Prior use of second-line anti-TB drugs more than quadrupled the risk of extremely drug-resistant tuberculosis (XDR-TB) in an 8-country prospective study. XDR-TB was more frequent in women than in men.
The World Health Organization defines XDR-TB as “resistance to the two most powerful anti-TB drugs, isoniazid and rifampicin, also known as multidrug-resistance (MDR-TB), in addition to resistance to any of the fluoroquinolones (such as ofloxacin or moxifloxacin) and to at least one of three injectable second-line drugs (amikacin, capreomycin or kanamycin).”
XDR-TB was first identified in a population including many HIV-positive people and it poses a grave threat to people with HIV. In many countries TB remains the most frequent complication and cause of death in people with HIV.
Researchers consecutively enrolled adults with locally confirmed pulmonary MDR-TB and starting second-line treatment from 1 January 2005 to 31 December 2008. Patients were seen in 8 countries—Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Anti-TB drug susceptibility testing was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs.
Among 1278 TB patients studied, 43.7% had Mycobacterium tuberculosis resistant to at least one second-line drug, while 20.0% had resistance to at least one second-line injectable drug, and 12.9% had resistance to at least one fluoroquinoline. The XDR-TB rate was 6.7% and ranged from 0.8% to 15.2% across countries.
Prior treatment with a second-line anti-TB drug was “consistently the strongest risk factor for resistance to these drugs,” more than quadrupling the risk of XDR-TB (risk ratio [RR] 4.75, 95% confidence interval [CI] 3.05 to 7.42). Prior treatment with fluoroquinolones also more than quadrupled risk of XDR-TB (RR 4.21, 95% CI 2.73 to 6.49), as did prior treatment with another oral second-line drug (RR 4.05, 95% CI 2.60 to 6.31) and previous treatment with a third-line drug (RR 4.18, 95% CI 2.13 to 8.21).
Fluoroquinoline resistance and XDR-TB were more frequent in women than in men. Three factors raised the risk of resistance to second-line injectable drugs across countries—unemployment, alcohol abuse, and smoking.
Prevalence of resistance to anti-TB drug was lowest in countries where such drugs were available for 10 or fewer years (Thailand, Philippines, Peru) and highest in countries where those drugs were available for more than 20 years (South Korea, Russia).
The authors suggest that “representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies.”