Antibiotics versus Surgery for Uncomplicated Acute Appendicitis in Adults: A Meta-Analysis of Randomized Controlled Trials
Abstract
Introduction: Appendectomy has been used to treat appendicitis for a century, but randomized controlled trials (RCTs) have challenged its efficacy in uncomplicated disease. We performed a meta-analysis to quantify 1-year antibiotic-first efficacy and compare complications with appendectomy in adults.
Methods: Following PRISMA 2020, MEDLINE, Embase, CENTRAL, and trial registries were searched to June 2026 for RCTs comparing antibiotics with appendectomy in adults (≥16 years) with imaging- or clinically diagnosed uncomplicated appendicitis. The co-primary outcomes were overall treatment-related complications (risk ratio [RR], random-effects DerSimonian–Laird model) and pooled 1-year efficacy of antibiotics (proportion avoiding appendectomy, logit-transformed model). Heterogeneity (I²), leave-one-out sensitivity analyses, subgroup analysis by diagnostic modality, and Egger’s test were performed; bias was assessed with RoB 2.
Results: Eight RCTs (3,202 participants) were included. Pooled 1-year efficacy of antibiotics was 70.9% (95% CI 65.3–76.0%; I²=43%), consistent across imaging-confirmed (71.4%) and clinically diagnosed (70.0%) appendicitis. For complications, the pooled RR was 0.91 (95% CI 0.19–4.48; I²=90%), with very high heterogeneity explained by trial design: omitting the single trial using open appendectomy reversed the estimate and removed heterogeneity (RR 2.25, 95% CI 1.39–3.64; I²=4%), indicating that antibiotics do not reduce, and may increase, complications versus contemporary laparoscopic surgery, particularly with an appendicolith.
Conclusion: An antibiotics-first strategy allowed seven of ten adults to avoid appendectomy at one year and is reasonable for uncomplicated appendicitis. However, it does not reduce complications compared to laparoscopic appendectomy and carries recurrence. Shared decision-making, appendicolith exclusion, and follow-up are essential.
Keywords: Appendicitis, Appendectomy, Antibiotics, Non-Operative Management, Meta-Analysis, Randomized Controlled Trial
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- 1. Ferris M, Quan S, Kaplan BS. The global incidence of appendicitis: a systematic review of population-based studies. Ann Surg. 2017;266(2):237-241.PubMedGoogle Scholar
- 2. The GBD 2021 Appendicitis Collaborator Group. Trends and levels of the global, regional, and national burden of appendicitis between 1990 and 2021: findings from the Global Burden of Disease Study 2021. Lancet Gastroenterol Hepatol. 2024;9(9):825-858.PubMedGoogle Scholar
- 3. McBurney C. Experience with early operative interference in cases of disease of the vermiform appendix. N Y Med J. 1889;50:676-684.PubMedGoogle Scholar
- 4. Bhangu A, Søreide K, Di Saverio S, Assarsson JH, Drake FT. Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. Lancet. 2015;386(10000):1278-1287.PubMedGoogle Scholar
- 5. Eriksson S, Granström L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg. 1995;82(2):166-169.PubMedGoogle Scholar
- 6. Styrud J, Eriksson S, Nilsson I. Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial. World J Surg. 2006;30(6):1033-1037.PubMedGoogle Scholar
- 7. 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 Scholar
- 8. Vons C, Barry C, Maitre S. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomized controlled trial. Lancet. 2011;377(9777):1573-1579.PubMedGoogle Scholar
- 9. Salminen P, Paajanen H, Rautio T. Antibiotic therapy vs appendectomy for the treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348.PubMedGoogle Scholar
- 10. Talan DA, Saltzman DJ, Mower WR. Antibiotics-first versus surgery for appendicitis: a US pilot randomized controlled trial allowing outpatient antibiotic management. Ann Emerg Med. 2017;70(1):1-11.e9.PubMedGoogle Scholar
- 11. Flum DR, Davidson GH, Monsell SE. CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med. 2020;383(20):1907-1919.PubMedGoogle Scholar
