Antibiotics vs Surgery for Uncomplicated Pediatric Appendicitis

Source: St Peter SD, Noel-MacDonnell JR, Hall NJ, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial. Lancet. 2025;405(10474):233-240; doi: 10.1016/S0140-6736(24)02420-6.Investigators from multiple institutions conducted a randomized non-inferiority trial to compare the effectiveness of antibiotic treatment or appendectomy for children with uncomplicated appendicitis. Study participants were children 5–16 years old with a clinical diagnosis of uncomplicated appendicitis who were treated at 11 children’s hospitals in Canada, the US, Finland, Sweden, and Singapore. At enrollment, participants were assigned randomly to the antibiotic or appendectomy group. Those randomized to antibiotics received at least 12 hours of intravenous antibiotics, with the specific medication based on standard local practice. If a child failed to improve in 1–2 days, they underwent appendectomy. Conversely, if the patient improved symptomatically, they were discharged on oral antibiotics for 10 days. Patients randomized to the appendectomy group underwent immediate surgery. The primary outcome was treatment failure, defined as need for appendectomy within 1 year for those in the antibiotic group, and a negative appendectomy or complication requiring general anesthesia within 1 year for children in the appendectomy group. Prior to starting the study, it was determined that antibiotic treatment would be non-inferior to appendectomy if the upper bound of the 90% confidence interval (CI) of the difference in the treatment failure rates was <20%. Secondary outcomes included length of stay (LOS) of the initial hospital stay and all hospital stays for appendicitis within 1 year of diagnosis.A total of 477 children were randomized to the antibiotics group and 459 to the appendectomy group. The median ages of children in the 2 treatment groups were 10.9 and 10.6 years, respectively. At the 1-year follow-up, data on the primary outcome were available for 846 (90%) patients, including 452 of those randomized to antibiotic treatment and 394 in the appendectomy group. Treatment failure occurred in 153 (34%) of those in the antibiotic group and 28 (7%) of participants assigned to appendectomy. The difference in treatment failure rate was 26.7% (90% CI, 22.4, 30.9), thus the non-inferiority criterion was not met. Among children with treatment failures in the antibiotic group, 72 underwent appendectomy at the initial hospitalization and 81 after discharge. Among those in the appendectomy group with treatment failure, 27 had a normal appendix at surgery and 1 underwent general anesthesia for another procedure. Overall, 25 (35%) of the 72 patients in the antibiotic group who failed treatment and required an appendectomy during the initial hospitalization had a perforated appendix, compared to 28 (6%) of those treated with immediate appendectomy. LOS was significantly longer for those in the antibiotic group than in participants randomized to appendectomy, during both the initial hospitalization (median, 1.25 and 1 days, respectively; P <0.0001) and the entire 1-year study period (median, 1.6 and 1.0 days, respectively; P <0.0001).The authors conclude that the effectiveness of treatment of uncomplicated appendicitis with antibiotics was inferior to treatment with immediate appendectomy.Dr Goyal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Appendicitis, estimated to affect up to 8% of the general population, is the most common pediatric surgical emergency in children.1 Within the past few years, there has been growing interest among clinicians and families in treating uncomplicated appendicitis without surgery, with a documented increase in management with antibiotics alone. (See AAP Grand Rounds. 2022;48[3]:30.)2 However, there has been a lack of data from prospective, randomized studies to support this practice shift and inform shared decision-making.The current trial addresses this research gap, with almost 1,000 children in 5 countries randomized to 1 of 2 study arms of immediate appendectomy vs initial antibiotic therapy.3 The study demonstrated a treatment failure rate of 34% in the antibiotic group compared with 7% in the appendectomy group, leading investigators to conclude that antibiotic therapy is inferior to surgery for this condition. There were several strengths of this study, including the large, multinational sample and the investigation of multiple secondary outcomes, as well as a high 1-year follow-up rate. Children in the antibiotic group experienced higher rates of perforated appendix and a longer LOS on average, but they also reported fewer days to return to normal activity and fewer days of pain medication use. Furthermore, satisfaction with care at 1-year follow-up was equivalent between the 2 groups. No serious adverse outcomes or death occurred in either group.Overall, the current study findings further inform shared decision-making with families seeking to avoid surgery.4 As almost two-thirds of patients with antibiotics alone were successfully treated, the data from this trial also may support future research on how to better risk-stratify patients for this treatment option.Antibiotic treatment alone for uncomplicated pediatric appendicitis is inferior to appendectomy, with approximately one-third of children experiencing treatment failure.