Clinical and Microbiological Aspects of Linezolid Resistance Mediated by the cfr Gene Encoding a 23S rRNA Methyltransferase

Abstract

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), the erm(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette mec type I. We were unable to detect the cfr gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the cfr gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of cfr-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method.

Identification and Characterization of the Multidrug Resistance Gene cfr in a Panton-Valentine Leukocidin-Positive Sequence Type 8 Methicillin-Resistant Staphylococcus aureus IVa (USA300) Isolate

“…However, the Vitek-2 software recommended that the linezolid susceptibilities should be manually changed to 4 g/ml and that the isolate should be reported as susceptible to linezolid. While the authors of a 2008 study (1) did not encounter problems using the Vitek system, they did report problems with detecting cfr-mediated linezolid resistance using disk diffusion and Etest. The authors found that a cfr-positive MRSA isolate was reported as linezolid susceptible after 24 h of incubation with the Etest and suggested that a longer incubation period was required to detect this resistance phenotype (1).…”

“…A cfr-positive MRSA isolate from a Colombian patient belonged to ST5/ST221-MRSA-I, and cfr was chromosomally located (1,45). A cfr-positive methicillin-susceptible S. (26).…”

Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

“…In Staphylococcus spp., oxazolidinone resistance is conferred by the Cfr rRNA methylase, encoded by the cfr gene (14,221,223,382). This enzyme methylates the 23S rRNA at position 2503 (382), and the gene is associated with mobile elements (41,243,382).…”

Investigation of Linezolid Resistance in Staphylococci and Enterococci

“…Mutation of linezolid binding sites is the most common mechanisms of resistance; however, acquired resistance mechanisms have now been described (7). One example of nonmutational resistance is acquisition of the natural cfr (chloramphenicol-florfenicol resistance) gene, which is a plasmid-carried gene encoding a protein which catalyzes the posttranscriptional methylation of the C-8 atom of a key residue (A2503) in the 23S rRNA (8).…”