Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management - 27/09/17

Doi : 10.1016/j.annemergmed.2016.08.446

David A. Talan, MD ^a,^b,^⁎ , Darin J. Saltzman, MD, PhD ^c, William R. Mower, MD, PhD ^e, Anusha Krishnadasan, PhD ^a, Cecilia M. Jude, MD ^d, Ricky Amii, MD ^a, Daniel A. DeUgarte, MD, MS ^f,^g, James X. Wu, MD ^g, Kavitha Pathmarajah, MPH ^a, Ashkan Morim, MPH ^a, Gregory J. Moran, MD ^a,^b
for the
Olive View–UCLA Appendicitis Study Group
Robert Bennion, MD, Paul Schmit, MD, Melinda Gibbons, MD, MSHS, Darryl Hiyama, MD, Formosa Chen, MD, MPH, Ali Cheaito, MD, F. Charles Brunicardi, MD, Steven Lee, MD, James Dunn, MD, David Flum, MD, MPH, Giana Davidson, MD, MPH, Annie Ehlers, MD, Rodney Mason, MD, Fredrick M. Abrahamian, DO, Tomer Begaz, MD, Alan Chiem, MD, Jorge Diaz, MD, Pamela Dyne, MD, Joshua Hui, MD, Luis Lovato, MD, Scott Lundberg, MD, Amir Rouhani, MD, Mathew Waxman, MD, Maureen McCollough, MD, MPH, Breena Taira, MD, MPH, Raquel Torrez, BS, Eva Gonzalez, BA, Christine Sayegh, BS, Paula Seloadji, PharmD, Noemi Quinteros, BS, Gabina Martin, BSN, RN, Roee Salem, BA, Lisandra A. Uribe, BS, Justin A. De La Guerra, BS, Alexander Garrett, BS, Arthur C. Jeng, MD

^a Department of Emergency Medicine, Olive View–UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
^b Department of Medicine, Division of Infectious Diseases, Olive View–UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
^c Department of Surgery, Olive View–UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
^d Department of Radiology, Olive View–UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
^e Department of Emergency Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
^f Division of Pediatric Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
^g Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA

^∗Corresponding Author.

Abstract

Study objective

Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy.

Methods

Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate.

Results

Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group.

Conclusion

A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

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Plan

Introduction

Background

Importance

Goals of This Investigation

Materials and Methods

Study Design and Setting

Selection of Participants

Methods of Measurement

Characteristics of Study Participants

Main Results

Limitations

Discussion

	Please see page 2 for the Editor’s Capsule Summary of this article.
	Supervising editor: Steven M. Green, MD
	Author contributions: DAT, DJS, WRM, DAD, JXW, and GJM developed the study methods. DAT, DJS, AK, RA, and GJM supervised study implementation. DAT drafted the article. WRM and AK conducted data analysis. AK served as project director. CMJ developed radiology methods. DAD, JXW, and KP assisted with study implementation. KP supervised the study coordinators. AM conducted chart reviews, entered data, and ensured data quality and integrity. DAT takes responsibility for the paper as a whole.
	All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
	Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org/). This study was supported by a grant from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (1R21DK102048-01A1, to Drs. Talan and Moran). Dr. Talan reports serving on a speakers bureau for Allergan; providing consultation, serving on an advisory board, and conducting research for Allergan and Cempra; and creating an educational video for Merck. Dr. Moran reports conducting research for Cempra, Allergan, Cerexa, and Cubist Astra Zeneca.
	Trial registration number: NCT02447224
	The NIH/NIDDK had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
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