Efficacy and Safety of Linezolid for the Treatment of Extensively Drug Resistant Tuberculosis: A Prospective, Multicenter, Randomized Study in China

Abstract

PURPOSE: The treatment of XDR-TB is less effective than that of other forms of TB because of the lack of efficacious anti-TB drugs so that the infection is frequently fatal. To investigate the efficacy and safety of linezolid containing chemotherapy in patients with XDR-TB in China. METHODS: We conducted a multicenter, prospective, randomized, controlled trial in five large-scale Tuberculosis Specialized Hospitals in China. 65 patients were randomly assigned to linezolid therapy group and control group. Patients in two groups were adopted two years of individual-based chemotherapy regimens based on the patient medication history and drug susceptibility test results. Linezolid therapy group was added to linezolid that started at a dose of 1200 mg per day for 4 to 6 weeks, followed by 300 to 600 mg per day for at least 6 months. Sputum conversion rate, cavity closure rate, treatment outcomes and adverse events were compared between two groups. RESULTS: The proportion of sputum-culture conversion in the Lzd group was 78.8% by 24 m, significantly higher than that in the control group (37.6%, P < 0.001). The cavity closure rate in the Lzd group was 69.7% by the end 24th month respectively, significantly higher than that of the control group (P <0.05). The treatment success rate in Lzd group was 69.7%, significantly higher than that in control group (34.4%, P<0.004), whereas poor treatment outcomes were more common in control group than in the Lzd group (65.6 vs. 30.3%; P=0.004). 27 (81.8%) patients had clinically significant adverse events in the Lzd group, of whom 25 patients (75.8%) had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid. CONCLUSIONS: Linezolid containing chemotherapy for treatment of XDR-TB may significantly promote cavity closure, accelerate sputum culture conversion and improve treatment success rates. Meanwhile adverse reaction might be tolerated and resolve after suitable intervention.