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The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid (LZD). The mobilecfr gene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinicalcfr -positive strain was the 2005 Colombian methicillin-resistantStaphylococcus aureus (MRSA) isolate CM05. Here, through retrospective analysis of LZDr clinical strains from a U.S. surveillance program, we identified acfr -positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100,spa type t002, and multilocus sequence type 5 (ST5). In addition tocfr , LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the ∼37-kb conjugative p1128105cfr -bearing plasmid from 1128105 intoS. aureus ATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kbcfr -containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinaryProteus vulgaris isolate PV-01 and in U.S. clinicalS. aureus isolate 1900, although the presence of IS431 -like sequences is unique to p1128105. Thecfr gene environment in this early clinicalcfr -positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination.

Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing thecfrMultidrug Resistance Gene