This article is more than 5 years old. Information may no longer be current.
Pyrazinamide, fluoroquinolone resistance varies among TB-burdened countries
Recent data describing the prevalence of drug resistance among several countries highly affected by tuberculosis indicated pyrazinamide resistance rates range from 3% to 42%, yet the drug may remain effective in as many as 63% of patients with rifampicin-resistant strains.
Although fluoroquinolone resistance also varied between countries, the findings suggested that this resistance outnumbered that of pyrazinamide in Pakistan and Bangladesh and could be indicative of frequent fluoroquinolone use in these regions.
“An understanding of the background prevalence of resistance to all drugs included in new regimens is needed to assess the feasibility of shorter regimens and the need for drug-susceptibility testing to accompany regimen introduction,” Matteo Zignol, MD, scientist for WHO’s Global TB Program, and colleagues wrote. “Whereas levels of rifampicin and isoniazid resistance are routinely monitored in most tuberculosis-endemic countries, susceptibility testing to fluoroquinolones and pyrazinamide is not routinely performed as part of drug resistance surveillance.”
To improve surveillance data, Zignol and colleagues collected sputum samples from TB patients living in Azerbaijan, Bangladesh, Pakistan, Belarus and South Africa. After culturing and testing these samples for first-line TB drug resistance, the researchers then submitted the isolates to WHO reference laboratories for further pyrazinamide and fluoroquinolone resistance testing.
Among the 4,972 patients tested for pyrazinamide resistance, rates ranged from 3% in Pakistan to 42.1% is Belarus’ Minsk city. While pyrazinamide resistance was significantly associated with rifampicin resistance in all settings, only 36.7% of rifampicin-resistant cases in Bangladesh also were nonsusceptible to pyrazinamide.
In the 5,015 cases submitted for fluoroquinolone testing, resistance to ofloxacin (range, 1%-16.6%), levofloxacin (range, 0.5%-12.4%) and low concentrations of moxifloxacin (0.9%-14.6%) was generally similar between countries, and lower for high doses of moxifloxacin (0% to 5.1%) and gatifloxacin (0% to 2.5%). Fluoroquinolone resistance rates were significantly lower than pyrazinamide resistance rates in all countries but Pakistan and Bangladesh.
These findings suggest that rifampicin nonsusceptibility is becoming increasingly concurrent with pyrazinamide and early-generation fluoroquinolones in these high-burden settings, according to the researchers.
“Choices about prioritization and introduction of new regimens and algorithms for drug-susceptibility testing must take these data into consideration, and surveillance approaches need to be rethought so that better data are available to understand levels of resistance,” they wrote. “Without this information, the risk of introducing ineffective regimens that are not curative and might amplify development of drug resistance, including new agents, remains high.”
In a related editorial, Giovanni Sotgiu, PhD, MD, of the clinical epidemiology and medical statistics unit at the University of Sassari, and Giovanni Battista Migliori, MD, of the WHO Collaborating Center for TB and Lung Diseases, wrote that Zignol and colleagues provided timely epidemiologic information for public health experts and clinicians working within these countries. Sotgiu and Migliori said additional caution should be taken when prescribing alternative regimens, and that new methods of detecting these underlying resistances is a growing priority.
“The variability in drug resistance patterns calls for understanding of national and subnational epidemiology, and emphasizes the need for rapid molecular methods and drug susceptibility testing to exclude drug resistance whenever there is suspicion that it might be present, they said. “Only with accurate and timely diagnosis will the spread of drug-resistant TB be contained.” – by Dave Muoio
Disclosure: The researchers report no relevant financial disclosures.