A Single Daily Dose of Metronidazole is Non‐Inferior to Three Daily Doses in Children With Perforated Appendicitis: A Real‐World Randomized Trial

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).