RAPID PREDICTION OF RIFAMPIN SUSCEPTIBILITY OF MYCOBACTERIUM-TUBERCULOSIS

We evaluated the relationship between rifampin (RIF) susceptibility an d amino acid substitution in rpoB gene of Mycobacterium tuberculosis a nd the usefulness of rpoB gene sequencing in the rapid prediction of R IF susceptibility of M. tuberculosis in clinical specimens. A total of 76 genetic alterations in the 69 bp core region of rpoB gene were det ected in 74 of 130 M. tuberculosis strains. Examination of the correla tion between the minimum inhibitory concentrations (MICs) of RIF and a mino acid substitutions in the 69 bp core region of rpoB gene revealed that all 43 strains containing amino acid substitution with Leu or Tr p in codon 531 showed RIF-resistant phenotypes, with MICs greater than or equal to 64 mu g/ml. In contrast, a variable level of RIF suscepti bility was observed among strains containing amino acid substitutions in either codon 516 or codon 526. In the clinical study, we tested 26 sputum samples, two gastric lavages, and one synovial fluid sample obt ained from patients with tuberculosis. The RIF susceptibility predicte d by direct rpoB sequencing was satisfactorily compatible with the res ults of the RIF-susceptibility test and the MICs of RIF against isolat ed organisms. Our results suggest that rpoB gene sequencing is useful for the detection of M. tuberculosis in clinical samples as well as th e rapid prediction of RIF susceptibility of these strains.