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- Title
Non-actionable Results, Accuracy, and Effect of First- and Second-line Line Probe Assays for Diagnosing Drug-Resistant Tuberculosis, Including on Smear-Negative Specimens, in a High-Volume Laboratory.
- Authors
Pillay, Samantha; Vos, Margaretha de; Derendinger, Brigitta; Streicher, Elizabeth Maria; Dolby, Tania; Scott, Leeré Ann; Steinhobel, Amy Debra; Warren, Rob Mark; Theron, Grant
- Abstract
Background Rapid tuberculosis (TB) drug susceptibility testing (DST) is crucial. Genotype MTBDR sl is a widely deployed World Health Organization (WHO)–endorsed assay. Programmatic performance data, including non-actionable results from smear-negative sputum, are scarce. Methods Sputa from Xpert MTB/RIF individuals (n = 951) were routinely-tested using Genotype MTBDR plus and MTBDR sl (both version 2). Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing. Findings 89% (849 of 951) of individuals were culture-positive (56%, 476 of 849 smear-negative). MTBDR plus had at least 1 nonactionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92 of 476) of smear-negatives; for MTBDR sl , 40% (171 of 427) were nonactionable (28%, 120 of 427 false-negative TB; 17%, 51 of 427 indeterminate). In smear-negatives, MTBDR sl sensitivity for fluoroquinolones was 84% (95% confidence interval, 67%–93), 81% (54%–95%) for second-line injectable drugs, and 57% (28%–82%) for both. Specificities were 93% (89%–98%), 88% (81%–93%), and 97% (91%–99%), respectively. Twenty-three percent (172 of 746) of Xpert rifampicin-resistant specimens were MTBDR plus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDR sl improved (6 [5–7] vs 37 [35–46]; P <.001). Conclusions MTBDR sl did not generate a result in 4 of 10 smear-negatives, resulting in substantial missed resistance. However, if MTBDR sl generates an actionable result, that is accurate in ruling-in resistance. Isoniazid DST remains crucial. This study provides real-world, direct, second-line susceptibility testing performance data on non-actionable results (that, if unaccounted for, cause an overestimation of test utility), accuracy, and care cascade impact.
- Subjects
SPUTUM microbiology; PATHOLOGICAL laboratories; RESEARCH evaluation; SEQUENCE analysis; SPUTUM; MICROSCOPY; FLUOROQUINOLONES; GENOTYPES; DISEASE susceptibility; DESCRIPTIVE statistics; RESEARCH funding; DIAGNOSTIC errors; SENSITIVITY &; specificity (Statistics); DATA analysis software; PHENOTYPES
- Publication
Clinical Infectious Diseases, 2023, Vol 76, Issue 3, pe920
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciac556