Antibiotics Safe for Appendicitis, 5-Year Follow-up Data Show

Nicola M. Parry, DVM

September 25, 2018

Antibiotics may be a feasible alternative to surgery for patients with uncomplicated acute appendicitis, 5-year follow-up data from a randomized trial show.

"Long-term follow up of patients with uncomplicated acute appendicitis suggests that initial treatment with antibiotics rather than surgery may be a feasible alternative," write Paulina Salminen, MD, PhD, from the University of Turku, Finland, and colleagues. The researchers published the results online today in JAMA.

Although appendectomy has been the mainstay of treatment for acute appendicitis for more than 100 years, recent advances in diagnostic imaging and antibiotic therapies have allowed clinicians to consider antibiotic treatment as a viable alternative strategy in some cases.

In a recent randomized clinical trial, Salminen and colleagues found that 73% of all patients with acute uncomplicated appendicitis who received antibiotics alone did not require surgery at 1-year follow-up. However, questions remained regarding the long-term outcomes for these patients.

With this in mind, Salminen and colleagues sought to investigate the long-term recurrence rate among trial participants. The randomized Appendicitis Acuta trial was conducted at 6 hospitals in Finland and enrolled 530 adults (329 men; 201 women) with uncomplicated acute appendicitis. Of those, 273 underwent appendectomy (median age, 35 years) and 257 initially received antibiotic treatment (median age, 33 years).

With 5 years of follow-up, 3 patients had died: 2 in the appendectomy group and 1 in the antibiotics group. However, none of the deaths was considered related to the trial.

Among the 257 patients who initially received antibiotics, 100 underwent appendectomy during follow-up. Of those, 70 experienced their recurrent appendicitis within 1 year of the first episode (27.3%; 95% confidence interval [CI], 22.0% - 33.2%; 70/256), and 30 patients required an appendectomy at between 1 and 5 years (16.1%; 95% CI, 11.2% - 22.2%; 30/186).

The cumulative incidence of recurrent appendicitis among patients who initially received antibiotics alone was 34.0% (95% CI, 28.2% - 40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3% - 41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2% - 43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1% - 45.3%; 100/256) at 5 years

"Nearly 2/3 of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy," the authors write.

"These findings demonstrate the feasibility of treating appendicitis with antibiotics and without surgery," Salminen and colleagues conclude.

In an accompanying editorial, Edward H. Livingston, MD, deputy editor at JAMA, emphasizes that one of the most important findings from this study is that patients in the antibiotics group who eventually needed surgery experienced no major complication because of delaying surgery.

"The findings from the [Appendicitis Acuta] trial dispel the notion that uncomplicated acute appendicitis is a surgical emergency," he emphasizes. "Given that access to a surgeon is not always available, these results may have implications in many different settings and in many different countries."

Future studies should address factors such as the optimal regimen to use for antibiotic treatment of appendicitis, says Livingston, as well as how to manage suspected recurrent appendicitis in patients who initially receive antibiotics alone.

In the AAPAC trial, patients in the antibiotics group received ertapenem (1 g/day) intravenously for 3 days while in hospital, followed by 7 days of levofloxacin (500 mg, once daily) and metronidazole (500 mg, 3 times daily). However, Livingston explains that this regimen is likely more aggressive than needed, and should be reevaluated.

The next step in appendicitis research should expand on the results from this trial to enhance nonsurgical treatment of appendicitis, he continued. "Further studies should be designed using a noninferiority approach, comparing different antibiotic approaches to that used in the [Appendicitis Acuta] study," he concluded.

This study was supported by the Mary and Georg C. Ehrnrooth Foundation, a government research grant (EVO Foundation) awarded to Turku University Hospital, and a Turku University research grant. Salminen has reported receiving personal fees for lectures from Merck, Lilly, and Orion Pharma. The remaining authors and the editorialist have reported no financial conflicts of interest.

JAMA. Published online September 25, 2018.

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