Cryptococcal meningitidis

Question 1

Define Cryptococcal meningitidis

Answer 1

A fungal infection of the Meninges of the brain in immunocompromised patients.

Question 2

What is the causative organism?

Answer 2

Cryptococcal neoformans
Encapsulated yeast that colonizes airways

Question 3

What are the risk factors?

Answer 3

Immunocompromised e. g
°HIV (AIDS defining illness)
°Chemo patients
°CD4 count < 100cells/microL
°Transplant patients
°Corticosteroid usage
•Men (have prostate)

Question 4

Which areas are mostly affected by cryptococcals

Answer 4

SPREAD VIA BLOODSTREAM
Brain- neoformans
Lungs- pulmonary cryptococcosis
Skin- cutaneous manifestations
Prostate

Question 5

How is it ‘spread’?

Answer 5

°Inhaling spores (have no effect on immunocompetent)

Question 6

What blood tests aid in diagnosis of CM

Answer 6

°Fungal culture and susceptibility test
°Cryptococcal serology
°Cryptococcal antigen testing

Question 7

What cerebrospinal fluid tests are diagnostic for CM

Answer 7

°Fungal culture and susceptibility test (sensitivity>90%)
°Cryptococcal antigen testing
°India ink smear
°Elevated lymphocytes
°Hypoglycorrhachia (CSF glucose:serum glucose < 60%)
°Increased Intracranial pressure
°CSF clear or turbid

Question 8

What differential tests are performed to verify CM

Answer 8

CSF antigen test with 90% sensitivity (negative result doesn't mean stop treatment) CT or MRI to rule out brain tumor (do before lumbar puncture if presenting with focal neurologic deficits)
IN HIV PATIENT
Immune Reconstruction Inflammatory Syndrome (IRIS) if HIV and severely immunosuppressed Migraine headache
Bacterial/meningococcal meningitis Cytomegalovirus ventriculiencephalitis

Question 9

Signs and symptoms of CM

Answer 9

Headache/fever/N/V Malaise
Altered mental status with somnolence Photophobia
Increased Intracranial pressure=papilledema (swollen optic disc) Visual disturbances
Stiffness/Nuchal rigidity Confusion/Irritable/psychosis/psychomotor retardation

Question 10

What are the goals of management in CM?

Answer 10

°Eradicate infection
°Reduce morbidity and mortality
°Prevent CM complications
°Prevent ADRs and toxicity related to meds

Question 11

What are the 3 phases of CM treatment?

Answer 11

°Induction
°Consolidation
°Maintenance therapy

Question 12

In the induction phase of CM treatment, what are the 1st line AND alternative therapies

Answer 12

1ST LINE
Amphotericin B deoxycholate 0. 7mg/kg IV ALTERNATIVE Liposomal amphotericin B 3mg/kg IV

Both With or without Flucytosine 25mg/kg PO q6h

Question 13

Compare Liposomal amphotericin with amphotericin b deoxycholate

Answer 13

Liposomal=fewer infusion related side effects e. g blurred vision, convulsions
less nephrotoxicity
more expensive than deoxycholate

Question 14

If the induction therapy with amphotericin b was successful (evidence led by clinical improvement and negative CSF culture), what is included in the consolidation phase?

Answer 14

°Fluconazole 400mg OD 8 weeks
°Then Fluconazole 200mg OD chronic maintenance therapy
OR
°Itraconazole 200mg PO BID then Fluconazole 200mg OD maintenance phase

Discontinue maintenance when CD4>100cells/microL and viral load is suppressed for at least 3 months and patient is on ART.

Question 15

When do you suspect cytomegalovirus (CMV) in the patient?

Answer 15

If severely immunosuppressed

Question 16

How do you manage cytomegalovirus?

Answer 16

Combination therapy
°Ganciclovir and Foscarnet
(this the initial therapy until symptomatic improvement)

Maintenance
°Valganciclovir 900mg/day until ART related immune reconstitution

Question 17

Describe the mechanism of action of antifungals

Answer 17

°Alter DNA/RNA
°Intracellular accumulation of peroxide
°Intracellular accumulation of sodium causing cell rupture

Question 18

What is the mechanism of action of amphotericin b (antifungal)

Answer 18

°Rapid onset of action
°Accumulates sterols in fungal cytoplasmic membrane
°Increase cytoplasmic membrane permeability to monovalent ions e. g Na and Mg
°Fungistatic
°Release free radicals (toxic)

Question 19

List the ADRs of amphotericin b

Answer 19

Renal impairment (MONITOR RENAL FUN) Bone marrow suppression (MONITOR FBC)
GIT effects (anorexia, N/V/D) Hypokaelemia, hypomagnesemia
Pain at injection site General malaise
Tachypnea Hypotension

Question 20

Patient may begin experiencing symptoms 1-3hours after infusion is started. What are infusion related side effects of Amphotericin b.

Answer 20

Fever
Chills
Loss of appetite
Shortness of breath
headache

Question 21

How do you prevent infusion related side effects of amphotericin b

Answer 21

Slow the infusion rate
Premedicate with
• paracetamol,
• diphenhydramine,
• hydrocortisone

Question 22

Which meds interact with amphotericin b causing nephrotoxicity

Answer 22

Amikacin
Cyclosporins
Tacrolimus

Question 23

How do you treat Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV patients

Answer 23

°Prednisolone 0. 5mg/kg/day
OR
°Dexamethasone 0. 3mg/kg/day