Thin layer agar-based direct phenotypic drug-susceptibility testing on sputum in Eswatini rapidly detects growth and rifampicin resistance, otherwise missed by WHO endorsed diagnostic tests.
de la Tour, R
Page, A L
Van Deun, A
de Jong, B C
MetadataShow full item record
AbstractBACKGROUND: Xpert®MTB/RIF rapidly detects resistance to rifampicin (RR), however this test misses the I491F-RR conferring rpoB mutation, common in Southern Africa. In addition, Xpert®MTB/RIF does not distinguish between viable and dead Mycobacterium tuberculosis (MTB). OBJECTIVE: To investigate the ability of thin layer agar (TLA) direct drug-susceptibility testing (DST) to detect MTB and its drug-resistance profiles in field conditions in Eswatini. DESIGN: Consecutive samples were tested in parallel with Xpert®MTB/RIF and TLA for rifampicin (1.0 μg/ml) and ofloxacin (2.0 μg/ml). TLA results were compared at the Reference Laboratory in Antwerp with indirect DST on Löwenstein-Jensen or 7H11 solid media and additional phenotypic and genotypic testing to resolve discordance. RESULTS: TLA showed a positivity rate for MTB detection of 7.1% versus 10.0% for Xpert®MTB/RIF. Of a total of 4547 samples included in the study, 200 isolates were available for comparison to the composite reference. Within a median of 18.4 days, TLA detected RR with 93.0% sensitivity (CI-77.4-98.0) and 99.4% specificity (CI 96.7-99.9), versus 62.5% (CI 42.7-78.8) and 99.3% (CI 96.2-99.9) for Xpert®MTB/RIF. Eight isolates, 28.6% of all RR confirmed isolates, carried the I491F mutation, all detected by TLA. TLA also correctly identified 183 of the 184 ofloxacin-S isolates (99.5% specificity, CI 97.0-99.9). CONCLUSIONS: In field conditions, TLA rapidly detects RR, and in this specific setting contributed to detection of additional RR patients over Xpert®MTB/RIF, mainly but not exclusively due to I491F. TLA also accurately excluded fluoroquinolones resistance.
PublisherAmerican Society for Microbiology
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