Absence of hybridization with the wild-type and mutant rpoB probes in the Genotype MTBDRplus assay detects 'disputed' rifampicin mutations.

Autor:	Abanda NN; Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Mānoa, HI, USA; Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon., Djieugoué JY; Centre Pasteur du Cameroun, Yaoundé, Cameroon., Khadka VS; Bioinformatics Core, Department of Complementary & Integrative Medicine, John A. Burns School of Medicine, University of Hawaii at Mānoa, HI, USA., Pefura-Yone EW; Pneumology Service, Yaoundé Jamot Hospital, Yaoundé, Cameroon., Mbacham WF; Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon., Vernet G; Centre Pasteur du Cameroun, Yaoundé, Cameroon., Penlap VM; Centre Pasteur du Cameroun, Yaoundé, Cameroon., Deng Y; Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon., Eyangoh SI; Centre Pasteur du Cameroun, Yaoundé, Cameroon., Taylor DW; Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Mānoa, HI, USA. Electronic address: dwtaylor@hawaii.edu., Leke RGF; Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon.
Jazyk:	angličtina
Zdroj:	Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases [Clin Microbiol Infect] 2018 Jul; Vol. 24 (7), pp. 781.e1-781.e3. Date of Electronic Publication: 2017 Dec 05.
DOI:	10.1016/j.cmi.2017.11.021
Abstrakt:	Objective: Mycobacterium tuberculosis isolates that fail to hybridize to at least one rpoB wild-type or any mutation probe on the Genotype MTBDRplus strip are assumed to be rifampicin-resistant. However, the precise mutation(s) are unknown. We sought to identify the mutations in isolates with such hybridization patterns and determine if the mutations are associated with resistance to rifampicin. Methods: In this study, 275 M. tuberculosis isolates were screened with the Genotype MTBDRplus assay to identify isolates with the hybridization pattern. These isolates were sequenced and their minimum inhibitory concentrations (MIC) determined using the Bactec MGIT 960 system. Results: Among the 275 isolates tested, 15 (6%) isolates with the hybridization pattern were identified. Sequencing showed that failure to hybridize to rpoB wild-type probes resulted from the presence of 'disputed' rifampicin mutations, which are mutations not always associated with a rifampicin-resistant phenotype. All, except 3/15, isolates had a rifampicin-resistant phenotype (MIC > 1 μg/mL). One of the three isolates with a rifampicin-susceptible phenotype had the same mutation at position 526 (His526Leu) as another isolate that had a rifampicin-resistant phenotype. Conclusion: The recommendation of the Genotype MTBDRplus assay to assume rifampicin resistance based solely on failure to hybridize to rpoB wild-type probe allows the identification of important RIF-resistant isolates. About 20% (3/15) of such isolates could be missed by relying only on the standard MGIT 960 DST assay for drug susceptibility testing. (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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