Cryptococcus meningitis

Question 1

Cryptococcal meningitis commonly occurs in patients with _________

Answer 1

Late stage HIV-infection

Question 2

Cryptococcosis is an illness caused by infection with Cryptococcus fungi in your _______ or _______. It can also spread to many areas of your body (_________ ________).

Answer 2

Cryptococcosis is an illness caused by infection with Cryptococcus fungi in your brain or lungs. It can also spread to many areas of your body (disseminated cryptococcosis).

Question 3

When you have a Cryptococcus infection in your brain, it’s called _____________

Answer 3

When you have a Cryptococcus infection in your brain, it’s called cryptococcal meningitis

Question 4

Cryptococcus infection in lungs is called __________

Answer 4

In lungs, it’s sometimes called cryptococcal pneumonia or pulmonary cryptococcosis.

Question 5

What causes cryptococcosis?

Answer 5

The fungi Cryptococcus gattii (C. gattii) and Cryptococcus neoformans (C. neoformans) cause cryptococcosis. They live in the environment — in dirt (soil), on trees and in bird poop.

Question 6

Clinical features of cryptococcal meningitis

Answer 6

fever, headaches and neck stiffness

Question 7

Diagnose of CM

Answer 7

CSF analysis ( culture, screening for cryptococcal antigen) definite diagnosis

Serum cryptococcal antigen test (CAT) and blood cultures

Indian ink

Question 8

Cellular and biochemical response in cryptococcal meningitis include:

Answer 8

CSF proteins are greater than 0.4g/L ( 1-3 g/L)

CSF blood glucose is less than 50%

predominantly mononuclear leucocytes (lymphocytes)

Question 9

How many phases are there in the treatment CM?

Answer 9

3
Induction therapy
Consolidation therapy
Maintenance therapy

Question 10

Goals of therapy

Answer 10

To rapidly control the infection and stabilise the patient to minimise morbidity and mortality

Question 11

Induction therapy:

Answer 11

•2 weeks therapy of intravenous amphotericin B deoxycholate (0.7 – 1mg/kg/day) ± flucytosine (100mg/kg/day i.v or p.o in divided doses

Question 12

Addition of flucytosine results in ____________________________________________________________________________________

Answer 12

Addition of flucytosine results in quicker clearance of yeasts from the CSF( due to synergism) and reduces the relapse rate in patients not on HAART but associated with additional toxicity

Question 13

Consolidation therapy:

Answer 13

Fluconazole 400mg/day p.o for at least 8–10 weeks.

Question 14

Maintenance therapy (_________________):

Answer 14

Maintenance therapy (reduces incidence of relapse):
•Fluconazole 200mg daily p.o continued for life, or until immune function restored( CD4 count > 100cells/mm3 + undetectable viral load for 3 months)

Question 15

Types of amphotericin B

Answer 15

Lipid formulations of amphotericin B e.g. liposomal amphotericin B, at doses of 4 – 6mg/kg/day have comparable efficacy to, and fewer side effects, than conventional amphotericin B at a dose of 0.7mg/kg/day.

Question 16

Premedication

Answer 16

Promethazine 25mg i.v ( to prevent nausea and vomiting)

•Hydrocortisone 25 – 50mg may be added to the infusion solution( to control anaphylactoid reactions-Anaphylactoid reactions are immediate systemic reactions that mimic anaphylaxis but are not caused by IgE-mediated immune responses. )

•Premedication prevents chills, fever and tachypnoea - rapid breathing)

•Pre – and post amphotericin B sodium loading with 1L normal saline to prevent hypotension and nephrotoxicity (electrolyte derangements)

•Antipyretics e.g. paracetamol

Question 17

Amphotericin B administration

Answer 17

Amphotericin B deoxycholate is given by slow IV infusion in dextrose 5% over 2 – 4 hours

•Amphotericin B should not be given in electrolyte – containing fluids ( normal saline, dextrose normal saline, ringers lactate) as it will precipitate out.

•Concentration of amphotericin B should be 0.1mg/mL

pH of dextrose 5% must not be below 4.2 (inactivated at low pH values)

-Should be protected from light (disrupt colloidal suspension)…cover with aluminium foil

Question 18

Adverse effects of Amphotericin B

Answer 18

•Infusion related: avoid rapid infusion (risk of arrhythmias)
•Chills
•fever
•Nausea and vomiting
•hypotension
•Headache
•rigors

Non – infusion related:
•Nephrotoxicity(most serious) .i.e. causes acute tubular necrosis e.g. hypokalemia and hypomagnesemia (increased urinary excretion of potassium and magnesium)
– monitor renal function on alternate days
- Discontinue if serum creatinine > 250µmol/L until Cr levels fall below this limit
•Azotaemia (uraemia) observed after first few infusions

Thrombophlebitis (irritates venous endothelium)
•Abnormal liver function (discontinue treatment).
•Blood disorders (inhibits erythropoiesis)

Question 19

Amphotericin B lipid formulations

Answer 19

Advantages of the expensive lipid formulations delivered as amphotericin encapsulated in liposomes or a complex with lipid molecules:

•Higher unit doses can be given

•Reduction in toxicity

Question 20

Flucytosine

Answer 20

Synthetic fluorinated nucleotide analogue
Mode of action
•Following uptake by the cell (dependent on presence of cytosine permease), flucytosine is deaminated to 5-fluorouracil by cytosine deaminase)
•5 – fluorouracil is incorporated into fungal RNA in place of uracil, impairing protein synthesis.
•A metabolite of 5 – fluorouracil inhibits thymidylate synthetase leading to inhibition of DNA synthesis.
•Host cells have absent or weak cytosine deaminase activity ( selective toxicity of flucytosine)

Side effects
•Dose – related myelosuppression with neutropenia and thrombocytopenia
•Hepatoxicity
•Teratogenicity