Comparison of sitafloxacin monotherapy versus doxycycline plus rifampicin for acute uncomplicated human brucellosis: a multicenter, randomized, open-label, non-inferiority trial.

Background: Sitafloxacin has demonstrated superior in vitro activity against Methods: This multicenter, open-label, randomized, non-inferiority clinical trial was conducted from August 2023 to July 2025 at three hospitals in China and included 238 adult patients with brucellosis symptoms for less than 3 months who met the study criteria. They were randomized in a 1:1 ratio to receive sitafloxacin monotherapy (100 mg once daily) or combined doxycycline (100 mg every 12 h) and rifampicin (10 mg/kg daily) for 6 weeks. Adherence, efficacy, and safety were evaluated over a 12-month follow-up period. The primary outcome was the clinical response rate at the end of 6 weeks, and the secondary outcomes were treatment failure rate, relapse during follow-up, and safety profiles. The non-inferiority margin was 12%. Findings: In the intention-to-treat population, the clinical response rate was 89.9% in the sitafloxacin group and 83.2% in the doxycycline-rifampicin group (risk difference [RD] = 6.7%; 95% CI: -2.0 to 15.7). In the per-protocol population, the response rates were 97.3% and 96.1%, respectively (RD, 1.2%; 95% CI: -4.4 to 7.2). The symptom relapse rates were 2.7% and 1.9% in the sitafloxacin and doxycycline-rifampicin groups, respectively (RD, 0.8%; 95% CI: -4.4 to 6.0). The adverse event-related treatment discontinuation rate was numerically lower in the sitafloxacin group (2.5% vs. 6.7%, RD, -4.20%; 95% CI: -10.5 to 1.3), although the difference did not reach statistical significance. Similarly, the overall incidence of treatment-related adverse events was also numerically lower in the sitafloxacin group (10.9% vs. 19.3%; Interpretation: Sitafloxacin monotherapy was non-inferior to doxycycline-rifampicin for treating acute uncomplicated brucellosis, and showed a favorable safety and tolerability profile. Thus, sitafloxacin monotherapy may have potential as an alternative regimen in this clinical setting. Funding: This work was supported by the National Key Research and Development Program of China (2023YFC2308800)and the Natural Science Foundation of Shandong Province (ZR2023MH169). Trial registration: ChiCTR2300072703.