Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci.
To assess the potential for emergence of resistance during the use of linezolid, we tested 10 clinical isolates of vancomycin-resistant enterococci (VRE) (four Enterococcus faecalis, five Enterococcus faecium, and one Enterococcus gallinarum) as well as a vancomycin-susceptible control (ATCC 29212) strain of E. faecalis. The enterococci were exposed to doubling dilutions of linezolid for 12 passes. After the final passage, the linezolid plate growing VRE contained a higher drug concentration with E. faecalis than with E. faecium. DNA sequencing of the 23S rRNA genes revealed that linezolid resistance in three E. faecalis isolates was associated with a guanine to uracil transversion at bp 2576, while the one E. faecium isolate for which the MIC was 16 microg/ml contained a guanine to adenine transition at bp 2505.
Prystowsky
J
J
Department of Medicine, Division of Infectious Diseases, Northwestern University Medical School, Chicago, Illinois, USA.
Siddiqui
F
F
Chosay
J
J
Shinabarger
D L
DL
Millichap
J
J
Peterson
L R
LR
Noskin
G A
GA
D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D016983:Enterococcus / Q000187:drug effects / Q000235:genetics*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D023303:Oxazolidinones / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000032:analysis; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics*; D020713:Vancomycin Resistance / Q000235:genetics*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid