A randomized, double-blinded, controlled, multicenter clinical trial of linezolid versus vancomycin in the treatment of gram positive bacterial infection

Objective: To evaluate the efficacy and safety of linezolid for injection in the treatment of gram positive bacterial infection. Methods: In this randomized, double-blinded, controlled, multicenter clinical trial, patients with pneumonia or complicated skin and soft-tissue infections due to suspected or known gram-positive pathogens were randomized to receive either linezolid or vancomycin intravenously. Results: A total of 144 patients were enrolled and 142 patients received study medication. The modified intention-to-treat (MITT) set was 141. The per-protocol (PP) set was 116. The safety set was 142. In the analysis with PP set, at follow-up, the clinical efficacy rates of linezolid group and vancomycin group were 86.9% (53/61) and 61.7% (37/ 60) respectively with statistically significant difference. In the population of pneumonia, the efficacy rates were 78.6% (22/28) and 52.9% (18/34). In the population of complicated skin and soft tissue infection, the efficacy rates were 78.6% (22/28) and 52.9% (18/34). the bacterial eradication rate was 79.2% (42/53) in linezolid group and 61.5% (32/52) in vancomycin group, with statistically significant difference. In the population of pneumonia. the bacterial eradication rates were 77.3% (17/22) and 53.6% (15/28); in the population of complicated skin and soft tissue infection, the bacterial eradication rates were 80.6% (25/31) and 70.8%% (17/24). In the analysis with safety set, the incidence of drug-related adverse event was 25.4% (18/71) in linezolid group, including 14.1% (10/71) clinical adverse reaction, such as fever, rash, dyspepsia, and 15.5% (11/71) laboratory abnormality, such as liver function abnormality, mild leukopenia, thrombocytopenia. The incidence of drug-related adverse event in vancomycin group was 16.9% (12/71), including 15.5% (11/71) clinical adverse reaction, such as fever, rash, red man syndrome, and 5.2% (3/71) laboratory abnormality, mainly liver function abnormality. Discontinuation rate due to adverse event (AE) was 5.6% in linezolid group and 11.3% in vancomycin group. Discontinuation rate due to drug-related adverse reaction was 1.4% and 5.6%, respectively. All the isolated pathogens were susceptible to linezolid and vancomycin. Conclusions: Linezolid for injection is well-tolerated and effective in the treatment of pneumonia and complicated skin and soft tissue infection caused by gram-positive pathogens.