MIAMI BEACH — An effective fight against increasing resistance to tuberculosis treatment worldwide may require rethinking of the World Health Organization's recommended standard treatment regimen, David Olson, M.D., said at the annual meeting of the American Society of Tropical Medicine and Hygiene.
“The feeling now is that the standardized retreatment regimen is going to cause greater drug resistance. We're going to have to abandon that protocol and start patients on second-line therapies sooner with susceptibility testing,” said Dr. Olson of Médecins Sans Frontièrs in New York City. However, second-line agents come with their own challenges.
Of the estimated 8 million people infected with tuberculosis worldwide, there are 300,000 with multidrug-resistant infections, according to the WHO. “It means we're not all going to die tomorrow, but it means these people can infect other people,” Lee B. Reichman, M.D., executive director of the New Jersey Medical School National Tuberculosis Center at the University of Medicine and Dentistry of New Jersey, Newark, said in an interview.
In 2003, foreign-born individuals accounted for 53% of all tuberculosis in the United States. “Every American doctor has to be concerned, especially if they see foreign-born individuals,” Dr. Reichman said. Tuberculosis acquired abroad poses a risk of infection to Americans when these individuals enter or return to the United States. The risk is greatest at ports of entry—in particular, Hawaii, California, Massachusetts, Florida, and New York.
Many factors contribute to multidrug-resistant tuberculosis (MDRTB). For example, a physician who does not recognize a resistant case might prescribe first-line treatment and delay more effective, second-line therapy. Also, patient noncompliance can be an issue, as can HIV coinfection or patients who require repeated treatment.
Duration of treatment also affects compliance. Recommended first-line treatment is prescribed for 6 months, compared with 18 months-2 years for second-line agents. Watching patients take their medication is a strategy in the WHO's Directly Observed Treatment, Short-Course-Plus (DOTS-Plus) initiative.
“Studies have shown that many patients with MDRTB can be cured by combinations of reserve second-line anti-TB drugs. Unfortunately, these drugs are weaker than standard therapy, cause adverse reactions difficult for patients to tolerate, have to be taken for prolonged periods to prevent relapse, and are very expensive,” WHO experts noted in a 2000 report, “DOTS-Plus Pilot Projects for the Management of Multidrug-Resistant Tuberculosis.”
The WHO-recommended regimen for new cases of tuberculosis is isoniazid, rifampin, pyrazinamide, and ethambutol taken daily or 3 times a week under direct observation. Isoniazid and rifampicin are the most powerful weapons against tuberculosis bacilli, but growing resistance—particularly to isoniazid—may necessitate a different approach for the WHO to meet its goal of 85% cure of sputum smear-positive cases by 2005.
There have been no new classes of drugs approved specifically for tuberculosis in more than 40 years. Experts agree that the availability of new tuberculosis agents would help combat resistance, especially shorter duration treatments. “A drug that would work in 2 months would decrease costs by 65%, expand access to treatment, slow or stop resistance, and allow health personnel to be redeployed,” Joelle Tanguy, director of advocacy for the Global Alliance for TB Drug Development, New York City, said during a separate presentation at the meeting.
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