The APPAC randomized clinical trial provides the first long-term data exceeding five years on non-operative management for appendicitis. Specifically, the ten-year follow-up confirms the feasibility and safety of Uncomplicated Appendicitis Antibiotics for adults. This analysis compares the outcomes of appendectomy versus antibiotic treatment over a decade. Researchers sought to determine the 10-year appendicitis recurrence and appendectomy rate after initial antibiotic therapy.
The APPAC Trial Design and Interventions
The study was a 10-year observational follow-up of the original APPAC trial cohort. Patients aged 18 to 60 years with computed tomography (CT)-diagnosed uncomplicated acute appendicitis participated. They were initially randomized to either open appendectomy (n=273) or a course of antibiotics (n=257). The antibiotic regimen involved intravenous ertapenem sodium (1 g/d) for three days. Following this, patients received seven days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times/d). This specific protocol ensured a robust comparison against the definitive surgical approach. The main outcomes focused on late (after 1 year) appendectomy and recurrence.
Long-Term Recurrence with Uncomplicated Appendicitis Antibiotics
At the ten-year mark, researchers successfully assessed 253 of 257 patients in the antibiotic arm (98.4%). The true appendicitis recurrence rate, confirmed by histopathology, was 37.8% (95% CI, 31.6%-44.1% [87/230]). Furthermore, the cumulative appendectomy rate in this group reached 44.3% (95% CI, 38.2%-50.4% [112/253]) over the decade. Therefore, more than half of the patients who received the initial antibiotic treatment successfully avoided surgery for ten years. Other major trials, such as the CODA trial, showed similar long-term trends, emphasizing the risk of later appendectomy is a trade-off for avoiding initial surgery.
Complication Rates and Key Differences
A compelling finding relates to the complication rates between the two groups. The 10-year cumulative complication rate for the surgical group was significantly higher at 27.4% (95% CI, 21.6%-33.3% [62/226]). Meanwhile, the complication rate for patients initially treated with antibiotics was only 8.5% (95% CI, 4.8%-12.1% [19/224]). This difference was statistically significant (P < .001). Consequently, patients who opt for surgery face a much higher risk of immediate and long-term complications. Post hoc analysis also showed no statistically significant difference in the detection of appendiceal tumors between the antibiotic (0.9%) and appendectomy (1.5%) groups (P=.70). Therefore, non-operative management does not appear to increase the risk of missing malignancy.
Frequently Asked Questions
Q1: What were the 10-year appendectomy and recurrence rates in the antibiotic group?
The 10-year cumulative appendectomy rate was 44.3%, and the true, histopathologically confirmed appendicitis recurrence rate was 37.8%.
Q2: How did the long-term complication rates compare between the two groups?
The complication rate at 10 years was significantly lower in the antibiotic group (8.5%) compared to the appendectomy group (27.4%, P < .001).
Q3: What specific antibiotics were used in the APPAC trial intervention?
The intervention involved three days of intravenous ertapenem sodium, followed by seven days of oral levofloxacin and metronidazole.
References
- Salminen P et al. Antibiotic Therapy for Uncomplicated Acute Appendicitis: Ten-Year Follow-Up of the APPAC Randomized Clinical Trial. JAMA. 2026 Jan 21. doi: 10.1001/jama.2025.25921. PMID: 41563747.
- Most patients with appendicitis can have antibiotics as their first treatment, rather than appendectomy. American College of Surgeons. Published October 25, 2021. Available at: https://www.facs.org/for-medical-professionals/news-publications/news-and-articles/bulletin/2021/october-2021-volume-106-issue-10/most-patients-with-appendicitis-can-have-antibiotics-as-their-first-treatment-rather-than-appendectomy/
- Kumar SS et al. Guideline for the Diagnosis and Treatment of Appendicitis – A SAGES Publication. Surg Endosc. 2023 Jul;37(7):5329-5353. doi: 10.1007/s00464-023-09941-z.