Predicting differential rifamycin resistance in clinical Mycobacterium tuberculosis isolates by specific rpoB mutations
OBJECTIVE: To determine if specific rpoB mutations reliably predict differential phenotypic resistance to RMP and RBT.
DESIGN: We selected 60 clinical M. tuberculosis isolates from a repository of multinational multidrug-resistant tuberculosis isolates and stratified them into two groups: 1) those with rpoB mutations suspected to confer differential resistance to RMP and RBT, and 2) those expected to be cross-resistant to RMP and RBT. These assumptions were tested by comparing the phenotypic susceptibilities of RMP/RBT with those predicted by mutations in the rpoB gene.
RESULTS: Of 20 suspected RMP-resistant/RBT-susceptible isolates, 15 were RMP-resistant but RBT-susceptible, 3 were RMP- and RBT-susceptible, and 2 were cross-resistant to both RMP and RBT. In comparison, 40 of 40 suspected cross-resistant isolates were both RMP- and RBT-resistant.
CONCLUSION: Our data support the association between specific rpoB mutations and differential resistance of M. tuberculosis to RMP and RBT. Clinical studies are required to investigate the efficacy of RBT in the treatment of M. tuberculosis harboring these mutations.
Keywords: MDR-TB; diagnostics; rifabutin; rifampin
Document Type: Research Article
Affiliations: 1: Department of Medicine, University of California San Diego, San Diego, USA 2: Department of Medicine, Stanford University School of Medicine, Stanford, USA 3: California Department of Public Health, Richmond, California, USA 4: Department of Microbiology, P D Hinduja Hospital Medical Research Centre, Veer Sarvarkar Marg, Mumbai, India 5: Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa 6: Microbiology and Morphology Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova 7: Tropical Disease Foundation/Makati Medical Center, Makati City, The Philippines
Publication date: 01 October 2015
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