Does Appendicitis Have to Be Treated With Surgery?

Lara C. Pullen, PhD

June 18, 2015

Antibiotic treatment of patients with computed tomography (CT)-proven, uncomplicated appendicitis may be as effective as appendectomy, according to a new study. The majority of patients randomly assigned to receive antibiotic treatment did not require an appendectomy during 1 year of follow-up, and those who did receive an appendectomy did not have significant complications. Despite this, when the two treatments were compared in a noninferiority trial, the investigators found that antibiotic treatment did not meet the prespecified criterion for noninferiority.

Paulina Salminen, MD, PhD, from the Turku University Hospital in Finland, and colleagues published the results of the Appendicitis Acuta (APPAC) multicenter trial in the June 16 issue of JAMA.

The researchers randomly assigned patients to either a surgery group to receive an appendectomy performed using the standard open technique or to an antibiotic group to receive broad-spectrum antibiotics (ertapenem, levofloxin, and metronidazole). The investigators note that many patients elected to receive surgery, and the investigators had difficulty recruiting patients willing to be assigned to the antibiotic group. Of those who underwent appendectomy, 15 (5.5%) patients underwent laparoscopic appendectomy.

"To our knowledge, the APPAC trial is the largest multicenter, open-label, noninferiority [randomized controlled trial] of antibiotic treatment for appendicitis conducted to date. When the trial was designed, we assumed that there would be sufficient benefits from avoiding surgery and that a 24% failure rate in the antibiotic group would be acceptable. Instead, we found a failure rate of 27.3% (95% confidence interval, 22.0%-33.2%) and were not able to establish the noninferiority of antibiotic treatment for appendicitis," the authors write.

The investigators did find that 72.7% (95% confidence interval, 66.8% - 78.0%) of patients with uncomplicated acute appendicitis recovered after receiving only antibiotic therapy. Eight patients randomly assigned to the antibiotic group were mistakenly identified as having complicated appendicitis and received an appendectomy that may not have been required. These eight patients may have confounded the results of the study.

Patients in the antibiotic group had a longer median length of hospital stay than patients in the surgery group. The investigators note, however, that the minimal length of hospital stay for patients in the antibiotic group was specified in the treatment protocol and could likely be shortened in the future.

Previous trials have addressed the role of antibiotic therapy as a treatment for appendicitis. These trials were limited, however, by their reliance on clinical diagnosis of acute appendicitis, duration of antibiotic treatment, and poor determination of the primary endpoint. Not surprisingly, the results from these previous trials have been mixed.

Appendicitis may present as uncomplicated and acute, or it may be complicated by a perforation, intraabdominal abscess, and/or appendicoliths. A previous study, for example, found that patients with appendicoliths were more likely to have complicated acute appendicitis and to fail antibiotic treatment.

The current study attempted to avoid this problem by enrolling only patients with a CT-confirmed diagnosis of uncomplicated acute appendicitis. They excluded, for example, patients with appendicoliths.

CT imaging made such patient selection feasible. The authors explained the benefits of CT imaging: "Another feature of our study was the low negative appendectomy rate attributable to CT imaging. Use of CT also enabled us to identify uncomplicated acute appendicitis that was successfully treated with antibiotics alone in the majority of patients enrolled in our study," the authors write.

Another strength of the current study was the investigators' choice of antibiotics. They emphasized in their article that successful antibiotic treatment of appendicitis requires the selection of an antibiotic that provides broad-spectrum coverage of the many pathogens that might cause appendicitis.

The authors suggest that patients diagnosed with CT-proven uncomplicated acute appendicitis be given the opportunity to make an informed decision between antibiotic treatment and appendectomy.

Edward Livingston, MD, from Northwestern University Feinberg School of Medicine in Chicago, Illinois, and Corrine Vons, MD, PhD, from Johns Hopkins School of Medicine in Baltimore, Maryland, agree and penned an accompanying editorial to that effect. They write that, "[t]he time has come to consider abandoning routine appendectomy for patients with uncomplicated appendicitis. The operation served patients well for more than 100 years. With development of more precise diagnostic capabilities like CT and effective broad-spectrum antibiotics, appendectomy may be unnecessary for uncomplicated appendicitis, which now occurs in the majority of acute appendicitis cases."

Monica E. Lopez, MD, a surgeon at Baylor College of Medicine in Houston, Texas, who was not involved in the study, remains, however, unconvinced: "Overall, I don't think the findings of the study warrant a change in practice," she explained in an email to Medscape Medical News.

Dr Salminen reported receiving personal fees for lectures from Merck and Roche. The other authors, the editorialists, and Dr Lopez have disclosed no relevant financial relationships.

JAMA. 2015;313:2340-2348. Article abstract, Editorial extract

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