UMEM Educational Pearls

Which septic patients should receive empiric antifungal therapy?

Patients with fungemia only make up about 5% of patients presenting with septic shock, but invasive fungal infections are associated with increased hospital mortality (40-50%), prolonged ICU and hospital length of stay, and increased costs of care.¹

The EMPIRICUS trial showed no mortality benefit to empiric antifungals for all, even patients with candidal colonization and recent exposure to antibiotics.²

Bottom Line

Therapy should always be tailored to the specific patient, but providers should strongly consider admininistering empiric echinocandin (micafungin, caspofungin) over fluconazole in patients with severe sepsis/septic shock and:

• Immunosuppression (chronic steroids, neutropenia, organ transplant)
• Prolonged central venous catheters
• TPN
• Yeast colonization
• Severe pancreatitis
• Recent abdominal surgeries or procedures (perforation repairs, resections, etc.) or concern for impaired gut integrity

*Especially consider addition of antifungal in patients who do not show improvements after initial management with IVF and broad spectrum antibiotics in the ED.*

Additional Information

Which septic patients should receive empiric antifungal therapy?

Patients with fungemia only make up about 5% of patients presenting with septic shock, but invasive fungal infections are associated with increased hospital mortality (40-50%), prolonged ICU and hospital length of stay, and increased costs of care.¹

The EMPIRICUS trial showed no mortality benefit to empiric antifungals for all, even patients with candidal colonization and recent exposure to antibiotics. (It demonstrated decreased rate of new invasive fungal infection, but did not increase survival).²

Risk factors for invasive fungal infections include:³

• Immunosuppresion
• Prolonged central venous catheter
• Total parenteral nutrition (TPN)
• Renal failure/dialysis
• Recent broad spectrum antibiotics
• Yeast colonization (as noted by previous urine or bronch cultures)
• Recent abdominal surgery (especially with disruption of intestinal wall)
• Severe pancreatitis

Which antifungal agent should we use?

Although older studies have not shown benefits to echinocandin, such as micafungin, over fluconazole as initial empiric antifungal therapy,^4,5 a recent study by Garnacho-Montero et al. demonstrated improved 30 and 90-day mortality in patients with candidemia whose initial antibiotic was an echinocandin rather than fluconazole.⁶  

References

1. Xie GH, Xiang-Ming F, Qiang F, et al. Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients.
2. Timsit JF, Azoulay E, Schwebel C, et al. Empirical micafungin treatment and survival without invavsive fungal infection in adults with ICU-aquired sepsis, candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial. JAMA 2016;316(15): 1555-64.
3. Muskett H, Shahin J, Eyres G, et al. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review. Crit Care 2011;15(6): R287.
4. Murri R, Scoppettuolo G, Ventura G, et al. Initial antifungal strategy does not correlate with mortality in patients with candidemia. Eur J Clin Microbiol Infect Dis 2016; 35:187–93.
5. López-Cortés LE, Almirante B, Cuenca-Estrella M, et al. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: A propensity score-derived analysis of a population-based, multicentre prospective cohort. Clin Microbiol Infect 2016; 22:733.e1–733.e8
6. Garnacho-Montero J, Díaz-Martín A, Cantó-Bulnes L, et al. Initial antifungal strategy reduces mortality in critically ill patients with candidemia: a propensity score-adjusted analysis of a multicenter study.  Crit Care Med 2018;46(3): 384-93.