Resistance to Linezolid Is Mediated by thecfrGene in the First Report of an Outbreak of Linezolid‐ResistantStaphylococcus aureus

Gracia Morales, Juan J. Picazo, Elvira Baos, Francisco J. Candel, Ana Arribi, Beatriz Peláez, Raquel Andrade, María‐Ángeles de la Torre, José Fereres, Miguel Sánchez‐García
2010 Clinical Infectious Diseases  
Background. From April through June 2008, we identified 12 patients in the intensive care unit and 3 patients on other wards infected with methicillin-resistant Staphylococcus aureus that was also resistant to linezolid. We investigated the mechanism of resistance-point mutations in domain V of 23S ribosomal RNA (rRNA) or presence of the cfr gene-involved in the outbreak. Methods. Strains for the study were obtained in the intensive care unit and other wards. Minimal inhibitory concentrations
more » ... re determined using automated methods, the E-test, or dilution in Mueller-Hinton agar in accordance with Clinical and Laboratory Standards Institute guidelines. Strains were genotyped using pulsed-field gel electrophoresis and were sequenced to determine the presence of point mutations in 23S rRNA. The presence of the cfr gene was determined by specific polymerase chain reaction. Results. The minimal inhibitory concentrations of linezolid ranged from 16 mg/L to 32 mg/L, and all the strains were susceptible to tigecycline, vancomycin, and daptomycin. Typing of strains sequentially isolated by pulsed-field gel electrophoresis showed that each patient carried only 1 clonal type of linezolid-resistant, methicillinresistant S. aureus as detected by sequential isolations. The presence of the cfr gene was confirmed in all the isolates. Furthermore, sequencing of domain V of 23S rRNA showed that the most common mechanism of linezolid resistance reported to date, mutation G2576T, was not detected in any of the strains analyzed. Conclusions. We report the presence of the cfr gene underlying the resistance mechanism involved in a clinical outbreak of linezolid-resistant S. aureus. Linezolid is an oxazolidinone with antimicrobial activity against resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and Streptococcus species [1] . The drug binds to domain V of the 23S ribosomal RNA (rRNA) of the 50S subunit of bacterial ribosomes, thus inhibiting protein synthesis [1, 2]. Because linezolid is a completely synthetic drug, no natural reservoir of resistance genes would be expected to favor the appearance of clinical resistance. In fact, the
doi:10.1086/650574 pmid:20144045 fatcat:uwqhjkw7jjc5vgedf57cd3xb6m