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8/21/2000

Disregard for TB Guidelines Spurs Drug Resistance

Katherine M. Bennett

Adoption by governments and public health organizations of recommendations from international scientific groups could effectively prevent the emergence of drug resistance in patients with tuberculosis (TB), asserts an expert on the problem.

Although the current World Health Organization TB-control strategy of directly observed short-course treatment has been shown to cure more than 80 percent of patients, the impact of drug resistance on the outcome of standardized therapy in developing countries is largely unknown. Thus, public-health researchers conducted two studies, published in the March 13 issue of Archives of Internal Medicine, to document levels of resistance to antitubercular drugs in infected Mexican patients and to assess control efforts.

In the first article, researchers studied patients from an urban Mexican region with a well-established TB program that included directly observed short-course treatment and a three-drug regimen for new cases. Between March 1995 and February 1998, 232 patients with persistent cough and sputum containing microscopically detected acid-fast bacilli (AFB) were enrolled in the study. These patients were monitored for a median of 24 months after treatment was started.

About 28 percent of the patients harbored mycobacterial strains resistant to at least one drug; 20.8 percent of patients received treatment for at least the second time. Multidrug resistance was noted in the sputum samples from 10.8 percent of the patients. Not unexpectedly, statistical analysis revealed that patients who had received previous antitubercular treatment had a higher likelihood of having drug-resistant strains than new cases and that retreated patients had a higher likelihood of treatment failure than new cases.

In the second article, another group of researchers studied the population of tuberculosis patients in three Mexican states where new cases received three-drug regimens without direct observation. From April through October 1997, 816 patients whose sputum sample contained microscopically detected AFB were enrolled in the study.

The researchers found high rates of resistance to at least one of the first-line drugs: 12 percent of new cases and 43 percent of repeat cases showed resistance to isoniazid, rifampin, or pyrazinamide. Multidrug resistance was noted in 2.4 percent of new cases and 22.4 percent of repeat cases.

Using the data on drug resistance, the researchers predicted the impact of changing from the current three-drug initial antitubercular regimen to a regimen incorporating four of the five drugs recommended for retreatment cases by the World Health Organization. Such a change would reduce by 33 percent the number of patients receiving therapy with only one effective drug.

Donald A. Enarson, M.D., of the International Union Against Tuberculosis and Lung Disease, used the findings from the two studies to critique Mexico’s national tuberculosis program. In his accompanying editorial, Enarson wrote that "much of [the TB problems in Mexico] could have been avoided if the government had adopted or would fully adopt the recommendations of international scientific bodies." Enarson’s group offers the following recommendations:

  • Use at least four drugs in the initial intensive treatment phase,   
  • For patients who previously received treatment, use a different regimen than before,   
  • Use combination products containing rifampin only if bioavailability has been proven,   
  • Directly observe patients swallow their medications whenever rifampin is to be administered, and   
  • Provide rifampin only through a structured national tuberculosis program.