Antibiotic therapy was noninferior to appendectomy for treating appendicitis, according to a randomized trial published in The New England Journal of Medicine.

Study authors conducted a pragmatic, nonblinded, noninferiority trial to propose antibiotic therapy as an alternative to surgery for the treatment of appendicitis. Of the total 1552 patients included, 414 had an appendicolith. Both treatment groups had 776 patients who received either a 10-day course of antibiotics or an appendectomy.

The primary outcome was 30-day health status, assessed by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. The EQ-5D scores were 0.92±0.13 for patients on antibiotics and 0.91±0.13 for patients who received an appendectomy (difference, 0.01 points; 95% CI, -0.001 to 0.03). These results indicate that antibiotics are noninferior to an appendectomy. In both the per-protocol analysis (difference, 0.01 points; 95% CI, -0.002 to 0.03) and an analysis using multiple imputations for missing primary outcome data (difference, 0.01 points; 95% CI, −0.004 to 0.02), the results were similar.

In the antibiotics group, 11%, 20%, and 29% of patients received an appendectomy by 48 hours, 30 days, and 90 days, respectively. Of the patients who underwent an appendectomy by 90 days, 41% had an appendicolith and 25% of patients did not have an appendicolith.

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While there were no deaths reported in the trial, the antibiotics group reported higher incidence of complications (8.1 vs 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); this disparity could be attributed to patients with an appendicolith (20.2 vs 3.6 per 100 participants; rate ratio, 2.28; 95% CI, 1.30-3.98) as they experienced more complications than patients without an appendicolith (3.7 vs 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45-2.43). Serious adverse events occurred at a rate of 4.0 and 3.0 per 100 participants in the antibiotics and appendectomy group, respectively (rate ratio, 1.29; 95% CI, 0.67 to 2.50).

The study was limited in that only 90-day follow-up data was available, which underrepresents recurrence and long-term complications. The trial was also not blinded and the protocol did not specify requirements for hospitalization or a given antibiotic regimen.

“For the treatment of appendicitis, antibiotics were noninferior to appendectomy,” investigators concluded. While nearly 3 in 10 participants receiving antibiotics had an appendectomy by day 90, investigators highlight that 7 in 10 participants were able to avoid surgery, be treated on an outpatient basis, and missed less time at work.

Disclosures: Several authors report advisory board fees or grant support from pharmaceutical companies. Please refer to the original reference for full disclosure details.


Flum DR, Davidson GH, Monsell SE, et al; The CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med. 2020;383(20):1907-1919. doi: 10.1056/NEJMoa2014320.