Are antifungal agents indicated in the management of gastric perforation?

Antifungal Therapy in Gastric Perforation

Routine empiric antifungal therapy is NOT indicated for gastric perforations in non-critically ill, immunocompetent patients and does not improve mortality or morbidity outcomes.

Primary Recommendation

Do not routinely administer empiric antifungal agents in patients with gastric perforation. 1 The most recent and highest quality evidence—including the 2022 World Journal of Emergency Surgery guidelines and a 2025 multi-center prospective cohort study—demonstrates no benefit in organ-space surgical site infections, mortality, or hospital length of stay when empiric antifungals are added to standard broad-spectrum antibiotics. 1, 2

Evidence Base

The recommendation against routine antifungal use is supported by:

• 2025 multi-center prospective study (N=192): No difference in organ-space SSI rates between patients receiving empiric antifungals versus standard antibiotics alone (17.5% vs. 17.5%, p=0.99), even after propensity score matching. 2

• Multiple retrospective analyses: A 133-patient study of perforated peptic ulcer with Candida species isolated from peritoneal fluid showed no survival benefit from antifungal therapy. 1

• Randomized trial data: One multicenter RCT evaluating intra-abdominal perforations (including perforated peptic ulcer) found no efficacy of antifungal agents in improving outcomes. 1, 3

High-Risk Patients Who MAY Benefit from Antifungals

Reserve antifungal therapy ONLY for patients with the following high-risk features: 1, 4

• Critically ill/septic shock requiring ICU care and vasopressors
• Severely immunocompromised (transplant recipients, chemotherapy, HIV/AIDS)
• Advanced age (>64 years) with multiple comorbidities 1
• Healthcare-acquired infections (recent hospitalization, prior antibiotics)
• Prolonged ICU stay (>7 days)
• Unresolved intra-abdominal infection despite adequate source control beyond 7 days 1, 4

Clinical Context: Why Fungal Isolates Don't Always Matter

While fungal isolates from peritoneal fluid in gastric perforation are common and associated with worse outcomes in observational studies, this represents a marker of disease severity rather than a causative pathogen requiring treatment. 1 Key points:

• Fungal growth is a predictor of critical illness but not an independent predictor of adverse perioperative outcomes. 1
• Patients with positive fungal cultures who are critically ill have poor outcomes regardless of antifungal therapy—the underlying shock and APACHE score >20 are the true mortality drivers. 1
• Even in critically ill patients with IAI involving fungal organisms, shorter antimicrobial courses showed no difference in treatment failure rates, suggesting fungi may not independently require longer therapy. 1

Standard Antimicrobial Approach

Focus on adequate source control and appropriate antibacterial coverage: 1

• Collect peritoneal fluid samples for bacterial AND fungal cultures before starting antibiotics 1
• Start broad-spectrum antibiotics immediately (piperacillin-tazobactam 4.5g IV q6h or equivalent) covering gram-positive, gram-negative, and anaerobic bacteria 1
• Duration: 3-5 days or until inflammatory markers normalize after adequate source control 1
• De-escalate based on culture results and clinical response 1

Common Pitfalls to Avoid

• Over-treating based on positive fungal cultures alone: Candida isolation does not automatically warrant antifungal therapy in immunocompetent patients. 1
• Prolonging antibiotics unnecessarily: Even with fungal organisms present, shorter courses (3-4 days) are effective with adequate source control. 1
• Ignoring the real problem: Inadequate surgical source control is the primary issue—no amount of antifungal therapy compensates for poor surgical management. 1
• Using antifungals as a "safety net": The 2025 prospective study specifically cautions against routine empiric use given lack of benefit and potential for resistance. 2

Exception: Recurrent Perforations

One notable exception exists for recurrent gastrointestinal perforations or anastomotic leakages, where a 1999 RCT showed fluconazole prophylaxis (400mg IV daily) reduced intra-abdominal candidiasis from 35% to 4% (p=0.02). 5 However, this specific high-risk surgical scenario differs from initial gastric perforation presentation.