Gastroenterol Res
Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website https://www.gastrores.org

Editorial

Volume 14, Number 6, December 2021, pages 311-312


Oral Antibiotics for Uncomplicated Acute Appendicitis: The Role of Extended-Spectrum Beta-Lactamase Risk Factor Stratification

Stelios F. Assimakopoulosa, d, Ioannis Maroulisb, Christos Triantosc, Markos Marangosa

aDivision of Infectious Diseases, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
bDepartment of Surgery, University of Patras Medical School, Patras, Greece
cDivision of Gastroenterology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
dCorresponding Author: Stelios F. Assimakopoulos, Division of Infectious Diseases, Department of Internal Medicine, University of Patras Medical School, Patras 26504, Greece

Manuscript submitted December 1, 2021, accepted December 9, 2021, published online December 21, 2021
Short title: Oral Antibiotics for Acute Appendicitis
doi: https://doi.org/10.14740/gr1489

The World Society of Emergency Surgery 2020 guidelines recommend antibiotics as an effective and safe alternative to appendectomy for managing patients with computed tomography-confirmed uncomplicated acute appendicitis without appendicolith [1]. The safe avoidance of hospitalization for surgical patients is an important task during the coronavirus disease 2019 (COVID-19) pandemic, therefore this recommendation was also acknowledged by the American College of Surgeons (COVID-19 Guideline for Triage of Emergency General Surgery Patients) [2]. However, up to now, the optimum antibiotic regimen for the non-operative management of uncomplicated acute appendicitis has not been defined [1]. The results of the Appendicitis Acute (APPAC) II randomized controlled trial, comparing 7 days of oral moxifloxacin with 2 days of intravenous ertapenem followed by 5 days of oral levofloxacin and metronidazole, have been recently published [3]. This study showed that antibiotic therapy resulted in success rates at 1 year greater than 65% in both groups (70.2% for patients treated with oral antibiotics and 73.8% for patients treated with intravenous followed by oral antibiotics), but failed to demonstrate noninferiority (P = 0.26) of the only oral moxifloxacin regimen as compared to sequential intravenous to oral antibiotic treatment.

Moxifloxacin has the advantage of once daily administration exerting an excellent oral bioavailability of 86% [4], and was selected as a broad-spectrum antibiotic that could overwhelm antibiotic resistance issues. However, the two study arms present important differences in the antibiotics’ antimicrobial spectrum. According to the Study for Monitoring Antimicrobial Resistance Trends (SMART), the resistance rates of Escherichia coli isolates from intraabdominal infections in Europe in the period 2008 - 2009, when the APPAC II study started, were 23.6% for ciprofloxacin and 21% for levofloxacin, whereas only 0.2% for ertapenem [5]. The difference in resistance rates was more profound in Escherichia coli isolates with production of extended-spectrum beta-lactamases (ESBLs), which were highly resistant to quinolones (73.9% resistance rate to ciprofloxacin and 69.9% to levofloxacin), whereas resistance to ertapenem was only 0.3% [5]. The prevalence of ESBL-producing pathogens for the corresponding period in Europe was 11% and since then is steadily increasing. These epidemiological data if extrapolated in the patient population of the APPAC II study may reflect an incidence of about 8% of inappropriate antibiotic treatment, owing to quinolone resistance, in the oral moxifloxacin arm. ESBL-producing bacteria are typically associated with co-resistance to quinolones, aminoglycosides and trimethoprim-sulfamethoxazole, because multiple resistance genes often reside on the same plasmid [5]. Despite most patients with acute appendicitis in the APPAC II study were young (median age (IQR), 34 (26 - 45) years), a minority might possess risk factor(s) for infection with ESBL-producing Enterobacteriaceae, like recent exposure to antibiotics, recent hospitalization, or comorbidities. By excluding those patients from the study’s results analysis, the positive outcome of the oral therapy with moxifloxacin would be reasonably increased potentially rendering this option noninferior to sequential intravenous to oral therapy. In addition, considering the problem of increasing resistance to carbapenems worldwide, the use of this class of antibiotics is not recommended for treatment of community-acquired infections without ESBL risk factors [1].

Therefore, careful stratification of patients according to their individual risk for infection with resistant microorganisms is the key for appropriate antibiotic selection. In clinically stable patients with uncomplicated acute appendicitis who do not present ESBL risk factors per oral antibiotic monotherapy with moxifloxacin seems appropriate. In patients with ESBL risk factors, treatment with ertapenem seems to be appropriate, either as initial intravenous therapy followed by per oral antibiotics or as outpatient parenteral antibiotic therapy (OPAT) to avoid hospitalization.

Acknowledgments

None to declare.

Financial Disclosure

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of Interest

The authors declare no competing financial interests.

Author Contributions

SFA: conception and design, and writing of the manuscript. IM, CT and MM: critical revision of the manuscript for important intellectual content. All authors read and gave final approval of the manuscript.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Abbreviations

APPAC: Appendicitis Acute; SMART: Study for Monitoring Antimicrobial Resistance Trends; ESBL: extended-spectrum beta-lactamases; OPAT: outpatient parenteral antibiotic therapy


References▴Top 
  1. Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, Boermeester M, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg. 2020;15(1):27.
    doi pubmed
  2. COVID 19: elective case triage guidelines for surgical care. American College of Surgeons. 2020. Updated December 8, 2020. https://www.facs.org/covid-19/clinical-guidance/elective-case/emergency-surgery [Assessed November 25th, 2021].
  3. Sippola S, Haijanen J, Gronroos J, Rautio T, Nordstrom P, Rantanen T, Pinta T, et al. Effect of oral moxifloxacin vs intravenous ertapenem plus oral levofloxacin for treatment of uncomplicated acute appendicitis: the APPAC II randomized clinical trial. JAMA. 2021;325(4):353-362.
    doi pubmed
  4. Stass H, Kubitza D. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother. 1999;43(Suppl B):83-90.
    doi pubmed
  5. Hawser SP, Bouchillon SK, Lascols C, Hackel M, Hoban DJ, Badal RE, Canton R. Susceptibility of European Escherichia coli clinical isolates from intra-abdominal infections, extended-spectrum beta-lactamase occurrence, resistance distribution, and molecular characterization of ertapenem-resistant isolates (SMART 2008-2009). Clin Microbiol Infect. 2012;18(3):253-259.
    doi pubmed


This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gastroenterology Research is published by Elmer Press Inc.

 

Browse  Journals  

 

Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

 

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

 

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

 

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

 

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 
       
 

Gastroenterology Research, bimonthly, ISSN 1918-2805 (print), 1918-2813 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.

This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.gastrores.org   editorial contact: editor@gastrores.org    elmer.editorial@hotmail.com
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.


Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.