Update on Antifungals in Critical
Care
Development of a Local Guideline
Dr Donald Inverarity
Consultant Microbiologist
NHS Lanarkshire
Disclaimer
• I’m a clinical microbiologist not primarily a
mycologist
• Not covering Neonates, Paediatrics, Solid
Organ Transplant patients or patients with
Haematological Malignancies
NHS Lanarkshire
• 3 District General Hospitals
• 3 Intensive Care Units
• 3 Different Prescribing Patterns and
Pharmacy Bills for Antifungals in ITU
Mould and Yeast
• Mould
– Fluffy or slimy
– Multicoloured or black
– Hyphae
– Not best detected using Gram Stain
Mould and Yeast
• Yeast
– Smells like baking bread or beer
– Predominantly Candida in UK
– Can be seen on Gram Stain (Gram positive,
ovoid, budding, clusters)
From Bassetti et al, Critical Care 2010 14: 244
Candida Chromogenic Agar
Candida tropicalis Candida glabrata Candida albicans
From Bassetti et al, Critical Care 2010 14: 244
“Azoles”
• Structurally have an imidazole or triazole ring
• At low concentrations may only be fungistatic
• Fluconazole and voriconazole are well absorbed orally but itraconazole is not.
• Fluconazole is eliminated in urine (mainly unchanged) and removed during haemodialysis
• Voriconazole is eliminated in urine and extensively metabolized by liver
• Itraconazole is mainly metabolized by liver and excreted in bile
Echinocandins
• Caspofungin, anidulafungin, micafungin,
• Cause fungal cell lysis by interfering with glucan
formation (polysaccharide of D- glucose
monomers)
• Generally active against Candida resistant to
“azoles”
• Only available intravenously
• Caspofungin is metabolised by liver
• Caspofungin is not cleared by haemodialysis
Polyenes
• Amphotericin B is the only systemically delivered polyene
• Originally a fermentation product of Streptomyces nodosus (from soil on the banks of the Orinoco River, Venezuela)
• Original formulation associated with several toxicities most notably renal impairment
• Liposomal amphotericin B less toxic
Lipid Associated Amphotericin B
• Less toxicity
• 3 lipid associated formulations with different pharmacokinetics
– Amphotericin B encapsulated in phospholipidcontaining liposomes
– Amphotericin B colloidal dispersion (small lipid disks containing cholesterol sulphate)
– Amphotericin B lipid complex (complexed with phospholipids to produce ribbon-like structures)
From Bassetti et al, Critical Care 2010 14: 244
From Bassetti et al, Critical Care 2010 14: 244
C A R E BCommodity Action Report & Eps Bulletin
Antifungal Medicines (NP39011)
Prepared by:
Andy Stewart
Commodity Manager
National Procurement
14th October 2011
Summary
• Candida in blood always requires appropriate antifungal treatment, line changes, ophthalmological assessment
• Choice of antifungal is based on severity of sepsis, type of fungus grown, sites of infection, side-effect profiles and cautions
• Early treatment is the goal
• Early treatment can be facilitated by more rapid laboratory identification of Candida but only if it grows
• Prophylaxis may be indicated based on patients’underlying diagnoses, recent exposure to antifungals or fungal culture from non-invasive sites
• Empirical treatment is influenced by severity of sepsis, site of fungal infection and species of Candida grown