Authors' objectives:

The aim of this report was to briefly review the usefulness of linezolid in its main indications.

Authors' results and conclusions: Nosocomial Pneumonia The Argentine Society of Infectology (Sociedad Argentina de Infectologia) (SADI), in its recently published Latin American Consensus on Nosocomial Pneumonia and the American Chest Society both recommend the use of linezolid as an alternative to vancomycin when this condition is caused by methylicin-resistant staphylococcus aureus (MRSA). Wunderlink, in a retrospective analysis of two prospective studies on Staphylococcus Aureus nosocomial pneumonia conclude that initial therapy with linezolid was associated to a significantly longer survival and higher clinical cure rates than vancomycin with an OR of 2.2; CI 95% (1.0 to 4.8; p<0.05). In a subgroup analysis, linezolid proved to be more effective than vancomycin in MRSA pneumonias, (80% vs. 63.5%; p=0.015). Another study done in patients with ventilator-associated pneumonia (Kollef, 2004) considers linezolid as an independent survival predictor. Cure rates were higher for linezolid than for vancomycin (84.1% vs 61.7%; p=0.02) in this subgroup. Skin and soft tissue infections Weigelt published one study comparing linezolid versus vancomycin in severe skin and soft tissue infections, in 2005. It is a multicenter, multinational, open-label RCT. A sample of 1,200 patients with suspected or confirmed MRSA infections was selected, with clinical diagnoses of cellulitis, abscesses, infected ulcers or burns. In the intention to treat analysis, 92.2% and 88.5% of the subjects treated with linezolid and vancomycin respectively were clinically cured (p=0.057). Results with linezolid were better in the MRSA patient subgroup (p<0.001). Differences in results were also statistically significant in the subgroup of patients with major skin infections and infections at the surgical site (p=0.026). In Itani's study, a sub-analysis of the previous one, the use of linezolid reduced hospital stay and length of intravenous therapy when compared with vancomycin for severe skin and soft tissue MRSA infections. Rates of discharge during the first 2 weeks were significantly higher with linezolid than with vancomycin (p<0.05), the difference exceeded 20% during the first week. In addition, therapy was not associated with increased rates of readmission related to the infection in question. Another analysis of the subgroup shows that linezolid was better at eradicating MRSA from surgical sites. 87 vs 48%) CI 95% of 16.5-60.3 p=0.002. Other indications It has been tested as a promising alternative for multiresistant tuberculosis, osteomyelitis, arthritis, prosthetic infections, central nervous system infections and endocarditis. In patients with enterococcal bacteremia, resistance to vancomycin is independently related to higher mortality and the U.S. FDA has granted linezolid with a license for this use. Adverse effects Most common adverse effects are gastrointestinal. Also, myelosuppression (mild-moderate) and reversible thrombocytopenia are described, especially in adult patients.

Authors' recommendations: The evidence currently available suggests that linezolid is as effective as any other antibiotic for most indications it was studied for. Its main application is in severe vancomycin-resistant Cocci Gram-positive infections, especially in the treatment of vancomycin-resistant enterococci (VRE). Even though there are studies suggesting that linezolid is more effective than vancomycin in staphylococcal infections, the application of these results is controversial due to some methodological issues. The concern about the emergence of resistance makes it reasonable to limit its use to those cases where no response to vancomycin is obtained, with suspected or confirmed etiology due to MRSA, particularly in nosocomial pneumonia, ventilator-associated pneumonia and skin/soft tissue infections in adult and pediatric patients.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)