Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Apr 29;4(4):CD015038.
doi: 10.1002/14651858.CD015038.pub2.

Appendectomy versus antibiotic treatment for acute appendicitis

Brett Doleman  1 , Siv Fonnes  2 , Jon N Lund  3 , Hannah Boyd-Carson  4 , Hannah Javanmard-Emamghissi  5 , Susan Moug  6 , Marianne Hollyman  7 , Gillian Tierney  8 , Samson Tou  9 , John P Williams  1
Affiliations
Meta-Analysis

Appendectomy versus antibiotic treatment for acute appendicitis

Brett Doleman et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery.

Objectives: To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications.

Search methods: We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication.

Selection criteria: We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic).

Data collection and analysis: We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group.

Main results: We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence).

Authors' conclusions: Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

PubMed Disclaimer

Conflict of interest statement

BD: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review (Javanmard‐Emamghissi 2021). Has previously peer reviewed and received honorarium from Research Square.

SF: Managing Editor at Cochrane Colorectal Group, but had no involvement in the editorial processes.

JNL: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review (Javanmard‐Emamghissi 2021).

HBC: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review (Javanmard‐Emamghissi 2021).

HJE: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review (Javanmard‐Emamghissi 2021). Has published two papers from an observational cohort study comparing operative and non‐operative management of appendicitis.

SM: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review. (Javanmard‐Emamghissi 2021).

MH: collaborator on an acute appendicitis study in UK called COVIDHarem, which was not eligible for inclusion in the review (Javanmard‐Emamghissi 2021).

GT: collaborator on an acute appendicitis study in UK called COVIDHarem, which is not eligible for inclusion in the review (Javanmard‐Emamghissi 2021). Association of Surgeons of Great Britain and Ireland President. Often asked to comment in the press/social media/broadcast on behalf of the organisation.

ST: Editor, Cochrane Colorectal Group, but had no involvement in the editorial processes.

JPW: none.

All review authors work as health professionals.

Figures

1
1
PRISMA flow chart.
2
2
Duration, specific drug, and drug class of the intervention antibiotics in included studies. The different drug classes are coloured and can be seen in the top right corner. The duration of antibiotic is depicted on the x‐axis in days. Faded colours depict when a specific duration was not reported. Full details on the interventions can be seen in the Characteristics of included studies table. *Various regimens: the use of different antibiotic regimens for participants in the antibiotic group depending on, for example, the preferences or guidelines of the included hospital. Copyright © 2022 Siv Fonnes.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
Forest plot for success of treatment.
6
6
Funnel plot for length of stay.
1.1
1.1. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 1: Mortality
1.2
1.2. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 2: Success of treatment
1.3
1.3. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 3: Clostridium difficile diarrhoea
1.4
1.4. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 4: Wound infection
1.5
1.5. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 5: Pneumonia
1.6
1.6. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 6: Venous thromboembolism
1.7
1.7. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 7: Intra‐abdominal abscess or collection
1.8
1.8. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 8: Ileus
1.9
1.9. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 9: Reoperation
1.10
1.10. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 10: Complicated appendicitis at surgery
1.11
1.11. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 11: Pain score (acute)
1.12
1.12. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 12: Pain score (chronic)
1.13
1.13. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 13: Length of hospital stay
1.14
1.14. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 14: Period of sick leave
1.15
1.15. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 15: Negative appendectomy rate (normal histology)
1.16
1.16. Analysis
Comparison 1: Antibiotics versus appendectomy, Outcome 16: Postoperative quality of life
2.1
2.1. Analysis
Comparison 2: Subgroup analysis, Outcome 1: Success of treatment
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD015038

