Background: No consensus has been reached regarding the most advantageous duration of antibiotic prophylaxis to decrease post-operative infection complications of appendectomy for acute complex appendicitis. This study aimed to determine the efficacy of short-term antibiotic treatment on post-operative complications in children with complex appendicitis. Methods: A multi-center, parallel group, randomized study was conducted in patients younger than 14 years of age with complicated appendicitis at three hospitals in China. The qualified patients were randomized prospectively to either the restrictive 72-hour short-term antibiotic strategy or the standard antibiotic usage. A comparison of the complications within 24 months, including infectious complications and long-term results, were conducted between the two groups. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR), number ChiCTR1900023941 and is complete. Results: A shorter duration of antibiotic treatment had no effect on intestinal function recovery, antibiotic-associated diarrhea, and health-care-associated Clostridium difficile infection and infectious complication, including intra-abdominal abscess development (17.9% vs. 18.0%, p = 0.52). Furthermore, no substantial difference for re-admission requirement and re-operation were found between the two treatment strategies. A sizeable decrease in total duration of hospitalization (p < 0.001) and average total antibiotic duration (p < 0.001) were observed for the restrictive antibiotic strategy group. Conclusion: In complicated appendicitis, the restrictive antibiotic usage was equivalent to standard antibiotic usage in terms of short- and long-term outcomes, but with shorter hospital stays and fewer antibiotic agents.

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