The Role of Empiric Antifungal Therapy in Patients With Perforated Peptic Ulcer: An Updated Systematic Review and Meta-Analysis

Fungal growth is common in intraoperative cultures of patients with perforated peptic ulcer (PPU) leading to the common use of empiric antifungal therapy, with current evidence not clearly supporting this practice. The goal of this updated systematic review and meta-analysis was to synthesize the effect of empiric antifungals in patients with PPU. Eligible studies were identified through a comprehensive literature search in the MEDLINE (PubMed) and EMBASE databases, following the PRISMA 2020 statement. A total of eight studies were identified reporting on 1802 patients. The population consisted of 67.3% males (n = 121/1802), with a mean age of 59.1 +/- 13.2 years. Most of the population underwent surgery (n = 1763/1802, 97.8%), which was most frequently omental patch (n = 1169/1411, 82.8%), while 12.8% (n = 140/1096) underwent laparoscopic repair. Intraoperative cultures were obtained in 73.7% (n = 1262/1713); blood cultures were obtained in 54.5% (n = 467/857) and were positive for fungus in 44.1% (n = 558/1262) and in 5.6% (n = 26/467), respectively. Empiric antifungal treatment was administered in 19.6% (n = 353/1802). The most common agent was fluconazole reported in 6 studies. At a mean follow-up of 34.4 +/- 9.9 days, 191/1787 (10.7%) patients died. Patients with fungus-positive intraoperative cultures had significantly increased odds of having diabetes mellitus (OR: 1.55; 95% CI: 1.05-2.30), history of malignancy (OR: 2.80; 95% CI: 1.22-6.45), being on steroids (OR: 5.13; 95% CI: 1.37-19.3), and increased mortality (OR: 2.49; 95% CI: 1.67-3.70). Empiric antifungal therapy did not significantly decrease the odds for death (OR: 1.45; 95% CI: 0.33-6.41). The presence of fungi in the peritoneal fluid is associated with increased risk of death, that is not affected by administration of empiric antifungal therapy.