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Appendicitis: Toss-Up for Antibiotics vs Surgery

— Prospective trial shows most patients can avoid surgery, but it's still no bed of roses

MedpageToday
A close up of a man clutching his stomach

Antibiotics were non-inferior to appendectomy according to health status by a standard 30-day quality of life score in a randomized open-label trial.

But 29% of patents assigned to antibiotics in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) study had undergone appendectomy at 90 days, reported David R. Flum, MD, MPH, of the University of Washington in Seattle, and co-authors .

The pragmatic study of 1,552 patients at 25 U.S. centers reported a negligible and non-significant difference between groups in the study's primary outcome of mean 30-day scores on the European Quality of Life-5 Dimensions (0.92 with antibiotics vs 0.91 with immediate appendectomy).

By week 1, resolution of appendicitis symptoms was similar in both arms, and the mean time to discharge after randomization was 1.33 days in the antibiotic arm and 1.30 days after surgery. Those receiving antibiotics missed fewer days of work: 5.26 days on average compared with 8.73.

Complications, however, were more than twice as frequent in the drug therapy group at 8.1 versus 3.5 per 100 participants (rate ratio 2.28, 95% CI 1.30-3.98), and the number of emergency department visits was nearly three times greater. In addition, 11% required at least one additional course of antibiotics within 90 days.

As well, the rate of serious adverse events was somewhat higher in the antibiotics group at 4.0 versus 3.0 per 100 participants in the surgical group (rate ratio 1.29, 95% CI 0.67-2.50). No deaths occurred.

Flum and colleagues preferred to focus on the avoided surgery for the 70% of patients assigned to antibiotics, along with their faster return to work and reduced caregiver burden.

"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," the investigators wrote.

Unlike previous of antibiotics for appendicitis, they added, CODA did not exclude important subgroups such as appendicolith patients.

In the study, patients were randomized equally to antibiotics or immediate surgery from May 2016 to February 2020. They were recruited consecutively at emergency departments with diagnoses of acute appendicitis. Mean age was about 38 and 63% were men.

Participants in the drug therapy arm received intravenous antibiotics for at least 24 hours followed by pills for a total course of 10 days. Of these patients, 414 had an appendicolith and 47% were not hospitalized for the index treatment. In the surgical arm, 96% had a laparoscopic procedure.

Antibiotic recipients with an appendicolith were at greater risk of National Surgical Quality Improvement Program–defined complications, and 41% of antibiotic recipients with this complicating feature eventually underwent appendectomy versus 25% of those without.

Additionally, 11% in the antibiotic arm had proceeded to appendectomy within 48 hours and 20% by 30 days.

Previous research has pointed to similar downsides with antibiotic therapy for appendicitis.

In , Danny Jacobs, MD, MPH, of Oregon Health and Science University in Portland, called the study an important contribution to the literature on antibiotics versus appendectomy for appendicitis.

But he stopped well short of calling it a win for antibiotics as initial treatment, and in fact suggested that surgery would remain preferable for most clinicians and patients.

Jacobs, who was not involved in the trial, stressed that all the pros and cons of different treatments should be discussed with patients, who may prioritize outcomes differently.

"Considering that laparoscopic appendectomy is a highly effective therapy – rapidly resolving pain and allowing patients to return to normal activities while avoiding the subsequent risks of recurrent appendicitis and hospitalization – I believe that most providers would recommend surgical treatment for uncomplicated appendicitis if that option is available," Jacobs wrote.

Moreover, he worried that "vulnerable populations" might be pressured to accept antibiotic treatment "preferentially or without adequate education regarding the longer-term implications."

But Jacobs agreed that the strain placed by the COVID-19 pandemic on healthcare facilities could, in some cases, tip the balance in favor of nonsurgical treatment.

Among several study limitations, the authors cited its unblinded nature, which could have affected the primary and other outcomes, as well as its 90-day follow-up, which precluded observation of long-term complications and recurrence.

The study may also have been prone to selection bias since only 30% of eligible patients overall agreed to be randomized, and this percentage varied across study sites. Moreover, the pragmatic design did not specify requirements for hospitalization or the antibiotic regimens to be used.

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    Diana Swift is a freelance medical journalist based in Toronto.

Disclosures

This study was funded by the Patient-Centered Outcomes Research Institute (PCORI).

The authors disclosed grants from the PCORI during the conduct of the study. Co-author Winchell reported fees from Stryker Corporation outside of the submitted work.

Jacobs reported having no competing interests.

Primary Source

New England Journal of Medicine

Flum DR, et al "A randomized trial comparing antibiotics with appendectomy for appendicitis" N Engl J Med 2020; DOI: 10.1056/NEJMoa2014320.

Secondary Source

New England Journal of Medicine

Jacobs D "Antibiotics for appendicitis – proceed with caution" N Engl J Med 2020; DOI: 10.1056/NEJMe2029126.