Setting: A national tuberculosis control programme (NTP) disposing of baseline drug resistance rates and using 2EHRZ/6TH in the treatment of new cases.
Objective: To estimate the extent of drug resistance created by the NTP.
Design: 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.
Results: 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.
Conclusions: 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.