Tuberculosis

Study Shows Extensively Drug-resistant TB is Becoming More Common Worldwide

More than 40% of people with multidrug-resistant pulmonary tuberculosis in a multi-country study were found to be resistant to at least 1 second-line anti-tuberculosis agent and 7% had extensively drug-resistant disease, researchers reported in the August 29, 2012, advance online edition of The Lancet.

Multidrug-resistant tuberculosis (MDR-TB), or Mycobacterium tuberculosis resistant to at least the 2 standard first-line drugs isoniazid and rifampicin, is now widespread throughout the world. Extensively drug-resistant tuberculosis (XDR-TB), referring to bacteria resistant to the usual second-line agents as well, is a growing concern.

Resistance typically develops when people do not compete a full course of therapy, which can last 6 months. Treatment options are limited for people with highly resistant TB, and the cost is much higher, duration of therapy is longer, and side effects are more problematic.

Tracy Dalton, PhD, from the U.S. Centers for Disease Control and Prevention (CDC) and fellow investigators with the Global Preserving Effective TB Treatment Study (PETTS) team prospectively analyzed resistance to second-line anti-TB treatment in 8 countries.

Between January 2005 and December 2008, the researchers enrolled a total of 1278 adult patients in Estonia, Latvia, Peru, the Philippines, Russia, South Africa, South Korea, and Thailand. The CDC centrally tested sputum samples for susceptibility to 11 first-line and second-line agents.

Participants had confirmed pulmonary MDR-TB and were about to start second-line treatment. About two-thirds were men and the median age was around 30 years; 13% were HIV positive.

Results

• 44% of participants showed resistance to at least 1 second-line TB drug, with rates ranging from 33% in Thailand to 62% in Latvia.
• 20% had evidence of resistant to at least 1 injectable second-line agent, with rates starting at 2% in the Philippines and again topping off at 47% in Latvia.
• 13% were resistant to at least 1 drug in the fluoroquinolone class.
• Overall, 7% of patients had evidence of XDR-TB -- defined as resistance to both an injectable agent and a fluoroquinolone -- with rates ranging from just under 1% in the Philippines to 15% in South Korea.
• Previous treatment with second-line drugs was the strongest risk factor for developing resistance to these drugs, and this increased the risk of XDR-TB by more than 4-fold.
• Fluoroquinolone-resistant TB and XDR-TB were more common among women compared with men.
• Other factors consistently associated with resistance to second-line TB drugs included unemployment, incarceration, heavy alcohol use, and smoking; other risk factors varied across countries.

Rates of XDR-TB seen in this study were higher that previously thought, the study authors noted. Prevalence in South Korea and Russia (15% and 11%, respectively), for example, was twice as high as the global World Health Organization (WHO) estimate of about 5%.

"Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis," they concluded. "Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies."

"Information remains insufficient to give a clear view of the worldwide distribution and true magnitude of XDR tuberculosis," Sven Hoffner from the Swedish Institute for Communicable Diseases wrote in an accompanying editorial. "Updated information on MDR tuberculosis and investigation of the trends are urgently needed, especially since the true scale of the burden of MDR and XDR tuberculosis might be underestimated and seem to be rapidly increasing."

9/11/12

Reference

T Dalton, P Cegielski, S Akksilp, L Asencios, et al. Prevalenceof and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study. The Lancet. August 29, 2012 (Epub ahead of print).

S Hoffner. Unexpected high levels of multidrug-resistant tuberculosis present new challenges for tuberculosis control. The Lancet. August 29, 2012 (Epub ahead of print).