Invasive Fungal Infection

Fluconazole: IV/PO

→ only azole that must be dose reduced for poor renal function

• Covers: 

  • Candida spp. 

Does not cover: C. krusei (intrinsically resistant)

• Strong CYP interactions…

ADDITIVE QTc Prolongation and Increased Liver Function Tests

Voriconazole

requires LIVER dose adjustments

• Covers: 

  • Aspergilus ***

  • Candida

  • Fusarium

Cyclodextrin Toxicity: Solvent for IV, do NOT use with CrCl < 50 mL/min

• Trough Monitoring 

• Non-linear pharmacokinetics - therefore small increases in dose is safer

STRONG CYP Inhibition, and ADRs of VISUAL DISTUBRANCES and QTc prolongation

Posaconazole

Preferred use: delayed release tablets and IV solution due to poor absorption and fatty meal requirement (or low pH drink)

• Saturable absorption 

• Covers

  • Active against all clinically relevant yeasts and molds

STRONG CYP3A4 Inhibitor, QTc prolongation and increased LFTs

Isavuconazole - pro drug 

→ covers most clinically relevant yeasts and molds

• Aspergilliosis and Mucormycosis treatment

• ONLY AZOLE FOR C. GLABRATA

Echinocandin Spectrum of Activity…

Caspofungin, Micafungin, Anidulafungin

• Candida spp. (YEAST>?)

• C. glabrata 

• C. krusei

DOES NOT COVER ASPERGILLIUS (MUST USE AZOLE)

Amphotericin

clinically relevant yeasts and molds, Candida spp.

• Does NOT cover - Aspergilus terreus, candida lusitaniae

ADR: renal dysfunction (acute kidney damage), and infusion reactions

Lipid formulations have shown to improve ADR but STILL LAST LINE FOR FUNGAL

Candida Spp.

Candida kruseii - intrinsic resistance to fluconazole

Candida glabrata - variable resistance to ALL azoles 

Candida parapsilosis - elevated echnicocandin MIC’s but NOT resistance 

Candidemia/Candidasis: Risk Factors…

1. Central venous catheters

2. Prolonged hospitalization 

3. Renal failure, hemodialysis 

4. TPN (parental nutrition) 

5. Transplantation,  immunosuppression

6. Surgery: abdominal surgery

(1,3)-B-D-glucan

→ detects part of fungal cell wall in Candida spp. and Aspergillus spp.

Likely a better indicator for negative predictions, due to high false positive rate

Candidema/Candiasis Treatment

1. First line = Echincocandins are first line 

   1. Clinically stable patients MAY be transitioned to Fluconazole after

      1. Step down from Echinocandin to azole therapy following 5-7 days of clinical stability 

Duration of Antifungals?

Antifungals should be continued for at least 14 days from FIRST NEGATIVE culture in candidemia