Disclosures: Flum reports receiving grants from PCORI during conduct of the study. Jacobs reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
November 28, 2020
2 min read

Study: Antibiotics noninferior to appendectomy for appendicitis

Disclosures: Flum reports receiving grants from PCORI during conduct of the study. Jacobs reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Antibiotic treatment was noninferior to appendectomy for appendicitis, according to the results of a pragmatic, nonblinded, noninferiority, randomized trial published in The New England Journal of Medicine.

The finding, from a study of more than 1,500 patients randomly assigned to receive antibiotics or undergo appendectomy, was based on a self-assessed measure of 30-day health status.

“In the antibiotics group, participants with an appendicolith were at a higher risk for both appendectomy and complications than participants without an appendicolith,” David R. Flum, MD, MPH, associate chair of the University of Washington School of Medicine’s department of surgery, and colleagues wrote. “These 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.”

Flum and members of the Comparison of the Outcomes of antibiotic Drugs and Appendectomy (CODA) collaborative enrolled 1,552 adults with appendicitis at 25 centers in the United States. They assessed 30-day health status for each patient using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, which asks patients to rank quality of life on a scale of 1 to 5. The researchers also assessed the need for appendectomy among the patients given antibiotics, and complications through 90 days.

Among the participants, 776 were randomly assigned to receive antibiotics and 776 were randomly assigned to undergo an appendectomy. According to the researchers, antibiotics were noninferior to appendectomy, with an average difference in EQ-5D of 0.01 (95% CI, –0.001 to 0.03). A total of 29% of patients in the antibiotics arm underwent an appendectomy, and complications were more common among patients given antibiotics than those who had an appendectomy (8.1 vs. 3.5 per 100 patients; rate ratio = 2.28; 95% CI, 1.3-3.98).

Previous research showed that patients with appendicitis who were given antibiotic treatment and did not require surgery afterward were as satisfied with their treatment experience as those who had surgery.

Flum and colleagues said their study’s major limitations included it being nonblinded and using only 90-day follow-up data, which may underrepresent recurrence and long-term complications.

“Although we prespecified a plan to assess outcomes according to the presence or absence of an appendicolith, our observations in these subgroups must be considered in the context of the small numbers of several individual complications,” the authors wrote. “Furthermore, there was no adjustment for multiple testing of secondary outcomes.”

Danny Jacobs, MD, MPH, president of Oregon Health and Science University, said the study raised “at least two questions.”

“First, what other factors relevant to medical care and treatment should be considered in comparing these treatment options? Second, would patients and their providers accept an alternative to appendectomy, depending on the circumstances?” Jacobs wrote in a related editorial.

“In practical terms,” he wrote, “because patients may appropriately prioritize different outcomes, the pros and cons of all treatment options should be presented and discussed. Considering that laparoscopic appendectomy is a highly effective therapy ... I believe that most providers would recommend surgical treatment for uncomplicated appendicitis if that option is available. I know I would.”

Jacobs agreed with the authors that the “advantages of antibiotic treatment relative to surgery may be greater during the COVID-19 pandemic or other public health emergencies in which operating room capacity and other resources are severely constrained.” He also noted that the pandemic “has highlighted ongoing, dreadful health care disparities in the United States and the adverse impact of social determinants, as well as structural bias and racism, on health and health outcomes.”

“It will be important to ensure that some people, in particular vulnerable populations, are not offered antibiotic therapy preferentially or without adequate education regarding the longer term implications,” Jacobs wrote.