Journal Article

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

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

2023

Overview

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. 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. Between April 12, 2017, and June 3, 2021, 13 267 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. 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. The Netherlands Organization for Health Research and Development.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Abdomen / Abscesses / Anti-Bacterial Agents / Antibiotics / Antimicrobial agents / Antimicrobial resistance / Appendectomy / Appendicitis / Appendicitis - drug therapy / Appendicitis - surgery / Clinical medicine / Cohort analysis / Costs / Drug resistance / Health services / Hospitals / Humans / Informed consent / Intravenous administration / Laboratories / Laparoscopy / Length of stay / Mortality / Patients / R&D / Randomization / Referral and Consultation / Research & development / Side effects / Surgical site infections / Systematic review / Telephone / Treatment Outcome