References

References to studies included in this review

Ahmad 2021 {published data only (unpublished sought but not used)}
    1. Ahmad S, Ali K, Nasim A, Karim F. Comparison of conservative versus surgical management of acute appendicitis in terms of hospital stay. Pakistan Journal of Medical and Health Sciences 2021;15(8):1927-30. [DOI: 10.53350/pjmhs211581927] - DOI
APPAC 2015 {published data only}
    1. Paajanen H, Grönroos JM, Rautio T, Nordström P, Aarnio M, Rantanen T, et al. A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial). BMC Surgery 2013;13(1):1-7. [DOI: 10.1186/1471-2482-13-3] - DOI - PMC - PubMed
    1. Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA 2015;313(23):2340-8. [DOI: 10.1001/jama.2015.6154] - DOI - PubMed
    1. Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA 2018;320(12):1259-65. [DOI: 10.1001/jama.2018.13201] - DOI - PMC - PubMed
    1. Sippola S, Grönroos J, Tuominen R, Paajanen H, Rautio T, Nordström P, et al. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial. British Journal of Surgery 2017;104(10):1355-61. [DOI: 10.1002/bjs.10575] - DOI - PubMed
    1. Sippola S, Haijanen J, Viinikainen L, Grönroos J, Paajanen H, Rautio T, et al. Quality of life and patient satisfaction at 7-year follow-up of antibiotic therapy vs appendectomy for uncomplicated acute appendicitis: a secondary analysis of a randomized clinical trial. JAMA Surgery 2020;155(4):283-9. [DOI: 10.1001/jamasurg.2019.6028] - DOI - PMC - PubMed
Bervell 2019 {unpublished data only}
    1. Bervell J. The Use of Antibiotics vs Appendectomies for Uncomplicated Acute Appendicitis [Masters thesis]. Boston (US): Boston University School of Medicine, 2019. [WEB ADDRESS: hdl.handle.net/2144/36682]
Ceresoli 2019 {published data only (unpublished sought but not used)}
    1. Ceresoli M, Pisano M, Allievi N, Poiasina E, Coccolini F, Montori G, et al. Never put equipoise in appendix! Final results of ASAA (antibiotics vs. surgery for uncomplicated acute appendicitis in adults) randomized controlled trial. Updates in Surgery 2019;71(2):381-7. [DOI: 10.1007/s13304-018-00614-z] - DOI - PubMed
Chauhan 2020 {published data only}
    1. Chauhan A, Datt CK, Chandel H, Sharma S. Antibiotics versus a emergency open appendectomy conservative management – a primary treatment of uncomplicated acute appendicitis: a randomized controlled trial. Journal of Medical Science and Clinical Research 2020;8(5):346-52. [DOI: 10.18535/jmscr/v8i5.64] - DOI
CODA 2020 {published and unpublished data}
    1. CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. New England Journal of Medicine 2020;383(20):1907-19. [DOI: 10.1056/NEJMoa2014320] - DOI - PubMed
    1. CODA Collaborative. Antibiotics versus appendectomy for acute appendicitis – longer-term outcomes. New England Journal of Medicine 2021;385(25):2395-7. [DOI: 10.1056/NEJMc2116018] - DOI - PubMed
COMMA 2021 {published and unpublished data}
    1. O'Leary DP, Walsh SM, Bolger J, Baban C, Humphreys H, O'Grady S, et al. A randomized clinical trial evaluating the efficacy and quality of life of antibiotic-only treatment of acute uncomplicated appendicitis: results of the COMMA trial. Annals of Surgery 2021;274(2):240-7. [DOI: 10.1097/SLA.0000000000004785] - DOI - PubMed
Eriksson 1995 {published and unpublished data}
    1. Eriksson S, Granström L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. British Journal of Surgery 1995;82(2):166-9. [PMID: 10.1002/bjs.1800820207] - DOI - PubMed
Khan 2020 {published data only}
    1. Khan J, Kashif M, Ramzan, Bilal M. Comparison of outcomes between antibiotics treatments versus appendectomy patients with uncomplicated acute appendicitis. Medical Forum 2020;31(5):78-81.
Sabir 2019 {published data only (unpublished sought but not used)}
    1. Sabir F, Akhtar N, Rehman S, Rehman N, Altaf A. Comparison of antibiotic therapy and appendectomy in acute appendicitis. Pakistan Journal of Surgery 2019;35(2):120-4.
Styrud 2006 {published and unpublished data}
    1. Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, et al. Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial. World Journal of Surgery 2006;30(6):1033-7. [DOI: 10.1007/s00268-005-0304-6] - DOI - PubMed
Talan 2017 {published data only}
    1. Talan DA, Saltzman DJ, Mower WR, Krishnadasan A, Jude CM, Amii R, et al. Antibiotics-first versus surgery for appendicitis: a US pilot randomized controlled trial allowing outpatient antibiotic management. Annals of Emergency Medicine 2017;70(1):1-11. [DOI: 10.1016/j.annemergmed.2016.08.446] - DOI - PMC - PubMed
Vons 2011 {published data only}
    1. Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet 2011;377(9777):1573-9. [DOI: 10.1016/S0140-6736(11)60410-8] - DOI - PubMed

