Cross-resistance Between Rifampicin and Rifabutin and Its Relationship with rpoB Gene Mutations in Clinically Isolated MDR-TB Strains

Background : Despite the emerging danger of MDR-TB to human beings, there have only been a limited number of drugs developed to treat MDR-TB since 1970.This study investigated the cross-resistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDR-TB.In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDR-TB and RFP resistance. Methods :The MICs of RBU were tested against 126 clinical isolates of MDR-TB submitted to the clinical laboratory of National Masan TB Hospital in 2004.Five different concentrations (10-160μg/ml) were used for the MICs.The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing.Results : The rate of cross-resistance between RFP and RBU was 70.5%(74/105) at 20μg/ml RBU(ed note: How much RFP?)Most mutations (86.3%) occurred in the 524~534 codons.The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU.Conclusion : Based on the cross-resistance rate between RFP and RBU, RBU may be used effectively in some MDR-TB patients.Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed.However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.