Drug Resistance Testing Is Essential for TB Prognosis

Tuberculosis is diagnosed in the laboratory by staining sputum smears with the Ziehl-Neelsen acid-fast stain.

However, multi-drug-resistant tubercle bacilli (MDR-TB) cannot be identified by this method. The standard way to test for drug susceptibility is by culturing the bacteria Mycobacterium tuberculosis on Löwenstein-Jensen (LJ) or by the microscopic observation drug susceptibility (MODS) assay.

A study on MDR-TB with 93 participants in a larger study of directly observed therapy was conducted at the Imperial College London (London, UK). The median time for smears and cultures to turn negative was 17.5 days and 38.5 days, respectively. Most patients (90%) were smear-negative by 47.5 days and culture-negative by 93 days. In Peru, for example, the authors found that only 25% of patients with culture-positive MDR-TB were sputum smear-positive after two months of anti-tuberculosis treatment.

The authors point out that when treatment began, 66.7% of patients with culture-positive MDR-TB had positive sputum smears. After two months of treatment, only 25% had positive smears, and after four months, only 20% were smear-positive.

However, more than half of MDR patients remained culture positive even after six months of treatment. Overall, among patients who remained culture positive after two months of directly observed treatment, only 18.8% were sputum smear positive. Persistent smear positivity at day 60 is a poor predictor of MDR and thus not a good surrogate for drug susceptibility testing.

David A. Moore, M.D., the senior author of the study, said, "The industrialized-world convention of universal baseline drug sensitivity testing for tuberculosis patients should become the standard of care in multidrug resistance-affected resource-limited settings. Patients are more infectious on treatment than we previously believed, even when they are on the right treatment." This is important in developing countries where diagnosis of drug resistance is delayed due to lack of drug sensitivity testing and patients remain infectious for longer periods.

The study, published in August 2010 in Clinical Infectious Diseases demonstrates that patients with TB who have fully susceptible disease remain sputum culture positive for much longer than is conventionally believed, regardless of baseline smear status. The influence of baseline sputum bacillary load on smear and culture conversion is relatively minor except at very high smear positivity. Conversion from smear or culture positivity to negativity is significantly delayed by both MDR and resistance that is not MDR, but the relative importance varies, depending on the drug susceptibility test method used to define resistance.

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Imperial College London