TB drug susceptibility testing in high fluoroquinolone resistance settings
BACKGROUND: The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront scree...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
International Union Against Tuberculosis and Lung Disease (The Union)
2024-05-01
|
| Series: | IJTLD Open |
| Subjects: | |
| Online Access: | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000005/art00006 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832592292526948352 |
|---|---|
| author | F. Saluzzo F. Masood V. Batignani F. Di Marco U. Majeed A. Ghazal D.M. Cirillo S. Tahseen |
| author_facet | F. Saluzzo F. Masood V. Batignani F. Di Marco U. Majeed A. Ghazal D.M. Cirillo S. Tahseen |
| author_sort | F. Saluzzo |
| collection | DOAJ |
| description | BACKGROUND: The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront screening. This study aims to assess MTB/XDR's performance in detecting FQs and isoniazid resistance, proposing a renewed diagnostic algorithm for drug-resistant TB (DR-TB). METHODS: This cross-sectional prospective study, approved by the local ethical committee, collected samples from people newly and previously diagnosed with TB over 6 months. Xpert® MTB/RIF Ultra, MTB/XDR, Genotype® MTBDRplus, Genotype® MTBDRsl, culture, and phenotypic drug susceptibility testing (pDST) for relevant drugs (including bedaquiline and levofloxacin) were performed. Next-generation sequencing (NGS) resolved discordances between MTB/XDR and pDST results. RESULTS: The analysis showed that MTB/XDR has 91.5% and 88.2% sensitivity and 99.5% and 97.7% specificity in detecting respectively isoniazid (INH) and resistance to FQs, demonstrating that MTB/XDR meets the WHO targets for INH resistance detection at the peripheral level. NGS effectively resolved discordances between MTB/XDR and pDST results. CONCLUSIONS: The obtained results allowed designing the proposed diagnostic algorithm for rapid identification of DR-TB, ensuring rapid and equitable access to drug susceptibility testing for TB, ultimately improving TB care and control. |
| format | Article |
| id | doaj-art-77ddbc9a6c1c438f8342725754ee8785 |
| institution | Kabale University |
| issn | 3005-7590 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | International Union Against Tuberculosis and Lung Disease (The Union) |
| record_format | Article |
| series | IJTLD Open |
| spelling | doaj-art-77ddbc9a6c1c438f8342725754ee87852025-01-21T10:40:46ZengInternational Union Against Tuberculosis and Lung Disease (The Union)IJTLD Open3005-75902024-05-011523023510.5588/ijtldopen.24.00066TB drug susceptibility testing in high fluoroquinolone resistance settingsF. Saluzzo0F. Masood1V. Batignani2F. Di Marco3U. Majeed4A. Ghazal5D.M. Cirillo6S. Tahseen7Vita Salute San Raffaele University, Milan,National TB Control Programme, Islamabad,IRCCS San Raffaele Scientific Institute, Milan, Italy;IRCCS San Raffaele Scientific Institute, Milan, Italy;National TB Control Programme, Islamabad,National TB Control Programme, Islamabad,IRCCS San Raffaele Scientific Institute, Milan, Italy;National TB Control Programme, Islamabad,BACKGROUND: The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront screening. This study aims to assess MTB/XDR's performance in detecting FQs and isoniazid resistance, proposing a renewed diagnostic algorithm for drug-resistant TB (DR-TB). METHODS: This cross-sectional prospective study, approved by the local ethical committee, collected samples from people newly and previously diagnosed with TB over 6 months. Xpert® MTB/RIF Ultra, MTB/XDR, Genotype® MTBDRplus, Genotype® MTBDRsl, culture, and phenotypic drug susceptibility testing (pDST) for relevant drugs (including bedaquiline and levofloxacin) were performed. Next-generation sequencing (NGS) resolved discordances between MTB/XDR and pDST results. RESULTS: The analysis showed that MTB/XDR has 91.5% and 88.2% sensitivity and 99.5% and 97.7% specificity in detecting respectively isoniazid (INH) and resistance to FQs, demonstrating that MTB/XDR meets the WHO targets for INH resistance detection at the peripheral level. NGS effectively resolved discordances between MTB/XDR and pDST results. CONCLUSIONS: The obtained results allowed designing the proposed diagnostic algorithm for rapid identification of DR-TB, ensuring rapid and equitable access to drug susceptibility testing for TB, ultimately improving TB care and control.https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000005/art00006tb diagnosisdrug-resistant tuberculosisxpert® mtb/xdrtb diagnostic algorithmfq resistance |
| spellingShingle | F. Saluzzo F. Masood V. Batignani F. Di Marco U. Majeed A. Ghazal D.M. Cirillo S. Tahseen TB drug susceptibility testing in high fluoroquinolone resistance settings IJTLD Open tb diagnosis drug-resistant tuberculosis xpert® mtb/xdr tb diagnostic algorithm fq resistance |
| title | TB drug susceptibility testing in high fluoroquinolone resistance settings |
| title_full | TB drug susceptibility testing in high fluoroquinolone resistance settings |
| title_fullStr | TB drug susceptibility testing in high fluoroquinolone resistance settings |
| title_full_unstemmed | TB drug susceptibility testing in high fluoroquinolone resistance settings |
| title_short | TB drug susceptibility testing in high fluoroquinolone resistance settings |
| title_sort | tb drug susceptibility testing in high fluoroquinolone resistance settings |
| topic | tb diagnosis drug-resistant tuberculosis xpert® mtb/xdr tb diagnostic algorithm fq resistance |
| url | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000005/art00006 |
| work_keys_str_mv | AT fsaluzzo tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT fmasood tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT vbatignani tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT fdimarco tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT umajeed tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT aghazal tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT dmcirillo tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings AT stahseen tbdrugsusceptibilitytestinginhighfluoroquinoloneresistancesettings |