References to studies excluded from this review

Hansson 2009 {published data only}
    1. 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. British Journal of Surgery 2009;96(5):473-81. [DOI: 10.1002/bjs.6482] - DOI - PubMed
Laila 2017 {published data only}
    1. Laila RN, Momen MA, Ullah MA, Sarkar MH, Rahman MM. Antibiotics versus appendectomy for acute appendicitis: a randomized trial. Clinical Surgery 2017;2:1659.
Malik 2009 {published data only}
    1. Malik AA, Bari SU. Retracted article: conservative management of acute appendicitis. Journal of Gastrointestinal Surgery 2009;13(5):966-70. [DOI: 10.1007/s11605-009-0835-5] - DOI - PubMed
Turhan 2009 {published data only}
    1. Turhan AN, Kapan S, Kütükçü E, Yiğitbaş H, Hatipoğlu S, Aygün E. Comparison of operative and non operative management of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2009;15(5):459-62. [PMID: ] - PubMed

References to ongoing studies

ACTRN12620000537954 {published data only}
    1. ACTRN12620000537954. Antibiotics versus key-hole surgery for treatment of acute appendicitis (the TRAIN trial) [Laparoscopic appendicectomy versus antibiotics for imaging confirmed acute uncomplicated appendicitis: a multisite randomised controlled trial]. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12620000537954 (first received 1 May 2020).
EUCTR2011‐002977‐44‐IT {published data only (unpublished sought but not used)}
    1. EUCTR2011-002977-44-IT. Antibiotics vs surgery in acute appendicitis: an intention to treat prospective randomised controlled study, the ASAA-study. www.clinicaltrialsregister.eu/ctr-search/trial/2011-002977-44/IT (first received 7 March 2012).
NCT04748120 {published data only (unpublished sought but not used)}
    1. NCT04748120. Operative vs non-operative management of acute appendicitis and acute cholecystitis in COVID-19 positive patients. clinicaltrials.gov/ct2/show/NCT04748120 (first received 10 February 2021).

