APPAC Trial: Antibiotic Treatment Alone, A Feasible and Alternative Option to Surgery for Uncomplicated Acute Appendicitis

Introduction

Appendicitis Acuta (APPAC) trial compared the antibiotic treatment with appendectomy for patients with computed tomography (CT) confirmed acute uncomplicated appendicitis. The 1-year results showed that 73% of all patients with appendicitis treated with antibiotics alone did not require surgery at 1 year. Appendicitis could have recurred in those patients, so it was important to report long-term outcomes for these patients. The present study reports the 5-year outcomes for all the patients enrolled in the original APPAC trial.

Aim

To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.

Patients Profile

• N=530
• Patients aged 18 to 60 years
• CT confirmed uncomplicated acute appendicitis

Methods

• A multicenter randomized clinical trial conducted in Finland  

• Baseline demographic characteristics between the study groups were similar
• Patients were randomized to receive either appendectomy or antibiotic treatment with intravenous ertapenem sodium (1 g/d) for 3 days, followed by 7 days of oral  levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times/d)

Endpoint

• 5-year follow-up outcomes that included
  • late recurrence (after 1 year) of acute appendicitis after antibiotic treatment
  • overall post-intervention complications (surgical site infections, incisional hernias, abdominal or incisional pain, obstructive symptoms, length of hospital stay (both primary hospitalization and all additional hospital stays)
  • the amount of sick leave (both primary recovery period and all additional appendicitis treatment–associated sick leave days)
  • post intervention pain scores (visual analog scale [VAS] score range
  • 0-10 [0 indicates no pain; 10 indicates the worst possible pain])
  • treatment costs

Results

• In antibiotics group, 85 patients who subsequently underwent appendectomy for recurrent appendicitis
  • 76 had uncomplicated appendicitis
  • 2 had complicated appendicitis
  •  7 did not have appendicitis
• The overall complication(surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) observed at 5 years follow-up in appendectomy group was significantly higher than in the antibiotic group
  • 24.4% (n = 60/246) in the appendectomy group
  • 6.5% n = 16/246) in antibiotic group (P < .001)
• No statistically significant difference was observed between surgically treated patients in the antibiotic group patients vs those who were randomized to the appendectomy group
  • overall appendectomy complication rate, 17.8% [n = 16/90) (difference, 6.6 percentage points; P =.20)
• The median length of hospital stay was 3 days in the appendectomy group and 3 days in the antibiotic group
• There was a significant difference in sick leave (11 days more for the appendectomy group)
  • 22 days after appendectomy
  • 11 days after antibiotic therapy (P < .001; difference, 11 days)

Conclusion

• The study demonstrated that the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.
• Nearly 2/3 of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy.
• The lower complication rate observed in the antibiotic group suggests that it might be considered as a preferable approach for the initial treatment of appendicitis in resource-limited settings.

JAMA. 2018; 320(12):1259-1265.