Trends in Antituberculosis Drug Resistance and Associated Factors: A 31-Year Observational Study at a Tertiary Hospital in Barcelona

<b>Objective</b>: To analyze trends in resistance to antituberculous drugs over a 31-year period (1991-2022) at a hospital in Barcelona and to identify associated epidemiological determinants. <b>Methods</b>: This study included culture-confirmed tuberculosis cases diagnosed between 1991 and 2022. Drug susceptibility testing was conducted with clinical data from hospital records and epidemiological data from the Barcelona Public Health Agency. The primary outcome was resistance to first-line drugs. A subset of isolates was tested for second-line drugs. Trends were compared between the periods 1991-2000 and 2001-2022, aligning with increased immigration. Factors associated with resistance were examined using multivariate regression analysis. <b>Results</b>: Among the 2448 patients included, tuberculosis cases peaked in the 1990s and subsequently declined, while drug resistance increased. Overall, 12.2% of isolates showed resistance to at least one drug: 8.5% were monoresistant, 2.3% multiresistant, and 1.4% polyresistant. The 2001-2022 period had a higher resistance rate (OR 1.63; 95%CI 1.28-2.09) but lower multiresistance (OR 0.40; 95%CI 0.23-0.69). Resistance among new cases doubled from 6.4% to 12.8%, while rates among previously treated cases remained stable. The predictors of resistance were foreign-born (OR 1.52; 95%CI 1.21-1.91) and previous tuberculosis treatment (OR 2.88; 95%CI 2.17-3.81). A total of 90% of isolates remained susceptible to fluoroquinolones and aminoglycosides. <b>Conclusions</b>: Although tuberculosis incidence has declined over the past three decades, antibiotic resistance has increased, driven by foreign-born and retreatment cases. Ongoing drug susceptibility testing, access to second-line therapies, and targeted public health interventions for high-risk populations are essential to maintain control in low-incidence settings.