Evaluation of tuberculosis control by periodic or routine susceptibility testing in previously treated cases

A national tuberculosis control programme (NTP) disposing of baseline drug resistance rates and using 2EHRZ/6TH in the treatment of new cases.

To estimate the extent of drug resistance created by the NTP.

Resistance rates in 2EHRZ/6TH failure and relapse cases were compared to baseline, and resistance profiles of repeat isolates were checked. Numbers of observed resistant failures were compared to numbers expected due to pre-existing resistance. Trends of resistance in combined new and previously treated cases were extrapolated.

High drug resistance rates were observed. Changes in resistance to streptomycin, the virtual absence of documented acquired resistance and a close match of observed with expected resistant failures all indicated accumulation of primary drug resistance as the main mechanism. Resistance in relapse/failure cases showed a significantly declining trend, and estimated combined drug resistance decreased rapidly.

Drug resistance in previously treated cases seems to consist of passed-on primary rather than true acquired resistance. A one-time survey is thus confusing, but continuous routine testing may constitute the best drug resistance monitoring method. Cases previously treated with short-course chemotherapy may show drug resistance much more frequently than generally assumed, and all should receive a re-treatment regimen. The 2EHRZ/6TH regimen proved very safe under field conditions, causing no 'amplification' towards multidrug resistance and almost no acquired isoniazid resistance. Implementation of this regimen, together with a standardised re-treatment regimen, seemed to rapidly reduce isoniazid as well as multidrug resistance levels, despite the fact that directly observed treatment was not strictly applied.