Linezolid-resistant<i>cfr</i>-positive MRSA, Italy

Antonelli, Alberto; D’Andrea, Marco Maria; Galano, Angelo; Borchi, Beatrice; Brenciani, Andrea; Vaggelli, Guendalina; Cavallo, Annalisa; Bartoloni, Alessandro; Giovanetti, Eleonora; Rossolini, Gian María

doi:10.1093/jac/dkw108

Cited by 31 publications

(13 citation statements)

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“… 1 The first report of linezolid resistance was in a staphylococci clinical isolate in 2001. 2 Since this time, linezolid-resistant MRSA 3 – 6 and the linezolid-resistant CoNS strains 7 – 8 have been increasingly isolated from the health care setting.…”

Section: Introductionmentioning

confidence: 99%

Dissemination of cfr-mediated linezolid resistance among Staphylococcus species isolated from a teaching hospital in Beijing, China

et al. 2018

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ObjectiveThe aim of the present study was to report the dissemination of cfr and fexA genes mediated by linezolid resistance among Staphylococcus species.MethodsThree methicillin-resistant staphylococci that were collected from a teaching hospital in Beijing were identified as linezolid-resistant. These three staphylococci were Staphylococcus aureus, S. haemolyticus, and S. cohnii. Mutations in domain V of 23S ribosomal RNA, ribosomal proteins, and the cfr, fexA, and optrA genes were analysed.ResultsThe three isolates had no mutations of 23S ribosomal RNA, but showed mutations in the cfr and fexA genes. Mutations in the gene for ribosomal protein L3, which resulted in the amino acid exchanges Gly108Glu, Ser158Phe, and Asp159Tyr, were identified in S. cohnii X4535.ConclusionsThis is the first report of the cfr gene in clinical linezolid-resistant methicillin-resistant S. aureus isolated from Beijing. L3 mutations coupled with the cfr and fexA genes may act synergistically. Potential transmissibility of this agent, even without prior exposure to linezolid, may have serious epidemiological repercussions.

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Section: Introductionmentioning

confidence: 99%

Dissemination of cfr-mediated linezolid resistance among Staphylococcus species isolated from a teaching hospital in Beijing, China

et al. 2018

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“…Recently, other molecular mechanisms of linezolid resistance in MRSA have been reported in clinical isolates, including mutations in ribosomal proteins L3, L4, and L22 encoded by the rplC , rplD , and rplV genes, respectively [35]. In addition, plasmid-mediated resistance, including the optrA , cfr (chloramphenicol-florfenicol resistance), and cfr (B) genes, has been described as a resistance mechanism underlying horizontal transmission between different species [678].…”

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confidence: 99%

Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus in Korea: High Rate of False Resistance to Linezolid by the VITEK 2 System

et al. 2020

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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.

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“…The cfr context (6,098 bp) was located between orf7 and orf14 ( orf39 and orf40 of pRE25) and consisted of the cfr gene flanked by two IS Enfa5 elements, inserted in turn into the lnu (E) gene. The same genetic context of cfr [including the direct repeats and the lnu (E) gene] has been reported in China in a plasmid from a Streptococcus suis isolate from an apparently healthy pig ( Wang et al, 2013 ) and in Italy in an MRSA isolated from a patient with cystic fibrosis ( Antonelli et al, 2016 ), with cfr being untransferable in both instances. Very recently, the cfr gene, flanked by only one IS Enfa5 , inserted upstream, has been described in a chromosomal fragment shared by three pig isolates of Staphylococcus sciuri ( Fan et al, 2017 ).…”

Section: Resultsmentioning

confidence: 53%

Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

et al. 2018

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Enterococcus faecium E35048, a bloodstream isolate from Italy, was the first strain where the oxazolidinone resistance gene optrA was detected outside China. The strain was also positive for the oxazolidinone resistance gene cfr. WGS analysis revealed that the two genes were linked (23.1 kb apart), being co-carried by a 41,816-bp plasmid that was named pE35048-oc. This plasmid also carried the macrolide resistance gene erm(B) and a backbone related to that of the well-known Enterococcus faecalis plasmid pRE25 (identity 96%, coverage 65%). The optrA gene context was original, optrA being part of a composite transposon, named Tn6628, which was integrated into the gene encoding for the ζ toxin protein (orf19 of pRE25). The cfr gene was flanked by two ISEnfa5 insertion sequences and the element was inserted into an lnu(E) gene. Both optrA and cfr contexts were excisable. pE35048-oc could not be transferred to enterococcal recipients by conjugation or transformation. A plasmid-cured derivative of E. faecium E35048 was obtained following growth at 42°C, and the complete loss of pE35048-oc was confirmed by WGS. pE35048-oc exhibited some similarity but also notable differences from pEF12-0805, a recently described enterococcal plasmid from human E. faecium also co-carrying optrA and cfr; conversely it was completely unrelated to other optrA- and cfr-carrying plasmids from Staphylococcus sciuri. The optrA-cfr linkage is a matter of concern since it could herald the possibility of a co-spread of the two genes, both involved in resistance to last resort agents such as the oxazolidinones.

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Linezolid-resistantcfr-positive MRSA, Italy

Cited by 31 publications

References 10 publications

Dissemination of cfr-mediated linezolid resistance among Staphylococcus species isolated from a teaching hospital in Beijing, China

Dissemination of cfr-mediated linezolid resistance among Staphylococcus species isolated from a teaching hospital in Beijing, China

Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus in Korea: High Rate of False Resistance to Linezolid by the VITEK 2 System

Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

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