Antibiotics Noninferior to Appendectomy for Treatment of Appendicitis

Antibiotics, pills
Antibiotics, pills
Investigators of the randomized controlled trial compared antibiotic therapy with appendectomy.

Antibiotic therapy was found to be noninferior to appendectomy for the treatment of appendicitis, according to findings from a randomized study published in The New England Journal of Medicine.

The trial enrolled 1552 adults with appendicitis from participating surgical sites around the United States who were randomly assigned to receive either antibiotic therapy (n=776; 10-day course) or appendectomy (n=776). Patients with recurrent appendicitis or severe symptomatology were excluded.

The primary outcome was 30-day health status, measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Participants were first surveyed 24 hours after hospital discharge. Follow-up surveys were administered at 1, 2, and 4 weeks post-discharge, quarterly per year for 1 year, and then yearly thereafter. Secondary outcomes included patient-reported resolution of symptoms and adverse events.

Linear regression was used to identify between-group differences in EQ-5D score over follow-up. Kaplan-Meier curves were used to estimate appendectomy-free survival in the antibiotics group.

Thirty day health-related quality of life outcomes were comparable between patients who received antibiotic therapy (EQ-5D score, 0.92±0.13) and patients who underwent appendectomy (EQ-5D score 0.91±0.13). The difference of 0.01 points (95% CI, -.001 to .03), demonstrated antibiotic therapy’s inferiority 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),” the study authors said.

Appendectomy was performed in 11%, 20%, and 29% of patients in the antibiotics group at 48 hours, 30 days, and 90 days after admission, respectively. Nearly 70% of patients who were assigned to initial antibiotic therapy did not undergo subsequent appendectomy. Of the patients who received an appendectomy at 90 days, 41% had an appendicolith and 25% did not.  

The rates of serious adverse events were comparable between treatment groups; however, the antibiotics arm had a greater incidence of complications (8.1 vs 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98). This higher incidence was largely due to the number of patients who received an appendicolith. These patients (20.2 vs 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11-15.38) experienced significantly higher complication rates than patients who did not undergo appendectomy (3.7 vs 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45-2.43). Serious adverse events were reported 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).

Primary limitations to this study included the short follow-up period for surgical outcomes; appendectomies past the 90-day point were not included. Additionally, the unblinded status may have influenced treatment outcomes.

“[T]his comparative effectiveness trial showed that…antibiotics were noninferior to appendectomy on the basis of…general health status, at least in the short term,” the investigators wrote. “[T]hese data may be particularly relevant during the Covid-19 pandemic, as patients and clinicians weigh the benefits and risks of each approach, considering individual characteristics, preferences, and circumstances.”

Disclosure: Multiple study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of the authors’ disclosures.

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