It's Time to Deconstruct Treatment-Failure: A Randomized Controlled Trial of Nonoperative Management of Uncomplicated Pediatric Appendicitis with Antibiotics Alone

Abstract Background Published data demonstrate that management of uncomplicated pediatric appendicitis with antibiotics-alone is safe and frequently successful. Randomized controlled trials (RCT) comparing antibiotics-alone to appendectomy are lacking, alongside insight into drivers of failure. We sought to validate the antibiotics-alone approach and identify barriers to success using an RCT design. Methods Patients aged 6–17 years with uncomplicated appendicitis were randomized to appendectomy or intravenous piperacillin/tazobactam for 24–48 h followed by 10 days of oral ciprofloxacin/metronidazole. Enrollment required symptoms Results Among 39 children enrolled over 31 months, 20 were randomized to antibiotics-alone and 19 to surgery. At 1 year, 6 nonoperative patients underwent appendectomy (70% success). Four cases were not true antibiotic failures but instead reflected “pragmatic” challenges to executing nonoperative algorithms. Only 2 cases represented recurrent/refractory appendicitis, suggesting a 90% adjusted 1-year success rate. Parental PedsQL™ scores were similar between treatment cohorts (91.3 vs 90.2, P = 0.32). Children treated with antibiotics-alone had faster return to activity (2.0 vs 12 days, P = 0.001) and fewer parental missed work days (0.0 vs 2.5, P = 0.03). Conclusions These data corroborate findings from non-randomized studies suggesting 70–90% of uncomplicated pediatric appendicitis can be treated with antibiotics-alone, with fewer disability days. Failures appear multifactorial, often reflecting practical hurdles and not antibiotic limitations. As surgeons consider nonoperative protocols for uncomplicated appendicitis, these data further inform the variability of treatment success. Level of evidence 1; randomized controlled trial.