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We report our experience with linezolid in an investigation of its use against resistant gram-positive bacterial infections. Fifteen patients who had renal failure (n= 6), recent liver transplantation (n= 5) or surgery (n= 6), cancer (n= 3), endocarditis (n= 2), or human im-munodeficiency virus infection (n= 1), along with infections due to vancomycin-resistant entero-coccus (VRE), and 2 patients with infections due to methicillin-resistantStaphylococcusspecies who had adverse reactions to vancomycin were treated with linezolid (600 mg every 12 h for 5-42 days (mean ± SD, 20.5 ± 3.5 days). Abscess drainage or prosthetic device removal was undertaken. Microbiological cure occurred in all 10 patients who completed therapy, and all 7 patients alive at follow-up were free of infection. No deaths were attributable to the index infection. Adverse events associated with linezolid use were mild leukopenia in 1 patient and nausea in another. It appears that administration of linezolid, in conjunction with surgical intervention or device removal, is an effective treatment option for serious resistant gram-positive bacterial infections.