Chimie médicale

Investigation of Cross-Resistance between Rifampin and Rifabutin in Multi-Drug Resistant Mycobacterium tuberculosis

Abstract

Liping Yan, Li Gao, Zhenling Cui, Zhongyi Hu, Junmei Lu, Xiaona Shen and Heping Xiao

Objective: In order to indicate the cross-resistance between rifampin (RFP) and rifabutin (RFB) in multi-drug resistant Mycobacterium tuberculosis (MDR-TB) clinical strains and to provide the laboratory data for using rifabutin in the treatment of MDR-TB.
Methods: The minimal inhibitory concentrations (MICs) of RFB and RFP in 7H10 Middlebrook medium against 99 MDR-TB clinical strains were determined by microplate assays.
Results: Among these 99 isolates, 85 were resistant to rifabutin at concentrations >0.5 μg/ml. The cross-resistance ratio between rifampin and rifabutin was 85.86%. The MICs of RFB were 8-32 times lower than those of RFP (χ²=125.905, p<0.001). The crossresistance ratio increased with the resistance level of RFP. The cross-resistance strains in the lower (the MICs of RFB 2 ~ 4 μg/ml) and the medium groups (the MICs of RFB 8 ~ 16 μg/ml) were 0/9 and 5/9 respectively, while in the high rifampin-resistant group (the MICs of RFB ≥ 32 μg/ml) almost all of the strains but one were cross-resistant (98.8%, 80/81).
Conclusion: RFB has the activities against MDR-TB clinical strains in vitro. The cross-resistance ratio between rifampin and rifabutin increased with the resistance level of RFP. RFB is one of alternativese for the treatment of MDR-TB.