荷兰伊拉斯姆斯大学医学中心Anne Loes van den Boom团队比较了复杂阑尾炎术后2天与5天的抗生素治疗对患者预后的影响。这一研究成果发表在2023年1月17日出版的《柳叶刀》杂志上。

复杂阑尾炎术后使用抗生素的合适时间尚不清楚。抗微生物药物耐药性的全球威胁越来越大，亟需限制抗生素的使用，这也可以减少副作用、住院时间和成本。

研究组在荷兰15家医院进行了一项实用性、开放性、非劣效性试验，招募复杂性阑尾炎（年龄≥8岁）患者并将其随机分配（1:1），在阑尾切除术后2天或5天静脉注射抗生素。随机分组按中心分层，治疗医生和患者不受治疗分配的影响。主要终点是90天内感染性并发症和死亡的综合结局。主要结局是主要终点的绝对风险差异（95%CI），根据年龄和阑尾炎严重程度进行校正，非劣效性边缘为7.5%。结果评估基于电子病历和阑尾切除术后90天的电话咨询。对意向治疗人群和符合方案人群的疗效进行了分析。对意向治疗人群的安全性结果进行了分析。

2017年4月12日至2021年6月3日共筛选了13267名患者，其中1066名患者被随机分配，每组533人。2天组中有31例因招募或同意错误而被排除在意向治疗分析之外，5天组中有30例被排除在外。1005例患者中，955例（95%）采用腹腔镜行阑尾切除术。1005名患者中有664名（66%）完成了电话随访。

2天组502名患者中有51名（10%）发生主要终点，5天组503名患者中有41名（8%），校正后的绝对风险差异为2.0%。试验组之间的并发症发生率和再干预率相似。与5天组相比，2天组502名患者中有45名（9%）出现抗生素不良反应，显著少于5天组（503名患者中有112名[22%]；优势比[OR]为0.344）。2天组502名患者中有58名（12%）再次入院，5天组503名患者中有29名（6%）；OR为2.135。没有与治疗相关的死亡。

研究结果表明，复杂阑尾炎术后2天静脉注射抗生素的感染并发症和90天内的死亡率均不逊于5天静注抗生素，非劣效性边缘为7.5%。这些发现适用于在资源充足的医疗机构中进行的腹腔镜阑尾切除术。采用这种策略将减少抗生素的副作用和住院时间。

附：英文原文

Title: 2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

Author: Elisabeth M L de Wijkerslooth, Evert-Jan G Boerma, Charles C van Rossem, Joost van Rosmalen, Coen I M Baeten, Frédérique H Beverdam, Johanna W A M Bosmans, Esther C J Consten, Jan Willem T Dekker, Marloes Emous, Anna A W van Geloven, Anton F Gijsen, Luc A Heijnen, An P Jairam, Damian C Melles, Augustinus P T van der Ploeg, Pascal Steenvoorde, Boudewijn R Toorenvliet, Maarten Vermaas, Bas Wiering, Bas P L Wijnhoven, Anne Loes van den Boom, C.I.M. (Coen) Baeten, F.H. (Frederique) Beverdam, E.G. (Evert-Jan) Boerma, A.L. (Anne Loes) van den Boom, J.W.A.M. (Anne-Claire) Bosmans, T.A. (Thijs) Burghgraef, E.C.J. (Esther) Consten, J.W.T. (Jan Willem) Dekker, M. (Marloes) Emous, A.A.W. (Nanette) van Geloven, A.F. (Anton) Gijsen, L.A. (Luc) Heijnen, F. (Floor) Heinink, S.A. (Sander) Huisman, A.P. (An) Jairam, P.T.J.H.M. (Paul) Janssen, J. (Joske) de Jonge, D. (Daniela) Jou-Valencia, S. (Sanne) Klaphake, J. (Jurian) Kloeze, L.F. (Leonard) Kroese, H.R. (Hester) Langeveld, M.D.P. (Misha) Luyer, D.C. (Damian) Melles, B.J. (Bo) Noordman, A.P.T. (Stijn) van der Ploeg, F.B. (Floris) Poelmann, C.C. (Charles) van Rossem, J. (Joost) van Rosmalen, W.H. (Hermien) Schreurs, P. (Pascal) Steenvoorde, B.R. (Boudewijn) Toorenvliet, M. (Maarten) Vermaas, J. (Jol) Shapiro, F.P.R. (Floris) Verbeek, J. (Joost) Verhelst, H.P. (Hendt) Versteegh, J.L.A. (Jeroen) van Vugt, B. (Bas) Wiering, B.J. (Bart) van Wijk, E.M.L. (Elisabeth) de Wijkerslooth, B.P.L. (Bas) Wijnhoven

Issue&Volume: 2023-01-17

Abstract:

Background

The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs.

Methods

In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946.

Findings

Between April 12, 2017, and June 3, 2021, 13267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI 1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths.

Interpretation

2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay.

DOI: 10.1016/S0140-6736(22)02588-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02588-0/fulltext