Cryptococcal Menigitis

Question 1

Define cryptococcal meningitis and likely pathogen

Answer 1

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

Question 2

Which other areas can be affected

Answer 2

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

Question 3

Aetiology CM

Answer 3

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

Question 4

Pathophysiology CM

Answer 4

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

Question 5

Diagnosis CM

Answer 5

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%

Question 6

Differential diagnosis of meningitis in patients with HIV

Answer 6

Migraine headache
Neurosyphillis
Bacterial/meningococcal meningitis
Neurosyphilis

Question 7

Clinical presentation

Answer 7

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

Question 8

Treatment of CM

Answer 8

A. Induction phase
B. Consolidation
C. Maintenance

Question 9

What drugs do we give in induction phase

Answer 9

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

Question 10

Compare convention amphotericin B with liposomal one

Answer 10

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

Question 11

Consolidation and maintenance phase

Answer 11

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

Question 12

When is therapy discontinued for CM

Answer 12

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

Question 13

Cytomegalovirus meningitis

Answer 13

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

Question 14

Mechanism of amphotericin B

Answer 14

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

Question 15

ADR of amphotericin B

Answer 15

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

Question 16

Infusion related reaction

Answer 16

Fever, chills, dyspnea, N/V , headache

Question 17

Interactions of amphotericin B

Answer 17

Nephrotoxic with tacrolimus, cyclosporine,

Question 18

Monitoring parameters for Cryptococcal meningitis

Answer 18

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

Question 19

Discuss moa of fluconazole, flucytosine and itraconazole

Answer 19

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

Question 20

Side effects of flucytosine, itraconazole, fluconazole

Answer 20

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