Colon to Rectum
Lancet Gastroenterol Hepatol. 2025;10(3):222-233
Antibiotic treatment versus appendicectomy for acute appendicitis in adults: An individual patient data meta-analysis
Background: Randomised controlled trials (RCTs) have found antibiotics to be a feasible and safe alternative to appendicectomy in adults with imaging-confirmed acute appendicitis. However, patient inclusion criteria and outcome definitions vary greatly between RCTs. The authors aimed to compare antibiotics with appendicectomy for the treatment of acute appendicitis using individual patient data and uniform outcome definitions. Methods: In this individual patient data meta-analysis, the authors searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions between database inception and June 6, 2023, for RCTs comparing appendicectomy with antibiotics for the treatment of adults (≥ 18 years) with imaging-confirmed acute appendicitis. Studies without 1-year follow-up data on complications were excluded, as were patients. Corresponding authors of eligible studies were contacted and invited to share data; individual patient data were merged after validation. One-stage meta-analyses were conducted using a generalised, mixed-effects linear regression model, accounting for clustering of patients within studies. The primary outcome was the complication rate at 1-year follow-up, uniformly harmonised across trials using the Clavien-Dindo classification. Complications were further divided into minor (grade 1–2 or equivalent) and major (grade 3–5 or equivalent) complications. Appendicectomy rate during 1 year was a key secondary outcome but not considered a complication for the antibiotics group. Outcomes were described separately for patients with and without an appendicolith. Findings: Of 887 potentially relevant articles, 8 were eligible for inclusion, of which 6 RCTs could provide data for 2101 eligible patients (1050 assigned to antibiotics and 1051 assigned to appendicectomy; 830 [39.5%] women and 1271 [60.5%] men). All studies raised some bias concerns due to absence of blinding. One study was judged to have a high risk of bias due to the exclusion of eligible patients after randomisation, but these patients were eligible for inclusion in the authors’ meta-analysis. At 1 year, 57 (5.4%) of 1050 patients randomly assigned to antibiotics had a complication compared with 87 (8.3%) of 1051 patients randomly assigned to appendicectomy (odds ratio [OR] = 0.49 [95% confidence interval {CI}: 0.20–1.20]; risk difference -4.5 percentage points [95% CI: -11.6–2.6]). At 1 year, 1025 (97.5%) patients in the appendicectomy group had undergone appendicectomy compared with 356 (33.9%) patients in the antibiotics group. In patients with an appendicolith at pre-interventional imaging, there were more complications at 1 year among patients who received antibiotic treatment than among those who underwent appendicectomy (29/193 [15.0%] patients vs. 12/190 [6.3%] patients; OR = 2.82 [95% CI: 1.11–7.18]; risk difference 13.2 percentage points [95% CI: 2.3–24.2]). In the antibiotics group, 94 (48.7%) of 193 patients with an appendicolith underwent appendicectomy within 1 year versus 262 (30.6%) of 857 patients without an appendicolith.
Interpretation: This meta-analysis showed that antibiotic treatment in adults with imaging-confirmed acute appendicitis was a safe alternative to surgery and resulted in around two-thirds of patients avoiding appendicectomy during the first year. In patients with an appendicolith, initial antibiotic treatment increased the risk of complications compared with appendicectomy, and around half of these patients assigned to antibiotics underwent step-up appendicectomy within 1 year. These data should be key components in shared decision making.
DOI: 10.1016/s2468-1253(24)00349-2
Prof. Dr. Peter Hasselblatt
Deputy Director Department of Internal Medicine II, University Medical Center Freiburg (Germany)
What is the optimal treatment for acute appendicitis – antibiotics or surgery?
Recent studies have evaluated the option of conservative antibiotic therapy instead of appendectomy for acute uncomplicated appendicitis. The 2020 multicenter CODA study, which included 1552 patients with acute appendicitis, found that antibiotic therapy was not inferior to appendectomy in terms of health-associated quality of life. However, 30% of patients in the study who initially received antibiotic therapy had to undergo surgery within 90 days. The presence of appendicolithiasis was a risk factor for subsequent surgery or complications. The available evidence on antibiotic therapy versus surgery for uncomplicated appendicitis has now also been evaluated in a meta-analysis that included individual patient data from 2580 adults with uncomplicated appendicitis derived from 6 trials (Scheijmans et al.). The complication rate in patients treated with antibiotics was slightly lower than in those who underwent surgery (5.4% vs. 8.3%). However, according to this meta-analysis, a third of the patients treated with antibiotics also had to undergo surgery within 1 year. Again, the presence of appendicoliths was a significant risk factor for complications or subsequent surgery (around half of the patients receiving antibiotics had to undergo surgery later). Based on these data, adult patients presenting with appendicitis are candidates for conservative management; however, appendicolithiasis should be excluded as a contraindication, and patients should be counseled regarding the approximately 30% risk of progression to appendectomy within the follow-up period.
Do these options also apply to children? To answer this question, a multicenter randomized study involving 936 children with uncomplicated appendicitis was conducted at 11 centers (St. Peter et al.). The primary endpoint was non-inferiority of antibiotic therapy compared to surgery with regard to treatment failure. In patients receiving antibiotic therapy, failure was defined as subsequent surgery, while in patients primarily receiving surgery, it was defined as the absence of inflammatory alterations on histology. Non-inferiority was defined by a margin of 20%. Treatment failure occurred in 34% versus 7% of the children treated by antibiotics versus surgery and the endpoint of non-inferiority was not met. These data indicate that a third of children who received antibiotic therapy also had to undergo surgery later. Although children in the antibiotic group were able to resume their normal daily routine earlier (after 1 day vs. 4 days) and return to school earlier (after 2 days vs. 3 days), these differences were rather small. The duration of hospitalization at first manifestation was also significantly shorter in those receiving antibiotic therapy, but the difference was very small (1.0 day vs. 1.25 days). Given these results and the generally uncomplicated disease course following an appendectomy, we should continue to offer surgery rather than antibiotic therapy for children with uncomplicated appendicitis. The likelihood of requiring surgery after antibiotic therapy remains high, while the associated quality-of-life benefits appear minimal.