The lack of comprehensive studies on microbiologic data and susceptibility patterns explained the lack of a uniform treatment protocol. A retrospective, monocentric study on antibiotic susceptibility was conducted on 1,258 pediatric patients with appendectomies between 2012 and 2020. Regression analysis was used to identify predictors for longer length of stay (LOS), comorbidities, and objective criteria for broad-spectrum antibiotic regimens. The effectiveness of several antibiotic regimens against discovered bacterial susceptibility data was simulated. Elevated preoperative C-reactive protein levels, high intraoperative severity gradings, and poor initial antibiotic treatment were the most important indicators of longer LOS and a higher likelihood of infection complications. According to the findings, a simple antibiotic treatment of cefuroxime-metronidazole (C-M) or ampicillin-sulbactam (AS) was sufficient in around 85% of all patients; both alternatives were similarly effective. C-M and AS have a 31% and 32% chance of causing resistance in severe appendicitis, respectively. The rate of bacterial resistance drops to 12% for piperacillin-tazobactam and C-M-tobramycin. Treatment with AS-tobramycin reduced resistance to just 8%. Patients with a high intraoperative severity grading. In severe intraabdominal findings, evidence suggested that an insufficient antibiotic regimen was linked to a longer LOS and a higher likelihood of infection complications, suggesting the expansion of a simple antibiotic prescription. A basic antibiotic treatment with AS was indicated in all other situations.