The CODA Trial — Antibiotics vs. Appendectomy

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What’s the preferred method for patients with acute appendicitis?

The well-established, standard treatment for acute appendicitis is surgical appendectomy.  However, recent research has challenged the dominance of the surgical approach in looking at antibiotics alone. The available literature on non-operative treatment of appendicitis (NOTA) has important limitations: exclusion of patients with appendicoliths, small sample size and predominance of open appendectomy over laparoscopic appendectomy.


A recent publication from the CODA collaborative (Comparison of Outcomes of Antibiotic Drugs and Appendectomy) published in the NEJM 2020[1] asked a simple question: In adult patients with acute appendicitis are antibiotics non-inferior to surgery?

This was a pragmatic, nonblinded, noninferiority randomized trial at 25 US centers in which adults ≥18 years of age were randomized to:

  • Antibiotics: At least 24 hours of IV antibiotics followed by a 10d course of oral antibiotics OR
  • Surgery: Laparoscopic or conventional (open) appendectomy (96% of appendectomies were performed laparoscopically)

Patients with septic shock, diffuse peritonitis, recurrent appendicitis, evidence of severe phlegmon on imaging, walled-off abscess, free air or free fluid and evidence suggestive of neoplasm were all excluded from enrollment.


The primary outcome was the 30-day health status assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire.  This questionnaire focuses on mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Of 1,552 randomized study patients, there was no difference between study groups in the composite scores on the EQ-5D questionnaire. However, in the antibiotics group, 11% underwent surgery by 48 hours, 20% underwent surgery by 30 days, and 29% underwent surgery by 90 days.  Additionally, there were three times more ED visits and two times more complications (i.e. perforation, percutaneous drainage, reactions to antibiotics, etc…) with antibiotics patients compared to surgery patients.  The mean number of missed workdays for patients was 5.26 days in the antibiotics group and 8.73 days in the appendectomy group. Most importantly, no one died in either group.

The authors also looked at a subgroup of patients with an appendicolith present.  Of 414 study participants with appendicoliths, there were far more complications with antibiotics (20% vs. 3.6%). Additionally, 61% of patients with appendicoliths had perforation while 24% of patients without appendicoliths had perforation.

This is the largest randomized controlled trial investigating non-operative treatment of acute appendicitis to date.  There are some important limitations to keep in mind:


  1. This was an unblinded trial with a subjective primary outcome that could influence the results of the trial. Obviously surgical intervention vs. no surgical intervention cannot be blinded, but knowing which arm of a trial a person was randomized to can affect subjective outcomes (i.e., survey of pain/anxiety). This is not as much of an issue with objective outcome measures such as death.
  2. A 90-day follow-up may be too short a time to see recurrence rate and long-term complications in the antibiotic group. We know that at 90 days almost 30% of patients in the antibiotics group ended up requiring surgery. What would this percentage be if followed out to six months or even 12 months?


Although an “antibiotic first” strategy was non-inferior to appendectomy in this trial, nearly three in 10 patients in the “antibiotic first” group had undergone appendectomy by 90 days. The antibiotic-first group had three times more ED visits than primary appendectomy group, and the antibiotic-first group had twice as many complications as the primary appendectomy group.

Patients with an appendicolith are at a much higher risk of complications and need for surgical intervention, therefor an antibiotic-first strategy should not be recommended.


EDITOR-IN-CHIEF Dr. Rezaie is founder and editor of R.E.B.E.L EM.

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