title: In vitro synergistic activity of clofazimine and other antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis isolates.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China.
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Li
authors.affiliation: Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China.
authors.forename: Geping
authors.initials: G
authors.lastname: Qu
authors.affiliation: 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. Electronic address: pangyu@chinatb.org.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pang
authors.affiliation: 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.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D002681:China; D002991:Clofazimine / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D002991:Clofazimine
keywords: Clofazimine; Multidrug resistance; Synergy; Tuberculosis