Surgical Infection Society Multi-Center Observational Study: Empiric Anti-Fungal Coverage after Non-Colonic Gastrointestinal Perforation

Abstract

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.