Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study.
OBJECTIVE
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.
Cepeda
Jorge A
JA
Department of Clinical Microbiology, Pharmacy Department, University College London Hospitals, Grafton Way, London WC1E 6DB, UK.
Whitehouse
Tony
T
Cooper
Ben
B
Hails
Janeane
J
Jones
Karen
K
Kwaku
Felicia
F
Taylor
Lee
L
Hayman
Samantha
S
Shaw
Steven
S
Kibbler
Christopher
C
Shulman
Robert
R
Singer
Mervyn
M
Wilson
A Peter R
AP
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000188:drug therapy / Q000382:microbiology; D003422:Critical Care; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy / Q000382:microbiology; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000382:microbiology; D017334:Teicoplanin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D017334:Teicoplanin; D000069349:Linezolid