Can fungal infections cause sepsis?

Can Fungal Infections Cause Sepsis?

Yes, fungal infections absolutely can cause sepsis and septic shock, though they account for less than 10% of sepsis cases compared to bacterial causes. Candida species are the predominant fungal pathogens responsible for sepsis in critically ill patients, representing the fourth most common bloodstream isolate in the United States and accounting for approximately 5% of all severe sepsis and septic shock cases 1, 2.

Epidemiology and Clinical Significance

• Fungal sepsis, particularly from Candida species, occurs in 10-15% of healthcare-associated infections and represents about one-third of all candidemia episodes in intensive care settings 2.
• Fungal sepsis carries substantial mortality risk, with attributable mortality rates ranging from 21.7% to 38% in documented cases 1.
• While bacteria cause more than 90% of sepsis cases, fungi—particularly Candida species—are increasingly recognized as important causative organisms 1.

High-Risk Patient Populations

Immunocompromised patients face dramatically elevated risk for fungal sepsis. The Surviving Sepsis Campaign identifies specific risk factors that should trigger consideration of empirical antifungal coverage 1, 3:

Primary Risk Factors:

• Immunocompromised status: neutropenia, active chemotherapy, solid organ or bone marrow transplant, diabetes mellitus, chronic liver failure, chronic renal failure 1, 3
• Prolonged invasive devices: central venous catheters, hemodialysis catheters 1, 3
• Prolonged broad-spectrum antibiotic administration and prolonged hospital/ICU admission 1, 3
• Recent major surgery, particularly abdominal procedures, and necrotizing pancreatitis 1, 3
• Total parenteral nutrition 1, 3
• Multisite Candida colonization and recent fungal infection 1, 3

Special Populations at Extreme Risk:

• AIDS patients: Catheter manipulation can lead to fungal contamination resulting in fungemia due to impaired clearance of fungal elements, and fungemia can occur during antifungal therapy for oral or esophageal candidiasis (which affects 70-100% of AIDS patients) 1.
• Oncology patients: Over 60% of catheter-related sepsis occurs during neutropenia (absolute count <500/mm³), with bone marrow transplant recipients particularly susceptible to fungal infections during and after conditioning therapy 1.

Pathophysiology and Routes of Infection

• Invasive Candida infections begin with colonization of the gastrointestinal tract or skin 1.
• Suppression of indigenous intestinal bacteria allows Candida overgrowth and mucosal adhesion, followed by translocation across small bowel mucosa once critical colonization levels are reached 1.
• In ICU settings, physiological stresses that impair mucosal integrity facilitate translocation at much lower colonization concentrations 1.
• Skin colonization provides a portal for invasive disease when integrity is breached by intravascular catheters or burns 1.

Clinical Recognition and Diagnostic Challenges

Clinical features of fungal sepsis are largely nonspecific, ranging from unexplained fever to full septic shock 1. This diagnostic difficulty contributes to delayed treatment and increased mortality 4, 2.

Specific Clinical Manifestations (Rare but Diagnostic):

• Candidal chorioretinitis: occurs in fewer than 15% of candidemic patients but when present is an absolute indication for antifungal therapy 1
• Skin lesions and septic arthritis: occur even less frequently 1

Diagnostic Approach:

• Blood cultures should be obtained before initiating antifungals when possible, though conventional culture methods are suboptimal 3, 2.
• In patients colonized with Candida at two or more sites who develop sepsis, blood cultures with lysis centrifugation (if available) should be performed 1.
• Isolates from sterile sites require speciation and sensitivity testing 1.

Empirical Antifungal Therapy Algorithm

When two or more Candida risk factors are present in a patient with septic shock, start an echinocandin empirically 3.

First-Line Therapy for Severe Illness/Septic Shock:

Echinocandins (anidulafungin, micafungin, or caspofungin) are the preferred agents for patients with 1, 3:

• Severe illness or septic shock
• Recent antifungal exposure
• Suspected Candida glabrata or Candida krusei infection based on prior culture data

Alternative Therapy for Stable Patients:

• Triazoles (e.g., fluconazole) are acceptable only in hemodynamically stable, less critically ill patients who have not had previous triazole exposure and are not colonized with azole-resistant species 1, 3.

Second-Line Options:

• Liposomal amphotericin B formulations are reasonable alternatives for patients with echinocandin intolerance or toxicity 1.

Mold Coverage:

• Do not provide empirical mold coverage in standard septic shock protocols 3.
• Mold-active therapy (voriconazole, posaconazole, or liposomal amphotericin B) should only be initiated when specific clinical features suggest invasive mold infection 3.

Critical Management Principles

Daily Reassessment:

• Reassess daily to de-escalate or discontinue antifungals if cultures remain negative and clinical improvement occurs 3.
• Obtain cultures before starting antifungals whenever possible 3.

Source Control:

• Central venous catheter removal is strongly recommended when candidemia is documented, as this improves outcomes 5.
• Source control for infected devices must be considered 4.

Monitoring:

• Serial blood cultures should be obtained after 48-72 hours of antifungal therapy and then every other day to establish clearance 5.
• Perform dilated ophthalmologic examination within the first week of therapy in non-neutropenic patients to detect endophthalmitis 5.
• For neutropenic patients, delay ophthalmologic examination until the first week after recovery from neutropenia 5.

Common Pitfalls to Avoid

• Do not delay empirical antifungal therapy in high-risk patients with septic shock while awaiting culture results, as delay in appropriate therapy increases mortality 4, 2.
• Do not assume isolated infection without ruling out disseminated disease, particularly in immunocompromised patients where hematogenous spread is common 5.
• Do not overlook candiduria in neutropenic patients with persistent unexplained fever, as this may represent disseminated candidiasis rather than simple colonization 5.
• Do not fail to remove central venous catheters when candidemia is documented 5.