate has only optrA . This ST has been identified in food animals and humans in Korea and other countries and is known as an optrA -carrying clone with a worldwide distribution [ 11 , 19 ]. In addition, EFS17 isolated from pork was identified as ST585, which coharbored optrA and fexA .…”

“…The optrA , poxtA , and cfr encoding enterococci has been reported in Korea and many countries such as China, Italy, Ireland, and Malaysia [ 3 ]. In particular, it was confirmed that all enterococci isolated from tertiary hospital patients in Korea possessed the optrA gene, but none of them were treated with linezolid [ 11 ]. Therefore, it was estimated that the optrA -positive linezolid nonsusceptible enterococci appeared at the hospital through the community onset [ 11 ].…”

“…In particular, it was confirmed that all enterococci isolated from tertiary hospital patients in Korea possessed the optrA gene, but none of them were treated with linezolid [ 11 ]. Therefore, it was estimated that the optrA -positive linezolid nonsusceptible enterococci appeared at the hospital through the community onset [ 11 ]. The optrA gene has been continuously found in enterococci from foods of animal origin in Korea, and optrA -encoding enterococci cocarrying the phenicol exporter gene fexA have been isolated [ 3 ].…”