Critical care patients with significant, resistant, gram-postive infections enrolled in the linezolid compassionate use protocol

PURPOSE: To examine the safety, tolerance, and efficacy of linezolid (LZD)in treating critically ill patients (pts) with significant, resistant gram-positive infections. METHODS: Pts at least 28 days old with a significant infection are given IV or PO LZD in an open label, noncomparative, compassionate use protocol. All enrollment and follow-up is facilitated by a study center at 1-800-836-3535. RESULTS: As of May 1999, 92 sites had enrolled 151 ICU pts. 44.5% have been female. Mean age of the adults is 56.3 years. Mean age of the 11 pediatric pte (<18) enrolled is 7.8 years (0.6-17). Types of infections (%) are bacteremia (53.9) including endocarditis (4.5), GI - abscesses and peritonitis (26.6), skin/soft tissue (13.0), LRTI (3.9), UTI (2.0) and osteomyelitis (0.7). Causative organisms (%) include VRE faecium (83.1), MRSA (9.1), VRE faecalis (3.2), VRE other (1.9), MRSE (1.3), and VSE (0.7). Adverse events (%)considered possibly or probably related to LZD include: elevated liver enzymes (4.6), thrombocytopenia (4.0), rash (3.3), nausea/diarrhea (2.6), hypotension (2.0), hypertension (2.0), leukopenia (1.3), and anaphylaxis (0.7). Four serious adverse events possibly related to LZD occurred: thrombocytopenia (3)anaphylazis (1). 17 pts died on therapy; 62 died prior to long-term follow-up. Overall tolerance(135): Well tolerated (83.1%); some problems, drug continued (12.1%); drug not tolerated and DC'd (4.8%). DISCUSSION: LZD has been well tolerated and is an excellent option for treating seriously ill pts with gram-postive infections caused by resistant organisms. Test of Cure Outcomes for Evaluable Patients (Beyond End of Therapy) OUTCOME CLINICAL (N=45) MICRO (N=38) CURE (%) 86.7 84.2 FAILURE (%) 2.2 15.8 INDETER(%) 11.1 0.