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1 Antifungal guidelines for CANDIDIASIS INFECTIONS (Adults) Proven infection: Targeted antifungal therapy should be prescribed for: o Positive cultures from a sterile site with clinical or radiological abnormality o Histology/cytochemistry showing yeasts/hyphae from a biopsy with evidence of tissue damage. Probable or possible infection: Empirical antifungal therapy should be prescribed. The most frequently implicated risk factors for invasive fungal infections include: o use of broad-spectrum antibacterial agents o use of central venous catheters o receipt of parenteral nutrition o receipt of renal replacement therapy by patients in ICUs o reduced cell mediated immunity, especially neutropenia o use of implantable prosthetic devices o receipt of immunosuppressive agents (including glucocorticosteroids, chemotherapeutic agents, and immunomodulators) or patients with sustained immunosuppression (post-transplant patients). Consider: o Host factors fever, neutropenia, pyrexia of unknown origin (PUO) to broad spectrum antibacterials o Clinical criteria o Microbiological criteria o Radiological criteria. Treatment should be reviewed against culture and sensitivity results and switched if appropriate. Early consultation with microbiology is essential in all cases. If patient <50kg, the dose of fluconazole should be adjusted (refer to latest BNF for mg/kg dose). If refractory/ salvage therapy required, contact Consultant microbiologist. Intravenous catheter removal is strongly recommended. Pregnancy: contact Consultant microbiologist. Title: Author: Speciality / Division: Directorate: CLINICAL GUIDELINES ID TAG Antifungal guidelines for candidiasis infections (adults) Dr Martin Brown and Mrs A McCorry Microbiology, Pharmacy Acute Date Uploaded: 13/03/2015 Review Date Clinical Guideline ID March 2017 CG0023 (2)

2 Antifungal guidelines for CANDIDIASIS INFECTIONS (Adults) Empirical treatment for SUSPECTED invasive candidiasis in NON-NEUTROPENIC patients: Fluconazole IV: loading dose of 800mg, then 400mg daily ( mg in ICU or severely ill patients). Anidulafungin IV: loading dose of 200mg, then 100mg daily Proceed to 2 nd line if: Severe illness Recent azole exposure Candida glabrata/krusei isolated Suspected: discontinue if cultures and or serodiagnostic tests are negative. Confirmed: Continue treatment for 2 weeks after first negative blood culture result and resolution of signs and symptoms associated with candidaemia. Candidaemia in NON-NEUTROPENIC patients Candidaemia in NEUTROPENIC patients Or Empirical treatment for SUSPECTED invasive candidiasis in NEUTROPENIC patients Anidulafungin IV: loading dose of 200mg, then 100mg daily If C. parapsilosis, C.guilliermondii and C.famata isolated: 2nd line: Caspofungin IV: loading dose of 70mg, then 50mg daily (70mg if weight >80kg) Continue treatment for 2 weeks after first negative blood culture result and resolution of signs and symptoms associated with candidaemia. Proceed to 2 nd line if: Candida glabrata isolated. Suspected: discontinue if cultures and or serodiagnostic tests are negative. Confirmed: Continue treatment for 2 weeks after first negative blood culture result and resolution of signs and symptoms associated with candidaemia. Candida isolated from respiratory secretions Treatment not recommended. Candida LRTI is rare and requires histopathologic evidence to confirm a diagnosis. Contact Consultant Microbiologist for further advice.

3 Guidelines for initial therapy for CANDIDIASIS (Adults) CNS candidiasis Contact consultant microbiologist immediately for advice. Echinocandins not recommended. Treatment is based on liposomal amphotericin B in combination with other agents as per sensitivities. Removal of intraventricular devices is recommended. Renal Candidiasis Symptomatic UTI +/- Urinary fungus balls Surgical removal strongly recommended. Candida osteoarticular infection Osteomyelitis Septic arthritis Asymptomatic candiduria is not routinely treated. Fluconazole: loading dose of 800mg, then 400mg daily (continue mg in ICU or severely ill patients). If fluconazole resistant or fails to respond: Contact Consultant Microbiologist Fluconazole IV: loading dose of 800mg, then 400mg daily ( mg in ICU or severely ill patients). (5mg/kg daily if prosthetic joint and surgery is not possible) (to be used for 2 weeks only, then switched to fluconazole for completion). Duration: 2 weeks Change or remove urinary catheter. If suspected disseminated candidiasis and renal candidiasis discuss with microbiology. Duration: Osteomyelitis: 6-12 months. Septic arthritis: at least 6 weeks - discuss with Consultant microbiologist Surgical debridement is required in all cases. If prosthetic joint infected, removal is recommended. If this is not possible, long term suppressive therapy may be required following completion of IV s-contact microbiology for advice.

4 Guidelines for initial therapy for CANDIDIASIS (Adults) Candida infection of the cardiovascular system Endocarditis Myocarditis Pericarditis Infected pacemaker, ICD, or VAD Non-genital mucocutaneous candidiasis Oropharyngeal Oesophageal Vulvovaginal candidiasis Caspofungin* IV: loading dose of 70mg, then 50mg daily (70mg if weight >80kg) Or Liposomal amphoteracin B** IV: (5mg/kg daily if prosthetic valve and surgery is not possible) *preferred in C. krusei **preferred in C.parapsilosis, C.guilliermondii and C.famata. Oropharyngeal: Mild: Nystatin PO: suspension or pastilles 6 hourly Moderate to severe: Fluconazole PO: mg daily Oesophageal: Fluconazole PO: 400mg daily Anidulafungin IV loading dose of 200mg, then 100mg daily Clotrimazole PV: 500mg pessary Stat at night Plus Clotrimazole cream: 1% applied 2-3 times daily 2 nd line Fluconazole PO:150mg stat Contact microbiology for advice Valve/ device replacement is strongly recommended. Duration: Endo/myocarditis: 6 weeks after valve replacement and should continue for longer in patients with perivalvular abscesses and other complications Pericarditis: 8 weeks in combination with either a pericardial window or pericardiectomy Infected device: 4 weeks post removal (6 weeks post wire removal if wire involvement) Some patients may require long term suppressive therapy following completion of IV s Duration: 14 days Rule out underlying immunosuppression. Duration: 7 days. If recurrent episodes ( 4/yr), contact microbiology.

5 References: 1. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (Suppl. 7): ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012; 18 (Suppl. 7): Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America. 4. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy