Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial

JAMA. 2021 Jan 26;325(4):353-362. doi: 10.1001/jama.2020.23525.


Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known.

Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis.

Design, setting, and participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019.

Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days.

Main outcomes and measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference.

Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin.

Conclusion and relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.

Trial registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.

Publication types

  • Comparative Study
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Appendectomy
  • Appendicitis / diagnostic imaging
  • Appendicitis / drug therapy*
  • Appendicitis / surgery
  • Drug Therapy, Combination
  • Ertapenem / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Levofloxacin / therapeutic use
  • Male
  • Metronidazole / therapeutic use
  • Middle Aged
  • Moxifloxacin / therapeutic use
  • Tomography, X-Ray Computed
  • Young Adult


  • Anti-Bacterial Agents
  • Metronidazole
  • Levofloxacin
  • Ertapenem
  • Moxifloxacin

Associated data

  • ClinicalTrials.gov/NCT03236961