Additional references

APPAC 2018
    1. Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA 2018;320:1259-65. [DOI: 10.1001/jama.2018.13201] - DOI - PMC - PubMed
Bhangu 2015
    1. Bhangu A, Soeride K, Di Saverio S, Hansson Assarsson J, Thurston D. Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. Lancet 2015;386(10000):1278-87. [DOI: 10.1016/S0140-6736(15)00275-5] - DOI - PubMed
Biondi 2016
    1. Biondi A, Di Stefano C, Ferrara F, Bellia A, Vacante M, Piazza L. Laparoscopic versus open appendectomy: a retrospective cohort study assessing outcomes and cost-effectiveness. World Journal of Emergency Surgery 2016;11:44. [DOI: 10.1186/s13017-016-0102-5] - DOI - PMC - PubMed
Carr 2000
    1. Carr NJ. The pathology of acute appendicitis. Annals of Diagnostic Pathology 2000;4(1):46-58. [DOI: 10.1016/s1092-9134(00)90011-x] - DOI - PubMed
Chan 2017
    1. Chan SW, Tulloch E, Cooper ES, Smith A, Wojcik W, Norman JE. Montgomery and informed consent: where are we now? BMJ 2017;357:j2224. [DOI: 10.1093/bjsopen/zrab058] - DOI - PubMed
Doleman 2018
    1. Doleman B, Sutton AJ, Sherwin M, Lund JN, Williams JP. Baseline morphine consumption may explain between-study heterogeneity in meta-analyses of adjuvant analgesics and improve precision and accuracy of effect estimates. Anesthesia & Analgesia 2018;126(2):648-60. [DOI: 10.1213/ANE.0000000000002237] - DOI - PubMed
Doleman 2019
    1. Doleman B, Williams JP, Lund J. Why most published meta-analysis findings are false. Techniques in Coloproctology 2019;23(9):925-8. [DOI: 10.1007/s10151-019-02020-y] - DOI - PubMed
Doleman 2020
    1. Doleman B, Freeman SC, Lund JN, Williams JP, Sutton AJ. Funnel plots may show asymmetry in the absence of publication bias with continuous outcomes dependent on baseline risk: presentation of a new publication bias test. Research Synthesis Methods 2020;11(4):522-34. [DOI: 10.1002/jrsm.1414] - DOI - PubMed
Doleman 2021b
    1. Doleman B, Mathiesen O, Jakobsen JC, Sutton AJ, Freeman S, Lund JN, et al. Methodologies for systematic reviews with meta-analysis of randomised clinical trials in pain, anaesthesia, and perioperative medicine. British Journal of Anaesthesia 2021;126:903-11. [DOI: 10.1016/j.bja.2021.01.004] - DOI - PubMed
Egger 1997
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315(7109):629-34. [DOI: 10.1136/bmj.315.7109.629] - DOI - PMC - PubMed
Ergul 2007
    1. Ergul E. Heredity and familial tendency of acute appendicitis. Scandinavian Journal of Surgery 2007;96(4):290-2. [DOI: 10.1177/145749690709600405] - DOI - PubMed
Fair 2014
    1. Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Perspectives in Medicinal Chemistry 2014;6:25-64. [DOI: ] - PMC - PubMed
Ferris 2017
    1. Ferris M, Quan S, Kaplan BS, Molodecky N, Ball CG, Chernoff GW, et al. The global incidence of appendicitis: a systematic review of population-based studies. Annals of Surgery 2017;266(2):237-41. [DOI: 10.1097/SLA.0000000000002188] - DOI - PubMed
Fraser 2004
    1. Fraser N, Gannon C, Stringer MD. Appendicular colic and the non-inflamed appendix: fact or fiction? European Journal of Pediatric Surgery 2004;14:21-4. [DOI: 10.1055/s-2004-815775] - DOI - PubMed
Guinane 2013
    1. Guinane CM, Tadrous A, Fouhy F, Ryan CA, Dempsey EM, Murphy B, et al. Microbial composition of human appendices from patients following appendectomy. mBio 2013;4(1):e00366-12. [DOI: ] - PMC - PubMed
Guller 2004
    1. Guller U, Hervey S, Purves H, Muhlbaier LH, Peterson ED, Eubanks S, et al. Laparoscopic versus open appendectomy: outcomes comparison based on a large administrative database. Annals of Surgery 2004;239(1):43-52. [DOI: 10.1097/01.sla.0000103071.35986.c1] - DOI - PMC - PubMed
Hansson 2009
    1. 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. British Journal of Surgery 2009;96(5):473-81. [DOI: 10.1002/bjs.6482] - DOI - PubMed
Harper 2018
    1. Harper NJ, Cook TM, Garcez T, Farmer L, Floss K, Marinho S, et al. Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6). British Journal of Anaesthesia 2018;121(1):159-71. [DOI: 10.1016/j.bja.2018.04.014] - DOI - PubMed
Herrod 2022
    1. Herrod PJ, Kwok AT, Lobo DN. Randomized clinical trials comparing antibiotic therapy with appendicectomy for uncomplicated acute appendicitis: meta-analysis. BJS Open 2022;6(4):zrac100. [DOI: 10.1093/bjsopen/zrac100] - DOI - PMC - PubMed
