Transcript Presentation - Direct Relief

Cryptococcal Meningitis in
Patients with AIDS
Clinical Case
• 30-year-old male with AIDS
• CD4 25 cells/mm3
• Gradual increasing headache for past five
days
• Low-grade fever
• Neck stiffness
• Nausea
What is your diagnosis?
Cryptococcus neoformans
Learning Objectives
• Upon completion of this activity,
participants should be able to:
– Describe symptoms of cryptococcal
meningitis
– Discuss methods for diagnosing cryptococcal
meningitis
– Review treatments for cryptococcal meningitis
Overview of Cryptococcal Meningitis
• Caused by the fungus Cryptococcus
neoformans
• Fungus is found in soil contaminated by
bird feces (droppings)
• Inoculation by inhalation of the fungus
• AIDS defining condition (CD4 <100
cells/mm3)
Overview
• Prompt diagnosis and treatment crucial
• Fatal if untreated
• Less frequent since introduction of HAART
Clinical Presentation
• Meningismus or meningeal irritation (neck
stiffness)
• Headache, often insidious (gradual)
• Low-grade fever
• Photophobia (light sensitivity)
• Nausea
• Can also present with malaise, confusion,
vomiting, obtundation (depressed levels
of consciousness), seizure and psychosis
Clinical Presentation of CNS Disease
• Meningitis is the most common
presentation of central nervous system
(CNS) disease in patients with AIDS
• However, CNS disease can also present as
multiple or single focal mass lesions called
cryptococcomas (less common)
Increased Intracranial Pressure
• Common in patients with AIDS
• Clinical signs and symptoms: focal neurological
signs, papilledema (optic disc swelling caused
by increased intracranial pressure), severe
headache
• Can lead to herniation, cranial nerve deficit and
death
• Treatment aimed at decompressing cerebral
spinal fluid (CSF) volume and reducing pressure
Laboratory Diagnosis: CSF Studies
• Examination of the CSF provides useful
diagnostic information
– Opening pressure (<200mmH2O in 75%)
– Cell count and differential (mononuclear
pleocytosis—5–100 mg/dL)
– Protein (50–150 mg/dL)
– Cryptococcus antigen (positive in >95%)
– Fungal culture (positive in >95%)
– India ink (positive in 60–80%)
More on Diagnosis
• Blood cultures (positive in 50–70%)
• Serum cryptococcus antigen (positive in
>95%)
Lumbar Puncture: Contraindications
• CNS imaging should be performed prior to
lumbar puncture in patients with focal
neurologic deficits and/or papilledema to
evaluate for CNS mass lesions
• Patients with mass lesions within the brain,
focal neurologic deficits and/or
papilledema should not undergo lumbar
puncture due to increased risk of
herniation
Diagnostic Imaging Studies
• CNS Imaging
–
–
Indicated in patients with focal neurologic
signs, papilledema and/or obtundation
To diagnose lesions that contraindicate
lumbar puncture (cryptococcomas)
Pharmacological Treatment
• Induction Phase:
– Amphotericin B IV 0.7–1.0mg/kg daily +
Flucytosine 100–150 mg/kg daily x 14 days
• Lipid formulations of amphotericin B can be used if available
for patients with impaired renal function
• Consolidation Phase:
– Fluconazole 400 mg po daily for 8–10 weeks
Pharmacological Treatment
• Maintenance Phase:
– Fluconazole 200 mg po daily
– Can be discontinued following immune
reconstitution with HAART
– Otherwise fluconazole may be needed for
lifetime
Alternative Pharmacological Treatment
• Induction Phase
– Fluconazole 400 mg daily PO x 8–10 weeks +
Flucytosine 100 mg/kg daily PO x 6–10 weeks
• Consolidation Phase
– Itraconazole 200 mg twice-daily PO
• Fluconazole 800 mg PO daily x 8 weeks
also used in some resource-limited
settings for induction and consolidation
phases
Treatment of Increased Intracranial Pressure
• CSF drainage for opening pressure >250
mmH2O
• Treatment involves serial LPs,
ventriculoperitoneal shunts or lumbar
drain aimed at reducing opening pressure
to <200 mmH2O
• Repeat lumbar drainage as needed until
achieving stable opening pressure
Toxicities Related to Drugs
Flucytosine
• Bone marrow suppression
Fluconazole
• GI and hepatotoxicity
Amphotericin B
• Renal toxicity and electrolyte
abnormalities
Treatment Failure
• Repeat lumbar puncture if no
improvement or worsening of symptoms
• Consider alternative diagnosis
• Fluconazole and amphotericin resistance
(rare)
• Consider immune reconstitution syndrome
(IRIS)
Prognostic Indicators
Poor Prognosis
• Increased intracranial pressure
• Altered mental status
• Low white blood cell count on CSF
• Positive India ink
Summary
• Cryptococcus meningitis is fatal if
untreated
• Elevated intracranial pressure is
associated with a poor prognosis and
must be managed promptly
• Obtain brain image prior to lumbar
puncture in patients with focal
neurological deficits, papilledema and/or
obtundation
Summary
• Treatment is a three-phase process of
induction, consolidation and maintenance
therapy
• Maintenance treatment with fluconazole
may be discontinued following immune
reconstitution with HAART
• Otherwise fluconazole may be needed for
lifetime
References
• Lenders A, Reiss P, Portegies P et al. 1997. Liposomal
amphotericin B (AmBisome) compared with
amphotericin B both followed by oral fluconazole in the
treatment of AIDS-associated cryptococcal meningitis.
AIDS. 11:1463-71.
• Saag M, Graybill R, Larsen R et al. 2000. Practice
guidelines for the management of cryptococcal
disease. Infectious Diseases Society of America. Clin
Infec Dis. Apr; 30(4):710-8.
• Saag M, Powderly W, Cloud G et al. 1992. Comparison of
amphotericin B with fluconazole in the treatment of
acute AIDS-associated cryptococcal meningitis. The
NIAID Mycoses Study Group and the AIDS Clinical Trials
Group. N Engl J Med. Jun; 326:83-9.
References
• Sobel J. 2000. Practice guidelines for the
treatment of fungal infections. For the Mycoses
Study Group. Infectious Diseases Society of
America. Clin Infect Dis. Apr; 30(4):652.
• van de Horst C, Saag M, Cloud G et al. 1997.
Treatment of cryptococcal meningitis
associated with the acquired immunodeficiency
syndrome. National Institute of Allergy and
Infectious Diseases Mycoses Study Group and
AIDS Clinical Trials Group. N Engl J Med. Nov;
337:15-21.