Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

Abdul Wahid; Abdul Ghafoor; Abdul Wali Khan; Yaser Mohammed Al-Worafi; Abdullah Latif; Nisar Ahmed Shahwani; Muhammad Atif; Fahad Saleem; Nafees Ahmad

doi:10.3389/fphar.2022.973713

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

Front Pharmacol. 2022 Sep 6:13:973713. doi: 10.3389/fphar.2022.973713. eCollection 2022.

Authors

Abdul Wahid¹, Abdul Ghafoor², Abdul Wali Khan², Yaser Mohammed Al-Worafi³, Abdullah Latif², Nisar Ahmed Shahwani⁴, Muhammad Atif⁵, Fahad Saleem¹, Nafees Ahmad¹

Affiliations

¹ Department of Pharmacy Practice, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Pakistan.
² National TB Control Program, Islamabad, Pakistan.
³ Department of Clinical Pharmacy, University of Science and Technology of Fujairah, Fujairah, United Arab Emirates.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Pakistan.
⁵ Department of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

Abstract

Objective: To compare the effectiveness of second line injectables containing shorter (duration 9-12 months) and longer treatment regimens (LTR, duration ≥ 20 months) among multidrug-resistant tuberculosis (MDR-TB) patients with no documented resistance and history of treatment with any second-line anti-TB drug (SLD) for ≥ 1 month. Methods: This was an observational cohort study of MDR-TB patients treated at eight PMDT units in Pakistan. Patients' data from baseline until treatment outcomes were collected from Electronic Nominal Recording and Reporting System. The treatment outcomes of "cured" and "treatment completed" were grouped together as successful, whereas "death," "treatment failure," and "lost to follow-up" were collectively grouped as unsuccessful outcomes. Time to sputum culture conversion (SCC) was analyzed using the Kaplan-Meier method and the differences between groups were compared through the log-rank test. Multivariate Cox proportional hazards and binary logistic regression analyses were used to find predictors of time to SCC and unsuccessful treatment outcomes. A p-value < 0.05 was considered statistically significant. Results: A total 701 eligible MDR-TB patients [313 treated with shorter treatment regimen (STR) and 388 treated with LTR at eight centres in Pakistan were evaluated]. Time to achieve SCC was significantly shorter in STR group [mean: 2.03 months, 95% confidence interval (CI):1.79-2.26] than in LTR group (mean: 2.69 months, 95% CI: 2.35-3.03) (p-value<0.001, Log-rank test). Treatment success was higher in STR (83.7%) than in LTR (73.2%) group (p-value <0.001) due to high cure (79.9% vs. 70.9%, p-value = 0.006) and low death (9.9% vs. 18.3%, p-value = 0.002) rates with STR. Treatment with STR emerged the only predictor of early SCC [adjusted Hazards ratio (aHR) = 0.815, p-value = 0.014], whereas, patient's age of 41-60 (OR = 2.62, p-value<0.001) and >60 years (OR = 5.84, p-value<0.001), baseline body weight of 31-60 (OR = 0.36, p-value = 0.001) and >60 kg (OR = 0.23, p-value <0.001), and treatment with LTR (OR = 1.88, p-value = 0.001) had statistically significant association with unsuccessful treatment outcomes. Conclusion: STR exhibited superior anti-microbial activity against MDR-TB. When compared LTR, treatment with STR resulted in significantly early SCC, high cure, and lower death rates among MDR-TB patients who had no documented resistance and history of treatment with any SLD ≥ 1 month.

Keywords: MDR-TB; cure; death; longer treatment regimen; shorter treatment regimen; sputum culture conversion.