期刊
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
卷 19, 期 2, 页码 185-190出版社
INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
DOI: 10.5588/ijtld.14.0651
关键词
tuberculosis; drug resistance; surveillance; rifampicin; rpoB gene
资金
- Damien Foundation Belgium
SETTING: Greater Mymensingh area, Bangladesh. OBJECTIVES: To document among new tuberculosis (TB) patients the proportions and treatment outcomes of silent, non-disputed and disputed (generally missed by rapid drug susceptibility testing [DST]) rpoB mutations, and their detection by commercial molecular assays. DESIGN: Retrospective analysis of rpoB sequences from randomly selected ethanol-preserved diagnostic sputum samples; comparison of sequencing with conventional DST results and standard first-line treatment outcome; retesting of samples with mutations using the Xpert (R) MTB/RIF and Geno Type (R) MTBDRplus assays. RESULTS: Of 1091 samples, 5.8% failed amplification, and six contained other mycobacteria. In 2005 and 2010, respectively 2/500 (0.4%) and 11/522 (2.1%) amplicons showed non-silent mutations. At least 7/13 of these belonged to the disputed group, with 5/7 patients suffering adverse treatment outcome. One silent mutation went undetected by commercial assays. Following routine DST indications, only three cases with a nonsilent mutation were eventually detected. CONCLUSiONS: Disputed rpoB mutations may be responsible for the majority of rifampicin (RMP) resistance among new cases, and lead to adverse outcomes of first-line treatment. Silent mutations do not necessarily cause Xpert or line-probe assay false RMP-resistant results. Molecular RMP DST could greatly simplify resistance surveillance, in addition to offering the best prospects for early and accurate individual diagnosis.
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