Antibiotics for Appendicitis: 10-Year Safety & Feasibility

For patients who received antibiotics for uncomplicated acute appendicitis, rates of recurrence and subsequent appendectomy at 10 years indicated that the strategy is a safe and feasible alternative to surgery, according to follow-up results from a randomized trial. In the decade after participating in the Appendicitis Acuta (APPAC) trial, 37.8% of patients who received antibiotics instead of appendectomy had a true, histopathologically confirmed recurrence of appendicitis, while the cumulative appendectomy rate was 44.3%, reported Paulina Salminen, MD, PhD, of the University of Turku in Finland, and colleagues. Overall, the cumulative complication rates at 10 years were 27.4% in the appendectomy group and 8.5% in the antibiotic group (P<0.001). Tumor prevalence rates weren't significantly different between the groups (1.5% vs 0.9%, P=0.70), they noted in JAMA. "This secondary 10-year analysis confirms 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," Salminen and colleagues wrote. "The overall cost and resource savings will potentially be markedly further increased in the future by outpatient treatment." In an accompanying editorial, Anthony Charles, MD, MPH, of the University of Vermont in Burlington, noted that this study "underscores the role of shared decision-making in the management of uncomplicated appendicitis." "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," he wrote, adding that antibiotic therapy is "highly likely to be cost-effective from a societal perspective." Despite that potential economic advantage, he cautioned, "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." A patient who decides to take antibiotics in this situation must have long-term access to follow-up care, Charles said, a potential challenge for those without insurance or in underserved populations. The new follow-up data mirror the findings from a 2023 long-term analysis of two Swedish randomized trials in the 1990s comparing appendectomy and antibiotics for acute appendicitis. That analysis found that 60% of patients randomized to antibiotics across both trials did not experience appendicitis recurrence up to 25 years later, and 71% who were discharged without appendectomy successfully avoided surgery. The multicenter, open-label, noninferiority APPAC trial ran from November 2009 to June 2012 and included a total of 530 patients ages 18-60 with uncomplicated acute appendicitis confirmed by CT who were randomized to open appendectomy or to antibiotic treatment with intravenous ertapenem sodium for 3 days, followed by 7 days of oral levofloxacin and metronidazole. The trial's initial primary endpoint was treatment success at 1 year of follow-up. In the antibiotic group, 27.3% of patients underwent appendectomy within 1 year after presenting with appendicitis. At 10-year follow-up, 98.4% of patients randomized to receive antibiotics were assessed for appendicitis recurrence. Median age was 33, and 40.3% were female. The primary aim of the 10-year analysis was to assess the rates of late appendicitis recurrence and appendectomy. Secondary endpoints included overall complications, detection of possible appendiceal tumors, quality of life, and patient satisfaction. Follow-up for the 10-year analysis ended in April 2024. The study's protocol called for laparoscopic appendectomy in patients with clinically suspected appendicitis recurrence. Quality of life was similar between the two treatment groups, with a median health index value of 1.0 in both groups. Among patients initially randomized to antibiotics, 67.3% said they'd choose the same treatment, compared with 78% of those who underwent initial appendectomy. Among those in the antibiotic group who had no appendectomy over the 10-year follow-up, 90.9% said they'd choose antibiotics again. Only 46.6% of those in the antibiotic group who subsequently underwent an appendectomy said they'd choose antibiotics again. Study limitations included the protocol's mandated laparoscopic appendectomy for all patients who had clinically suspected recurrence of appendicitis, a rule that led to more appendectomies than were medically warranted. In addition, 41 patients in the antibiotic group who had intact appendixes didn't undergo follow-up MRIs. The use of open appendectomy in the original trial, rather than laparoscopic appendectomy, may have impacted surgical complications, treatment costs, and patient satisfaction.