JAC Advance Access published online on January 7, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh048
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Clinical
Microbiology, University College London Hospitals, Grafton Way, London WC1E 6DB;
* Corresponding author. E-mail: peter.wilson{at}uclh.org.
Received 8 May 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
Linezolid versus teicoplanin in the treatment of
Gram-positive infections in the critically ill: a randomized, double-blind,
multicentre study
2 Bloomsbury Institute of Intensive
Care Medicine, Department of Medicine, UCL, London;
3 Department of Clinical
Microbiology, University College London Hospitals, Grafton Way, London WC1E 6DB: Department of Medical Microbiology, Royal Free
Hospital, London, UK;
4 Intensive Care Unit, Royal Free
Hospital, London, UK;
5 Intensive Care Unit, Royal Free
Hospital, London, UK
6 Department of Medical Microbiology, Royal Free
Hospital, London, UK;
7 Pharmacy Department,
University College London Hospitals, Grafton Way, London WC1E 6DB;
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