Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Hepatol Commun. 2024 Jan 5;8(1). doi: 10.1097/HC9.0000000000000356. eCollection 2024 Jan 1.
Infections frequently complicate hospital admission among patients with cirrhosis and are associated with adverse outcomes. In specific settings, administration of prophylactic antibiotics has been shown to improve outcomes. In this pilot study, we aimed to assess the feasibility of a randomized study of whether prophylactic ceftriaxone (CTX), administered to hospitalized patients with advanced cirrhosis (Model for End-Stage Liver Disease-Sodium ≥ 18) without known infection, could reduce the incidence of infection. We also sought to determine whether we could identify patients most likely to benefit through the use of clinical and laboratory parameters.
Hospitalized patients with cirrhosis, with Model for End-Stage Liver Disease-Sodium ≥ 18 and no known infection after evaluation, were randomly assigned in a double-blinded fashion to receive either CTX 1 gr/day or placebo for up to 7 days. Subjects were monitored for incident infection and other outcomes of interest, including adverse reactions such as the development of C. difficile infection. Biomarkers of interest, including C-reactive protein and procalcitonin, were measured before initiation of treatment.
Thirty subjects were enrolled and received CTX or placebo (15 subjects each) per protocol. There were no observed statistically significant differences between groups in incidence of infection, mortality, length of stay, or key laboratory parameters, including C-reactive protein and procalcitonin. Adverse events related to treatment were rare and clinically of minor significance.
Overall, enrollment of subjects proved feasible, and results from this pilot study, while inadequate for confirmation of the potential efficacy of CTX, provide evidence of study feasibility for future, more definitive clinical trials.
感染常使肝硬化患者的住院治疗复杂化，并与不良结局相关。在特定环境下，给予预防性抗生素治疗已被证明可以改善结局。在这项初步研究中，我们旨在评估一项随机研究的可行性，即对于无已知感染的晚期肝硬化（钠模型终末期肝病≥18）住院患者，给予预防性头孢曲松（CTX）是否可以降低感染发生率。我们还试图确定是否可以通过使用临床和实验室参数来识别最有可能受益的患者。
对经过评估后无已知感染的肝硬化住院患者，采用双盲法随机分配至 CTX 1g/天或安慰剂组，接受为期 7 天的治疗。监测患者的感染及其他感兴趣的结局，包括艰难梭菌感染等不良反应。在开始治疗前，测量了感兴趣的生物标志物，包括 C 反应蛋白和降钙素原。
根据方案，共纳入 30 名患者，每组 15 名患者分别接受 CTX 或安慰剂治疗。两组间感染发生率、死亡率、住院时间或关键实验室参数（包括 C 反应蛋白和降钙素原）无统计学显著差异。与治疗相关的不良事件罕见且临床意义较小。
总体而言，纳入患者的可行性已得到证实，虽然这项初步研究的结果尚不足以证实 CTX 的潜在疗效，但为未来更明确的临床试验提供了研究可行性的证据。
