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

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.

Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis

“…Although appendectomy has been the treatment of choice for patients with appendicitis during the past century, conservative treatment is now suggested as an alternative choice by authors of multiple randomized controlled trials. In light of our results, which revealed CT features that are consistently specific in the diagnosis of complicated appendicitis, we reviewed whether these features were indeed included in the trials in which conservative treatment was applied to presurgical diagnosis of uncomplicated appendicitis (4,5,10,11,(48)(49)(50). However, even in the trials in which CT was used for preclusion of complicated appendicitis, CT criteria used were often limited in scope or not specified.…”

The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: Systematic review and network meta-analysis of randomized controlled trial

“…Briefly, the initial treatment success was defined as therapeutic efficacy at initial hospitalization, which was pathologically confirmed appendicitis after surgery for appendectomy but this was variously defined in antibiotic uses including improvement with subsequent hospital discharge in that admission, dischargeable without recurrence or need for surgery within 1e3 months or even 1 year of follow up. Overall complications included any of the following: clinical wound infection occurring within 30 days after the appendectomy which was diagnosed by a surgeon with/without a positive bacteria culture, 2, 29e31 wound rupture/dehiscence, 30e32 wound hernia, 2,7 peritonitis, 31 abscess, 7,32 re-operation, 31,32 small bowel obstruction, 2,7,32 venous thromboembolism (VTE), 31 postoperative cardiac problems, 31,32 and ileocecal resection 31 ( Supplementary Table s3). Recurrence was considered and compared only among antibiotic uses, which was defined as recurrence of appendicitis within 1 month to 1 year.…”

“…The characteristics of the 9 RCTs 2,7, 29e32 , 36e38 are described in Table 1. Among 9 RCTs, 2 30,36 and 6 2,7,29,31,32,37,38 RCTs studied children and adults respectively, while the remaining RCT (37) included a mixed population (although the majority of patients were adults). This RCT was therefore combined with adult studies in further analyses.…”

“…30 The mean age of children ranged from 9.5 to 11 years and WBC count ranged from 14.00 Â 10 9 /L to 17.20 Â 10 9 /L. Among the 7 adult RCTs, 2,7,29,31,32,37,38 interventions and comparators were as follows: Cep þ Met versus appendectomy (N ¼ 3), 29,32,37 Beta-lac versus appendectomy (N ¼ 2), 2,31 Betalac þ Pen versus appendectomy (N ¼ 1), 38 and Pen versus appendectomy (N ¼ 1). 7 All 7 RCTs 2,7,29,31,32,37,38 in adults reported treatment success and LOS, whereas overall complications and recurrence were reported in 6 RCTs 2,7,29,31,32,37 and 4 RCTs 2,7,29,37 respectively.…”

Alternatives to Appendectomy for Acute Appendicitis

“…To counter the concern that these children were not truly receiving NOM for appendicitis, the authors cite a 2016 report of adults and children over 13 years of age who underwent outpatient NOM of appendicitis. 3 However, there were only 16 outpatients in this study, and ED discharge of children with acute appendicitis, even by strong proponents of NOM, seems highly unusual.…”