阿奇霉素与头孢曲松治疗儿童无并发症伤寒：随机对照试验的系统评价与荟萃分析。
完整摘要 · 中文译文
背景：由肠道沙门菌伤寒血清型引起的伤寒仍是低收入和中等收入国家儿童发热性疾病的主要原因，尤其是在南亚和东南亚。多重耐药（MDR）和广泛耐药（XDR）菌株的不断出现大幅限制了可用的治疗选择，并凸显了对有效口服疗法的需求。阿奇霉素和头孢曲松常用于儿童无并发症伤寒；然而，比较二者疗效和安全性的证据仍然有限。 目的：通过随机对照试验的系统评价和荟萃分析，比较阿奇霉素与头孢曲松治疗儿童无并发症伤寒的疗效和安全性。 方法：按照PRISMA 2020指南，在PubMed、Cochrane Library、ClinicalTrials.gov、Google Scholar和WHO ICTRP中进行了从建库至2026年4月的全面文献检索。纳入比较阿奇霉素与头孢曲松治疗18岁以下无并发症伤寒儿童的随机对照试验。主要结局为临床治愈率。次要结局包括退热时间、微生物学治愈、复发和不良事件。数据提取和使用Cochrane偏倚风险2工具进行的偏倚风险评估由两名评价者独立完成。采用随机效应模型进行荟萃分析，并使用I²统计量评估异质性。 结果：六项随机对照试验共纳入 纳入492名儿童（阿奇霉素组=244；头孢曲松组=248）。所有研究均为在埃及、印度、巴基斯坦和孟加拉国开展的非盲试验。总体偏倚风险被评为存在一定担忧，主要由于非盲研究设计。荟萃分析显示，阿奇霉素与头孢曲松在临床治愈率（RR=0.98，95%CI 0.93-1.03；P=0.43）或退热时间方面无显著差异。同样，各组间微生物学治愈和不良事件特征相似，但由于报告异质性无法进行正式合并。然而，与头孢曲松相比，阿奇霉素与较少的复发相关，但鉴于证据确定性低，该发现应谨慎解读。退热时间的证据确定性极低，复发率的证据确定性低。各结局的异质性不一，以退热时间最高。 结论：对于儿童无并发症伤寒的治疗，阿奇霉素的疗效和安全性似乎与头孢曲松相当，并呈复发较少的趋势，但需谨慎解读。其口服给药可在流行地区作为胃肠外头孢曲松的实用替代方案。需要进一步开展采用标准化结局报告的大规模随机试验，以加强当前证据基础。 临床试验编号：不适用。 系统评价注册：PROSPERO方案编号：CRD420261383999。链接：https://www.crd.york.ac.uk/PROSPERO/view/CRD420261383999。
完整摘要 · 英文原文
BACKGROUND: Typhoid fever caused by Salmonella enterica serovar Typhi remains a major cause of febrile illness among children in low- and middle-income countries, particularly in South and Southeast Asia. The increasing emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has substantially limited available treatment options and highlighted the need for effective oral therapies. Azithromycin and ceftriaxone are commonly used for uncomplicated typhoid fever in children; however, evidence comparing their efficacy and safety remains limited. OBJECTIVE: To compare the efficacy and safety of azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children through a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive literature search was conducted in PubMed, the Cochrane Library, ClinicalTrials.gov, Google Scholar, and WHO ICTRP from inception to April 2026 in accordance with PRISMA 2020 guidelines. Randomized controlled trials comparing azithromycin with ceftriaxone in children under 18 years of age with uncomplicated typhoid fever were included. The primary outcome was the clinical cure rate. Secondary outcomes included fever clearance time, microbiological cure, relapse, and adverse events. Data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 tool were performed independently by two reviewers. Meta-analysis was conducted using a random-effects model, and heterogeneity was assessed using the I² statistic. RESULTS: Six randomized controlled trials involving 492 children (azithromycin = 244; ceftriaxone = 248) were included. All studies were open-label trials conducted in Egypt, India, Pakistan, and Bangladesh. Overall risk of bias was judged to be of some concern, mainly due to the open-label study design. Meta-analysis showed no significant difference between azithromycin and ceftriaxone in clinical cure rate (RR = 0.98, 95% CI 0.93-1.03; P = 0.43) or fever clearance time. Similarly, microbiological cure and adverse event profiles were similar across groups but could not be formally pooled due to heterogeneous reporting. However, azithromycin was associated with fewer relapses than ceftriaxone, though this finding should be interpreted with caution given the low certainty of the evidence. The certainty of evidence was very low for fever clearance and low for the relapse rate. Heterogeneity varied across outcomes, with the highest for fever clearance time. CONCLUSION: Azithromycin appears to have comparable efficacy and safety to ceftriaxone for the treatment of uncomplicated typhoid fever in children, with a trend toward fewer relapses that warrants cautious interpretation. Its oral administration may provide a practical alternative to parenteral ceftriaxone in endemic settings. Further large-scale randomized trials with standardized outcome reporting are needed to strengthen the current evidence base. CLINICAL TRIAL NUMBER: Not applicable. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Protocol Number: CRD420261383999. LINK: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261383999 .