Diagnosis and Management of Cryptococcosis

Publication Date: February 8, 2024
Last Updated: February 15, 2024

Key Points

  • Accurate delineation of the cryptococcosis clinical syndrome is important as it guides antifungal treatment choice and duration; cryptococcosis syndromes are divided into CNS, disseminated disease, isolated pulmonary disease, or direct skin inoculation.
  • Liposomal amphotericin B 3–4 mg/kg daily and flucytosine 25 mg/kg four times a day is the most optimal induction therapy option for cryptococcal meningitis, disseminated cryptococcosis, and severe isolated pulmonary cryptococcosis in high-income settings.
  • In low-income settings, patients with HIV-associated cryptococcal meningitis are best treated with liposomal amphotericin B 10 mg/kg as a single-dose, with 14 days of flucytosine 25 mg/kg four times a day and fluconazole 1200 mg daily as induction therapy; this induction therapy has not been trialled in non-HIV-associated cryptococcal meningitis or other non-CNS cryptococcosis syndromes.
  • Optimise outcomes by providing the most effective antifungal therapy while preventing, monitoring, and managing potential toxicity; do not stop or switch to an inferior regimen too early or unnecessarily.
  • Expect and monitor for clinical relapse and investigate thoroughly for causality; review adherence to antifungal therapy and consider drug–drug interactions; during treatment follow-up, do not escalate antifungal therapy for persistent blood antigenemia (blood cryptococcal antigen), persistently positive CSF cryptococcal antigen, visible cryptococci in CSF (without culture positivity), or abnormal CSF microscopy or biochemistry, as they are not necessarily indicators of microbiological failure.
  • Adapt and adopt these ECMM global guidelines to suit local practices, while constantly advocating for better antifungal access, scrutinising new trial data, and reviewing local data to improve patient outcomes.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Diagnosis and Management of Cryptococcosis

Authoring Organizations

International Society for Human & Animal Mycology

European Confederation of Medical Mycology

Endorsing Organization

American Society for Microbiology

Publication Month/Year

February 8, 2024

Last Updated Month/Year

April 1, 2024

Document Type

Guideline

Country of Publication

Global

Document Objectives

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.
 

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment

Diseases/Conditions (MeSH)

D003453 - Cryptococcosis

Keywords

fungal infection, cryptococcosis

Source Citation

Chang CC, Harrison TS, Bicanic TA, Chayakulkeeree M, Sorrell TC, Warris A, Hagen F, Spec A, Oladele R, Govender NP, Chen SC, Mody CH, Groll AH, Chen YC, Lionakis MS, Alanio A, Castañeda E, Lizarazo J, Vidal JE, Takazono T, Hoenigl M, Alffenaar JW, Gangneux JP, Soman R, Zhu LP, Bonifaz A, Jarvis JN, Day JN, Klimko N, Salmanton-García J, Jouvion G, Meya DB, Lawrence D, Rahn S, Bongomin F, McMullan BJ, Sprute R, Nyazika TK, Beardsley J, Carlesse F, Heath CH, Ayanlowo OO, Mashedi OM, Queiroz-Telles Filho F, Hosseinipour MC, Patel AK, Temfack E, Singh N, Cornely OA, Boulware DR, Lortholary O, Pappas PG, Perfect JR. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM. Lancet Infect Dis. 2024 Feb 9:S1473-3099(23)00731-4. doi: 10.1016/S1473-3099(23)00731-4. Epub ahead of print. PMID: 38346436.