{"doi":"10.1128/aac.01671-24","title":"Xpert MTB/RIF Ultra-resistant and MTBDR <i>plus-</i> susceptible rifampicin results in people with tuberculosis: utility of FluoroType MTBDR and deep sequencing","abstract":"ABSTRACT Xpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDR plus . There are limited data on discordant results, including when re-tested using newer methods, like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing. MTBDR plus rifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads (SMOR; rpoB , inhA , katG ) on isolate DNA were done (SMOR was used as a reference standard). Between 1 April 2021 and 30 September 2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDR plus -susceptible. Of 89% (97/109) isolates with a sequenceable rpoB , SMOR resolved most in favor of Ultra (79% [77/97]). Sputum with lower mycobacterial load was associated with Ultra false-positive resistance (46% [11/24] of “very low” Ultra had false resistance vs 12% [9/73; P = 0.0004] of ≥“low”), as were Ultra heteroresistance calls (all wild-type probes, ≥1 mutant probe) (62% [23/37 vs 25% 15/60] for Ultra without heteroresistance calls; P = 0.0003). Of the 91% (88/97) of isolates successfully tested by FT-MTBDR, 55% (48/88) were FT-MTBDR rifampicin-resistant and 45% (40/88) susceptible, translating to 69% (47/68) sensitivity and 95% (19/20) specificity. In the 91% (99/109) of isolates with inhA and katG sequenced, 62% (61/99) were SMOR isoniazid-susceptible. When Ultra and MTBDR plus rifampicin results are discordant, Ultra is more likely to be correct, and FT-MTBDR agrees more with Ultra than MTBDR plus ; however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra–MTBDR plus discordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.","journal":"Antimicrobial Agents and Chemotherapy","year":2025,"id":531057,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1410974,"name":"Aysha Ahmed","orcid":"0009-0004-1014-5104","position":1,"is_corresponding":false},{"id":826255,"name":"Natalie Beylis","orcid":"0000-0003-1860-6345","position":2,"is_corresponding":false},{"id":1410975,"name":"Sarishna Singh","orcid":"0000-0002-1794-4126","position":3,"is_corresponding":false},{"id":1410976,"name":"Christoffel J. Opperman","orcid":"0000-0002-6676-5431","position":4,"is_corresponding":false},{"id":670591,"name":"Fahd Naufal","orcid":"0000-0001-6106-3177","position":5,"is_corresponding":false},{"id":481302,"name":"Megan Folkerts","orcid":"0000-0001-7430-1701","position":6,"is_corresponding":false},{"id":376250,"name":"David M. Engelthaler","orcid":"0000-0001-5945-059X","position":7,"is_corresponding":false},{"id":1267528,"name":"Erick Auma","orcid":"0000-0001-7076-4944","position":8,"is_corresponding":false},{"id":523475,"name":"Rouxjeane Venter","orcid":"0000-0002-8710-8166","position":9,"is_corresponding":false},{"id":1410977,"name":"Ghowa Booley","orcid":"0000-0002-5017-5576","position":10,"is_corresponding":false},{"id":387484,"name":"John Metcalfe","orcid":"0000-0002-2279-7036","position":11,"is_corresponding":false},{"id":89652,"name":"Robin M. Warren","orcid":"0000-0001-5741-7358","position":12,"is_corresponding":false},{"id":244855,"name":"Grant Theron","orcid":"0000-0002-9216-2415","position":13,"is_corresponding":false},{"id":826254,"name":"Yonas Ghebrekristos","orcid":"0000-0003-2002-5240","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39918315","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}