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.

Figure 1

Screening, randomization, and follow-up of patients with the ED diagnosis of appendicitis. *All patients with a presumptive emergency department diagnosis of appendicitis by an emergency medicine attending physician. ^†Of the 31 patients who did not meet inclusion criteria, 11 had imaging that was interpreted as equivocal for appendicitis, 5 had imaging that was interpreted as equivocal for distinguishing complicated from uncomplicated appendicitis, 10 had imaging that was interpreted as complicated appendicitis, 4 had imaging suggesting acute uncomplicated appendicitis but did not have clinical confirmation by a surgeon, and 1 did not speak English or Spanish. ^‡Of the 41 patients who met exclusion criteria, 23 had an appendicolith, 11 had intravenous antibiotics >6 hours prior to enrollment, 2 were prisoners, 2 had ulcerative colitis, 1 had high-risk diabetes, 1 was immunocompromised, and 1 had another infection that required antibiotic treatment. Radiographic identification of an appendicolith was initially an exclusion criterion but was later allowed (after 11 of 30 participants were enrolled) because of lack of consistent evidence of this being a risk factor for antibiotic failure. ^§One antibiotics-first participant was lost to follow-up at the day 10-18 visit. ^‖One appendectomy participant was intubated at the day 2 visit, so the visit was not completed.

Figure 2

Modified Alvarado scores* at day 1 (◆) and day 2 (■) for 16 participants with the diagnosis of acute uncomplicated appendicitis randomized to antibiotics-first treatment. *The modified Alvarado score consists of the following components (points): right lower quadrant tenderness (0/2); elevated temperature (≥37.3°C [99.1°F]) (0/1); rebound tenderness (0/1); anorexia (0/1); nausea or vomiting (0/1); leukocytosis >10,000 cells/mL (0/2); polymorphonuclear cells >75% (0/1). The modified score does not include migration of pain to the right lower quadrant since this variable would not be applicable for comparison of serial scores among a cohort of patients with imaging-confirmed appendicitis. The maximum modified Alvarado score is 9 instead of 10 for the original score. There was no change between day 1 and day 2 scores for participant numbers 15 and 16.