EXECUTIVE SUMMARY

Data from a large, multicenter, randomized study show 70% of patients with appendicitis who were treated with antibiotics avoided surgery at 90 days. This creates possibilities for patients and providers for a common diagnosis in the ED.

  • The early results pertain to 1,552 patients with appendicitis assigned to receive either surgery or antibiotics between May 2016 and February 2020.
  • Roughly half treated with antibiotics were discharged from the ED straight away. However, investigators reported 30% of participants in the antibiotic group returned to undergo an appendectomy within three months.
  • A subgroup of patients in the antibiotic group experienced appendicolith more often than those in the surgery treatment arm. Nevertheless, investigators reported that in most patients with no evidence of an appendicolith, complications and serious safety events were rare and similar between the antibiotic and surgical treatment groups.

Acute appendicitis is a common diagnosis in the ED. In the United States, the prescribed treatment is appendectomy. However, intriguing data suggest many of these patients could safely delay surgery or avoid the procedure altogether through a course of antibiotics.

These revelations come from the Comparison of the Outcomes of antibiotic Drugs and Appendectomy (CODA) trial, a large, randomized, controlled study funded by the Patient-Centered Outcomes Research Institute (PCORI).1 The trial is ongoing, but investigators have reported early results pertaining to 1,552 patients with appendicitis assigned to receive either surgery or antibiotics between May 2016 and February 2020.

The data include participants from 25 sites in 14 states, and they represent outcomes at 90 days. Among the outcomes tracked, investigators report that just three in 10 participants in the antibiotic group returned to undergo an appendectomy within a three-month period. While there are pros and cons to both the surgical and antibiotic treatment routes, it is clear these findings create fresh possibilities for patients and their providers.

David Talan, MD, FACEP, FIDSA, co-principal investigator on the CODA trial and a professor of emergency medicine and infectious disease at UCLA, says the research will better inform patients and their physicians about care options.

“In the past, appendectomy was the only recommended treatment. Prior to the CODA trial, other studies supported the effectiveness of antibiotics as a safe alternative to avoid surgery in most patients. However, in the U.S., antibiotics were uncommonly used,” he explains. “Going forward, I believe there will be greater consideration of antibiotic treatment. I would expect that emergency physicians will often be the first to initiate these discussions with patients soon after they confirm the diagnosis during the course of their emergency care.”

In terms of general health status, Talan says that at 30 days, antibiotic treatment was no worse than appendectomy. Over the course of 90 days, 70% of participants who received antibiotics avoided surgery as well as the general anesthesia and hospitalization that go along with it.

“About one-half of those treated with antibiotics were discharged from the ED straight away, and thus got to be home instead of having to be in the hospital. Patients treated with antibiotics also got back to work sooner than those having appendectomy,” Talan notes. “However, the flip side was that almost 30% of those treated with antibiotics had an appendectomy later, mostly for recurrence [of acute appendicitis].”

What should clinicians consider when determining whether a patient with acute appendicitis is a good candidate for antibiotic treatment? More data will shed additional light on this question, but investigators have already gleaned some important information from the early findings.

For example, unlike previous studies of this issue, the CODA trial allowed enrollment of all patients who typically would be offered appendectomy, including those with an appendicolith revealed via imaging.

“Whereas other studies excluded these patients, CODA specifically included them to be analyzed as a separate subgroup, and they accounted for about one-quarter of all patients,” Talan says.

Complications occurred more commonly in this subgroup of patients with appendicoliths who received antibiotic treatment than those who received surgery. However, Talan reports that for most patients with no evidence of an appendicolith, complications and serious safety events were rare and similar between the treatment groups. “Based on CODA’s findings, patients with appendicolith do not appear to fare as well with antibiotic treatment as those without this finding,” he explains. “Future CODA papers will attempt to determine other patient characteristics that might favor one treatment versus the other.”

More Research Ahead

David Flum, MD, MPH, another CODA co-principal investigator and chair of surgery at the University of Washington, notes the early results show one size does not necessarily fit all when it comes to treatment for acute appendicitis.

“Antibiotics may be right for many, but probably not all patients,” he says. “In the COVID era, it’s particularly important to know that nearly half of the patients in the antibiotics arm of the trial did not require hospitalization for their initial treatment. Seven in 10 avoided appendectomy by three months. That may be appealing to many patients.”

Flum says the treatment decision on how to proceed should involve both the emergency physician and the surgeon. “Emergency physicians and surgeons are a team caring for patients with appendicitis,” he says. “While antibiotic treatment may be initiated by emergency physicians, surgeons should be involved in all aspects of that decision and follow-up care.”

The results unveiled so far were revealed after just 90 days of follow-up because of concerns related to the COVID-19 pandemic. Investigators intend to publish additional results after follow-up of one year or more.

“We expect to see some more recurrences in the antibiotic group, although how many is still to be determined,” Talan says. “Other analyses will compare outcomes among those who agreed to be in the randomized trial vs. patients who, with their surgeon, chose their treatment. We will also examine the extent to which ED discharge was safe across the range of illness severity.”

Flum adds future reports from the trial should help patients “find themselves” in the data with a predictive score to determine their chance of performing well with antibiotics. “We also look forward to reporting longer-term results related to recurrence, complications, and missed neoplasms [tumors],” Flum adds.

REFERENCE

  1. Flum DR, Davidson GH, Monsell SE, et al. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med 2020; Oct 5. doi: 10.1056/NEJMoa2014320. [Online ahead of print].