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Cryptococcal meningitis

Key sources
The following summarized guidelines for the evaluation and management of cryptococcal meningitis are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2023), the World Health Organization (WHO 2022), and the Infectious Diseases Society of America (IDSA 2010).


1.Screening and diagnosis

Indications for screening
As per CDC 2023 guidelines:
Obtain routine surveillance testing for serum cryptococcal antigen in patients with newly diagnosed HIV with no overt clinical signs of meningitis, if the CD4 counts are ≤ 100 cells/mm³, especially if ≤ 50 cells/mm³.
Obtain prompt CSF evaluation for CNS infection in patients with a positive test (BIII), particularly when the serum cryptococcal antigen lateral flow assay titer is ≥ 1:160.
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2.Diagnostic investigations

Antigen testing
Obtain rapid serum, plasma or whole-blood cryptococcal antigen testing as the preferred diagnostic approach if both access to a cryptococcal antigen assay and rapid results (< 24 hours) are available in settings without immediate access to lumbar puncture or when lumbar puncture is clinically contraindicated.
Consider referring for further investigation and treatment promptly if a cryptococcal antigen assay is not available and/or rapid access to results is not ensured in settings without immediate access to lumbar puncture or when lumbar puncture is clinically contraindicated.

3.Diagnostic procedures

Lumbar puncture: as per WHO 2022 guidelines, perform s prompt lumbar puncture with measurement of CSF opening pressure and rapid cryptococcal antigen assay as the preferred diagnostic approach in adult, adolescent
and pediatric patients with HIV suspected of having a first episode of CM.
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4.Medical management

Antifungal therapy, induction, human immunodeficiency virus-positive, IDSA/HIVMA/CDC/NIH: initiate IV amphotericin B in combination with oral flucytosine as induction therapy in patients with CM.
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More topics in this section

  • Antifungal therapy, induction (organ transplant recipients)

  • Antifungal therapy, induction (HIV-negative, non-transplant recipients)

  • Antifungal therapy, consolidation (HIV-positive)

  • Antifungal therapy, consolidation (organ transplant recipients)

  • Antifungal therapy, consolidation (HIV-negative, non-transplant recipients)

  • Antifungal therapy, maintenance (HIV-positive)

  • Antifungal therapy, maintenance (organ transplant recipients)

  • Antifungal therapy, maintenance (HIV-negative, non-transplant recipients)

  • ART

  • Diuretics and corticosteroids

  • Management of medication adverse effects

  • Management of treatment failure

  • Management of relapse

5.Therapeutic procedures

Cerebrospinal fluid drainage: as per CDC 2023 guidelines, take measures to decrease ICP in all patients with confusion, blurred vision, papilledema, lower extremity clonus, or other neurologic signs indicative of increased ICP. Perform drainage of CSF via lumbar puncture for initial management.
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More topics in this section

  • Ventriculoperitoneal shunting

6.Specific circumstances

Pediatric patients: initiate amphotericin B deoxycholate 1 mg/kg/day IV plus flucytosine 100 mg/kg/day PO in 4 divided doses for 2 weeks (follow the treatment length schedule for adults in non-HIV-infected, non-transplant patients) followed by fluconazole 10-12 mg/kg/day PO for 8 weeks as induction and consolidation therapy in pediatric patients with CNS disease.
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More topics in this section

  • Pregnant patients

  • Patients with immune reconstitution inflammatory syndrome

  • Patients with cerebral cyptococcomas

  • Patients with Cryptococcus gattii infection

  • Resource-limited healthcare environments

7.Preventative measures

Primary prophylaxis, human immunodeficiency virus-positive, IDSA/HIVMA/CDC/NIH: do not initiate primary prophylaxis in HIV-positive patients in the US in the absence of a positive serum cryptococcal antigen test because of the relative infrequency of cryptococcal disease, lack of survival benefit associated with prophylaxis, possibility of drug-drug interactions, potential development of antifungal drug resistance, and costs.
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8.Follow-up and surveillance

Assessment of treatment response: do not monitor serum or CSF cryptococcal antigen titers for determination of initial response to therapy.