Mycobacteriology
Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex

https://doi.org/10.1016/j.diagmicrobio.2016.01.019Get rights and content
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Highlights

  • Differential resistance between RIF and RFB was studied in 164 clinical isolates.

  • 122 isolates had rpoB mutations; 42 were unique.

  • RFB and RIF MICs were determined for isolates with or without rpoB mutations.

  • We identified 10 rpoB mutations conferring RIF-resistance but RFB-susceptibility.

  • Clinical studies to assess RFB treatment in certain multidrug-resistant tuberculosis cases are recommended.

Abstract

Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 μg/mL by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 μg/mL and 0.5 μg/mL, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L, and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations using RFB to treat multidrug-resistant tuberculosis cases harboring those mutations are recommended.

Keywords

Mycobacterium tuberculosis
multi-drug resistant tuberculosis
rifabutin
molecular drug-susceptibility

Cited by (0)

Partial results of this study were presented at 2012 ASM General Meeting in San Francisco.

1

Current affiliation: San Mateo County Department of Health Public Health Laboratory, San Mateo, CA.

2

Current affiliation: Roche Molecular Diagnostics, Pleasanton, CA.

3

Current affiliation: Kern County Health Department Public Health Laboratory, Bakersfield, CA.