First Report of cfr-Mediated Resistance to Linezolid in Human Staphylococcal Clinical Isolates Recovered in the United States

JMI Laboratories, North Liberty, IA 52317, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 07/2008; 52(6):2244-6. DOI: 10.1128/AAC.00231-08
Source: PubMed


Linezolid resistance has dominantly been mediated by mutations in 23S rRNA or ribosomal protein L4 genes. Recently, cfr has demonstrated the ability to produce a phenotype of resistance to not only oxazolidinones, but also other antimicrobial
classes (phenicols, lincosamides, pleuromutilins, and streptogramin A). We describe the first detection of cfr-mediated linezolid resistance in Staphylococcus aureus and Staphylococcus epidermidis recovered from human infection cases monitored during the 2007 LEADER Program.

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Available from: Michael Saubolle
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    • "The most frequently reported mechanism of resistance involves mutation at nucleotide position 2576 (G2576T) in domain V of the 23S rRNA, and it is believed to occur sporadically as the mechanism of resistance has been shown not to be transferable to other strains or species. Recently, a new mechanism of linezolid resistance primarily in staphylococci has been reported (Mendes et al., 2008). In these cases, the resistance is mediated by acquisition of cfr (chloramphenicol-florfenicol) gene. "
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    ABSTRACT: Recent studies have described linezolid-resistant MRSA and vancomycin-resistant enterococci (VRE) occurring worldwide, including an outbreak of linezolid-resistant MRSA. The objective of this study was to determine if linezolid-resistant enterococci are present in clinical isolates in Ontario, Canada. From January 2010 to June 2012, all enterococcal isolates submitted to the Public Health Ontario Laboratory (PHOL) for confirmation of VRE and susceptibility testing were included in this study. Of 2829 enterococcal isolates tested, 12 Enterococcus faecium were found to be resistant to linezolid. All linezolid-resistant isolates were also resistant to ampicillin, ciprofloxacin, and vancomycin. In addition, 33% of isolates were non-susceptible to daptomycin, whereas 41% were resistant to quinupristin/dalfopristin. Molecular characterization of these isolates showed that 8/12 isolates (66.7%) contained the mutation G2576T in 23S rRNA, which has been associated with linezolid resistance. Amplification and sequencing of L3- and L4-coding genes did not reveal mutations associated with linezolid resistance. One isolate contained the cfr gene, which is associated with linezolid resistance, and has been found in staphylococcal species and E. faecalis. These data show that occurrence of linezolid resistance is still rare among enterococcal isolates referred to PHOL though detection of cfr in E. faecium is concerning as it has the potential to disseminate among other enterococci.
    Full-text · Article · Oct 2013 · Diagnostic microbiology and infectious disease
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    • "By 2001, resistant strains of MRSA and VRE were observed (Taubes, 2008). Linezolid is the only drug in its class approved for use, and it was highly surprising when resistance in the form of the cfr gene appeared (Mendes et al., 2008; Morales et al., 2010). Cfr confers resistance to several drugs – phenicols, lincosamides, oxazolidinones , pleuromutilins, and streptogramin A (PhLOPS A ). "

    Full-text · Article · Sep 2011 · Frontiers in Microbiology
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    • "However, the tnpA gene, which was located further upstream of the cfr gene on the pSCFS3 plasmid, yielded a negative result, suggesting that the upstream region of cfr on this isolate, significantly differed from that of the pSCFS3 plasmid [49]. In this S. epidermidis strain only the cfr gene was found [49]. "
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    ABSTRACT: Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development.
    Full-text · Article · Jul 2010 · Pharmaceuticals
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