| dc.description.abstract | Introduction: Sputum culture conversion in patients with pulmonary tuberculosis (PTB) is considered the most important interim indicator of the effectiveness of anti-TB treatment for drug resistant disease. Bedaquiline (Bdq) offers the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). Bdq-based regimens have now been adopted both internationally (in 2019) and nationally (in 2020) as the new standard of care for rifampin-resistant (RR) and MDR TB, replacing the oto-and-nephro toxic aminoglycosides. However, under programmatic conditions, the effectiveness of Bdq-based regimens as measured by time to sputum culture conversion (TTCC) have not been determined in Uganda.
General objective: To determine the median time to sputum culture conversion and associated factors among rifampicin-resistant and multidrug-resistant pulmonary tuberculosis patients treated with Bedaquiline regimens at Mulago hospital tuberculosis unit.
Methods: We conducted a retrospective cohort study at Mulago National Referral Hospital (MNRH) TB unit, of RR/MDR TB patients who received Bdq-based regimens under the TB program, and who were enrolled between January 2020 and June 2023. Using simple random sampling, 265 were enrolled. For each participant, data on socio-demographic factors, clinical factors including baseline TB disease severity measures, baseline chest X-ray (CXR) characteristics, TTCC, co-morbidities, substance abuse, and level of TB drug adherence was abstracted. Analysis for median TTCC was done using Kaplan Meir time-to-event analysis, and the log-logistic parametric Survival regression model was used to identify predictors for TTCC.
Results: Of the 265 enrolled participants, 196 (74.0%) were male. Median age was 35(IQR:27-42) years. The median TTCC was 7 (IQR:4-8) weeks from treatment initiation. Grade 2+ (adjusted Time Ratio (aTR):1.24, 95% CI:1.02 -1.51, p=0.029), and grade 3+ (aTR:1.62, 95% CI:1.30 - 2.01, p<0.001) baseline smear positivity significantly prolonged the TTCC. Cavitary disease on CXR (aTR:1.36, 95% CI:1.18 -1.56, p<0.001), and pleural effusion on CXR (aTR:1.81, 95% CI:1.43 -2.31, p<0.001) also significantly prolonged the TTCC. Diabetes mellitus significantly reduced the TTCC (aTR: 0.37, 95% CI: 0.22 — 0.60, p<0.001). Number of colony forming units (CFU) on baseline culture, GeneXpert cycle threshold (CT) value, and anemia were confounders to the relationship between the significant predictors and TTCC.
Conclusion: In this setting, the median TTCC in patients on Bdq-based regimens was 7 weeks implying that Bdq-based regimens remain efficacious in routine DR TB care. Ongoing integration of TB screening services at points of care of high-risk patients like diabetics remains important for early detection and prompt initiation of DR TB treatment for better outcomes. The TB program and clinicians should enhance and individualize support for RR/MDR TB patients with more severe disease to ensure optimum TTCC and successful treatment outcomes. | en_US |
