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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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Show simple item record Zignol, M. en_US Dean, A. S. en_US Alikhanova, N. en_US Andres, S. en_US Cabibbe, A. M. en_US Cirillo, D. M. en_US Dadu, A. en_US Dreyer, A. en_US Driesen, M. en_US Gilpin, C. en_US Hasan, R. en_US Hasan, Z. en_US Hoffner, S. en_US Husain, A. en_US Hussain, A. en_US Ismail, N. en_US Kamal, M. en_US Mansj”, M. en_US Mvusi, L. en_US Niemann, S. en_US Omar, S. V. en_US Qadeer, E. en_US Rigouts, L. en_US Ruesch-Gerdes, S. en_US Schito, M. en_US Seyfaddinova, M. en_US Skrahina, A. en_US Tahseen, S. en_US Wells, W. A. en_US Mukadi, Y. D. en_US Kimerling, M. en_US Floyd, K. en_US Weyer, K. en_US Raviglione, M. C. en_US 2017-12-18T12:56:11Z 2017-12-18T12:56:11Z 2016 en_US
dc.identifier.issn 1473-3099 en_US
dc.identifier.doi en_US
dc.identifier.other en_US
dc.identifier.other ITG-B9B; ITG-B23A; DBM; U-MYCOB; JIF; DOI; PDF; Abstract; DSPACE64 en_US
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 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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