1. Managing Candidemia JEANNE FORRESTER, PHARMD, BCPS PGY2 INFECTIOUS DISEASES PHARMACY RESIDENT MEDICAL UNIVERSITY OF SOUTH CAROLINA

2. Objectives Identify risk factors for candidemia Describe appropriate pharmacologic management for patients with candidemia

3. Candida species Candida are yeast (fungi) found throughout the environment Also commonly isolated from the GI tract, sputum, female genital tract, and urine (especially catheterized patients) However, rarely considered contaminant when isolated from sterile site Edwards JE. Candida species. In: Mandell, Douglas, and Bennett’s Prinicples and Practice of Infectious Diseases, 8 th ed.

4. Candidemia Candidemia refers to the presence of Candida in blood ◦One of the most common causes of healthcare-associated bloodstream infections Symptoms may range fever to sepsis Mortality: 10 to 47% Antifungal therapy should be initiated as soon as possible after positive culture Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1.

5. Risk Factors for Candidemia Broad-Spectrum Antibiotics Central Venous Catheters Parenteral Nutrition Renal Replacement Therapy NeutropeniaImmunosuppression Edwards JE. Candida species. In: Mandell, Douglas, and Bennett’s Prinicples and Practice of Infectious Diseases, 8 th ed.

6. Treatment of Candidemia Echinocandin Non- Neutropenic: fluconazole Neutropenic: liposomal amphotericin B First-Line: Alternatives: Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1.

7. Antifungal Mechanisms of Action Katzung BG, et al. Basic & Clinical Pharmacology, 11 th edition.

8. Echinocandins First-line therapy for candidemic patients per 2016 IDSA Candidiasis Guidelines Specific agents ◦Caspofungin: 70 mg x 1, then 50 mg daily ◦Micafungin: 100 mg daily ◦Anidulafungin: 200 mg x 1, then 100 mg daily Poor penetration into CNS, eye, and urinary tract Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1. Lexi-Comp Online.

9. Fluconazole Azole susceptibility should be performed on Candida blood isolates Transition to fluconazole (IV or PO) from echinocandin if susceptible and clinically stable ◦Dosing: 800 mg (12 mg/kg) load followed by 400 mg (6 mg/kg) daily ◦For C. glabrata, 800 mg (12 mg/kg) daily preferred Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1. Lexi-Comp Online.

10. Amphotericin B Lipid formulation ◦↑Cost ↓Toxicity Dosing of liposomal amphotericin B ◦3-5 mg/kg IV daily Adverse effects ◦Nephrotoxicity, electrolyte wasting, infusion reaction ◦“Salt loading” to prevent nephrotoxicity ◦Pre-treatment if infusion reaction occurs Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1. Lexi-Comp Online. Image: ambisome.com

11. Non-Pharmacologic Management Blood cultures should be done at least every other day until clear ◦Duration of therapy: 2 weeks from first negative blood culture if no complications ◦Neutropenic patients: treat until symptoms and neutropenia have resolved (minimum of 2 weeks after clearance of Candida) Remove central lines if possible Non-neutropenic patients should have dilated ophthalmological exam within the first-week of diagnosis ◦Neutropenic patients: should be done during the first week of recovery from neutropenia Pappas PG, et al. Clin Infect Dis. 2016;62(4):e1.

12. Conclusions Candidemia is a common healthcare-associated infection Prompt treatment with appropriate antifungal therapy, initially an echinocandin in most cases, is vital to clinical success

13. Managing Candidemia JEANNE FORRESTER, PHARMD, BCPS PGY2 INFECTIOUS DISEASES PHARMACY RESIDENT MEDICAL UNIVERSITY OF SOUTH CAROLINA