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Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial

Educational Objective
To understand the long-term efficacy of antibiotic therapy for the treatment of uncomplicated acute appendicitis.
1 Credit CME
Key Points

Question  What is the long-term recurrence rate in patients with uncomplicated acute appendicitis treated with antibiotics?

Findings  In this 5-year observational follow-up of 257 patients initially treated with antibiotics for uncomplicated acute appendicitis, the cumulative incidence of recurrent appendicitis at 1, 2, 3, 4, and 5 years was 27.3% at 1 year, 34.0% at 2, 35.2% at 3, 37.1% at 4, and 39.1% at 5 years.

Meaning  Long-term follow up of patients with uncomplicated acute appendicitis suggests that initial treatment with antibiotics rather than surgery may be a feasible alternative.

Abstract

Importance  Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.

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

Design, Setting, and Participants  Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography–confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.

Interventions  Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.

Main Outcomes and Measures  In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.

Results  Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).

Conclusions and Relevance  Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.

Trial Registration  ClinicalTrials.gov Identifier: NCT01022567

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Article Information

Corresponding Author: Paulina Salminen, MD, PhD, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland (paulina.salminen@tyks.fi).

Correction: This article was corrected on September 27, 2018, because of incomplete information in Figure 1.

Accepted for Publication: August 16, 2018.

Author Contributions: Drs Salminen and Grönroos had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Salminen had the final responsibility for the decision to submit the manuscript for publication.

Concept and design: Salminen, Tuominen, Paajanen, Rautio, Nordström, Aarnio, Rantanen, Hurme, Mecklin, Sand, Virtanen, Grönroos.

Acquisition, analysis, or interpretation of data: Salminen, Tuominen, Paajanen, Rautio, Nordström, Rantanen, Hurme, Jartti, Grönroos.

Drafting of the manuscript: Salminen, Tuominen, Paajanen, Nordström, Rantanen, Hurme, Grönroos.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Salminen, Tuominen, Hurme.

Obtained funding: Salminen.

Administrative, technical, or material support: Salminen, Rautio, Nordström, Sand, Virtanen, Grönroos.

Supervision: Salminen, Tuominen, Paajanen, Rautio, Nordström, Rantanen, Sand, Jartti, Grönroos.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Salminen reports receipt of personal fees for lectures from Merck, Lilly, and Orion Pharma. No other disclosures were reported.

Funding/Support: This trial was supported by the Mary and Georg C. Ehrnrooth Foundation, a government research grant (EVO Foundation) awarded to Turku University Hospital, and a Turku University research grant.

Role of the Funder/Sponsor: None of the funding entities had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.

References
1.
Livingston  E, Vons  C.  Treating appendicitis without surgery.  JAMA. 2015;313(23):2327-2328.PubMedGoogle ScholarCrossref
2.
Huang  L, Yin  Y, Yang  L, Wang  C, Li  Y, Zhou  Z.  Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children.  JAMA Pediatr. 2017;171(5):426-434.PubMedGoogle ScholarCrossref
3.
Salminen  P, Paajanen  H, Rautio  T,  et al.  Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis.  JAMA. 2015;313(23):2340-2348.PubMedGoogle ScholarCrossref
4.
Vons  C, Barry  C, Maitre  S,  et al.  Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis.  Lancet. 2011;377(9777):1573-1579.PubMedGoogle ScholarCrossref
5.
Paajanen  H, Grönroos  JM, Rautio  T,  et al.  A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).  BMC Surg. 2013;13:3.PubMedGoogle ScholarCrossref
6.
Hansson  J, Körner  U, Khorram-Manesh  A, Solberg  A, Lundholm  K.  Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients.  Br J Surg. 2009;96(5):473-481.PubMedGoogle ScholarCrossref
7.
Styrud  J, Eriksson  S, Nilsson  I,  et al.  Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial.  World J Surg. 2006;30(6):1033-1037.PubMedGoogle ScholarCrossref
8.
Harnoss  JC, Zelienka  I, Probst  P,  et al.  Antibiotics versus surgical therapy for uncomplicated appendicitis.  Ann Surg. 2017;265(5):889-900.PubMedGoogle ScholarCrossref
9.
Rollins  KE, Varadhan  KK, Neal  KR, Lobo  DN.  Antibiotics versus appendicectomy for the treatment of uncomplicated acute appendicitis.  World J Surg. 2016;40(10):2305-2318.PubMedGoogle ScholarCrossref
10.
Sallinen  V, Akl  EA, You  JJ,  et al.  Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis.  Br J Surg. 2016;103(6):656-667.PubMedGoogle ScholarCrossref
11.
Tanaka  Y, Uchida  H, Kawashima  H,  et al.  Long-term outcomes of operative versus nonoperative treatment for uncomplicated appendicitis.  J Pediatr Surg. 2015;50(11):1893-1897.PubMedGoogle ScholarCrossref
12.
Shindoh  J, Niwa  H, Kawai  K,  et al.  Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis.  J Gastrointest Surg. 2010;14(2):309-314.PubMedGoogle ScholarCrossref
13.
Sauerland  S, Jaschinski  T, Neugebauer  EA.  Laparoscopic versus open surgery for suspected appendicitis.  Cochrane Database Syst Rev. 2010;(10):CD001546.PubMedGoogle Scholar
14.
Fitz  R.  Perforating inflammation of the vermiform appendix.  Am J Med Sci. 1886;92:321-346.Google Scholar
15.
Park  HC, Kim  MJ, Lee  BH.  Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.  Br J Surg. 2017;104(13):1785-1790.PubMedGoogle ScholarCrossref
16.
Di Saverio  S, Sibilio  A, Giorgini  E,  et al.  The NOTA study (Non Operative Treatment for Acute Appendicitis): prospective study on the efficacy and safety of antibiotics (amoxicillin and clavulanic acid) for treating patients with right lower quadrant abdominal pain and long-term follow-up of conservatively treated suspected appendicitis.  Ann Surg. 2014;260(1):109-117.PubMedGoogle ScholarCrossref
17.
Talan  DA, Saltzman  DJ, Mower  WR  et al.  Antibiotics-first versus surgery for appendicitis: a US pilot randomized controlled trial allowing outpatient antibiotic management.  Ann Emerg Med. 2017;70(1):1-11.e19.Google ScholarCrossref
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