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For patients with uncomplicated acute appendicitis, the noninferiority of oral antibiotics alone compared with a combination of intravenous and oral antibiotics could not be demonstrated in a secondary analysis of the phase III APPAC II trial.

At 3-year follow-up, the rate of treatment success -- defined as the resolution of acute appendicitis and discharge from hospital without the need for appendectomy and no recurrence -- was 63.4% in the oral antibiotic monotherapy group versus 65.2% in the combination antibiotic group (P=0.14 for noninferiority), reported Paulina Salminen, MD, PhD, of Turku University Hospital in Finland, and colleagues.

Notably, there were no significant differences in adverse events, quality of life, patient satisfaction, and length of hospital stay or sick leave between the two groups. The overall complication rate was 6.1% in the monotherapy group compared with 7.3% in the combined antibiotic group, and no patients died during the follow-up period.

"These results encourage the assessment in future trials of oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis," the authors wrote in .

The cumulative appendectomy rate over the 3-year follow-up was 36.6% in the monotherapy group and 34.8% in the combined treatment group. Among the 208 patients who eventually underwent appendectomy, 78.4% had a recurrent episode of appendicitis within 1 year of initial presentation. In addition, for those who had their appendix removed, 8.7% had a histopathologically normal appendix, decreasing the true appendicitis recurrence rate of all patients to about 26%.

"It is necessary to recognize that appendicitis presents with varying degrees of severity and variable risk of progression," wrote Frederick Thurston Drake, MD, MPH, and Sabrina Sanchez, MD, MPH, of Boston University Chobanian and Avedisian School of Medicine, in. "Not all patients with acute appendicitis will progress to perforation. Some cases will require surgery, some will respond to antibiotics, and some will be self-limiting."

Previous results from the , as well as the CODA trial, showed that selected patients with uncomplicated appendicitis could be successfully treated with antibiotics alone, avoiding unnecessary surgery, at least in the short term. Furthermore, a secondary analysis of the CODA trial showed no greater risk of complications among those treated with antibiotics only.

Primary results of the found that treatment of uncomplicated acute appendicitis with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups. However, that trial also failed to demonstrate noninferiority of oral antibiotics alone.

"Although we cannot ascertain a pharmacological or pathophysiological reason that the route of initial treatment would affect risk of recurrence 2 to 3 years after resolution of the index episode, these longer-term data do contribute to the body of evidence that antibiotic treatment has lasting effectiveness" in uncomplicated appendicitis, Drake and Sanchez noted. The possibility that not all appendicitis requires surgery was "what 19th-century physicians intuited through experience and close observation: there is such a thing as mild appendicitis, which is not surgical disease," they added.

However, they said that further research is required to more clearly identify which patients can safely receive antibiotics in lieu of an appendectomy.

This secondary analysis of the looked at 3-year outcomes in 582 patients with CT-confirmed, uncomplicated acute appendicitis at nine university and central hospitals in Finland from April 2017 to November 2018, with last follow-up in November 2022. Median patient age was 33-34, and most were men. Notably children, adults over the age of 60, pregnant or lactating people, and those with renal disease, metformin use, or serious systemic illness were excluded.

Of the patients included, 295 received oral antibiotics only at the time of diagnosis and 287 received a combination of IV and oral antibiotics. Those in the oral antibiotics-only group received oral moxifloxacin 400 mg per day for 7 days. Those in the combined antibiotic group received IV ertapenem 1 g per day for 2 days, plus oral levofloxacin 500 mg per day and metronidazole 500 mg three times per day for 5 days.

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