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Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project

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dc.contributor.author Zignol, M. en_US
dc.contributor.author Dean, A. S. en_US
dc.contributor.author Alikhanova, N. en_US
dc.contributor.author Andres, S. en_US
dc.contributor.author Cabibbe, A. M. en_US
dc.contributor.author Cirillo, D. M. en_US
dc.contributor.author Dadu, A. en_US
dc.contributor.author Dreyer, A. en_US
dc.contributor.author Driesen, M. en_US
dc.contributor.author Gilpin, C. en_US
dc.contributor.author Hasan, R. en_US
dc.contributor.author Hasan, Z. en_US
dc.contributor.author Hoffner, S. en_US
dc.contributor.author Husain, A. en_US
dc.contributor.author Hussain, A. en_US
dc.contributor.author Ismail, N. en_US
dc.contributor.author Kamal, M. en_US
dc.contributor.author Mansj”, M. en_US
dc.contributor.author Mvusi, L. en_US
dc.contributor.author Niemann, S. en_US
dc.contributor.author Omar, S. V. en_US
dc.contributor.author Qadeer, E. en_US
dc.contributor.author Rigouts, L. en_US
dc.contributor.author Ruesch-Gerdes, S. en_US
dc.contributor.author Schito, M. en_US
dc.contributor.author Seyfaddinova, M. en_US
dc.contributor.author Skrahina, A. en_US
dc.contributor.author Tahseen, S. en_US
dc.contributor.author Wells, W. A. en_US
dc.contributor.author Mukadi, Y. D. en_US
dc.contributor.author Kimerling, M. en_US
dc.contributor.author Floyd, K. en_US
dc.contributor.author Weyer, K. en_US
dc.contributor.author Raviglione, M. C. en_US
dc.date.accessioned 2017-12-18T12:56:11Z
dc.date.available 2017-12-18T12:56:11Z
dc.date.issued 2016 en_US
dc.identifier.issn 1473-3099 en_US
dc.identifier.doi http://dx.doi.org/10.1016/S1473-3099(16)30190-6 en_US
dc.identifier.other http://lib.itg.be/pdf/itg/2016/2016lidi1185.pdf en_US
dc.identifier.other ITG-B9B; ITG-B23A; DBM; U-MYCOB; JIF; DOI; PDF; Abstract; DSPACE64 en_US
dc.identifier.uri http://hdl.handle.net/10390/9939
dc.description.abstract BACKGROUND: Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. METHODS: In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. FINDINGS: Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3.0-42.1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1.0-16.6% for ofloxacin, to 0.5-12.4% for levofloxacin, and 0.9-14.6% for moxifloxacin when tested at 0.5 mug/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 mug/mL was low in all countries. INTERPRETATION: Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. en_US
dc.language English en_US
dc.publisher Lancet Infectious Diseases en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/27397590 en_US
dc.subject Tuberculosis en_US
dc.subject Bacterial diseases en_US
dc.subject Drug resistance en_US
dc.subject Surveillance en_US
dc.subject Pyrazinamide en_US
dc.subject Fluoroquinolines en_US
dc.subject Developing countries en_US
dc.subject Global en_US
dc.title Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project en_US
dc.type Article en_US
dc.citation.issue 10 en_US
dc.citation.volume 16 en_US
dc.citation.pages 1185 en_US
dc.citation.abbreviation Lancet Infect Dis en_US


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