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane Collaboration, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Higgins 2021
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook. - PMC - PubMed
Hunter 2014
    1. Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ. In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. Journal of Clinical Epidemiology 2014;67(8):897-903. [DOI: 10.1016/j.jclinepi.2014.03.003] - DOI - PubMed
Hutchings 2019
    1. Hutchings MI, Truman AW, Wilkinson B. Antibiotics: past, present and future. Current Opinion in Microbiology 2019;51:72-80. [DOI: 10.1016/j.mib.2019.10.008] - DOI - PubMed
Ielpo 2021
    1. Ielpo B, Podda M, Pellino G, Pata F, Caruso R, Gravante G, et al, ACIE Appy Study Collaborative. Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study. British Journal of Surgery 2021;108(6):717-26. [DOI: 10.1002/bjs.11999] - DOI - PMC - PubMed
Jackson 2014
    1. Jackson HT, Mongodin EF, Davenport KP, Fraser CM, Sandler AD, Zeichner SL. Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis. PLOS One 2014;9(4):e95414. [DOI: ] - PMC - PubMed
Jaschinski 2015
    1. Jaschinski T, Mosch C, Eikermann M, Neugebauer EA. Laparoscopic versus open appendectomy in patients with suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials. BMC Gastroenterology 2015;15:48. [DOI: 10.1186/s12876-015-0277-3] - DOI - PMC - PubMed
Javanmard‐Emamghissi 2020
    1. Javanmard-Emamghissi H, Boyd-Carson H, Hollyman M, Doleman B, Adiamah A, Lund JN, et al. The management of adult appendicitis during the COVID-19 pandemic: an interim analysis of a UK cohort study. Techniques in Coloproctology 2020;15:1-11. [DOI: 10.1007/s10151-020-02297-4] - DOI - PMC - PubMed
Javanmard‐Emamghissi 2021
    1. Javanmard-Emamghissi H, Hollyman M, Boyd-Carson H, Doleman B, Adiamah A, Lund JN, et al. Antibiotics as first-line alternative to appendicectomy in adult appendicitis: 90-day follow-up from a prospective, multicentre cohort study. British Journal of Surgery 2021;108(11):1351-9. [DOI: 10.1093/bjs/znab287] - DOI - PMC - PubMed
Lamps 2010
    1. Lamps LW. Infectious causes of appendicitis. Infectious Disease Clinics of North America 2010;24(4):995-1018. [DOI: 10.1016/j.idc.2010.07.012] - DOI - PubMed
Lefebvre 2021
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M, et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Markar 2011
    1. Markar SR, Venkat-Raman V, Ho A, Karthikesalingam A, Kinross J, Evans J, et al. Laparoscopic versus open appendicectomy in obese patients. International Journal of Surgery 2011;9(6):451-5. [DOI: 10.1016/j.ijsu.2011.06.005] - DOI - PubMed
Markar 2012
    1. Markar SR, Blackburn S, Cobb R, Karthikesalingam A, Evans J, Kinross J, et al. Laparoscopic versus open appendectomy for complicated and uncomplicated appendicitis in children. Journal of Gastrointestinal Surgery 2012;16(10):1993-2004. [DOI: 10.1007/s11605-012-1962-y] - DOI - PubMed
Nelson 2017
    1. Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No: CD004610. [DOI: 10.1002/14651858.CD004610.pub5] - DOI - PMC - PubMed
Nyaga 2014
    1. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Archives of Public Health 2014;72(1):39. [DOI: 10.1186/2049-3258-72-39] - DOI - PMC - PubMed
Page 2021
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. [DOI: 10.1136/bmj.n71] [PMID: ] - DOI - PMC - PubMed
Parsons 2022
    1. Parsons C, Shapiro NI, Cooper R, Tichter A, Morris A, Wolfe B, et al. Patient factors associated with appendectomy within 30 days of initiating antibiotic treatment for appendicitis. JAMA Surgery 2022;157(3):e216900. [DOI: 10.1001/jamasurg.2021.6900] - DOI - PMC - PubMed
Peters 2006
    1. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA 2006;295(6):676-80. [DOI: 10.1001/jama.295.6.676] - DOI - PubMed
Podda 2019
    1. Podda M, Gerardi C, Cillara N, Fearnhead N, Gomes CA, Birindelli A, et al. Antibiotic treatment and appendectomy for uncomplicated acute appendicitis in adults and children: a systematic review and meta-analysis. Annals of Surgery 2019;270(6):1028-40. [DOI: 10.1097/SLA.0000000000003225] - DOI - PubMed
Retraction Watch Database 2020
