Rapid microarray-based assay for detection of pyrazinamide resistant Mycobacterium tuberculosis
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved..
Pyrazinamide (PZA) is a key antibiotic for the treatment of drug susceptible tuberculosis. PZA-resistance is mainly mediated by mutations in the pncA gene; however the current gold standard is a phenotypic drug susceptibility test requiring a well-adjusted pH-value for reliable results. Our melting curve assay detects a non-wild type genotype in selected pncA regions in at least 3750 gene copies/mL within 2.5 hours. The prototype assay was further evaluated by analyzing 271 Mycobacterium tuberculosis complex isolates from Swaziland originating from a previously published drug resistance survey and including 118 isolates with pncA mutations. Sensitivity was 83% (95% CI 75-89%) and specificity was 100% (95% CI 98-100%). Under consideration of further improvements with regard to the target range our melting curve assay has the potential as a rapid rule-in test for PZA susceptibility (wild type pncA), however false resistant results (mutant pncA, but PZA susceptible) cannot be ruled out completely.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:94 |
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| Enthalten in: |
Diagnostic microbiology and infectious disease - 94(2019), 2 vom: 01. Juni, Seite 147-154 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Havlicek, Juliane [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.08.2019 Date Revised 25.02.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.diagmicrobio.2018.12.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM293590184 |
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| 520 | |a Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Pyrazinamide (PZA) is a key antibiotic for the treatment of drug susceptible tuberculosis. PZA-resistance is mainly mediated by mutations in the pncA gene; however the current gold standard is a phenotypic drug susceptibility test requiring a well-adjusted pH-value for reliable results. Our melting curve assay detects a non-wild type genotype in selected pncA regions in at least 3750 gene copies/mL within 2.5 hours. The prototype assay was further evaluated by analyzing 271 Mycobacterium tuberculosis complex isolates from Swaziland originating from a previously published drug resistance survey and including 118 isolates with pncA mutations. Sensitivity was 83% (95% CI 75-89%) and specificity was 100% (95% CI 98-100%). Under consideration of further improvements with regard to the target range our melting curve assay has the potential as a rapid rule-in test for PZA susceptibility (wild type pncA), however false resistant results (mutant pncA, but PZA susceptible) cannot be ruled out completely | ||
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| 650 | 4 | |a Pyrazinamide resistance | |
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| 650 | 7 | |a DNA, Bacterial |2 NLM | |
| 650 | 7 | |a Pyrazinamide |2 NLM | |
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| 700 | 1 | |a Dachsel, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Slickers, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Andres, Sönke |e verfasserin |4 aut | |
| 700 | 1 | |a Beckert, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Feuerriegel, Silke |e verfasserin |4 aut | |
| 700 | 1 | |a Niemann, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Merker, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Labugger, Ines |e verfasserin |4 aut | |
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