Fluoroquinolone-based regimens increase therapeutic failure risk in patients with brucellosisFluoroquinolones show higher failure rates in treating brucellosis

INTRODUCTION: Brucellosis is a major zoonotic infection worldwide, with the highest burden reported in the Mediterranean region. The therapeutic role of fluoroquinolones in this disease continues to be controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of fluoroquinolone-containing regimens compared with standard non-fluoroquinolone regimens for the treatment of human brucellosis. METHODS: In accordance with PRISMA recommendations, this systematic review and meta-analysis assessed the efficacy and safety of fluoroquinolone-based regimens for treating brucellosis. It was prospectively registered in PROSPERO (CRD420251142019). A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was carried out, including studies published through August 2025. Randomized controlled trials comparing fluoroquinolones with conventional therapies (such as doxycycline with streptomycin or rifampicin) were included. Therapeutic failure, relapse, adverse events, and time to defervescence were the main outcomes. To compute pooled risk ratios and mean differences with 95%CIs, data were analyzed using STATA v18. The GRADE method and the RoB 2 tool were used to evaluate the risk of bias and the certainty of the evidence. RESULTS: The analysis comprised 9 clinical studies with 602 brucellosis patients. When compared to standard regimens, fluoroquinolone-based regimens were linked to a significantly higher risk of therapeutic failure (RR = 2.11, 95% CI: 1.26-3.51; P = 0.004) and a higher, though not statistically significant, risk of relapse (RR = 1.88, 95% CI: 0.94-3.74; P = 0.07). No statistically significant between-study heterogeneity was observed for either outcome (I² = 0%). Subgroup analyses showed a significantly increased risk of therapeutic failure in patients with uncomplicated brucellosis and in studies with treatment durations >8 weeks, although between-subgroup differences were not statistically significant. On the other hand, no statistically significant difference in adverse events was observed between fluoroquinolone-based and standard regimens under the random-effects model (RR = 0.62, 95% CI: 0.29-1.33; P = 0.22). Although the point estimate favored fluoroquinolone-based regimens, the confidence interval included the null effect. Fluoroquinolone-based regimens were also associated with a significantly longer time to defervescence compared with standard regimens (MD = 1.20 days, 95% CI: 0.66-1.74; P < 0.001). The certainty of evidence was moderate for therapeutic failure, and time to defervescence, and low for relapse and adverse events according to the GRADE evaluation. CONCLUSION: Compared with conventional doxycycline-based combinations, fluoroquinolone-based regimens were associated with a higher risk of therapeutic failure and longer time to defervescence, while the overall risk of relapse did not differ significantly. No significant difference in adverse events was observed with the random-effects model, although the point estimate favored fluoroquinolone-based regimens. Overall, these findings do not support the routine use of fluoroquinolones as first-line therapy for adult brucellosis. Further well-designed randomized controlled trials are needed.