Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank

Background: Long-term antibiotics are recommended for the prevention of recurrent urinary tract infections (rUTIs) but can cause antibiotic resistance, a growing global concern. Estimates of the absolute risk of resistance with prophylactic antibiotic use are limited. We aimed to estimate the effect of prophylactic antibiotic use on antibiotic resistance in women with rUTIs. Methods: We conducted a retrospective cohort study using the target trial framework and electronic health records held by the SAIL Databank. We emulated a pragmatic trial of women ≥18 years of age with rUTIs, comparing the initiation of prophylactic antibiotics versus non-initiation. The primary outcome was hospital admission with an antibiotic-resistant infection by 52 weeks. Secondary outcomes included hospital admission with an antibiotic-resistant urine infection and uropathogen antibiotic resistance to ≥1 antibiotic and ≥2 antibiotics on urine culture. Findings: We identified 48,297 women eligible for inclusion of whom 839 initiated prophylactic antibiotics (primary outcome). Prophylactic antibiotics did not increase the risk of hospital admission with an antibiotic-resistant infection or antibiotic-resistant urine infection. However, prophylactic antibiotics increased the risk of uropathogen resistance to ≥1 antibiotic on urine culture (relative risk (RR) 1·29 (1·14 to 1·44)) and resistance to ≥2 antibiotics on urine culture (RR 1·57 (1·37 to 1·79)). The absolute risk increases were 6·9% and 8·0%, and the number needed to harm (NNTH) were 14·6 and 12·5 for antibiotic resistance on urine culture to ≥1 antibiotic and ≥2 antibiotics respectively. Interpretation: Prophylactic antibiotic use increased the risk of uropathogen antibiotic-resistance and multi-drug antibiotic-resistance on urine culture. This study provides new evidence on the absolute risk and NNTH for individual-level antibiotic resistance that can be used to support shared decision-making discussions on rUTI prevention.