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Ruoyan Ying,1,2 Xiaochen Huang,1 Yaxian Gao,1,3 Jie Wang,1 Yidian Liu,2 Wei Sha,2 Hua Yang1 1Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 2Tuberculosis Center for Diagnosis and Treatment, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200043, People’s Republic of China; 3School of Public Health, Guizhou Medical University, Guiyang, Guizhou Province, 550004, People’s Republic of ChinaCorrespondence: Hua YangShanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of ChinaTel/Fax +86 21 65115006 ex 3037Email yanghua97065@tongji.edu.cnWei ShaTuberculosis Center for Diagnosis and Treatment, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200043, People’s Republic of ChinaTel/Fax +86 21 13671758200Email shfksw@126.comBackground: 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.Keywords: Retreatment tuberculosis, XDR-MTB, MDR-MTB, Combined drug sensitivity, FICI, MIC |
