Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project

作者：Matteo Zignol, Anna Dean, Natavan Alikhanova, Sönke Andres, Andrea Maurizio Cabibbe, Daniela María Cirillo, Andrei Dadu, Andries Dreyer, Michèle Driesen, Christopher Gilpin, Rumina Hasan, Zahra Hasan, Sven Hoffner, Ashaque Husain, Azhar Hussain, Nazir Ismail, Mostofa Kamal, Mikael Mansjö, Lindiwe Mvusi, Stefan Niemann, Shaheed Vally Omar, Ejaz Qadeer, Leen Rigouts, Sabine Ruesch-Gerdes, Marco Schito, Mehriban Seyfaddinova, Alena Skrahina, Sabira Tahseen, William A. Wells, Ya Diul Mukadi, Michael Kimerling, Katherine Floyd, Karin Weyer, Mario Raviǵlione · 发表于：The Lancet Infectious Diseases · 年份：2016 · DOI：10.1016/s1473-3099(16)30190-6 · 被引用次数：166 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、Pneumocystis jirovecii pneumonia detection and treatment

BACKGROUND: Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. METHODS: In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. FINDINGS: Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3·0-42·1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0-16·6% for ofloxacin, to 0·5-12·4% for levofloxacin, and 0·9-14·6% for moxifloxacin when tested at 0·5 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/mL was low in all countries. INTERPRETATION: Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resista...