Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis.
BACKGROUND
Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. However, clinical superiority has not been demonstrated.


OBJECTIVE
To test the hypothesis that linezolid may be superior to glycopeptides.


METHODS
Prospective randomized trials that tested linezolid vs. vancomycin or teicoplanin for treatment of nosocomial pneumonia were included. Heterogeneity was analyzed by I(2) and Q statistics. Meta-analysis relative risks were based on fixed and random-effects models. Outcomes evaluated consisted of clinical cure, microbiological eradication, and side effects.


RESULTS
Nine linezolid trials (vancomycin [7]; teicoplanin [2]) were included (n = 2329). The linezolid vs. glycopeptide analysis shows clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I(2) = 0%) and microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98 -1.22; p = .10; I(2) = 0%). Methicillin-resistant Staphylococcus aureus subgroup analysis yielded a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.87-1.38; p = .44; I(2) = 16%). If linezolid is compared with vancomycin only, then clinical cure relative risk is 1.00 (95% confidence interval, 0.90-1.12), microbiological eradication and methicillin-resistant Staphylococcus aureus relative risks are 1.07 (95% confidence interval, 0.90-1.26; p = .45) and 1.05 (95% confidence interval, 0.82-1.33; p = .71). The risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = .001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = .02) are higher with linezolid, but no differences are seen for renal dysfunction (relative risk, 0.89; 95% confidence interval, 0.56-1.43; p = .64) or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = .63).


CONCLUSIONS
Our study does not demonstrate clinical superiority of linezolid vs. glycopeptides for the treatment of nosocomial pneumonia despite a statistical power of 95%. Linezolid shows a significant two-fold increase in the risk of thrombocytopenia and gastrointestinal events. Vancomycin and teicoplanin are not associated with more renal dysfunction than linezolid.
Kalil
Andre C
AC
University of Nebraska Medical Center, Omaha, NE, USA. akalil@unmc.edu
Murthy
Madhu H
MH
Hermsen
Elizabeth D
ED
Neto
Felipe K
FK
Sun
Junfeng
J
Rupp
Mark E
ME
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D004502:Education, Medical, Continuing; D006801:Humans; D000069349:Linezolid; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000139:chemically induced; D017334:Teicoplanin / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D017334:Teicoplanin; D014640:Vancomycin; D000069349:Linezolid