A1 Journal article – refereed

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




List of Authors: Sippola S, Haijanen J, Grönroos J, Rautio T, Nordström P, Rantanen T, Pinta T, Ilves I, Mattila A, Rintala J, Löyttyniemi E, Hurme S, Tammilehto V, Marttila H, Meriläinen S, Laukkarinen J, Sävelä EL, Savolainen H, Sippola T, Aarnio M, Paajanen H, Salminen P

Publisher: AMER MEDICAL ASSOC

Publication year: 2021

Journal: JAMA: Journal of the American Medical Association

Journal name in source: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Journal acronym: JAMA-J AM MED ASSOC

Volume number: 325

Issue number: 4

Number of pages: 10

ISSN: 0098-7484

eISSN: 1538-3598

DOI: http://dx.doi.org/10.1001/jama.2020.23525


Abstract
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 infinity) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to infinity) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to infinity]; 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.Question Is treatment with oral antibiotics alone noninferior to a combination of intravenous and oral antibiotics for treatment of computed tomography-confirmed uncomplicated acute appendicitis? Findings This multicenter randomized clinical trial included 583 adults with uncomplicated acute appendicitis who were treated with either 7 days of oral moxifloxacin or 2 days intravenous ertapenem followed by 5 days of levofloxacin and metronidazole. Treatment success (discharge from hospital without need for surgery and no recurrent appendicitis within 1 year) occurred in 70.2% who received oral antibiotics alone vs 73.8% of patients who received intravenous followed by oral antibiotics, with the confidence limit of the difference exceeding the noninferiority margin of 6%. Meaning Patients with acute, uncomplicated appendicitis treated with oral antibiotics alone met the prespecified threshold for treatment success, but failed to demonstrate noninferiority relative to systemic antibiotics followed by oral antibiotics.


Last updated on 2021-05-11 at 08:54