Linezolid for the management of severe cocci gram-positive infections

PICHON-RIVIERE A,; AUGUSTOVSKI, F; ALCARAZ A; BARDACH, ARIEL; FERRANTE, D; GARCIA MARTÍ, SEBASTIAN; GLUJOVSKY, D; LOPEZ, A; REGUEIRO, A

Documentos de Evaluación de Tecnologías Sanitarias

IECS

Año: 2006 p. 1 - 30

1668-2793

The aim of this report was to briefly review the usefulness of linezolid in its main indications.A search was carried out on the main literature databases (MEDLINE, Cochrane Collaboration, DARE, LILACS, NHS NICE, EMBASE) Centre for Reviews and Dissemination, York University (CRD), U.S. Medicare and Medicaid, on the Internet s general search engines, health technology assessment agencies and health sponsors. Priority was given to meta-analysis, randomized controlled trials (RCTs), studies on the use of resources and cost-effectiveness. Also, case series and other retrospective studies were included. Assessment of sanitary technologies and economic evaluations; clinical practice guidelines and coverage policies of other health systems were also searched for. In addition, other local sources were consulted (Argentine Society of Infectology).Nosocomial PneumoniaThe 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 indicationsIt 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 effectsMost common adverse effects are gastrointestinal. Also, myelosuppression (mild-moderate) and reversible thrombocytopenia are described, especially in adult patients.Consumer price for daily treatment with 1 gr Vancomycin bid is $240 (Argentine pesos 2006). Similar treatment with linezolid at 600 mg bid ranges from $402.6 to 461.70$.