Background: Antibiotics are safe and efficient for CT-diagnosed uncomplicated acute appendicitis. Identifying predictive factors of primary non-responsiveness or recurrence would further improve antibiotic treatment success and safety.

Methods: All patients treated with antibiotics in two large RCTs (APPAC and APPAC II) were included. The primary non-responsiveness analysis compared patients operated on within 30 days after randomization for complicated appendicitis with either patients presenting with uncomplicated appendicitis at surgery within 30 days or patients with successful antibiotic treatment during 3-year follow-up. Prognostic factors for appendicitis recurrence were assessed by comparing patients with successful antibiotic treatment with patients with acute appendicitis operated on after 30 days of initial antibiotics.

Results: Of 856 patients randomized to antibiotics (mean(s.d.) age of 36(12) years; 365 (42.6%) were women), 832 were eligible for non-responsiveness analysis and 732 for appendicitis recurrence analysis. Findings associated with primary non-responsiveness on admission included an appendiceal diameter ≥15 mm (adjusted risk ratio (RR) 4.00 (95% c.i. 2.00 to 7.92) (P < 0.001)) and a body temperature >38°C (adjusted RR 2.76 (95% c.i. 1.27 to 6.03) (P = 0.011)). During the first 6-30 h after admission, C-reactive protein (CRP) ≥100 mg/l (negative predictive value of 99%) and leucocyte count ≥9 × 109/l were associated with primary non-responsiveness (adjusted RR 8.29 (95% c.i. 3.69 to 18.63) (P < 0.001) and adjusted RR 4.44 (95% c.i. 1.79 to 11.05) (P = 0.001) respectively). No prognostic findings for appendicitis recurrence were identified.

Conclusion: Patients with an appendiceal diameter ≥15 mm and a body temperature >38°C may not be optimal candidates for non-operative treatment for uncomplicated acute appendicitis. Patients with CRP <100 mg/l at 24 h of antibiotic treatment for uncomplicated acute appendicitis have a 99% likelihood of successful antibiotic therapy.

Registration numbers: NCT03236961 and NCT01022567 (http://www.clinicaltrials.gov).