Population-based resistance of mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project
AKU-Pakistan; Medical College Pakistan
Background Pyrazinamide and fl uoroquinolones 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 fl uoroquinolones 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 fl uoroquinolones 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 signifi cantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0–16·6% for ofl oxacin, to 0·5–12·4% for levofl oxacin, and 0·9–14·6% for moxifl oxacin when tested at 0·5 μg/mL. High levels of ofl oxacin resistance were detected in Pakistan. Resistance to moxifl oxacin and gatifl oxacin when tested at 2 μg/mL was low in all countries. Interpretation Although pyrazinamide resistance was signifi cantly 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 ofl oxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fl uoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fl uoroquinolones documented in all survey sites is an encouraging fi nding. Rational use of this class of antibiotics should therefore be ensured to preserve its eff ectiveness. Funding Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.
Dean, A. S.,
Cabibbe, A. M.,
Cirillo, D. M.,
Omar, S. V.,
Gerdes, S. R.,
Wells, W. A.,
Mukadi, Y. D.,
Raviglione, M. C.
(2016). Population-based resistance of mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project.
Available at: http://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/510