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Chinese Journal of Antituberculosis ›› 2015, Vol. 37 ›› Issue (4): 377-382.doi: 10.3969/j.issn.1000-6621.2015.04.010

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Investigation of cross-resistance between rifampin and rifabutin in multidrug-resistant M.tuberculosis strains

SHEN Jing,ZHAO Yan-lin,PANG Yu,ZHANG Shun,DU Chang-ting,LIU Jie   

  1. Tuberculosis Reference Laboratory,Chongqing Institution of Tuberculosis Control and Prevention,Chongqing 400050,China
  • Received:2014-06-23 Online:2015-04-10 Published:2015-04-03
  • Contact: ZHANG Shun E-mail:ZS52077@sina.com

Abstract: Objective  To investigate the antibacterial effect of rifabutin and the cross-resistance between rifabutin and rifampin in multidrug-resistant Mycobacterium tuberculosis(MDR-TB)strains, to understand the mutation characteristics of rpoB gene among the strains with rifampin and rifabutin cross-resistance. Methods Using interval sampling method, 131 MDR-TB clinical strains were obtained from 401 MDR-TB isolates of National Drug Resistance Tuberculosis Baseline Survey in 2007—2008. Minimum inhibitory concentrations (MICs) of rifampin and rifabutin for these MDR-TB isolates were determined by microplate Alamar blue assay method.The mutations of rpoB gene were determined by DNA sequencing, and analyzed the effect of the rpoB gene mutations on rifabutin and rifampin cross resistance. Using SPSS 11.0 statistical analysis software, the cross-resistance was compared with Chi-square test. The difference was considered as statistical significance when P<0.05.  Results Of 131 MDR-TB strains, the median of rifampin MICs was 256 μg/ml, and the median of rifabutin MICs was 2 μg/ml. The cross resistant rate between rifampin and rifabutin was 76.47%(91/119). In addition, 113 isolates(86.26%, 113/131) harbored rpoB mutations, in which there were 7 types of single mutations, including codon 531, 526, 516, 513, 511, 522, and 533, codon 531(56.50%, 74/131) and codon 526(16.03%, 21/131) were the most frequently observed. Besides, the mutations at codon 526 and 531 were associated with cross-resistance between rifampin and rifabutin, their cross-resistance rates were 90.48%(19/21) and 78.38%(58/74) respectively, which had no statistically significant difference(χ2 were 9.641 and 8.223, P<0.05).  Conclusion Rifabutin has cross-resistance with rifampin, but rifabutin showed better antimicrobial ability. The M. tuberculosis isolates with different rpoB mutations showed different cross-resistance between rifabutin and rifampin.

Key words: Mycobacterium tuberculosis, Drug resistance, multiple, bacterial, Rifabutin, Rifampin, Microbial sensitivity tests, Bacterial proteins