Cryptococcosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 2 Jun 2025

Last updated: 23 May 2025

Cryptococcosis can be fatal if unrecognized and untreated, regardless of immune status.

Microbiology, cryptococcal polysaccharide antigen (CrAg), or histopathology are required to make the diagnosis for cryptococcosis.

Treatment depends on the immunologic state and disease severity. For asymptomatic and mild to moderate disease with no central nervous system (CNS) involvement, oral fluconazole is the first-line treatment. For severe disease and CNS involvement, induction therapy with amphotericin-B plus flucytosine followed by consolidation therapy with fluconazole is recommended.

The lungs are generally the primary locus of infection, with extrapulmonary dissemination throughout the body with prominent symptomatic involvement of the brain and meninges and, less commonly, the skin, bones, prostate, and other organs.

Meningoencephalitis is life-threatening, particularly in immunosuppressed patients.

Screening for CrAg and preemptive treatment with high-dose fluconazole is effective in reducing mortality in adults who have HIV infection and CD4 count <100 cells/microliter.

Definition

Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus species. Cryptococcus neoformans var. grubii and Cryptococcus neoformans cause morbidity and mortality, especially in immunosuppressed populations, such as those with HIV. Occasionally, people with no apparent immune-system problems develop cryptococcosis, particularly with Cryptococcus var. gattii.

History and exam

Key diagnostic factors

constitutional symptoms
dyspnea
productive cough
dullness to percussion
diminished breath sounds
crackles
headache
alteration of consciousness
meningeal irritation
papilledema
skin lesions
coma

Full details

Other diagnostic factors

chest pain
cranial neuropathy
ocular manifestations

Full details

Risk factors

HIV infection
immunosuppression
exposure to Cryptococcus species
male sex
pregnancy and postpartum period

Full details

Diagnostic tests

1st tests to order

serum cryptococcal polysaccharide antigen (CrAg)
cerebrospinal fluid (CSF) cryptococcal polysaccharide antigen (CrAg)
pleural fluid cryptococcal polysaccharide antigen (CrAg)
cultures
HIV antibodies
chest x-ray
lumbar puncture
cerebrospinal fluid (CSF) microscopy
cerebrospinal fluid (CSF) white blood cell count (cells/microliter)

Full details

Tests to consider

CT chest
MRI brain
CT brain
bronchoscopy
biopsy

Full details

Emerging tests

cryptococcus polymerase chain reaction (PCR)

Treatment algorithm

ONGOING

without HIV

with HIV

Contributors

Authors

Radha Rajasingham, MD

Associate Professor of Medicine

Infectious Diseases and International Medicine

Department of Medicine

University of Minnesota

Minneapolis

Disclosures

RR receives grants from the US National Institutes of Health (NIH) for prevention of cryptococcal meningitis clinical trials. She is a consultant for the Pan American Health Organization for research in histoplasmosis screening. RR is an author of several references cited in this topic.

Acknowledgements

Dr Radha Rajasingham would like to gratefully acknowledge Dr David Boulware, Dr Renata L. Riha, and Dr Athanasia D. Pataka, previous contributors to this topic.

Disclosures

DRB has received research support from Gilead. RLR and ADP declare that they have no competing interests.

Peer reviewers

William Powderly, MD

Professor of Medicine

Washington University in St Louis

St Louis

Disclosures

WP declares that he is a member of advisory boards for Gilead and Merck and his institution has received research grants from Merck; none of these are related to antifungal therapy. WP is a member of the Board of Directors (Past President) of the Infectious Diseases Society of America. WP is an author of a reference cited in this topic.

Ricardo Negroni, MD

Consultant

Muñiz Hospital

Honorary Professor

University of Buenos Aires

Buenos Aires

Argentina

Disclosures

RN declares that he has no competing interests.

Aimee Zaas, MD, MHS

Assistant Professor of Medicine

Division of Infectious Diseases and International Health

Duke University Medical Center

Durham

Disclosures

AZ has received research funding from Enzon Pharmaceuticals and has been on the speaker's bureau for Astellas Pharma and Pfizer Inc.

Joseph Jarvis, BSc, MBBS, MRCP

Professor

Department of Clinical Research

Faculty of Infectious and Tropical Diseases

London School of Hygiene and Tropical Medicine

London

Disclosures

JJ declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006 Sep;20(3):507-44. Abstract

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: cryptococcosis. Oct 2024 [internet publication].Full text

World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. Jun 2022 [internet publication].Full text

Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010 Feb 1;50(3):291-322.Full text Abstract

Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. 2014 Jun 26;370(26):2487-98.Full text Abstract

Rolfes MA, Hullsiek KH, Rhein J, et al. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin Infect Dis. 2014 Dec 1;59(11):1607-14.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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- Tuberculosis
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- Skin manifestations of systemic infections
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Guidelines
- Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: cryptococcosis
- Global guideline for the diagnosis and management of cryptococcosis
More Guidelines
Videos
Diagnostic lumbar puncture in adults: animated demonstration
More videos
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Cryptococcosis

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Emerging tests

Treatment algorithm

without HIV

with HIV

Contributors

Authors

Radha Rajasingham, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

William Powderly, MD

Disclosures

Ricardo Negroni, MD

Disclosures

Aimee Zaas, MD, MHS

Disclosures

Joseph Jarvis, BSc, MBBS, MRCP

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Videos

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice