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In vitro Synergism of Six Antituberculosis Agents Against Drug-Resistant Mycobacterium tuberculosis Isolated from Retreatment Tuberculosis Patients
Infection and Drug Resistance ( IF 2.9 ) Pub Date : 2021-09-14 , DOI: 10.2147/idr.s322563 Ruoyan Ying 1, 2 , Xiaochen Huang 1 , Yaxian Gao 1, 3 , Jie Wang 1 , Yidian Liu 2 , Wei Sha 2 , Hua Yang 1
Infection and Drug Resistance ( IF 2.9 ) Pub Date : 2021-09-14 , DOI: 10.2147/idr.s322563 Ruoyan Ying 1, 2 , Xiaochen Huang 1 , Yaxian Gao 1, 3 , Jie Wang 1 , Yidian Liu 2 , Wei Sha 2 , Hua Yang 1
Affiliation
Background: 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 Mycobacterium tuberculosis (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.
Methods: 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.
Results: 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 MIC90 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.
Conclusion: 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.
中文翻译：
六种抗结核药物对复治结核病患者耐药结核分枝杆菌的体外协同作用
背景：再治疗结核病（TB）已成为耐药结核病的主要来源。与异烟肼 (INH) 和利福平 (RIF) 的联合用药相比，帕斯烟肼 (Pa) 和利福布丁 (RFB) 或利福喷丁 (RFP) 的联合用药似乎在体外对耐药结核分枝杆菌(MTB) 具有更好的活性，尤其是与莫西沙星 (MXF) 合用时。然而，关于 Pa、RFB、RFP 和 MXF 之间潜在协同作用的研究有限，或与标准 INH 和 RIF 组合的同时比较。
方法：针对 90 种耐药 MTB 评估了四种二药组合（INH 和 RIF、Pa 和 RFB、Pa 和 RFP、MXF 和 Pa）和两种三药组合（MXF 和 Pa 与 RFB 或 RFP 组合）的体外协同作用用棋盘法从复治结核病患者中分离菌株。计算每种组合的分数抑制浓度指数 (FICI)。
结果： Pa与RFB或RFP组合的协同活性高于INH和RIF或MXF和Pa，Pa与RFP组合的协同活性甚至高于RFB，尽管RFP产生MIC 9064 毫克/升，高于针对 90 种耐药 MTB 菌株的 8 毫克/升 RFB。同时，对于三药联用，MXF和Pa与RFB或RFP联用的协同作用相似。进一步的分层分析表明，对于 XDR-MTB 菌株，Pa 和 RFP 组合的协同作用也优于其他两种药物组合。
结论： Pa联合RFP的体外协同作用优于Pa联合RFB和标准INH联合RIF，可为结核病复治患者的新方案提供参考。
更新日期：2021-09-13
Methods: 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.
Results: 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 MIC90 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.
Conclusion: 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.
中文翻译：
六种抗结核药物对复治结核病患者耐药结核分枝杆菌的体外协同作用
背景：再治疗结核病（TB）已成为耐药结核病的主要来源。与异烟肼 (INH) 和利福平 (RIF) 的联合用药相比，帕斯烟肼 (Pa) 和利福布丁 (RFB) 或利福喷丁 (RFP) 的联合用药似乎在体外对耐药结核分枝杆菌(MTB) 具有更好的活性，尤其是与莫西沙星 (MXF) 合用时。然而，关于 Pa、RFB、RFP 和 MXF 之间潜在协同作用的研究有限，或与标准 INH 和 RIF 组合的同时比较。
方法：针对 90 种耐药 MTB 评估了四种二药组合（INH 和 RIF、Pa 和 RFB、Pa 和 RFP、MXF 和 Pa）和两种三药组合（MXF 和 Pa 与 RFB 或 RFP 组合）的体外协同作用用棋盘法从复治结核病患者中分离菌株。计算每种组合的分数抑制浓度指数 (FICI)。
结果： Pa与RFB或RFP组合的协同活性高于INH和RIF或MXF和Pa，Pa与RFP组合的协同活性甚至高于RFB，尽管RFP产生MIC 9064 毫克/升，高于针对 90 种耐药 MTB 菌株的 8 毫克/升 RFB。同时，对于三药联用，MXF和Pa与RFB或RFP联用的协同作用相似。进一步的分层分析表明，对于 XDR-MTB 菌株，Pa 和 RFP 组合的协同作用也优于其他两种药物组合。
结论： Pa联合RFP的体外协同作用优于Pa联合RFB和标准INH联合RIF，可为结核病复治患者的新方案提供参考。
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