Efficacy and safety of linezolid in methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infection (cSSTI): a meta-analysis.
OBJECTIVE
To evaluate the clinical and microbiological outcomes of linezolid versus vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) using a meta-analysis.


METHODS
Clinical trials were identified using PubMed, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts from inception to March 2009. Primary outcomes evaluated resolution of signs and symptoms of infection in clinically evaluable (CE) patients, and microbiological eradication in both the modified intent-to-treat (MITT) and MRSA evaluable (MRSA ME) patients. MITT patients had a culture-confirmed Gram-positive pathogen (S. aureus) at baseline. Secondary outcomes included mortality, adverse drug reactions (ADR), and discontinuation due to ADRs. The Mantel-Haenszel odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed effects model based on the assumption that there was little to no heterogeneity between the studies in the primary analysis. Sensitivity analyses were performed for each outcome by removing the most weighted study.


RESULTS
Five studies with a total of 2652 patients (1361/linezolid; 1291/vancomycin) were identified. Resolution of infection in CE patients (OR = 1.41; 95% CI: 1.03, 1.95) and MITT patients (OR = 1.91; 95% CI: 1.33, 2.76) favored the use of linezolid over vancomycin, but did not remain significant after sensitivity analyses (CE: OR = 1.29; 95% CI: 0.81, 2.05; MITT: OR = 1.73; 95% CI: 0.87, 3.41). Microbiological eradication in MRSA ME patients consistently favored the use of linezolid over vancomycin (OR = 2.90; 95% CI: 1.90, 4.41). No difference in mortality was observed between the two groups (OR = 1.17; 95% CI: 0.85, 1.62). Higher proportions of linezolid patients were found to have diarrhea (119/1361 vs. 52/1291), nausea (102/1361 vs. 46/1291) and thrombocytopenia (54/1121 vs. 8/1071), whereas a higher proportion of vancomycin patients were found to have renal insufficiency compared to linezolid (16/634 vs. 4/703). Inconsistent results were seen with the incidence of anemia and rash between the base-case (anemia: OR = 1.36; 95% CI: 0.90, 2.08; rash: OR = 0.26; 95% CI: 0.10, 0.68) and sensitivity analyses (anemia: OR = 2.33; 95% CI: 1.24, 4.37; rash: OR = 0.57; 95% CI: 0.12, 2.71). Discontinuation due to ADRs was not statistically different between linezolid and vancomycin (OR = 1.06; 95% CI: 0.75, 1.51).


CONCLUSIONS
Resolution of infection in CE and MITT patients were inconsistent; however, a sub-analysis revealed that linezolid was more likely to consistently achieve microbiologic eradication in MRSA ME patients. Apparent risks of thrombocytopenia, nausea, diarrhea, and possibly anemia may limit linezolid use in treating MRSA cSSTI. This study was limited due to an inability to assess for the effects of hetero-resistance and appropriate vancomycin dosing on outcomes. Moreover, the small number of studies made controlling for heterogeneity challenging.
Bounthavong
Mark
M
Veterans Affairs San Diego Healthcare System; UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, 3350 La Jolla Village Drive (119-E), San Diego, CA 92161, USA. mark.bounthavong@va.gov
Hsu
Donald I
DI
D000081:Acetamides / Q000009:adverse effects* / Q000627:therapeutic use*; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects* / Q000627:therapeutic use*; D018461:Soft Tissue Infections / Q000150:complications / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy; D013207:Staphylococcal Skin Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid