Cryptococcal Menigitis Flashcards

1
Q

Define cryptococcal meningitis and likely pathogen

A

Infection of the meninges of the brain caused by cryptococcus neoformans which is an encapsulated yeast that colonize airways
Severe in HIV pt, organ transplant, chemo, high dose and long term corticosteroid therapy

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2
Q

Which other areas can be affected

A

CNS -cryptococcal meningitis
Lungs-pulmonary cryptococcosis
Skin-cutaneous manifestations
Prostate

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3
Q

Aetiology CM

A

Pt with CD4 count <100cells/microL and AIDS as it is one of the AIDS defining illnesses spreads from lungs to rest of body

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4
Q

Pathophysiology CM

A

Inhalation of cryptococcus neoformans commonly found in soil contaminated with bird droppings. In Immunocompromised spreads from lungs to other areas , invades CNS and cover brain, spinal cord leading to meningitis. Immune response triggered then leads to formation of granulomas which can be found in meninges, brain parenchyma

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5
Q

Diagnosis CM

A

CSF and serum cryptococcal antigen tests
CT/MRI on patients suspected to have CM presenting with neurological deficits to rule out tumors
CSF analysis- increased protein level, increased intracranial pressure, increased lymphocytes, ratio of CSF glucose:serum glucose <60%

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6
Q

Differential diagnosis of meningitis in patients with HIV

A

Migraine headache
Neurosyphillis
Bacterial/meningococcal meningitis
Neurosyphilis

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7
Q

Clinical presentation

A

Headache, fever, malaise, stiff neck( nuchal rigidity) photophobia, papilledema
N/V
Altered mental status ie irritability, personality changes, confusion

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8
Q

Treatment of CM

A

A. Induction phase
B. Consolidation
C. Maintenance

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9
Q

What drugs do we give in induction phase

A

Amphotericin B deoxycholate 0.7-1.0 mg/kg IV daily with or without flucytosine 25 mg/kg PO q6h for at least 2 weeks
Alternative liposomal amphotericin B 3-4mg/kg IV daily with or without flucytosine

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10
Q

Compare convention amphotericin B with liposomal one

A

Conventional- made with deoxycholate admin IV ,other encased with lipids admin IV
Liposomal better tolerated ie s/e of infusion related rxns, hypotension less
Liposomal more expensive
Liposomal good for cases of renal toxicity or when rapid administration is needed
Conventional you need premedication with antihistamines, antipyretics, corticosteroids to prevent infusion related reactions

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11
Q

Consolidation and maintenance phase

A

2 weeks after successfully therapy
Fluconazole 400ng PO/IV w24 for 8 weeks
Followed by 200 mg daily maintenance for chronic maintenance
Alternative give itraconazole 200mg q12h for chronic then fluconazole 200mg for maintenance

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12
Q

When is therapy discontinued for CM

A

CD4>100cells/ mm3 and viral load suppressed for at least 3 months and pt on ART

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13
Q

Cytomegalovirus meningitis

A

Present in severe Immunocompromised
Consider combination foscarnet and ganciclovir maintenance with valganciclovir 900mg/day

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14
Q

Mechanism of amphotericin B

A

Medicine 1st choice , mister into cytoplasmic membrane lead to accumulation at sterol site and increase in permeability hence fungi static activity
Also release toxic free radicals

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15
Q

ADR of amphotericin B

A

Bone marrow suppression check FBC
Hypokalemia, hypomangesemia, hypotension, tachypnea, general malaise , pain at site of injection
Renal impaired

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16
Q

Infusion related reaction

A

Fever, chills, dyspnea, N/V , headache

17
Q

Interactions of amphotericin B

A

Nephrotoxic with tacrolimus, cyclosporine,

18
Q

Monitoring parameters for Cryptococcal meningitis

A

CSF pressure
Clinical signs and symptoms
Lab test
CSF
Electrolyte and chemistry
Renal -amphotericin B , flucytosine
IRIS in HIV give prednisone 0.5 mg/kg/ day

19
Q

Discuss moa of fluconazole, flucytosine and itraconazole

A

Fluconazole- inhibit synthesis of ergosterol , thus disruption CM
Flucytosine-converted to 5-flurouracil disrupt fungal RNA and protein synthesis thus cell death
Itraconazole- inhibit fungal CYP450 thus interfering synthesis of ergosterol

20
Q

Side effects of flucytosine, itraconazole, fluconazole

A

Fluconazole- Steven Johnson syndrome , hepatotoxicity and anaphylaxis, liver , renal and GIT test
Flucytosine-hematologic toxicity, ie leukopenia , bone marrow suppression
Itraconazole-QT prolongation , rash , headache