Fungal Causes for Gastric Perforation in Premature Babies
Candida albicans is the primary fungal pathogen causing gastric and intestinal perforation in premature infants, followed by Candida parapsilosis, and should be treated immediately with echinocandins (caspofungin, micafungin, or anidulafungin) as first-line therapy. 1, 2
Primary Fungal Pathogens
The fungal microbiome of preterm infants is dominated by Candida species in the first weeks to months of life, with the following hierarchy of causative organisms: 1
- Candida albicans: Most frequent cause of invasive candidiasis and intestinal perforation in neonates 1, 3
- Candida parapsilosis: Second most common species 1
- Candida tropicalis: Less common but documented 1
- Other Candida species: Rare causes 1
Important distinction: Unlike adults, Candida glabrata and Candida krusei are infrequent causes in the NICU setting 1
Clinical Presentation and Pathophysiology
Invasive Candida causes intestinal perforation through vascular invasion, leading to bowel ischemia, necrosis, and perforation: 4
- Fungi can be found intravascularly on histology, causing vascular occlusion 4
- Presents with black, discolored bowel surface that may be mistaken for necrotizing enterocolitis (NEC) 5
- The bowel discoloration is often a thick, black, serosal exudate of fungal elements rather than true necrosis 5
- Can occur at any site: lesser curvature, greater curvature, anterior/posterior wall, or esophageal junction 6
Risk Factors for Fungal Perforation
**Extremely premature infants (<1000g birth weight) have the highest risk** (>10% incidence of invasive candidiasis): 1
- Birth weight <750g: >10% incidence 1
- Birth weight 750-1000g: 5-10% incidence 1
- Gestational age 23-24 weeks: 10-20% incidence 1
- Central venous catheterization 1
- Abdominal surgery 1
- Necrotizing enterocolitis 1
- Broad-spectrum antibiotics (third-generation cephalosporins, carbapenems) 1
- Parenteral nutrition 1
- Antacid use 1
- Endotracheal intubation 1
Treatment Algorithm
First-Line Antifungal Therapy
Echinocandins are the preferred initial treatment for invasive candidiasis with perforation in critically ill neonates: 2
- Caspofungin: Dosing based on body surface area (50 mg/m² maintenance dose after loading) 7
- Micafungin: Preferred if Candida auris colonization or high local prevalence 3
- Anidulafungin: Alternative echinocandin 2
Alternative Regimens
Fluconazole 400 mg (6 mg/kg) daily may be used ONLY if: 2
- No recent azole exposure
- Not colonized with azole-resistant Candida species
- Patient is NOT critically ill
Amphotericin B lipid formulation (3-5 mg/kg daily) reserved for: 2, 8
- Intolerance to other antifungal agents
- Higher toxicity risk, requires intensive renal function monitoring 8
Duration and Monitoring
- Continue treatment for at least 2-3 weeks after resolution of symptoms and clearance of infection 2
- Obtain follow-up cultures to ensure clearance 2
- Monitor renal function, liver function, serum electrolytes (particularly magnesium and potassium), blood counts, and hemoglobin 8
Surgical Management
Source control with drainage and/or debridement is essential for successful treatment: 2
- Inadequate source control is associated with treatment failure regardless of appropriate antifungal therapy 2
- Surgical intervention necessary for necrotic tissue removal or abscess drainage 2
- Critical pitfall: Black, discolored bowel may NOT be necrotic—it can be fungal exudate on otherwise healthy bowel 5
- Avoid declaring bowel "incompatible with survival" based solely on appearance 5
Diagnostic Approach
Diagnosis requires appropriate cultures and histopathology: 2
- Direct visualization through endoscopy with biopsy for histopathology and culture 2
- Cultures of infected peritoneal fluid 2
- Blood cultures (pre- and post-mortem) 4
- Look for intravascular fungi on histology as pathognomonic finding 4
Critical Pitfalls to Avoid
- Delaying antifungal therapy in suspected intra-abdominal fungal infections significantly increases mortality 2
- Using fluconazole empirically in critically ill patients without knowing Candida species susceptibility leads to treatment failure 2
- Premature discontinuation of therapy before complete resolution 2
- Failure to consider fungal infection in patients with persistent symptoms despite antibacterial therapy 2
- Mistaking fungal exudate for bowel necrosis and declaring condition incompatible with survival 5
- Inadequate source control is a major cause of treatment failure 2
Prophylaxis Considerations
For prevention in high-risk infants (<1000g or <1500g if local incidence >2%): 3