10-year data support antibiotics treatment of uncomplicated acute appendicitis

Among adults who received antibiotic treatment for uncomplicated acute appendicitis in the APPAC* trial, the number of recurrences and subsequent appendectomies at 10 years demonstrates the viability of this nonsurgical treatment approach, as reported by the investigators.

Over the 10-year follow-up, histopathologically confirmed appendicitis recurrence occurred in 37.8 percent (95 percent confidence interval [CI], 31.6–44.1) of patients who received treatment with antibiotics, and 44.3 percent (95 percent CI, 38.2–50.4) underwent subsequent appendectomy. [JAMA 2026;doi:10.1001/jama.2025.25921]

The cumulative complication rate among patients who received antibiotic was 8.5 percent, significantly lower than the 27.4 percent recorded among those who initially underwent appendectomy (p<0.001). There was no significant difference observed in quality of life between the antibiotic and appendectomy groups (median health index value of 1 for both; p=0.18).

As for patient satisfaction, 78 percent of those in the appendectomy group and 67.3 percent in the antibiotics group said that they would choose the same treatment again. Among patients in the antibiotic group, 90.9 percent of those who did not undergo subsequent appendectomy and 46.6 percent of those who did undergo the procedure said they would choose antibiotics again.

“[The findings] confirm the feasibility and safety of antibiotics for uncomplicated acute appendicitis at long-term follow-up, because more than one-half of the patients treated nonoperatively avoided surgery,” noted lead investigator Dr Paulina Salminen from Turku University Hospital in Turku, Finland, and colleagues.

“This long-term safety also applies to the previous uncertainty of possible undetected appendiceal neoplasms,” they added.

The overall prevalence of appendiceal neoplasms in patients with uncomplicated acute appendicitis was low and did not significantly differ between the antibiotic group and the appendectomy group (0.9 percent vs 1.5 percent; p=0.70).

Shared decision-making

In an accompanying editorial, Dr Anthony Charles from the University of Vermont in Burlington, Vermont, US, highlighted the role of shared decision-making in the management of uncomplicated appendicitis, with antibiotics having been shown as a safe and feasible alternative to appendectomy. [JAMA 2026;doi:10.1001/jama.2025.26612]

“The issue is no longer about a right vs wrong management pathway but between a medically acceptable and a surgically definitive strategy with very different risk-benefit profiles,” Charles said.

He, however, noted that in terms of cost effectiveness, antibiotic therapy may have the advantage. “Even if the recurrence-related appendectomy is more expensive, the initial savings from the 62 percent who avoid surgery altogether is likely sufficiently substantial that the overall cost is likely to be lower and outweigh the added costs of treating recurrences.

“With an economic evaluation that may favour the use of antibiotics for uncomplicated appendicitis, the final management decision must still be shared, because the cost to an individual patient in terms of anxiety, time in the hospital, and potential future illness may outweigh the societal economic benefit,” Charles said.

The APPAC trial

APPAC involved 530 adult patients (aged 18‒60 years) with uncomplicated acute appendicitis diagnosed by computed tomography. These patients had been randomly assigned to undergo open appendectomy (n=273) or receive antibiotics (n=257). The antibiotic regimen comprised 3 days of intravenous ertapenem sodium (1 g/day) followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg three times/day).

The 10-year follow-up analysis included 253 patients in the antibiotic group (median age 33 years, 40.3 percent female) and 219 in the appendectomy group (median age 36 years, 38.8 percent female).

Salminen and colleagues acknowledged several study limitations. First, the study protocol required all patients with clinically suspected appendicitis recurrence to undergo laparoscopic appendectomy, which led to more appendectomies than were medically warranted. Second, there were 41 patients in the antibiotic group with an intact appendix who did not undergo follow-up MRI.  

Additionally, Charles advised caution regarding the interpretation of the differences in 10-year cumulative complication rates, noting that “open appendectomy is no longer the current standard of care, and the complication profile following laparoscopic appendectomy is indeed much lower than that for open appendectomy.”

It is also likely that the 10-year incidence of appendiceal malignancy reported in APPAC is an underestimate, “given the indeterminate sensitivity of MRI for appendiceal cancer in an asymptomatic cohort. It must also be assessed against the secular trend for rising incidence of appendiceal cancers in older adults,” he said.