Colon to Rectum
Lancet. 2023;401(10374):366–76
Two days versus 5 days of postoperative antibiotics for complex appendicitis: A pragmatic, open-label, multicenter, non-inferiority randomized trial
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. Randomization was stratified by center, and treating physicians and patients were not masked to treatment allocation. The primary end point was a composite end point of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% confidence interval [CI]) in the primary end point, 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 analyzed in the intention-to-treat (ITT) and per-protocol (PP) populations. Safety outcomes were analyzed in the ITT population.
Findings: 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 ITT 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 of 1005 patients (95%). The telephone follow-up was completed in 664 of 1005 patients (66%). The primary end point occurred in 51 of 502 patients (10%) analyzed in the 2-day group and 41 of 503 patients (8%) analyzed in the 5-day group (adjusted absolute risk difference, 2.0%, 95% CI: -1.6–5.6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45/502 patients [9%]) than in the 5-day group (112/503 patients [22%]; odds ratio [OR] = 0.344, 95% CI: 0.237–0.498). Re-admission to hospital was more frequent in the 2-day group (58/502 patients [12%]) than in the 5-day group (29/503 patients [6%]; OR = 2.135, 95% CI: 1.342–3.396). There were no treatment-related deaths.
Interpretation: Two 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.