Linezolid for the Treatment of Multidrug‐Resistant, Gram‐Positive Infections: Experience from a Compassionate‐Use Program

TLDR

Linezolid was administered under a compassionate‑use program to 796 patients with multidrug‑resistant gram‑positive infections, receiving 600 mg intravenously or orally every 12 h across 828 treatment courses. The program treated 796 patients with MDR gram‑positive infections, achieving clinical cure in 73.3 % (91.5 % at test of cure) and microbiological cure in 82.4 % (85.8 % at test of cure), with vancomycin‑resistant enterococci and methicillin‑resistant staphylococci comprising 66.3 % and 22.1 % of pathogens; the most frequent adverse events were gastrointestinal disturbances (9.8 %), thrombocytopenia (7.4 %), anemia (4.1 %), and skin reactions (4.0 %), demonstrating high efficacy and good tolerance.

Abstract

Linezolid was provided for treatment of multidrug-resistant, gram-positive infections through a compassionate-use program. Patients (n=796) received 600 mg of linezolid intravenously or orally every 12 h (828 treatment courses). Bacteremia was present in 46% of infections, endocarditis was present in 10.6%, and line-related infections were present in 31.1%. Other infections included intraabdominal infections (15.1%), complicated skin and skin-structure infections (13.3%), and osteomyelitis (10.7%). Causative pathogens included vancomycin-resistant enterococci (66.3%) and methicillin-resistant staphylococci (22.1%). Clinical intent-to-treat (ITT) outcomes in the evaluable population were as follows: cure, 73.3%; failure, 6.8%; and indeterminate, 19.9%. Microbiological ITT outcomes in evaluable patients were as follows: cure, 82.4%; failure, 14.1%; and indeterminate, 3.5%. At the test of cure assessment, the clinical cure and microbiological success rates were 91.5% and 85.8%, respectively. The most common adverse events possibly related to linezolid use were gastrointestinal disturbances (9.8% of cases), thrombocytopenia (7.4% of cases), decreased hemoglobin/hematocrit levels (4.1% of cases), and cutaneous reactions (4.0% of cases). Linezolid provided high rates of clinical cure and microbiological success in this complicated patient population, with very good overall tolerance.