Tuberc Respir Dis.  2006 Feb;60(2):171-179.

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

• Kim BJ
• Oh SH
• Cho EJ
• Park SK

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.

Keyword

MDR-TB; cross-resistance; rifabutin; rifampin; rpoB mutation

MeSH Terms

Codon
Humans
Oligonucleotide Probes
Rifabutin*
Rifampin*
Codon
Oligonucleotide Probes
Rifabutin
Rifampin

Figure

• 

  Figure 1 The representative figure of results of REBA MTB-Rifa® No.1 shows no rpoB mutation. All of 5 sensitive bands are there. No.2 shows TCG(Ser)531TTG(Leu) mutation. There is 531TTG band instead of wt5 band. No.3 indicates the isolate has a rpoB mutation other than TCG(Ser)531TTG(Leu) on wt5(530-532) because of missing 531TTG band. No.4 is GAC(Asp)516GTC(Val) mutation. No.5 shows the isolate is not M. tuberculosis because of missing TB band.

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