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Xpert MTB/RIF Ultra resistant and MTBDRplussusceptible rifampicin results in people with tuberculosis: utility of FluoroType MTBDR and deep sequencing

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Název: Xpert MTB/RIF Ultra resistant and MTBDRplussusceptible rifampicin results in people with tuberculosis: utility of FluoroType MTBDR and deep sequencing
Autoři: Yonas Ghebrekristos, Aysha Ahmed, Natalie Beylis, Sarishna Singh, Christoffel Opperman, Fahd Naufal, Megan Folkerts, David Engelthaler, Erick Auma, Rouxjeane Venter, Ghowa Booley, John Metcalfe, Robin Warren, Grant Theron
Přispěvatelé: Silverman, Jared A
Zdroj: Antimicrob Agents Chemother
Antimicrobial Agents and Chemotherapy, vol 69, iss 3
Informace o vydavateli: Cold Spring Harbor Laboratory, 2024.
Rok vydání: 2024
Témata: Bacterial Proteins (mesh), diagnosis, Drug Resistance, Antitubercular Agents, Catalase (mesh), Oxidoreductases (mesh), Lung (rcdc), rifampicin susceptibility, Rifampin (mesh), South Africa, 0605 Microbiology (for), Drug Resistance, Multiple, Bacterial, Tuberculosis, Multidrug-Resistant, 32 Biomedical and Clinical Sciences (for-2020), Humans (mesh), 3 Good Health and Well Being (sdg), 3107 Microbiology (for-2020), South Africa (mesh), High-Throughput Nucleotide Sequencing (mesh), High-Throughput Nucleotide Sequencing, Sputum (mesh), DNA-Directed RNA Polymerases, Catalase, Bacterial (mesh), Infection (hrcs-hc), tuberculosis, Mycobacterium tuberculosis (mesh), Rifampin, Antitubercular Agents (mesh), Oxidoreductases, DNA-Directed RNA Polymerases (mesh), Microbial Sensitivity Tests, Antimicrobial Resistance (rcdc), Emerging Infectious Diseases (rcdc), Rare Diseases (rcdc), Bacterial Proteins, Tuberculosis, Humans, Biodefense (rcdc), heteroresistance, Antibiotics, Antitubercular, 3202 Clinical Sciences (for-2020), 31 Biological Sciences (for-2020), 1115 Pharmacology and Pharmaceutical Sciences (for), Genetics (rcdc), Microbial Sensitivity Tests (mesh), 1108 Medical Microbiology (for), Sputum, Mycobacterium tuberculosis, 3207 Medical microbiology (for-2020), Infectious Diseases (rcdc), Susceptibility, Multidrug-Resistant (mesh), Microbiology (science-metrix), Orphan Drug (rcdc), Tuberculosis (rcdc), 3214 Pharmacology and pharmaceutical sciences (for-2020)
Popis: SummaryBackgroundXpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDRplus. There are limited data on discordant results, including re-tested using newer methods like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing.MethodsMTBDRplusrifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads deep (SMOR;rpoB, inhA, katG) on isolate DNA were done (SMOR reference standard).FindingsBetween 01/04/2021-30/09/2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDRplus-susceptible. Of 89% (97/109) isolates with a sequenceablerpoB, SMOR resolved most in favour of Ultra [79% (77/97)]. Sputum with lower mycobacterial load was associated with Ultra false-positive resistance [46% (11/24) of “very low” Ultras had false-resistance vs. 12% (9/73; p=0.0004) in those ≥“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 withinhAandkatGsequenced, 62% (61/99) were SMOR isoniazid-susceptible.InterpretationWhen Ultra and MTBDRplusrifampicin results are discordant, Ultra is more likely to be correct and FT-MTBDR agrees more with Ultra than MTBDRplus, however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra-MTBDRplusdiscordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.FundingThis work was supported by European & Developing Countries Trial Partnerships (EDCTP2; RIA2020I-3305, CAGE-TB), National Institutes of Health (D43TW010350; U01AI152087; U54EB027049; R01AI136894).
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
ISSN: 1098-6596
0066-4804
DOI: 10.1101/2024.10.25.24316070
DOI: 10.1128/aac.01671-24
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39918315
https://escholarship.org/uc/item/7zx169xr
https://escholarship.org/content/qt7zx169xr/qt7zx169xr.pdf
Rights: CC BY NC
CC BY
Přístupové číslo: edsair.doi.dedup.....80f688e7c6970a00b805a3b7a72a8965
Databáze: OpenAIRE
Popis
Abstrakt:SummaryBackgroundXpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDRplus. There are limited data on discordant results, including re-tested using newer methods like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing.MethodsMTBDRplusrifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads deep (SMOR;rpoB, inhA, katG) on isolate DNA were done (SMOR reference standard).FindingsBetween 01/04/2021-30/09/2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDRplus-susceptible. Of 89% (97/109) isolates with a sequenceablerpoB, SMOR resolved most in favour of Ultra [79% (77/97)]. Sputum with lower mycobacterial load was associated with Ultra false-positive resistance [46% (11/24) of “very low” Ultras had false-resistance vs. 12% (9/73; p=0.0004) in those ≥“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 withinhAandkatGsequenced, 62% (61/99) were SMOR isoniazid-susceptible.InterpretationWhen Ultra and MTBDRplusrifampicin results are discordant, Ultra is more likely to be correct and FT-MTBDR agrees more with Ultra than MTBDRplus, however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra-MTBDRplusdiscordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.FundingThis work was supported by European & Developing Countries Trial Partnerships (EDCTP2; RIA2020I-3305, CAGE-TB), National Institutes of Health (D43TW010350; U01AI152087; U54EB027049; R01AI136894).
ISSN:10986596
00664804
DOI:10.1101/2024.10.25.24316070