Title: Pseudo-outbreak of pre-extensively drug-resistant (Pre-XDR) tuberculosis in Kinshasa: collateral damage caused by false detection of fluoroquinolone resistance by GenoType MTBDRsl
Authors: Kaswa, Michel K ×
Aloni, Muriel
Nkuku, Léontine
Bakoko, Brian
Lebeke, Rossin
Nzita, Albert
Muyembe, Jean Jacques
de Jong, Bouke C
de Rijk, Pim
Verhaegen, Jan
Boelaert, Marleen
Ieven, Margareta
Van Deun, Armand #
Issue Date: Aug-2014
Publisher: American Society for Microbiology (ASM)
Series Title: Journal of Clinical Microbiology vol:52 issue:8 pages:2876-80
Article number: 10.1128/JCM.00398-14
Abstract: Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.
ISSN: 0095-1137
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical Bacteriology and Mycology
Department of Health and Technology - UC Leuven
× corresponding author
# (joint) last author

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