Merav Barzilai, MD

Internal Medicine B
Sheba medical center
Case no. 1
• 41 yo male
• s/p kidney transplant d/t GN (1991-R, 2006-L)
treated with cellcept , prograft, prednisone
• Chronic renal failure
• Post transplant gout
• Dyslipidemia
• FUO + weakness, nausea and
dizziness
Case no. 1- cont.
• Physical exam: VS ok, morbid obesity,
multiple tophi,multiple skin lesions,
bilateral lower limbs weakness 2/5.
• Blood tests: no leukocytosis, no
electrolyte abnormalities, maximal ESR
& CRP, sterile cultures.
• LP- MNC, high protein, high pressure
Cryptococcal life cycle
 Cryptoccocus Neoformans
• yeast-like fungus, pigeon
droppings
• C. Neoformans , C. Gatii
• Meningoencephalitis,
pneumonia, skin and soft
tissue infections
• Immunocompetent and
immunocompromised
 Diagnosis
• indian ink in CSF
• CSF culture
• CRAg
 Case no. 2
• 59 yo male, cypruss
• CRF d/t IgA nephropathy, treated with cellcept and
steroids
• Hepatitis B
• Photophobia, nuchal rigidity, cerebellar
signs
• Positive CRAg in CSF
So what’s new in the
management of cryptococcal
disease?
• The IDSA has updated the treatment guidelines for the management
of cryptococcal disease for the first time since 2000.

• three risk groups:

1. patients with HIV/AIDS
2. patients who have received an organ transplant
3. patients who may be a host of the disease but are HIV-negative
and have not been a recipient of an organ transplant.

• High risk patients: children, pregnant women, people in resource-

limited environments and those with Cryptococcus gattii infection.
 Key management
principles

• Primary therapy: induction and

consolidation
AmBd plus flucytosine for at least 2 weeks,
followed by fluconazole per day orally for
a minimum of 8 weeks
• Maintenance (suppressive) and
prophylactic therapy- Fluconazole
 Key management
principles
• Early TX of complications:
1. increased ICP
2. immune reconstitution inflammatory
syndrome (IRIS)
- in HIV-infected patients initiating
antiretroviral therapy (ART)
- paradoxical clinical worsening of a
known condition or the appearance of
a new condition after initiating therapy
 Other issues
• The use of lipid formulations of
amphotericin B regimens in patients
with renal impairment.
• Cryptococcus neoformans and
Cryptococcus gattii.
 Is it really so?
“ if the diagnosis is made early,
if clinicians adhere to the basic principles
of these guidelines,
and if the underlying disease is
controlled,
then cryptococcosis can be managed
successfully in the vast majority of
patients”
 Prognostic factors
• Positive CSF assay by indian ink
• High CSF pressure
• Low CSF glucose levels
• Low CSF pleocytosis
• Extraneural sites
• Absence of Ab
• CRAg LEVEL >1:32
• Steroid therapy
 Back to our patients….
Case 1
• Skin+ CNS infection
• Treated by protocol- ambisome+fluconazole
• Positive CSF –stopped
cellcept,prograft,steroids
• Complications: anemia, severe
hypoalbuminemia, acinetobacter bacteremia,
CDT, MOF
 Back to our patients….
Case 2
• CNS infection
• Treated by protocol- ambisome+fluconazole
• CSF sterile cultures
• Complications: severe sepsis, A/CRF,
addisonian crisis, MOF
 Take home message!
• Cryptococcal disease is a tough
disease with a harsh prognosis in
immunocompromised patients
• In addition to the traditional HIV carriers
risk population, there is a new
population of immunocompromised
patients- s/p transplant, reated with
cytotoxic medications.
Bibliography