- 12. O’Leary DP, Walsh SM, Bolger J. A randomized clinical trial evaluating the efficacy and quality of life of antibiotic-only treatment of acute uncomplicated appendicitis: results of the COMMA trial. Ann Surg. 2021;274(2):240-247.PubMedGoogle Scholar
- 13. Herrod PJJ, Kwok AT, Lobo DN. Randomized clinical trials comparing antibiotic therapy with appendicectomy for uncomplicated acute appendicitis: a meta-analysis. BJS Open. 2022;6(4):zrac100.PubMedGoogle Scholar
- 14. de Almeida Leite RM, Seo DJ, Gomez-Eslava B. Nonoperative vs operative management of uncomplicated acute appendicitis: a systematic review and meta-analysis. JAMA Surg. 2022;157(9):828-834.PubMedGoogle Scholar
- 15. Doleman B, Fonnes S, Lund JN. Antibiotics versus appendicectomy for the treatment of uncomplicated acute appendicitis in adults and children. Cochrane Database Syst Rev. 2024;(4):CD015038.PubMedGoogle Scholar
- 16. Poprom N, Numthavaj P, Wilasrusmee C. The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: systematic review and network meta-analysis. Am J Surg. 2019;218(1):192-200.PubMedGoogle Scholar
- 17. Harnoss JC, Zelienka I, Probst P. Antibiotics versus surgical therapy for uncomplicated appendicitis: systematic review and meta-analysis of controlled trials. Ann Surg. 2017;265(5):889-900.PubMedGoogle Scholar
- 18. Sallinen V, Akl EA, You JJ. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg. 2016;103(6):656-667.PubMedGoogle Scholar
- 19. Podda M, Gerardi C, Cillara N. Antibiotic treatment and appendectomy for uncomplicated acute appendicitis in adults and children: a systematic review and meta-analysis. Ann Surg. 2019;270(6):1028-1040.PubMedGoogle Scholar
- 20. Salminen P, Tuominen R, Paajanen H. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA. 2018;320(12):1259-1265.PubMedGoogle Scholar
- 21. CODA Collaborative. Antibiotics versus appendectomy for acute appendicitis—longer-term outcomes. N Engl J Med. 2021;385(25):e93.PubMedGoogle Scholar
- 22. Scheijmans JCG, Bom WJ, Ateca SG. Antibiotic treatment versus appendicectomy for acute appendicitis in adults: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2025;10(3):232-243.PubMedGoogle Scholar
- 23. Di Saverio S, Podda M, De Simone B. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg. 2020;15(1):27.PubMedGoogle Scholar
- 24. Page MJ, McKenzie JE, Bossuyt PM. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.PubMedGoogle Scholar
- 25. Sterne JAC, Savović J, Page MJ. RoB 2: a revised tool for assessing risk of bias in randomized trials. BMJ. 2019;366:l4898.PubMedGoogle Scholar
- 26. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188.PubMedGoogle Scholar
- 27. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558.PubMedGoogle Scholar
- 28. IntHout J, Ioannidis JPA, Rovers MM, Goeman JJ. Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open. 2016;6(7):e010247.PubMedGoogle Scholar
- 29. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.PubMedGoogle Scholar
- 30. Sippola S, Grönroos J, Tuominen R. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial. Br J Surg. 2017;104(10):1355-1361.PubMedGoogle Scholar
- 31. Syaputra A, Wijaya DW, Hanafie A. Patterns of Antibiotic Use in The One-Hour Bundle Treatment of Sepsis. Journal of Society Medicine. 2022;1(3):8-102.PubMedGoogle Scholar
- 32. Ginting MARG, Suwarman S. Management of Acute Pulmonary Edema in Kidney Transplant Patients in the ICU. Journal of Society Medicine. 2025;4(5):52-146.PubMedGoogle Scholar
- 33. Ginting MAR, Harahap AM, Putri Y, Sari H. Acute Exercise-Induced Hypoalgesia and Chronic Training Adaptations in Pain Perception Among Athletes: A Systematic Review, Meta-Analysis, and Meta-Regression. Journal of Society Medicine. 2026;5(6):10-200.PubMedGoogle Scholar
- 34. Khan AR, Iqbal M. Emerging Antimicrobial Resistance in Gram-Negative Pathogens: Protocol for a Pragmatic Cluster-Randomized Controlled Trial. Journal of Society Medicine. 2026;5(3):81-90.PubMedGoogle Scholar
