Safety of Short-Term Trimethoprim-Sulfamethoxazole Use for Uncomplicated Cystitis: A Nationwide Retrospective Cohort Study.

BACKGROUND

Trimethoprim-sulfamethoxazole (TMP-SMX) is associated with hypersensitivity and other adverse reactions. East Asian-specific genetic susceptibility may increase severe adverse events, limiting the therapeutic use of TMP-SMX for uncomplicated cystitis in Japan. However, data on its short-term safety in this population are scarce. This study compared the short-term safety of TMP-SMX with fluoroquinolones for the treatment of uncomplicated cystitis using a nationwide Japanese claims database.

METHODS

We conducted a retrospective cohort study using the JMDC Claims Database (2006-2022). We included female outpatients aged ≥ 18 years with acute uncomplicated cystitis who were newly treated with TMP-SMX or fluoroquinolones (levofloxacin, ciprofloxacin, or tosufloxacin). The primary outcome was drug-induced hypersensitivity (anaphylaxis or treatment-requiring rash) within 7 days after the prescription of these drugs. The secondary outcomes included treatment failure, all-cause hospitalization, and other adverse events. Propensity score-overlap weighting was applied to adjust for confounding. Subgroup analyses were stratified by age (< 50 or ≥ 50 years).

RESULTS

Among 50 773 eligible patients (TMP-SMX, 2.1%; fluoroquinolones, 97.9%), the baseline characteristics were well balanced after weighting. The incidence of hypersensitivity did not differ significantly between the groups (0.9% vs. 0.7%; risk difference, 0.3%; 95% confidence interval, -0.3% to 0.8%; p = 0.410). No significant differences were observed for secondary outcomes. Subgroup analyses showed consistent results.

CONCLUSIONS

Short-term use of TMP-SMX was not associated with increased risks of adverse events or treatment failure compared with fluoroquinolones. TMP-SMX may represent a reasonable first-line option for acute uncomplicated cystitis in Japan.