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Abstract & Commentary
Synopsis: A Staphylococcus aureus isolate with an MIC to linezolid > 32 mg/L was isolated from a peritoneal dialysis patient who had received prolonged linezolid therapy for MRSA peritonitis.
Source: Tsiodras S, et al. Lancet. 2001;358:207-208.
An 85-year-old patient receiving peritoneal dialysis developed MRSA peritonitis. Because of a history of vancomycin allergy, he was treated with oral linezolid, 600 mg every 12 hours. The dialysis catheter was left in place. Over the ensuing 3 weeks, multiple MRSA isolates susceptible to linezolid (MIC = 2 mg/L) were recovered from the peritoneal fluid. One month after linezolid was started, the patient was readmitted with symptoms of recurrent peritonitis. Peritoneal fluid cultures yielded MRSA with a linezolid MIC > 32 mg/L on 3 separate occasions. During the remainder of the hospitalization, the patient received multiple antibiotics, including quinupristin/dalfopristin, ampicillin, azithromycin, gentamicin, and levofloxacin as treatment for MRSA, as well as for Enterococcus faecalis isolated from blood and Pseudomonas isolated from peritoneal fluid. The peritoneal fluid was ultimately sterilized, but the patient subsequently died. A total of 11 linezolid-susceptible isolates obtained during linezolid therapy were identical by pulsed field gel electrophoresis (PFGE). The 3 resistant isolates differed from the susceptible isolates by more than 6 bands—but were themselves closely related—differing by no more than 1 band. The resistant isolates showed a single G to T mutation at the same position in 23S rRNA-encoding DNA sequence.
Comment by Robert Muder, MD
This disturbing, but not unexpected, report follows closely after the report of the emergence of linezolid resistance in vancomycin-resistant Enterococcus faecium in the same journal.1,2 As in the prior report, isolation of a linezolid-resistant strain occurred following prolonged linezolid therapy. However, the linezolid-resistant S aureus was clearly not clonally related to the original susceptible strain. It is not clear whether this strain was acquired during therapy, or emerged from a different susceptible strain that had been unapparently colonizing the patient.
The latter may be more likely, as Tsiodras and colleagues identified no other linezolid-resistant S aureus isolates in their facility. At present, many laboratories do not routinely perform susceptibility testing of S aureus against linezolid, assuming universal susceptibility. While the occurrence of a single episode of resistance may not be sufficient to alter current practices, it would be prudent to test selected MRSA isolates for linezolid susceptibility. At a minimum, this should be done when linezolid is used to treat life-threatening infections such as staphylococcal bacteremia or pneumonia, or when the clinical or microbiologic response to linezolid is inadequate.
1. Gonzales RD, et al. Lancet. 2001;357:1179.
2. Muder R. Update: Infectious Disease Alert. 2001;20: 117-118.
Robert Muder is Hospital Epidemiologist for the Pittsburgh VA Medical Center, Section Editor of Hospital Epidemiology, and Associate Editor of Infectious Disease Alert.