Fluoroquinolone-Doxycycline Oral Treatments for Adults With Uncomplicated Brucellosis

This is a prospective, multicenter, open-label, randomized controlled trial. Eligible adult patients diagnosed with uncomplicated brucellosis will be randomly assigned to two treatment groups. One group receives doxycycline plus rifampicin, and the other group receives doxycycline plus streptomycin. All participants will complete the scheduled treatment course and follow-up visits. The primary endpoint is treatment response at the end of therapy. Secondary endpoints include relapse rate, adverse reactions, symptom relief time and laboratory index recovery. This study intends to compare the efficacy and safety of the two regimens and provide evidence for clinical management of uncomplicated brucellosis.

• Doxycycline + Rifampicin (Drug): Standard first-line dual oral regimen recommended by WHO for brucellosis. Eligible patients with uncomplicated brucellosis take oral doxycycline combined with rifampicin continuously for an 8-week course.
• Doxycycline + Levofloxacin (Drug): Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with levofloxacin for a total of 8 weeks.
• Doxycycline + Moxifloxacin (Drug): Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with moxifloxacin for a total of 8 weeks.

Primary outcomes

• Clinical and microbiological composite cure rate at Week 6 (end of treatment) [6 weeks after randomization (end of 6-week treatment)]: Composite cure defined as resolution of clinical symptoms plus negative brucella culture / NGS test at the end of 6-week treatment.

Secondary outcomes

• Recurrence rate at 24 weeks after end of treatment [24 weeks post treatment completion]: Proportion of participants with confirmed brucellosis recurrence 24 weeks after stopping 6-week therapy.
• Recurrence rate at 48 weeks after end of treatment [48 weeks post treatment completion]: Proportion of participants with confirmed brucellosis recurrence 48 weeks after stopping 6-week therapy.
• Change in quality of life assessed by SF-36 [Baseline, week 6, week 24, week 48]: Change in SF-36 health-related quality of life score from baseline to week 6, 24 and 48.
• Treatment adherence rate [6-week treatment period]: Proportion of participants with ≥90% medication adherence during the 6-week treatment course.
• Incidence of treatment-related adverse events [From treatment start through week 48]: Treatment-related adverse events graded per CTCAE, including hepatic injury, gastrointestinal reactions, hematological abnormalities and other adverse events.

Sex: All, ages: 16 Years to 75 Years

Inclusion Criteria:1. The diagnostic basis for confirmed cases of brucellosis is the "Expert Consensus on the Diagnosis and Treatment of Brucellosis" published by the Editorial Board of the Chinese Journal of Infectious Diseases in 2017 and the "Diagnosis and Treatment Protocol for Brucellosis (2023 Edition)".

1. There is an epidemiological history, such as a history of contact with suspected or confirmed animals, patients, contaminated animal products, or cultures; living in an endemic area of brucellosis; or having a close relationship with the production, use, and research of vaccines.
2. At the same time, there are the following relevant clinical manifestations: fever, hyperhidrosis, joint pain, headache, fatigue, anorexia, myalgia, weight loss, arthritis, spondylitis, meningitis, or focal organ involvement such as endocarditis, hepatosplenomegaly, orchitis, or epididymitis.
3. In the serological screening, the Rose Bengal plate agglutination test is positive. For the tube agglutination test (SAT), the titer is 1:100 or higher with significant agglutination, or if the course of the disease is more than one year, the titer is 1:50 with significant agglutination or higher; or if there is a history of brucellosis vaccination within half a year, the titer reaches 1:100 with significant agglutination or higher. Accompanied by (or) positive culture of Brucella in the patient's blood, body fluids, or tissues. Or positive NGS detection of Brucella.

2\. On the basis of the above - mentioned diagnosis of brucellosis, spondylitis and sacroiliitis are also present.

Exclusion Criteria:1. Those with comorbid tuberculosis, severe cardiopulmonary dysfunction, advanced tumors, central nervous system diseases (such as a history of epilepsy), or other systemic diseases; 2. Those with comorbid neurological or mental disorders who are unable or unwilling to cooperate; 3. Pregnant or lactating women, or those with a recent plan to have children; 4. Patients with a history of using glucocorticoids, immunomodulators, anti - tuberculosis drugs, etc. within the past 3 months; 5. Patients with missing important information or abnormal mental states.