Antibiotics vs. Appendectomy for Appendicitis

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Posted by Carla Rothaus

What proportion of patients who were treated with antibiotics in the CODA trial underwent appendectomy by 90 days? 

The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial compared antibiotic therapy with appendectomy in adults with appendicitis, including those with an appendicolith. The authors had initially planned to report the results after all the participants had at least 1 year of follow-up, but given the Covid-19–related interest in the management of appendicitis, results based on the first 90 days after randomization were recently published. Read the NEJM Original Article here.

Clinical Pearls

Q: What factors have limited the use of antibiotics for appendectomy?

A: Appendectomy has long been the standard treatment for appendicitis, even though successful use of antibiotic therapy as an alternative was reported more than 60 years ago. Although there have been several randomized trials of antibiotics for appendicitis in adults, exclusion of important subgroups (in particular, patients with an appendicolith, who may be at an increased risk for complications), small sample sizes, and questions about applicability to the general population have limited the use of this treatment.

Q: In the CODA trial, was receipt of antibiotics noninferior to appendectomy regarding health status at 30 days?

A: The primary outcome, the mean 30-day health status as assessed with the European Quality of Life-5 Dimensions questionnaire, was 0.92±0.13 in the antibiotics group and 0.91±0.13 in the appendectomy group (difference, 0.01 points; 95% confidence interval [CI], −0.001 to 0.03); these findings are consistent with noninferiority of antibiotics to appendectomy. Results were similar in the per-protocol analysis (difference, 0.01 points; 95% CI, −0.002 to 0.03) and in an analysis performed with the use of multiple imputation for missing primary-outcome data (difference, 0.01 points; 95% CI, −0.004 to 0.02). Results in subgroups of participants with an appendicolith and those without an appendicolith also showed noninferiority of antibiotics with respect to the primary outcome.


Morning Report Questions 

Q: What proportion of patients who were treated with antibiotics in the CODA trial underwent appendectomy by 90 days?

A: In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days, and there were more emergency department visits and hospitalizations after the index treatment than in the appendectomy group. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. The mean number of missed work days for participants was 5.26 in the antibiotics group and 8.73 in the appendectomy group, and the mean number of missed work days for caregivers was 1.33 and 2.04, respectively. The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). 

Q: Describe another outcome relevant to the use of antibiotics rather than appendectomy for appendicitis.

A: Another relevant outcome is the potential for missed neoplasm in patients who are not undergoing appendectomy. Although almost all participants in the CODA trial underwent computed tomography, and those with evidence suggestive of a mass were excluded, appendiceal neoplasms were identified in nine participants (mean age, 47±17 years; range, 21 to 74) — seven in the appendectomy group and two in the antibiotics group who had undergone appendectomy. Eight of the neoplasms were carcinomas, and one was a mucocele.

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