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Title
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Thin-layeraAgar-based direct phenotypic drug susceptibility testing on sputum in Eswatini rapidly detects Mycobacterium tuberculosis growth and rifampicin resistance otherwise missed by WHO-endorsed diagnostic tests
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Author
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Abstract
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| Xpert MTB/RIF rapidly detects resistance to rifampicin (RR); however, this test misses I491F-RR conferring rpoB mutation, common in southern Africa. In addition, Xpert MTB/RIF does not distinguish between viable and dead Mycobacterium tuberculosis (MTB). We aimed 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. Consecutive samples were tested in parallel with Xpert MTB/RIF and TLA for rifampicin (1.0 mu g/ml) and ofloxacin (2.0 mu g/ml). TLA results were compared at the Reference Laboratory in Antwerp with indirect-DST on Lowenstein-Jensen or 7H11 solid media and additional phenotypic and genotypic testing to resolve discordance. TLA showed a positivity rate for MTB detection of 7.1% versus 10.0% for Xpert MTB/RIF. Of a total of 4,547 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 (95% confidence interval [CI], 77.4 to 98.0) and 99.4% specificity (95% CI, 96.7 to 99.9) versus 62.5% (95% CI, 42.7 to 78.8) and 99.3% (95% CI, 96.2 to 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-susceptible isolates (99.5% specificity; 95% CI, 97.0 to 99.9). In field conditions, TLA rapidly detects RR, and in this specific setting, it contributed to detection of additional RR patients over Xpert MTB/RIF, mainly but not exclusively due to I491F. TLA also accurately excluded fluoroquinolone resistance. |
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Language
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English
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Source (journal)
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Antimicrobial agents and chemotherapy. - Washington, D.C., 1972, currens
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Publication
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Washington, D.C.
:
American Society for Microbiology
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2021
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ISSN
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0066-4804
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DOI
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10.1128/AAC.02263-20
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Volume/pages
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65
:6
(2021)
, 11 p.
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Article Reference
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e02263-20
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ISI
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000654088300043
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Pubmed ID
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33722892
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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