JAC Advance Access originally published online on January 7, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 345-355
© 2004 The British Society for Antimicrobial Chemotherapy
Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study
1 Department of Clinical Microbiology, 5 Pharmacy Department, University College London Hospitals, Grafton Way, London WC1E 6DB; 2 Bloomsbury Institute of Intensive Care Medicine, Department of Medicine, UCL, London; 3 Department of Medical Microbiology, 4 Intensive Care Unit, Royal Free Hospital, London, UK
Received 8 May 2003; returned 3 October 2003; revised 3 November 2003; accepted 4 November 2003
Objectives: Linezolid, the only commercially available oxazolidinone, is indicated for the treatment of Gram-positive infections, although little has been published specifically on its use in the critically ill. A randomized, prospective study was therefore performed to compare linezolid with the glycopeptide antibiotic, teicoplanin, for the treatment of suspected or proven Gram-positive infections in an intensive care population.
Methods: Using a double-blind, double-dummy, prospective design, patients were randomized to (i) intravenous linezolid (600 mg/12 h) plus teicoplanin dummy [one dose/12 h for three doses then every 24 h intravenously (iv)] or (ii) teicoplanin (400 mg/12 h for three doses then 400 mg/24 h iv) plus linezolid dummy (one dose/12 h iv). Other antibiotics were used in combination with the trial agents in empirical treatment. Clinical and microbiological assessments were made daily in the first week, and at 8 and 21 days after treatment.
Results: One hundred patients received linezolid plus placebo–teicoplanin, whereas 102 received teicoplanin plus placebo–linezolid. Population baseline characteristics were similar in both groups. At end of treatment, clinical success [71 (78.9%) linezolid versus 67 (72.8%) teicoplanin] and microbiological success [49 (70.0%) versus 45 (66.2%)] rates were similar, as were adverse effects, intensive care unit mortality, and success rates at short- and long-term follow-up. Linezolid was superior at initial clearance of methicillin-resistant Staphylococcus aureus (MRSA) colonization (end of treatment, 51.1% versus 18.6%, P = 0.002). Two MRSA isolates showed reduced susceptibility to teicoplanin.
Conclusions: Linezolid has similar safety and efficacy to teicoplanin in treating Gram-positive infections in the critically ill. Short-term MRSA clearance achieved with linezolid suggests better skin and mucosal penetration.
Keywords: bloodstream infections, methicillin-resistant Staphylococcus aureus, MRSA, methicillin-susceptible Staphylococcus aureus, MSSA
* Corresponding author. Tel: +44-207-380-9516; Fax: +44-207-388-8514; E-mail: peter.wilson{at}uclh.org
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