A groundbreaking study conducted across seven drug-resistant tuberculosis units in the Dominican Republic has demonstrated promising results for a modified short-course treatment regimen for rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).
The prospective cohort study, conducted throughout 2022, evaluated 113 patients treated with a five-drug oral regimen comprising linezolid, bedaquiline, levofloxacin, clofazimine, and cycloserine. This marks a significant departure from traditional lengthy treatment protocols that often included injectable medications.
Treatment Outcomes and Effectiveness
The study achieved remarkable success rates, with 87% of patients showing culture conversion at two months. By the end of treatment, 79% of patients were successfully treated without relapse at six-month follow-up. The treatment duration was nine months for 92% of successful cases, with only a small number requiring extension to 11-12 months.
Dr. Hugo Mendoza National Center for Research coordinated the implementation, which saw 14% of patients lost to follow-up, 6% mortality rate, and only one case of treatment failure due to adverse drug reactions. These results compare favorably with previous treatment protocols in the Dominican Republic, which had shown success rates of 75% in 2020.
Safety Profile and Monitoring
Safety monitoring revealed that while 82% of patients experienced at least one adverse event of special interest (AESI), most were manageable. The most common adverse events included:
- QT interval prolongation (50% of cases)
- Elevated transaminases (23%)
- Anemia (17%)
- Thrombocytopenia (5%)
Serious adverse events occurred in 12% of patients, with only six cases directly related to the medication. The study employed careful monitoring protocols, particularly for patients receiving linezolid and bedaquiline.
Quality of Life Improvements
The treatment demonstrated significant positive impact on patients' quality of life. Using the EQ-5D-5L questionnaire, researchers observed improvements across all five measured dimensions:
- 100% improvement in mobility and usual activities
- 91% improvement in pain/discomfort and anxiety/depression
- Substantial improvement in self-care
The mean EQ-VAS score increased from 79 at baseline to 96 at treatment completion, representing a 15.5-point average improvement in overall health status.
Clinical Implications
This study's success has led to the adoption of this shortened treatment regimen as the recommended approach for RR/MDR-TB patients in the Dominican Republic since September 2023. The results are particularly significant given the country's position among the top five countries with highest MDR-TB rates in the Americas.
The findings suggest that this simplified, all-oral regimen could address several historical challenges in TB treatment, including poor compliance due to lengthy treatment duration and complications from injectable medications.
Future Considerations
While the results are promising, the study highlighted the need for improved fluoroquinolone molecular susceptibility testing coverage. Additionally, researchers emphasize the importance of strengthening patient-centered care approaches to further reduce loss to follow-up rates.
The success of this modified short-course treatment represents a significant advancement in MDR-TB management, potentially offering a more efficient and patient-friendly approach to treating this challenging disease.
