{"doi":"10.1101/2022.12.05.22283088","title":"To test or not? Xpert MTB/RIF as an alternative to smear microscopy to guide line probe assay testing for drug-resistant tuberculosis","abstract":"Abstract Background Xpert MTB/RIF (Xpert) revolutionised tuberculosis (TB) diagnosis, however, laboratory decision making on whether widely-used reflex drug susceptibility assays (MTBDR plus , MTBDR sl ) are done on specimens is often based on smear microscopy status. Method We performed receiver operator characteristic (ROC) curve analyses using sputum bacterial load measures [smear microscopy grade, Xpert semi-quantitation category and minimum cycle threshold (C Tmin ) values] for the classification of “likely non-actionable” (not resistant or susceptible) line probe assays results. We evaluated the actionable-to-non-actionable result ratio and pay-offs with missed isoniazid and fluoroquinolone resistance compared to if LPAs were done universally. Findings Smear-negatives were more likely than smear-positives to generate a non-actionable MTBDR plus [23% (133/559) vs. 4% (15/381)] or MTBDR sl [39% (220/559) vs. 12% (47/381)] result, however, excluding smear-negatives would result in missed rapid diagnoses [e.g., only 51% (273/537) of LPA-diagnosable isoniazid resistance detected if smear-negatives omitted]. Within smear-negatives, testing ≥ “medium” specimens had a high ratio of actionable-to-non-actionable results (12.8 or a 4-fold improvement vs. test all for MTBDR plus , 4.5 or 3-fold improvement for MTBDR sl ), which would capture 64% (168/264) and 77% (34/44) of LPA-detectable resistance. If C Tmin were used, greater resolution and higher ratios offset against fewer missed resistant cases were obtained. Conclusion Routinely-generated Xpert quantitative information permits identification of smear-negatives in whom the ratio of actionable-to-non-actionable LPA results may prove acceptably high to laboratories depending on their local contexts. Xpert C Tmin or, if unavailable, semiquantitation category should be used to guide reflex DST; permitting the rational expansion of direct DST to certain paucibacillary specimens.","journal":"medRxiv","year":2022,"id":313655,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":523478,"name":"Margaretha de Vos","orcid":"0000-0003-3059-2986","position":1,"is_corresponding":false},{"id":893881,"name":"Hojoon Sohn","orcid":"0000-0001-5837-3844","position":2,"is_corresponding":false},{"id":826254,"name":"Yonas Ghebrekristos","orcid":"0000-0003-2002-5240","position":3,"is_corresponding":false},{"id":524350,"name":"Tania Dolby","orcid":null,"position":4,"is_corresponding":false},{"id":89652,"name":"Robin M. Warren","orcid":"0000-0001-5741-7358","position":5,"is_corresponding":false},{"id":244855,"name":"Grant Theron","orcid":"0000-0002-9216-2415","position":6,"is_corresponding":false},{"id":589300,"name":"Selvan Pillay","orcid":"0000-0002-3889-3989","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"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":[]}