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Assistant Professor of Pharmacy Practice, School of Pharmacy, University of the Pacific, Stockton, California, Clinical Pharmacist, Veterans Affairs San Diego Healthcare System, San Diego
PharmD Student, School of Pharmacy, University of the Pacific
Clinical Pharmacist, Veterans Affairs San Diego Healthcare System
Research Professor, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York
Assistant Professor of Medicine, New York Medical College, Infectious Disease Staff Physician, Westchester Medical Center, Munger 245, Valhalla, New York 10595, fax 914-594-4673, george_sakoulas{at}nymc.edu
Published Online, March 18, 2008. www.theannals.com, DOI 10.1345/aph.1K613
Methods. All patients who received at least one dose of linezolid
600 mg for treatment of a MRSA infection, with daily MRSA culture data, and
known linezolid MIC (in a central lab, Clinical and Laboratory Standards
Institute dilution methods), were eligible. Patients were grouped by baseline
MRSA linezolid MIC: 2 mg/L or less, or 4 mg/L. TBE was the number of days
until bacterial eradication for subjects who achieved eradication or the
duration of treatment with linezolid until the patient was dropped from the
study. Continuous variables were compared using Kruskal-Wallis ANOVA.
Categorical variables were compared using the 
2 or
Fisher's exact test. Median TBE was compared using Kaplan-Meier survival
analysis and the log rank test. Statistical procedures were performed with
Systat 11 (Systat Software Inc., Point Richmond, CA) or Epi Info 3.4.3
(Centers for Disease Control and Prevention,
www.cdc.gov/epiinfo).
Results. Fifty-four patients (median age 63 y, range 25-86), were evaluated. The median duration of linezolid therapy was 25.5 (4-120) days; 33 patients had MRSA with linezolid MICs of 2 mg/L or less and 21 had linezolid MICs of 4 mg/L. A trend toward higher linezolid MICs was noted for MRSA-associated respiratory infections (Table 1). No significant differences were noted in median TBE based on whether patients received linezolid for vancomycin intolerance or treatment failure. Linezolid clinical success rates at the end of treatment were 92% for MRSA with linezolid MICs of 2 mg/L or less and 79% for MRSA with linezolid MICs of 4 mg/L (p = 0.211). At the test-of-cure visit, success rates were 81% and 65%, respectively (p = 0.258). Patients with eradication were considered clinical successes at the end of treatment and at the test-of-cure visit. The overall TBE was 9 days. The median TBE was significantly longer when the linezolid MIC was 4 mg/L (22.5 days; n = 21) compared with the MIC of 2 mg/L or less (4 days; n = 33; p = 0.026). Four patients demonstrated MRSA with increases in linezolid MIC during therapy: 3 patients with MIC 2-4 mg/L and 1 patient with MIC 1-2 mg/L. TBE was 9.5 days and 25 days in 2 patients whose linezolid MIC increased from 2 to 4 mg/L; MRSA was not eradicated in the third patient whose MIC increased from 2 to 4 mg/L (69 days) or in the patient whose linezolid MIC increased from 1 to 2 mg/L (74 days).
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Discussion. Longer TBE was found for linezolid-susceptible MRSA when the linezolid MIC was 4 mg/L. This was interesting, given the fact that infections treated with longer courses of antibiotic therapy (ie, osteomyelitis, bloodstream) were associated with lower linezolid MICs compared with infections requiring shorter treatment (ie, respiratory tract). None of the patients had prior linezolid exposure.
Findings from this study should be interpreted with caution, given that it was small and retrospective and therefore is subject to confounding factors whereby the link between linezolid MIC and clinical and micro-biological outcomes may be an epi-phenomenon of other unappreciated variables. More studies are needed to confirm these findings, ideally, ones performed in a prospective manner and with clinical endpoints.
References
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