A Single Daily Dose of Metronidazole is Non-Inferior to Three Daily Doses in Children With Perforated Appendicitis: A Real-World Randomized Trial
In brief
Once-daily metronidazole matches three daily doses for children with perforated appendicitis
In a randomized trial of 201 children who had open surgery, once-daily metronidazole with gentamicin was non-inferior to three daily doses for infection outcomes and treatment success; no severe antibiotic-related adverse events were recorded. The simpler regimen lowered metronidazole costs by an average of $1.71 per child, but the trial did not establish whether results apply beyond this setting.
- Journal
- World journal of surgery (Q1)
- Published
- 2 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Arthur Almeida Aguiar, Maria Júlia Gonçalves de Mello, Claudia Corrêa de Araújo
- PMID
- 42973154
- DOI
- 10.1002/wjs.70622
Why clinicians should know about it
- Picked for Pediatric Surgery (paper of the day, 4 November 2026): RCT metronidazole dosing in perforated appendicitis
Abstract
OBJECTIVE: To evaluate the effectiveness and safety of a single daily dose of metronidazole compared with three daily doses, both combined with gentamicin in children with perforated appendicitis. METHODS: A real-world, randomized, non-inferiority trial was conducted with children (< 14 years old) who underwent appendectomy for perforated appendicitis from 2022 to 2023. Participants were randomized into intervention (IG) and control (CG) groups: the former received a single dose of 30 mg/kg metronidazole, whereas the latter received three daily doses of 10 mg/kg metronidazole, both also received a single daily dose of 5 mg/kg gentamicin. Primary outcomes included the rate of patients with surgical site infection (SSI), incisional SSI (I-SSI), organ/space SSI (OSI), and treatment success at study end. Secondary outcomes included adverse events and antibiotic costs. RESULTS: A total of 201 (IG = 99 and CG = 102) children were included. All participants underwent open appendectomy. The intervention was non-inferior to the control regimen for SSI (risk ratio [RR] = 0.82; 95% CI 0.54-1.24), I-SSI (RR = 0.81; 95% CI 0.55-1.19), OSI (RR = 0.82; 95% CI 0.56-1.19), and treatment success at study end (RR = 1.01; 95% CI 0.92-1.12). No severe antibiotic-related adverse events were recorded. Median metronidazole treatment duration was 6 days in the IG group and 5.5 days in the CG group (range, 1-12 days; p = 0.650), while median gentamicin duration was 6 days in both groups (range, 2-12 days; p = 0.942). The IG group showed a mean reduction of US$1.71 in metronidazole cost per patient. CONCLUSION: A single daily dose of metronidazole combined with gentamicin was non-inferior in effectiveness to the fractionated regimen in children with PA. The simplified regimen reduced metronidazole costs and may offer practical advantages in routine care. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos, number RBR-95gbvmq (https://ensaiosclinicos.gov.br/rg/RBR-95gbvmq; Registered on April 04, 2023).
Abstract as published, via PubMed.
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