Disputed rpoB mutations can frequently cause important rifampicin resistance among new tuberculosis patients

Autor: A, Van Deun, K J M, Aung, A, Hossain, P, de Rijk, M, Gumusboga, L, Rigouts, B C, de Jong
Rok vydání: 2015
Předmět:
Zdroj: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 19(2)
ISSN: 1815-7920
Popis: Greater Mymensingh area, Bangladesh.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.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 MTB/RIF and GenoType MTBDRplus assays.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 non-silent mutation were eventually detected.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.
Databáze: OpenAIRE