Global Guideline on Candidiasis, Part II: Treatments
This is the second installment of a 2-part report on a new guideline on candidiasis from the European Confederation for Medical Mycology (ECMM) highlights selected treatment recommendations.
Oliver Cornely
Image credits: CECAD Cologne
A new global guideline for management of candidiasis includes treatment recommendations for several clinical circumstances, including prophylaxis for at-risk patients and targeting particular sites of infection.1 The guideline was developed by the European Confederation for Medical Mycology (ECMM) in collaboration with the American Society of Microbiology (ASM) and the International Society for Human and Animal Mycology (ISHAM).
Susceptibility testing is strongly recommended for guiding treatment in all invasive infections and for mucocutaneous infections that are not responsive to empirical therapy. It is also recommended for attaining epidemiological data. The guideline recommends use of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) or Clinical and Laboratory Standards Institute (CLSI) antifungal susceptibility testing.
"...the data suggest a relevant correlation between minimal inhibitory concentration and clinical outcome, as well as a correlation between minimal inhibitory concentrations and the presence of resistance mutations in target genes associated with clinical failures," indicated lead author Oliver Comely, MD, of the Institute of Translational Research at the Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD) of the University of Cologne, in Cologne, Germany, and colleagues.
Read the first installment of this 2-part series: Global Guideline on Candidiasis, Part I: Diagnostics
For the emerging pathogen, C auris, the guideline references the Centers for Disease Control and Prevention (CDC) definitions of tentative breakpoints to guide interpretation of CLSI broth microdilution results.
Prophylaxis with fluconazole, in a loading dose of 12 mg/kg followed by 6 mg/kg daily, is recommended for patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Prophylaxis with an echinocandin is suggested if a patient was recently exposed to azoles or if the hospital epidemiology indicates prevalence of azole-resistant Candida spp infections.
Fluconazole prophylaxis is also recommended for patients undergoing allogenic hematopoietic stem cell transplant for hematological malignancies."Primary antifungal prophylaxis with fluconazole has been shown to provide a survival benefit in the early period (ie, in the first few weeks to months) following transplant, as well as in long-term survival," Comely and colleagues point out.
Azoles are recommended as first line antifungal prophylaxis for patients with neutropenia from conditions such as intensive remission-induction chemotherapy for acute myeloid leukemia or myelodysplastic syndrome.
"Because of the shift in the pattern of invasive fungal disease in this clinical context, due primarily to increasing rates of filamentous fungi as well as increasing incidence of non-albicans species of Candida that have intrinsic resistance or limited susceptibility to fluconazole, primary antifungal prophylaxis with posaconazole or other mold-active drugs are recommended in patients with expected long-term neutropenia (ie, 7 days or longer)...," explain Comely and colleagues.
The guideline recommends the echinocandins as first-line treatment of candidemia. Rezafungin (Rezzayo; Melinta Therapeutics and Mundipharma) is the latest to be approved in this class, which also includes anidulafungin, caspofungin, and micafungin. They share a spectrum of activity and are thus considered interchangeable in the guideline based on susceptibility results.
"However, the choice of echinocandin should be determined by patient-specific pharmacokinetic considerations...and is often additionally directed by costs and hospital policy," Comey and colleagues point out.
Amphotericin B liposomal (LAmB) is recommended as a second-line or salvage treatment of candidemia when echinocandins cannot be used (ie, for patient intolerance or fungal resistance). Switching to oral fluconazole is then recommended as soon as feasible.
For central nervous system infection, and based on susceptibility testing, LAmB, usually in combination with flucytosine, is recommended. The guideline indicates that amphotericin deoxycholate should only be used for this indication if LAmB is unavailable. Fluconazole alone, or in combination with flucytosine, is recommended as oral consolidation therapy if testing indicates susceptibility.
For ocular candidiasis, systemic treatment with fluconazole or voriconazole are recommended, subject to azole-susceptibility. Systemic LAmB is a recommended alternative in the face of resistance to other agents.
For endocarditis, the guideline recommends initial therapy with either LAmB at 3-5 mg/kg daily, with or without flucytosine (25 mg/kg, 4 times daily), or with an echinocandin. The guideline recognizes that the dose of LAmB will be reduced if renal toxicity develops, but cautions that doses below 3 mg/kg daily are of only marginal strength recommendation.
Antifungal stewardship should be included as an essential component in antimicrobial stewardship programs and quality improvement management, Comely and colleagues urge."Additionally, we advocate for the establishment of national or international excellence centers that can provide professional advice."
