Findings highlight gaps in available testing, regimens
The first survey to assess tuberculosis that does not respond to common treatments across populations in multiple high-disease-burden countries shows a need for better understanding of the dynamics of drug-resistant disease, including through tests that do not yet exist.
The survey’s findings, detailed in The Lancet Infectious Diseases, show that tuberculosis that is resistant to the most common first-line drug may often also be resistant to a drug used in substitute therapies. But while resistance to the first drug, rifampicin, is increasingly readily detected in rapid GeneXpert diagnostic tests, no similar rapid test exists to detect resistance to pyrazinamide, which is used in both shorter course first-line treatments and recommended for second-line treatments. The information that a rapid test to determine resistance to pyrazinamide would provide is critical, the authors say, because the odds that the drug will be effective for patients whose disease is resistant to rifampicin vary widely, depending on the setting, from 19 to 63 percent.
In addition, the survey, which included testing of 5,000 patients in Azerbaijan, Bangladesh, Belarus, Pakistan and South Africa, found resistance to flouroquinolones, broadly used antibiotic drugs, also tended to be found in tuberculosis patients whose disease was resistant to rifampicin, but with that finding too, varying widely according to setting, and no existing rapid test to reveal resistance to those drugs.
Adding to the urgency to more quickly identify resistance to pyrazinamide and flouroquinolones, is that both are included in the World Health Organization’s most recently recommended regimen for multidrug resistant tuberculosis, a shorter, more tolerable regimen intended to improve patients’ odds of completing treatment.
The absence of rapid tests to identify resistance to those drugs poses the risk of ineffective treatment that leads to further resistance, the lead author of the article on the findings, Dr. Matteo Zignol notes.