    1. The Retraction Watch Database. The Retraction Watch Database. www.retractiondatabase.org (accessed 30 December 2020).
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: The Cochrane Collaboration, 2020.
RevMan 2021 [Computer program]
    1. Review Manager (RevMan). Version 4.16.2. Copenhagen: The Cochrane Collaboration, 2021. Available at revman.cochrane.org.
Rogers 2016
    1. Rogers MB, Brower-Sinning R, Firek B, Zhong D, Morowitz MJ. Acute appendicitis in children is associated with a local expansion of Fusobacteria. Clinical Infectious Diseases 2016;63(1):71-8. [DOI: ] - PubMed
Sadr Azodi 2009
    1. Sadr Azodi O, Andrén-Sandberg Å, Larsson H. Genetic and environmental influences on the risk of acute appendicitis in twins. British Journal of Surgery 2009;96(11):1336-40. [DOI: 10.1002/bjs.6736] - DOI - PubMed
Sartelli 2018
    1. Sartelli M, Baiocchi GL, Di Saverio S, Ferrara F, Labricciosa FM, Ansaloni L, et al. Prospective Observational Study on acute Appendicitis Worldwide (POSAW). World Journal of Emergency Surgery 2018;13(1):19. [DOI: ] - PMC - PubMed
Schünemann 2021
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, Guyatt GH. Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Snapshot Appendicitis Study Group 2019
    1. Wijkerslooth EM, Jonge J, den Boom AL, Geloven A, Bemelman W, Wijnhoven BP, et al, Snapshot Appendicitis Study Group. Postoperative outcomes of patients with nonperforated gangrenous appendicitis: a national multicenter prospective cohort analysis. Diseases of the Colon and Rectum 2019;62(11):1363-70. [DOI: 10.1097/DCR.0000000000001466] - DOI - PubMed
Southgate 2012
    1. Southgate E, Vousden N, Karthikesalingam A, Markar SR, Black S, Zaidi A. Laparoscopic vs open appendectomy in older patients. JAMA Surgery 2012;147(6):557-62. [DOI: 10.1001/archsurg.2012.568] - DOI - PubMed
Stata 2017 [Computer program]
    1. Stata. Version 16. College Station, TX, USA: StataCorp, 2017. Available at www.stata.com.
The 2019
    1. The S-M, Bakx R, Budding AE, Meij TG, Lee JH, Bunders MJ, et al. Microbiota of children with complex appendicitis: different composition and diversity of the microbiota in children with complex compared with simple appendicitis. Pediatric Infectious Disease Journal 2019;38(10):1054-60. [DOI: ] - PubMed
Thompson 2002
    1. Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Statistics in Medicine 2002;21(11):1559-73. [DOI: 10.1002/sim.1187] - DOI - PubMed
Thorland 2018
    1. Thorlund K, Engstrom J, Wetterslev J, Brok J, Imberger G, Gluud C. User Manual for Trial Sequential Analysis (TSA); 2nd edition. Copenhagen Trial Unit, 2018. Available from ctu.dk/tsa/learn-more 2018. [ctu.dk/tsa/downloads/]
Ukai 2016
    1. Ukai T, Shikata S, Takeda H, Dawes L, Noguchi Y, Nakayama T, et al. Evidence of surgical outcomes fluctuates over time: results from a cumulative meta-analysis of laparoscopic versus open appendectomy for acute appendicitis. BMC Gastroenterology 2016;16:1-2. [DOI: 10.1186/s12876-016-0453-0] - DOI - PMC - PubMed
Wickramasinghe 2021
    1. Wickramasinghe DP, Xavier C, Samarasekera DN. The worldwide epidemiology of acute appendicitis: an analysis of the global health data exchange dataset. World Journal of Surgery 2021;45(7):1999-2008. [DOI: 10.1007/s00268-021-06077-5] - DOI - PubMed
Zhong 2014
    1. Zhong D, Brower-Sinning R, Firek B, Morowitz MJ. Acute appendicitis in children is associated with an abundance of bacteria from the phylum Fusobacteria. Journal of Pediatric Surgery 2014;49(3):441-6. [DOI: ] - PubMed

References to other published versions of this review

Doleman 2021a
    1. Doleman B, Fonnes S, Lund JN, Boyd-Carson H, Javanmard-Emamghissi H, Moug S, et al. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database of Systematic Reviews 2021, Issue 9. Art. No: CD015038. [DOI: 10.1002/14651858.CD015038] - DOI - PMC - PubMed
Wilms 2010
    1. Wilms IM, Hoog DE, Visser DC, Janzing HM. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database of Systematic Reviews 2010, Issue 2. Art. No: CD008359. [DOI: 10.1002/14651858.CD008359] - DOI - PubMed
Wilms 2011
    1. Wilms IM, De Hoog DE, Visser DC, Janzing HM. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No: CD008359. [DOI: 10.1002/14651858.CD008359.pub2] - DOI - PubMed

Publication types

Substances

LinkOut - more resources