Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China; National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing 102206, People's Republic of China.
Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China.
Int J Antimicrob Agents. 2015 Jan;45(1):71-5. doi: 10.1016/j.ijantimicag.2014.09.012. Epub 2014 Oct 18.
Clofazimine (CLO) is a promising candidate drug for use in the management of multidrug-resistant tuberculosis (MDR-TB) patients. In this study, the minimum inhibitory concentration (MIC) method was used to investigate drug susceptibility to CLO as well as potential synergies between CLO and other antituberculous drugs, including ethambutol (EMB), levofloxacin (LEV), moxifloxacin (MOX), amikacin (AMK) and capreomycin (CAP), among MDR-TB isolates from China. A total of 195 MDR-TB isolates were collected from the national drug resistance survey conducted in China. Of the 195 MDR-TB isolates, 54 (27.7%) were classified as CLO-resistant, whilst 141 (72.3%) were CLO-susceptible with MICs of ≤ 1 μg/mL. In addition, the prevalence of CLO-resistant isolates among the extensively drug-resistant (XDR)-TB group was 61.5% (8/13), which was significantly higher than that of the MDR-TB group (23.0%) (P = 0.006). When fractional inhibitory concentration indexes (FICIs) were calculated for 24 isolates, synergy was found in 11 isolates (45.8%) against the CLO/EMB combination, 6 (25.0%) against the CLO/LEV combination, 8 (33.3%) against the CLO/MOX combination, 4 (16.7%) against the CLO/AMK combination and 5 (20.8%) against the CLO/CAP combination. In addition, <15% of MDR-TB isolates showed antagonistic effects against these five combinations. In conclusion, these findings demonstrate that the combination of CLO and EMB shows better synergism than the other combinations containing CLO. The CLO/MOX combination is more likely to show synergy against MDR-TB isolates than the CLO/LEV combination. Taken together, we suggest that CLO, in combination with EMB or MOX, may be a promising drug regimen for the treatment of MDR-TB.
氯法齐明（CLO）是一种有前途的候选药物，可用于治疗耐多药结核病（MDR-TB）患者。在这项研究中，采用最低抑菌浓度（MIC）法研究了 CLO 对 MDR-TB 分离株的药物敏感性以及 CLO 与其他抗结核药物（包括乙胺丁醇（EMB）、左氧氟沙星（LEV）、莫西沙星（MOX）、阿米卡星（AMK）和卷曲霉素（CAP））之间的潜在协同作用。共从中国全国耐药调查中收集了 195 株 MDR-TB 分离株。在 195 株 MDR-TB 分离株中，54 株（27.7%）被归类为 CLO 耐药，而 141 株（72.3%）对 CLO 敏感，MIC 值≤1μg/ml。此外，在广泛耐药（XDR）-TB 组中，CLO 耐药分离株的患病率为 61.5%（8/13），明显高于 MDR-TB 组（23.0%）（P=0.006）。当计算 24 株分离株的部分抑菌浓度指数（FICI）时，发现 CLO/EMB 组合有 11 株（45.8%）表现出协同作用，CLO/LEV 组合有 6 株（25.0%），CLO/MOX 组合有 8 株（33.3%），CLO/AMK 组合有 4 株（16.7%），CLO/CAP 组合有 5 株（20.8%）。此外，<15%的 MDR-TB 分离株对这五种组合表现出拮抗作用。总之，这些发现表明 CLO 与 EMB 联合使用比其他含有 CLO 的组合具有更好的协同作用。CLO/MOX 组合对 MDR-TB 分离株更有可能表现出协同作用，而 CLO/LEV 组合则不然。综上所述，我们建议 CLO 联合 EMB 或 MOX 可能是治疗 MDR-TB 的一种有前途的药物方案。
