Clinical efficacy and safety of rifampicin injection versus rifamycin sodium for injection combined with doxycycline in the treatment of human brucellosis
利福平注射液与注射用利福霉素钠联合多西环素治疗布鲁氏菌病的临床 疗效与安全性分析

摘要

目的 比较利福平注射液与注射用利福霉素钠分别联合多西环素治疗布鲁氏菌病（布病）的临床疗效与安全性，为静脉抗菌治疗方案的优化提供循证依据。方法 采用前瞻性、随机、开放性、平行对照设计。纳入符合《布鲁氏菌病诊断标准》的120例患者，采用计算机随机数字表法按1:1比例分为利福平注射液联合多西环素组（利福平组）和注射用利福霉素钠联合多西环素组（利福霉素钠组）。比较两组患者血沉（ESR）、超敏C反应蛋白（hs-CRP）改善情况及发热患者体温恢复正常时间；同时评价治疗期间肝功能、肾功能异常及药物相关不良反应发生情况。结果 利福平组ESR改善总有效率高于利福霉素钠组，差异具有统计学意义（P＜0.05）；两组hs-CRP改善总有效率及体温恢复正常时间比较差异均无统计学意义（P＞0.05）。两组肝功能指标异常发生率比较差异均无统计学意义（P＞0.05）；利福霉素钠组肌酐（Cr）异常发生率高于利福平组（P＜0.05），而利福平组药物相关不良反应发生率高于利福霉素钠组（P＜0.05）。结论 利福平注射液联合多西环素与注射用利福霉素钠联合多西环素均可有效治疗布病。利福平组在改善ESR方面具有一定优势，而利福霉素钠组Cr异常发生率较高、利福平组药物相关不良反应发生率较高。临床应结合患者病情、药物安全性及耐受性，合理选择静脉抗菌治疗方案。本研究将为深空长期载人任务抗感染药物储备提供了地面循证参考。

Abstract

Objective To compare the clinical efficacy and safety of intravenous rifampicin combined with doxycycline versus rifamycin sodium for injection combined with doxycycline in the treatment of human brucellosis, and to provide evidence for optimizing intravenous antimicrobial therapy.
Methods A prospective, randomized, open-label, parallel-controlled design was conducted. A total of 120 patients who met the Diagnostic Criteria for Brucellosis were enrolled and randomly assigned in a 1:1 ratio using a computer-generated random number table to receive either intravenous rifampicin plus doxycycline or rifamycin sodium for injection plus doxycycline. The primary efficacy endpoints included improvement in erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), and the time to defervescence in febrile patients. Safety was evaluated by monitoring abnormalities in liver and renal function as well as drug-related adverse events during treatment.
Results The overall response rate based on ESR improvement was significantly higher in the rifampicin group than in the rifamycin sodium group (P < 0.05). No significant differences were observed between the two groups in the overall response rate based on hs-CRP improvement or the time to defervescence (all P > 0.05). The incidences of abnormal liver function indicators were comparable between the two groups (all P > 0.05). The incidence of abnormal serum creatinine was significantly higher in the rifamycin sodium group than in the rifampicin group (P < 0.05), whereas the overall incidence of drug-related adverse events was significantly higher in the rifampicin group (P < 0.05).
Conclusion   Both intravenous rifampicin plus doxycycline and rifamycin sodium for injection plus doxycycline are effective for the treatment of human brucellosis. Intravenous rifampicin showed an advantage in improving ESR, whereas the rifamycin sodium group had a higher incidence of abnormal serum creatinine and the rifampicin group had a higher incidence of drug-related adverse events. Intravenous antimicrobial therapy should be selected according to disease severity, drug safety, and patient tolerance. Furthermore, the present study provides ground-based clinical evidence to inform the selection and strategic stockpiling of anti-infective agents for long-duration crewed deep-space exploration missions.