# Safety of Short‐Term Trimethoprim–Sulfamethoxazole Use for Uncomplicated Cystitis: A Nationwide Retrospective Cohort Study

## TL;DR

The study found that trimethoprim–sulfamethoxazole is as safe and effective as fluoroquinolones for short-term treatment of uncomplicated cystitis in Japanese women.

## Contribution

This is the first nationwide study in Japan to compare the short-term safety of TMP–SMX and fluoroquinolones for uncomplicated cystitis.

## Key findings

- TMP–SMX and fluoroquinolones had similar rates of hypersensitivity and adverse events.
- No significant differences were observed in treatment failure or hospitalization between the groups.
- Results were consistent across age subgroups and additional analyses.

## Abstract

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.

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).

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.

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.

East Asian–specific genetic susceptibility may increase the risk of adverse reactions to trimethoprim–sulfamethoxazole (TMP–SMX), potentially limiting its therapeutic use in this population.In a nationwide Japanese claims database, TMP–SMX use for acute uncomplicated cystitis was not associated with increased adverse events or treatment failure compared with fluoroquinolones.TMP–SMX represents a reasonable first‐line option for acute uncomplicated cystitis in Japan.

East Asian–specific genetic susceptibility may increase the risk of adverse reactions to trimethoprim–sulfamethoxazole (TMP–SMX), potentially limiting its therapeutic use in this population.

In a nationwide Japanese claims database, TMP–SMX use for acute uncomplicated cystitis was not associated with increased adverse events or treatment failure compared with fluoroquinolones.

TMP–SMX represents a reasonable first‐line option for acute uncomplicated cystitis in Japan.

Uncomplicated cystitis is a common bladder infection that is usually treated with short courses of oral antibiotics. A medication called trimethoprim–sulfamethoxazole (TMP–SMX) is recommended as a first‐line treatment in many countries, but its use is limited in Japan and other East Asian regions because certain genetic traits in these populations may increase the risk of severe allergic reactions. As a result, fluoroquinolones are used more often, despite concerns that their overuse contributes to antibiotic resistance. In this study, we used a large nationwide health insurance database in Japan to evaluate whether TMP–SMX is safe for short‐term use in women with uncomplicated cystitis. We examined more than 50 000 treatment episodes and compared patients who received TMP–SMX with those who received fluoroquinolones. We found that adverse reactions were uncommon and occurred at similar rates in both groups. These findings were consistent across age groups and additional analyses. Overall, our results suggest that TMP–SMX is effective and provides similar short‐term outcomes to fluoroquinolones in the treatment of uncomplicated cystitis in Japanese women, and may serve as a reasonable first‐line option while supporting efforts to reduce unnecessary fluoroquinolone use.