Background
The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The growing global threat of antimicrobial resistance justifies restrictive use of antibiotics, 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 (age ≥ 8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics. after appendectomy. Randomization was stratified by center, and treating physicians and patients were not blinded to treatment assignment.
The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The primary 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 appendectomy.
Efficacy was analyzed in the intention-to-treat and per-protocol populations . Safety results were analyzed in the intention-to-treat population. This trial was registered in the Netherlands Trial Register, NL5946.
Results
Between April 12, 2017 and June 3, 2021, 13,267 patients were screened and 533 were randomly assigned to each group. 31 were excluded from the intention-to-treat analysis from the 2-day group and 30 from the 5-day group due to errors in recruitment or consent.
Appendectomy was performed laparoscopically in 955 (95%) of 1005 patients. Telephone follow-up was completed in 664 (66%) of 1005 patients.
The primary endpoint occurred in 51 (10%) of 502 patients analyzed in the 2-day group and 41 (8%) of 503 patients analyzed in the 5-day group (adjusted absolute risk difference 2.0% , 95% CI − 1·6 to 5·6).
Complication and reintervention rates were similar between trial groups. Fewer patients had adverse effects from 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).
Hospital readmission was more common 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 appendectomy performed in a well-resourced healthcare setting. Adopting this strategy will reduce the adverse effects of antibiotics and the length of hospital stay. |
Fragment of the editorial
Aneel Bhangu, Pamela Buchwald, Faustin Ntirenganya. DOI: https://doi.org/10.1016/S0140-6736(22)02544-2
Postoperative Antibiotics May Be Reduced After Laparoscopic Surgery for Complex Appendicitis
Appendicitis is the most common surgical emergency worldwide and surgery remains the mainstay of treatment in more than 98% of cases. However, variations in management are extremely common and under-researched. For example, there is little agreement on the best preoperative diagnostic strategy, the role of antibiotics as primary treatment, and how to best implement laparoscopic appendectomy in low- and middle-income countries.
Evidence regarding the duration of antibiotics after surgery is scarce, and cautious behaviors tend to result in longer courses being prescribed. Postoperative antibiotics are justified if they reduce complications; Otherwise, they exacerbate costs, increase antimicrobial resistance, delay hospital discharge, and have a carbon consequence.
