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

Kim, Byoung Ju; Oh, Seung Hwan; Cho, Eun Jin; Park, Seung Kyu

doi:2006.60.2.171

Tuberc Respir Dis > Volume 60(2); 2006 > Article

Original Article

Tuberculosis and Respiratory Diseases 2006;60(2):171-179.
DOI: https://doi.org/10.4046/trd.2006.60.2.171 Published online February 1, 2006.

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

Byoung Ju Kim, Seung Hwan Oh, Eun Jin Cho, Seung Kyu Park

¹National Masan Hospital, Masan, Korea. byoungju_kim@yahoo.com
²International Tuberculosis Research Center, Masan, Korea.

Abstract

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 (10-160 microgram/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 20 microgram/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.

Key Words: MDR-TB, cross-resistance, rifabutin, rifampin, rpoB mutation