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 .

budding. clusters) .Mould and Yeast • Yeast – Smells like baking bread or beer – Predominantly Candida in UK – Can be seen on Gram Stain (Gram positive. ovoid.

Critical Care 2010 14: 244 .From Bassetti et al.

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Candida Chromogenic Agar Candida tropicalis Candida glabrata Candida albicans .

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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 .

• 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 .Echinocandins • Caspofungin. micafungin. anidulafungin.

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 phospholipid containing liposomes – Amphotericin B colloidal dispersion (small lipid disks containing cholesterol sulphate) – Amphotericin B lipid complex (complexed with phospholipids to produce ribbon-like structures) .

Critical Care 2010 14: 244 .From Bassetti et al.

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From Bassetti et al. Critical Care 2010 14: 244 .

CAREB Commodity Action Report & Eps Bulletin Antifungal Medicines (NP39011) Prepared by: Andy Stewart Commodity Manager National Procurement 14th October 2011 .

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recent exposure to antifungals or fungal culture from non-invasive sites • Empirical treatment is influenced by severity of sepsis. line changes. sites of infection. type of fungus grown. site of fungal infection and species of Candida grown . ophthalmological assessment • Choice of antifungal is based on severity of sepsis.Summary • Candida in blood always requires appropriate antifungal treatment. 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.