Rifampicin-resistant and multidrug-resistant tuberculosis treatment outcomes: a ten-year retrospective study

Background: Despite the global efforts promoted by the WHO, tuberculosis remains nowadays one of the most common and fatal infectious diseases. Presenting with more than 10 million incident cases in 2022 and being acknowledged as the world’s leading cause of death from a communicable agent. In recent years, through the implementation of new drugs and therapeutic regimens, significant improvements have been obtained in tuberculosis treatment, with the major obstacle to its eradication being identified in the insurgence of drug-resistant forms, that need long and complex therapeutic regimens, with suboptimal treatment success rates. Aims: Having recognized the complexity of drug-resistant tuberculosis, this dissertation aims to identify individuals’ characteristics and outcomes in patients diagnosed with drug-resistant tuberculosis (DR-TB). Methods: We performed a retrospective evaluation of the different therapeutic regimens employed in the treatment of rifampicin-monoresistant (RMR), multidrug-resistant (MDR), and pre-extensively drug-resistant (preXDR) tuberculosis and in the comparison of the treatment outcomes. Secondary objectives included: the analysis of the single drug regimens employed and their correlation with the treatment outcome and the evaluation of the resistance profiles of the different mycobacterial strains, and their correlation to the drugs included in the WHO MDR-TB shorter treatment regimen to evaluate the prescription appropriateness of the regimen itself. This study involved RMR, MDR, and preXDR-TB patients having been treated between 01/01/2014 and 31/12/2024 at the Amedeo di Savoia Hospital, the regional reference center for the management of tuberculosis in Piedmont. A retrospective analysis of the medical records was performed, evaluating demographical aspects, presence of comorbidities, resistance patterns, therapeutic regimens prescribed, changes to such regimens, and clinical, radiological, and microbiological outcomes. The chi-squared test has been employed to detect the potential presence of differences in treatment outcomes, therapeutic regimens, and resistance patterns among patients. Results: 21 patients were included in the study, the median age (IQR) at diagnosis was 43 (31.5-48.0) years and the majority of patients were males, 12 (57.1%). Pulmonary tuberculosis was diagnosed in 20 (95.2%) patients, extrapulmonary involvement was detected in 6 (28.6%). In 7 (33.3%) cases the patients had been previously treated for tuberculosis. RMR, MDR, and preXDR-TB were respectively detected in 4 (19.0%), 10 (47.6%), and 7 (33.3%) cases. Comparing the therapeutic outcomes among those three groups, the treatment success rates were numerically, but not statistically different, (75.0% vs 60.0% vs 42.9%, p=0.135). The reported treatment failure rates were respectively and the rate of patients lost to follow-up Only 6 (28.6%) patients were found to be susceptible to all the drugs included in the WHO MDR-TB shorter treatment regimen. Para-aminosalicylic acid (PAS) exposure was associated with an increased risk of therapeutic failure, p=0.013. Overall, 20 out of 21 (95.2%) patients experienced at least one adverse drug event (ADE), with a mean number (SD) of ADEs per patient of 3.14 (1.88). Conclusions: This study proved how the adequate investigation of the mycobacterial drug susceptibility profile is a fundamental resource in drug-resistant tuberculosis treatment. DST, indeed, enables the provision of tailored treatment regimens permitting to maximize the rate of treatment success, minimizing toxicity, and avoiding inadequate drug prescriptions.