Safety, efficacy and pharmacokinetics of linezolid for treatment of resistant Gram-positive infections in cancer patients with neutropenia.

BACKGROUND Linezolid is a recently approved oxazalidinone with extended activity against Gram-positive bacteria. We evaluated the results of linezolid therapy in neutropenic cancer patients with Gram-positive bacterial infections from a compassionate-use program. PATIENTS AND METHODS This was a prospective, multicenter, open-label, non-comparative, non-randomized compassionate-use treatment program in patients with serious Gram-positive infections. To qualify for enrollment patients were required to have an infection resistant to available antimicrobial agents, or in whom available agents had failed or to which they were intolerant. Patients with absolute neutrophil counts (ANC) <500 cells/mm(3) or <1000 cells/mm(3) and expected to decrease to <500 cells/mm(3), and who received linezolid 600 mg twice daily were included. Plasma samples for population pharmacokinetic analysis were collected. Clinical and microbiological assessments of outcomes were made at the end of therapy and at short-term follow-up. RESULTS Of the patients in the compassionate-use trial, 103 were neutropenic. The mean [standard deviation (SD)] age was 50.1 (17.5) years, 47% were female, and 47.6% had a baseline ANC </=100 cells/mm(3). The mean (SD) duration of linezolid therapy was 14.6 (11.4) days. The most common site of infection was the bloodstream (90.3%), and the most commonly identified pathogen was vancomycin-resistant Enterococcus faecium (83%). A total of 83 (80.5%) and 52 (50.4%) patients were evaluable for clinical and microbiological outcomes at the end of therapy, respectively. Clinical and microbiological cure rates in the evaluable patients were 79% and 86%, respectively. Linezolid was well-tolerated in this patient population, with an overall adverse event rate of 17.5%; 5% of patients required discontinuation of the drug due to side-effects. The pharmacokinetics of linezolid in patients with neutropenia did not differ from the overall compassionate-use population. CONCLUSIONS Linezolid was safe and effective in treating resistant Gram-positive infections in neutropenic cancer patients. Comparative clinical trials to evaluate further the effectiveness and safety of linezolid in this patient population are warranted.