Publication
Title
Specific gyrA gene mutations predict poor treatment outcome in MDR-TB
Author
Abstract
Mutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M. tuberculosis patients treated with fourth-generation fluoroquinolones. We analysed treatment outcome data in relation to the gyrA and gyrB sequences and MICs of ofloxacin, gatifloxacin and moxifloxacin for pretreatment M. tuberculosis isolates from 181 MDR-TB patients in Bangladesh whose isolates were susceptible to injectable drugs. The gyrA 90Val, 94Gly and 94Ala mutations were most frequent, with the highest resistance levels for 94Gly mutants. Increased pretreatment resistance levels (> 2 mg/L), related to specific mutations, were associated with lower cure percentages, with no cure in patients whose isolates were resistant to gatifloxacin at 4 mg/L. Any gyrA 94 mutation, except 94Ala, predicted a significantly lower proportion of cure compared with all other gyrA mutations taken together (all non-94 mutantsaEuroS+aEuroS94Ala) [ORaEuroS=aEuroS4.3 (95% CI 1.4-13.0)]. The difference in treatment outcome was not explained by resistance to the other drugs. Our study suggests that gyrA mutations at position 94, other than Ala, predict high-level resistance to gatifloxacin and moxifloxacin, as well as poor treatment outcome, in MDR-TB patients in whom an injectable agent is still effective.
Language
English
Source (journal)
The journal of antimicrobial chemotherapy. - London, 1975, currens
Publication
London : 2016
ISSN
0305-7453 [print]
1460-2091 [online]
Volume/pages
71:2(2016), p. 314-323
ISI
000372427600006
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
INTERRUPTB: Estimating the effective reproductive rate of M. tuberculosis from changes in molecular clustering rates, to measure the impact of public health interventions on TB transmission
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.05.2016
Last edited 16.09.2017
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