In Bangladesh, the Damien Foundation carried out the tuberculosis program on behalf of the government in a population of close to 30 million inhabitants. The program is organized with strict adherence to "DOTS Strategy" principles and the treatment results are excellent with fewer than 2% of treatment failures with the first-line regimen that was an 8-month, thioacetazone-based continuation phase regimen. Nevertheless, some patients failing on the first-line regimen, also failed on the re-treatment, rifampicin-throughout regimen, and a certain proporiton of these had expectedly laboratory-confirmed multidrug-resistance.
Regimen 1: In 1997, one of the then recommended standard regimens for the treatment of multidrug-resistant tuberculosis of 21 months duration was introduced after approval by the government. It differed slightly from the recommendation in that clofazimine, an antileprosy drug was included in the intensive phase. Patients completing treatment successfully were followed up for 24 months after cessation of chemotherapy for ascertainment of relapses.
Regimen 2: Because the regimen appeared excessively long and there were no relapses, the first change in the treatment regimen was to shorten it to 15 months without any deterioration in the results. These two regimens will be discussed together in the following.
Regimen 3: There was widespread concern among experts about the continued use of isoniazid despite demonstrated resistance by the laboratory. Isoniazid was thus dropped from regimen 3. The efficacy of the regimen (failure, relapse) dropped substantially with this change, in addition to the continued high frequency of adverse drug events that led to absconding of patients.
Regimen 4: In this regimen, isoniazid was thus re-introduced, but the thioamide 9prothionamide was used) was dropped from the continuation phase. This improved the results somewhat but seemingly prothionamide played a major role in the prevention of treatment failures and the results were still short of what was hoped to be achievable, but the frequency of adverse drug event were substantially
Regimen 5: In this regimen compensation for lost efficacy from dropping the thioamide was sought by adding clofazimine throughout. The efficacy of the regimen improved importantly, strongly suggesting that clofazimine played indeed a major role in the treatment of drug-resistant tuberculosis.
Regimen 6: The final adjustment in this regimen included several important changes: 1) the fluoroquinolone ofloxacin was replace by the then generically available fourth-generation fluoroquinolone gatifloxacin and because its superiority as a relapse-preventing drug, 2) the duration was shortened to a minimum of 9 months, 3) isoniazid was given only during the intensive phase, and 4) the minimum duration of the intensive phase was prolonged to 4 months, and if at 4 months still positive on microscopy, prolonged by one-month increments until sputum smears became negative or treatment failure had to be declared. |
