By Philip R. Fischer, MD, DTM&H
Synopsis: Some patients with acute uncomplicated appendicitis do well with initial antibiotic treatment and do not require surgical appendectomy. However, as with adults, approximately one-third of antibiotic-treated children eventually will require surgical removal of the appendix despite the initial short-term success of medical management.
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.
Acute appendicitis is common, affecting 7% to 8% of people. Surgical appendectomy has been the standard treatment since it first was described in the 1880s. Now, laparoscopic appendectomy has less risk than open removal of the inflamed appendix, but the associated general anesthesia carries some risk. Treatment of acute uncomplicated (that is, non-perforated) appendicitis with antibiotics without surgery has been successful for many patients. Comparing antibiotics with surgical treatment in adults, the quality of life during the initial 30 days is similar; however, failure rates with antibiotics leave approximately 30% of antibiotic-treated patients requiring surgical intervention within the following year anyway. Pediatric studies have been small and less conclusive.
Thus, St Peter and colleagues undertook a multicentered, international, randomized, non-blinded study of antibiotics vs. surgery for acute uncomplicated appendicitis in children aged 5-16 years. From 2016 through 2021, 936 children were studied, and one-year follow-up data were available from 846 of them. Children received care at 11 different children’s hospitals in Canada, Finland, Singapore, Sweden, and the United States.
Antibiotic-treated children received initial intravenous antibiotic therapy according to each hospital’s standard treatment, along with oral clear liquids advancing to a regular diet as tolerated. Children remained hospitalized for at least 12 hours and, if not recovering adequately after 24 hours of treatment, either were followed for longer as inpatients or sent for surgical appendectomy. Home treatment consisted of 10 days of either amoxicillin-clavulanic acid or ciprofloxacin with metronidazole.
Surgically treated children similarly received intravenous fluids and initial antibiotic treatment. Surgery was scheduled for the next available time. If the appendix was not perforated, ongoing antimicrobial treatment was not provided.
The primary outcome was treatment failure, defined as requiring surgical care for appendicitis within the subsequent 12 months in those treated only with antibiotics and as either having a normal appendix on operation or having a surgical complication requiring general anesthesia within the following year for those treated surgically.
Treatment failure was seen in 7% of children undergoing appendectomy and in 34% of those receiving antibiotic treatment. Among the antibiotic-treated children, 16% required surgery during the initial hospitalization, and 18% required re-hospitalization for appendectomy during the following 12 months. Since the a priori definition of a significant difference (suggesting inferiority of one treatment as compared to the other) had been set at 20%, the study showed that medical therapy was inferior to surgical intervention.
In the surgery group, 27 of the 28 treatment “failures” had been because of negative/normal findings on histopathological examination of the appendix. Similarly, 8% of the children in the medical group who ended up undergoing surgery also had normal appendices. Six percent of children assigned to surgical care had appendiceal histopathology suggesting perforation; 35% of children who failed initial antibiotic treatment had evidence of perforation when undergoing operation.
The median duration of hospital stay was one day with surgery and 1.25 days with medical treatment. Children in the antibiotic-treated group returned to school and normal activity more quickly than did those who underwent surgery (two days vs. three days).
At the 12-month follow-up, similar satisfaction rates were found with medical and surgical treatment. Those who were dissatisfied in the medical group had concerns about the ongoing risk of recurrence; those who were dissatisfied in the surgery group were sorry they had not avoided surgery.
The authors concluded that even though antibiotic treatment, as compared to surgical treatment, prompted children to return to school more quickly, medical treatment still was inferior to surgery in preventing treatment failures.
Commentary
Acute appendicitis is a problem around the world.1 In children, particularly, appendicitis is challenging since atypical presentations often make the diagnosis difficult, and perforation is more common than in adults.1,2 Using publicly available data from the Global Burden of Disease dataset, it was estimated that in 2021 there were approximately 2.2 million cases of appendicitis in children around the world, amounting to approximately 110 children with appendicitis that year per 100,000 children alive that year and representing 13% of all cases of appendicitis.1
However, the incidence of appendicitis varies markedly between different regions of the world, with much higher incidences in more highly resourced regions; the incidence of childhood appendicitis is more than five times higher in the United States than in sub-Saharan Africa.1 Over time, the incidence of appendicitis is rising each year in highly resourced areas.1 Dietary (especially higher fiber content and less-processed foods) and microbiome differences are factors postulated to relate to the varying geographical incidence rates of appendicitis.
In a meta-analysis including six randomized controlled trials of 2,101 adults receiving surgical care or antibiotics for acute appendicitis, medical treatment was deemed safe and was effective in avoiding appendectomy in two-thirds of the patients within the following year.3 Patients with appendicoliths were more likely to require surgery despite initial antimicrobial management.3 Is management of appendicitis with antibiotics alone adequate for adults? Not if we agree with St Peter and colleagues that requiring surgery within a year of having acute appendicitis represents treatment failure. However, some experts consider that appendectomy following initial antibiotic management is a normal part of the continuum of care and that avoiding surgical intervention in two-thirds of patients demonstrates the success of antibiotic-only initial care of acute appendicitis.3
In an editorial accompanying St Peter’s paper, it is stated that these new data seem to resolve the situation for high-resource settings: The “failure” to prevent surgery in more than one-third of patients shows that antibiotic-only treatment is inferior to immediate operative care.4 However, it is postulated, antibiotic-only treatment might be a better initial option in settings were safe operative care is not readily available and might allow the patient to safely wait until excellent surgical care is feasible.4
Philip R. Fischer, MD, DTM&H, is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
References
- He R, Lai J, Jiang O, Li J. The incidence and temporal trend of appendicitis in children: An analysis from the Global Burden of Disease Study 2021. J Gastrointest Surg 2025;29(2):101935.
- Srinivas S, Svetanoff WJ, Kalsotra S, et al. Missed opportunity for initial diagnosis in children with complex appendicitis. Pediatr Emerg Care 2024; Dec 30. doi: 10.1097/PEC.0000000000003326. [Online ahead of print].
- Scheijmans JCG, Haijanen J, Flum DR, et al. Antibiotic treatment versus appendicectomy for acute appendicitis in adults: An individual patient data meta-analysis. Lancet Gastroenterol Hepatol 2025; Jan 16:S2468-1253(24)00349-2. doi: 10.1016/S2468-1253(24)00349-2. [Online ahead of print].
- Farmer DL. Antibiotics alone versus appendicectomy for uncomplicated appendicitis in children. Lancet 2025;405(10474):176-178.
Some patients with acute uncomplicated appendicitis do well with initial antibiotic treatment and do not require surgical appendectomy. However, as with adults, approximately one-third of antibiotic-treated children eventually will require surgical removal of the appendix despite the initial short-term success of medical management.
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