Background: Empiric anti-fungals are frequently administered in patients with non-colonic gastrointestinal (GI) perforations, but there is limited evidence of their benefit. We hypothesized that empiric anti-fungals would offer no clinical benefit compared with a standard course of antimicrobial therapy. Methods: This multi-center prospective cohort study included patients ≥18 years old undergoing operative management for non-colonic GI perforations across 15 centers between August 2021 and January 2024. The primary outcome was organ-space surgical site infection (SSI). We performed propensity score matching to adjust for confounders and a backward stepwise regression model to identify predictors of an organ-space SSI. A subgroup analysis of spontaneous upper GI perforations was performed as well. Results: A total of 192 patients were included; 138 (71.88%) received empiric anti-fungal therapy, and 17.7% developed an organ-space SSI. Before matching, empiric anti-fungal use was frequent in critically ill patients although not associated with organ-space SSI. After matching, there were no differences in organ-space SSI (17.5% vs. 17.5%, p = 0.99). In multi-variable regression, American Society of Anesthesiologists physical status classification system (ASA) category 3 increased the risk of organ-space SSI (odds ratio [OR] 2.49, p = 0.04), whereas perioperative proton-pump inhibitor (PPI) use was protective (OR 0.15, p = 0.004). In the subgroup analysis (N = 150), empiric anti-fungal therapy did not reduce infection risk. Pre-operative shock increased the risk of organ-space SSI (OR 2.83, p = 0.04), whereas PPI use remained protective (OR 0.15, p = 0.01). Conclusion: Empiric anti-fungal use was not associated with reduced organ-space SSI, even after adjusting for confounders. Given the lack of benefit, we caution against the use of routine empiric anti-fungal therapy in non-colonic GI perforations.

Keywords: anti-fungal; antimicrobial; empiric antimicrobial therapy; gastrointestinal perforation; intra-abdominal infection.

背景: 经验性抗真菌治疗常用于非结肠消化道（GI）穿孔的患者，但其益处证据有限。我们假设经验性抗真菌治疗与标准抗菌疗程相比没有临床效益。方法: 这是一项多中心前瞻性队列研究，在2021年8月至2024年1月期间，纳入了在15个医疗中心接受非结肠GI穿孔手术管理的年龄≥18岁的患者。主要结局是器官部位手术部位感染（SSI）。我们采用倾向性评分匹配来调整混杂因素，并使用向后逐步回归模型识别器官部位SSI的预测因子。同时对自发性上消化道穿孔亚组进行了分析。结果: 共纳入192名患者；其中138人（71.88%）接受了经验性抗真菌治疗，17.7%的人发生器官部位SSI。在匹配前，危重患者的使用频率较高，但与器官部位SSI无关。匹配后，器官部位SSI无差异（17.5% vs. 17.5%，p = 0.99）。多变量回归分析显示，美国麻醉医师协会身体状况分类系统（ASA）类别3增加了器官部位SSI的风险（优势比[OR]2.49，p = 0.04），而术前质子泵抑制剂（PPI）的使用具有保护作用（OR 0.15，p = 0.004）。在亚组分析中（N = 150），经验性抗真菌治疗并未降低感染风险。术前休克增加了器官部位SSI的风险（OR 2.83，p = 0.04），而PPI使用仍然具有保护作用（OR 0.15，p = 0.01）。结论: 即使调整了混杂因素，经验性抗真菌治疗与减少器官部位SSI无关。鉴于缺乏益处，我们建议不要在非结肠GI穿孔中常规使用经验性抗真菌治疗。

关键词： 抗真菌；抗菌药物；经验性抗菌治疗；消化道穿孔；腹内感染。