Academic Day Seminar – Anti-fungals

I can’t believe it’s our last resident-led ADS. Julianna and Rob did a great job facilitating the session! They provided many clinical pearls and an excellent overview on anti-fungals!

My notes can be found here: Antifungal 2017 ADS Notes

Important tidbits to keep in mind when approaching anti-fungal infections:

  • Amphotericin B
    • Achieves high levels in kidney, primarily stored in kidney and slowly released (= long terminal half-life ~ 15ds) –> potential for renal toxicity (hypoMg, hypoK, and eventually renal tubular acidosis)
    • Liposomal Amphotericin B – ↓ nephrotoxicity, ↓ incidence of infusion reactions
      • At VGH and most other BC sites…tend to use liposomal right off the bat due to concerns with nephrotoxicity, regardless of baseline renal function
      • Deoxycholate has poor CNS penetration, Liposomal may have better CNS penetration and would be the alternate formulation in CNS aspergillosis
  • Flucytosine
    • *SAP* Indication for cryptococcal meningitis in combination with Amphotericin B
    • Possibly de-aminated to 5-FU (might be cause of bone marrow suppression and GI intolerance)..also causes hepatic suppression
  • Voriconazole – Candida, Aspergillus
    • Non-linear kinetics – half-life ~6 hrs (VARIABLE)
    • Hepatically metabolized by CYP2C9, 2C19 and 3A4
    • + Inhibits the above enzymes 2C9, 2C19 and 3A4
  • Itraconazole – role is limited due to moderate F, poor distribution…but has a broad spectrum of activity and may serve as salvage therapy for patients who have not recovered on other azoles
    • Posaconazole – “improved version of itraconazole” – and roles includeProphylaxis of invasive fungal infections in neutropenic patients, Refractory invasive fungal infections, Zygomycetes
  • Activity – triazoles (fungistatic to yeasts, fungicidal to aspergillosis); echinocandins (fungistatic to aspergillosis, fungicidal to candida)
  • Echinocandins – all highly protein bound, distributes well into tissues but has NO CSF penetration
    • large molecules = difficult to cross through CNS = won’t use for CNS infections
  • Therapeutic drug monitoring for flucytosine, voriconazole, posaconazole
    • Voriconazole + posaconazole levels sent to SPH (done once weekly)
  •  *remember to renally adjust* – Flucytosine, Fluconazole
    • Risk of toxicity via accumulation of IV vehicle in voriconazole in renal impairment – if appropriate, change to PO voriconazole
    • ?adjusting for renal dysfunction for amphotericin B – complicated
  • Do not consider candida as a contaminant in BCx (even if 1/4 or 2/4 +, would still treat)
  • SAP drugs – Isavuconazole, Flucytosine