PMID- 28961986 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20220318 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 72 IP - 12 DP - 2017 Dec 1 TI - Novel multiresistance cfr plasmids in linezolid-resistant methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (VRE) from a hospital outbreak: co-location of cfr and optrA in VRE. PG - 3252-3257 LID - 10.1093/jac/dkx292 [doi] AB - BACKGROUND: Linezolid is often the drug of last resort to treat infections caused by Gram-positive cocci. Linezolid resistance can be mutational (23S rRNA or L-protein) or, less commonly, acquired [predominantly cfr, conferring resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A compounds (PhLOPSA) or optrA, encoding oxazolidinone and phenicol resistance]. OBJECTIVES: To investigate the clonality and genetic basis of linezolid resistance in 13 linezolid-resistant (LZDR) methicillin-resistant Staphylococcus epidermidis (MRSE) isolates recovered during a 2013/14 outbreak in an ICU in an Irish hospital and an LZDR vancomycin-resistant Enterococcus faecium (VRE) isolate from an LZDR-MRSE-positive patient. METHODS: All isolates underwent PhLOPSA susceptibility testing, 23S rRNA sequencing, DNA microarray profiling and WGS. RESULTS: All isolates exhibited the PhLOPSA phenotype. The VRE harboured cfr and optrA on a novel 73 kb plasmid (pEF12-0805) also encoding erm(A), erm(B), lnu(B), lnu(E), aphA3 and aadE. One MRSE (M13/0451, from the same patient as the VRE) harboured cfr on a novel 8.5 kb plasmid (pSEM13-0451). The remaining 12 MRSE lacked cfr but exhibited linezolid resistance-associated mutations and were closely related to (1-52 SNPs) but distinct from M13/0451 (202-223 SNPs). CONCLUSIONS: Using WGS, novel and distinct cfr and cfr/optrA plasmids were identified in an MRSE and VRE isolate, respectively, as well as a cfr-negative LZDR-MRSE ICU outbreak and a distinct cfr-positive LZDR-MRSE from the same ICU. To our knowledge, this is the first report of cfr and optrA on a single VRE plasmid. Ongoing surveillance of linezolid resistance is essential to maintain its therapeutic efficacy. CI - (c) The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Lazaris, Alexandros AU - Lazaris A AD - Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland. FAU - Coleman, David C AU - Coleman DC AD - Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland. FAU - Kearns, Angela M AU - Kearns AM AD - Antimicrobial Resistance and Healthcare Infections Reference Unit, National Infection Service, Public Health England, London, UK. FAU - Pichon, Bruno AU - Pichon B AD - Antimicrobial Resistance and Healthcare Infections Reference Unit, National Infection Service, Public Health England, London, UK. FAU - Kinnevey, Peter M AU - Kinnevey PM AD - Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland. FAU - Earls, Megan R AU - Earls MR AD - Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland. FAU - Boyle, Breida AU - Boyle B AD - Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, St James's Hospital, Dublin, Ireland. FAU - O'Connell, Brian AU - O'Connell B AD - Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, St James's Hospital, Dublin, Ireland. AD - National MRSA Reference Laboratory, St James's Hospital, James's St, Dublin, Ireland. FAU - Brennan, Grainne I AU - Brennan GI AD - National MRSA Reference Laboratory, St James's Hospital, James's St, Dublin, Ireland. FAU - Shore, Anna C AU - Shore AC AD - Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland. LA - eng PT - Journal Article PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Anti-Bacterial Agents) RN - 0 (RNA, Ribosomal, 23S) RN - ISQ9I6J12J (Linezolid) SB - IM MH - Anti-Bacterial Agents/*pharmacology MH - Cross Infection/*epidemiology MH - Disease Outbreaks MH - *Drug Resistance, Bacterial MH - Enterococcus faecium/*drug effects/genetics/isolation & purification MH - Genes, Bacterial MH - Hospitals MH - Humans MH - Ireland/epidemiology MH - Linezolid/*pharmacology MH - Microarray Analysis MH - Microbial Sensitivity Tests MH - Plasmids/*analysis MH - RNA, Ribosomal, 23S/genetics MH - Sequence Analysis, DNA MH - Staphylococcus epidermidis/*drug effects/genetics/isolation & purification MH - Vancomycin-Resistant Enterococci/drug effects/genetics/isolation & purification MH - Whole Genome Sequencing EDAT- 2017/09/30 06:00 MHDA- 2018/07/03 06:00 CRDT- 2017/09/30 06:00 PHST- 2017/06/09 00:00 [received] PHST- 2017/07/19 00:00 [accepted] PHST- 2017/09/30 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] PHST- 2017/09/30 06:00 [entrez] AID - 4096430 [pii] AID - 10.1093/jac/dkx292 [doi] PST - ppublish SO - J Antimicrob Chemother. 2017 Dec 1;72(12):3252-3257. doi: 10.1093/jac/dkx292.