Ying Ruoyan, Huang Xiaochen, Gao Yaxian, Wang Jie, Liu Yidian, Sha Wei, Yang Hua
Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China.
Tuberculosis Center for Diagnosis and Treatment, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200043, People's Republic of China.
Infect Drug Resist. 2021 Sep 14;14:3729-3736. doi: 10.2147/IDR.S322563. eCollection 2021.
Retreatment tuberculosis (TB) has become a major source of drug-resistant TB. In contrast to the combination of isoniazid (INH) and rifampicin (RIF), that of pasiniazid (Pa) and rifabutin (RFB) or rifapentine (RFP) appears to have better activity in vitro against drug-resistant (MTB), especially when combined with moxifloxacin (MXF). However, there has been limited study of potential synergism among Pa, RFB, RFP, and MXF, or simultaneous comparison with the standard INH and RIF combination.
In vitro synergism of four two-drug combinations (INH and RIF, Pa and RFB, Pa and RFP, MXF and Pa) and two three-drug combinations (MXF and Pa combined with RFB or RFP) was evaluated against 90 drug-resistant MTB strains isolated from retreatment TB patients by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each combination.
The synergistic activity of the combination of Pa with RFB or RFP was higher than that of INH and RIF or MXF and Pa, and the synergistic activity of Pa in combination with RFP was even higher than that of RFB, although RFP yielded an MIC of 64 mg/liter, higher than that of RFB of 8 mg/liter against 90 drug-resistant MTB strains. Meanwhile, for three-drug combinations, the synergistic effects of MXF and Pa combined with RFB or RFP were similar. Further stratification analysis showed that, for XDR-MTB strains, the synergistic effect of the Pa and RFP combination was also better than those of other two-drug combinations.
The combination of Pa with RFP shows better in vitro synergism than Pa with RFB and standard INH with RIF combinations, which can provide a reference for new regimens for retreatment TB patients.
复治肺结核已成为耐多药结核病的主要来源。与异烟肼（INH）和利福平（RIF）联合使用相比，帕司烟肼（Pa）与利福布汀（RFB）或利福喷汀（RFP）联合使用在体外对耐药结核分枝杆菌（MTB）似乎具有更好的活性，尤其是与莫西沙星（MXF）联合使用时。然而，关于Pa、RFB、RFP和MXF之间潜在协同作用的研究有限，也缺乏与标准INH和RIF联合使用的同步比较。
采用棋盘法评估四种两药联合方案（INH和RIF、Pa和RFB、Pa和RFP、MXF和Pa）以及两种三药联合方案（MXF和Pa联合RFB或RFP）对90株从复治肺结核患者中分离出的耐药MTB菌株的体外协同作用。计算每种联合方案的部分抑菌浓度指数（FICI）。
Pa与RFB或RFP联合使用的协同活性高于INH和RIF或MXF和Pa联合使用，且Pa与RFP联合使用的协同活性甚至高于RFB，尽管在90株耐药MTB菌株中，RFP的最低抑菌浓度（MIC）为64mg/L，高于RFB的8mg/L。同时，对于三药联合方案，MXF和Pa联合RFB或RFP的协同效果相似。进一步的分层分析表明，对于广泛耐药MTB菌株，Pa和RFP联合使用的协同效果也优于其他两药联合方案。
Pa与RFP联合使用在体外显示出比Pa与RFB以及标准INH与RIF联合使用更好的协同作用，可为复治肺结核患者的新治疗方案提供参考。
