A Single Daily Dose of Metronidazole is Non‐Inferior to Three Daily Doses in Children With Perforated Appendicitis: A Real‐World Randomized Trial
Arthur Almeida Aguiar, Maria Júlia Gonçalves de Mello, Claudia Corrêa de AraújoABSTRACT
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 (