title: Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial.
abstract: OBJECTIVE
  An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.
  
  
  OBJECTIVE
  To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT).
  
  
  METHODS
  The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period.
  
  
  METHODS
  Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy.
  
  
  METHODS
  The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period.
  
  
  RESULTS
  There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment.
  
  
  CONCLUSIONS
  Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01022567.
authors.affiliation: Division of Digestive Surgery and Urology, Departments of Acute and Digestive Surgery, Turku University Hospital, Turku, Finland2Department of Surgery, Turku University, Turku, Finland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Salminen
authors.affiliation: Department of Surgery, Mikkeli Central Hospital, Mikkeli, Finland4Institute of Clinical Medicine, University of Eastern Finland, Joensuu, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Paajanen
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Rautio
authors.affiliation: Division of Surgery, Gastroenterology and Oncology, Tampere University Hospital, Tampere, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Nordström
authors.affiliation: Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Aarnio
authors.affiliation: Institute of Clinical Medicine, University of Eastern Finland, Joensuu, Finland8Department of Surgery, Kuopio University Hospital, Kuopio, Finland9Department of Surgery, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rantanen
authors.affiliation: Department of Public Health, University of Turku, Turku, Finland11Primary Health Care Unit, Hospital District of Southwest Finland, Turku, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Tuominen
authors.affiliation: Department of Biostatistics, University of Turku, Turku, Finland.
authors.forename: Saija
authors.initials: S
authors.lastname: Hurme
authors.affiliation: Department of Radiology, Turku University Hospital, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Virtanen
authors.affiliation: Institute of Clinical Medicine, University of Eastern Finland, Joensuu, Finland7Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.affiliation: Division of Surgery, Gastroenterology and Oncology, Tampere University Hospital, Tampere, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Sand
authors.affiliation: Department of Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Airi
authors.initials: A
authors.lastname: Jartti
authors.affiliation: Department of Radiology, Tampere University Hospital, Tampere, Finland.
authors.forename: Irina
authors.initials: I
authors.lastname: Rinta-Kiikka
authors.affiliation: Division of Digestive Surgery and Urology, Departments of Acute and Digestive Surgery, Turku University Hospital, Turku, Finland2Department of Surgery, Turku University, Turku, Finland.
authors.forename: Juha M
authors.initials: JM
authors.lastname: Grönroos
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001062:Appendectomy; D001064:Appendicitis / Q000188:drug therapy* / Q000601:surgery*; D001065:Appendix / Q000473:pathology; D004359:Drug Therapy, Combination; D004638:Emergency Treatment; D000077727:Ertapenem; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057194:Intention to Treat Analysis; D010535:Laparoscopy; D007902:Length of Stay; D064704:Levofloxacin / Q000627:therapeutic use; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D011183:Postoperative Complications; D017211:Treatment Failure; D055815:Young Adult; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D008795:Metronidazole; D064704:Levofloxacin; D000077727:Ertapenem