Confirmed cases in all regions of the world

Tuberculosis (TB) is a curable disease, but successful treatment requires rigorous management and patient compliance with a lengthy multidrug regimen. In resource-limited settings where TB is most prevalent, poorly managed care and patient noncompliance have given rise to multidrug-resistant tuberculosis (MDR-TB). Defined as resistance to at least isoniazid and rifampicin (the most powerful first-line drugs), MDR-TB takes longer to treat and requires second-line drugs that increase expense and adverse effects.

When anti-TB drugs are misused or mismanaged, extensively drug-resistant TB (XDR-TB) can develop, explains UAB TB expert Michael E. Kimerling, MD, MPH. The World Health Organization (WHO) first introduced the term XDR-TB in March 2006, and in October 2006 formalized its definition as resistance to isoniazid and rifampicin plus resistance to any fluoroquinolone and at least one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin).

“XDR-TB is a serious, emerging threat to public health,” Kimerling says. “To check the global spread of deadly TB strains, governments must strengthen basic TB care and infection control practices to prevent development of drug resistance, ensure prompt diagnosis and treatment of drug-resistant cases, and increase collaboration between TB and HIV control programs.”

In areas where XDR-TB coexists with high rates of HIV/AIDS, the risk of coinfection is high. In a recent TB outbreak in Tugela Ferry, South Africa, up to 80% of all patients were coinfected with HIV; 221 of 544 (40.6%) patients had MDR-TB, and 53 (9.7%) of those had XDR-TB. All but one of the patients with XDR-TB died within 25 days of diagnosis, including those taking antiretroviral therapy, the WHO reports. Drug-resistant TB is not limited to poverty-stricken areas in the developing world, Kimerling says. A survey by the Centers for Disease Control and Prevention (CDC) and the WHO found XDR-TB is present in all regions of the world, including the United States, where 4% of MDR-TB cases met criteria for XDR-TB.

XDR-TB is most prevalent in former Soviet bloc nations, where TB control programs have deteriorated along with crumbling government infrastructure, and in western Asia. In the two countries with the highest rates of XDR-TB, Latvia and South Korea, XDR-TB made up 19% and 15% of MDR-TB isolates, respectively. Worldwide, XDR-TB isolates grew from 5% of MDR-TB isolates in 2000 to 7% in 2004 (MMWR. 2006;55[11]:301-305).

“Without better TB control in HIV-infected populations, the spread of XDR-TB could accelerate and lead to a global epidemic,” he says.

With accurate diagnosis and prompt, appropriate drug therapy, XDR-TB is treatable. The WHO reports XDR-TB cure rates of 50% to 60% in HIV-negative individuals who are treated in well-managed TB control programs. Physicians should heighten awareness of drug-resistant TB, Kimerling says. “A thorough medical history is crucial. Previous use of anti-TB drugs, residence in an area where drug-resistant TB is common, or having spent time in a prison or refugee camp should raise suspicion of drug-resistant disease.” The CDC asks physicians to report all second-line drug-susceptibility results obtained during diagnosis and treatment of TB patients to local and state TB programs.

For more information
Dr. Michael Kimerling
1.800.UAB.MIST
mist@uabmc.edu