TY - JOUR
T1 - Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones
T2 - results from a multicountry surveillance project
AU - Zignol, Matteo
AU - Dean, Anna S.
AU - Alikhanova, Natavan
AU - Andres, Sönke
AU - Cabibbe, Andrea Maurizio
AU - Cirillo, Daniela Maria
AU - Dadu, Andrei
AU - Dreyer, Andries
AU - Driesen, Michèle
AU - Gilpin, Christopher
AU - Hasan, Rumina
AU - Hasan, Zahra
AU - Hoffner, Sven
AU - Husain, Ashaque
AU - Hussain, Alamdar
AU - Ismail, Nazir
AU - Kamal, Mostofa
AU - Mansjö, Mikael
AU - Mvusi, Lindiwe
AU - Niemann, Stefan
AU - Omar, Shaheed V.
AU - Qadeer, Ejaz
AU - Rigouts, Leen
AU - Ruesch-Gerdes, Sabine
AU - Schito, Marco
AU - Seyfaddinova, Mehriban
AU - Skrahina, Alena
AU - Tahseen, Sabira
AU - Wells, William A.
AU - Mukadi, Ya Diul
AU - Kimerling, Michael
AU - Floyd, Katherine
AU - Weyer, Karin
AU - Raviglione, Mario C.
N1 - Publisher Copyright:
© 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/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.
AB - 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 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/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.
UR - http://www.scopus.com/inward/record.url?scp=84990064441&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(16)30190-6
DO - 10.1016/S1473-3099(16)30190-6
M3 - Article
C2 - 27397590
AN - SCOPUS:84990064441
SN - 1473-3099
VL - 16
SP - 1185
EP - 1192
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 10
ER -
