Cryptococcal Meningitis (CM)

Clinical description

• CM mortality is high. Early diagnosis and treatment are essential.
• The new treatment regimen with liposomal amphotericin B, flucytosine and fluconazole

improves survival significantly and must be used whenever possible.

• Liposomal amphotericin B has much lower toxicity than the regular amphotericin B

deoxycholate. This means it can be given at higher doses which is more effective.

• Liposomal amphotericin B and TDF can be used together if kidney function is monitored.

Routine substitution to non-TDF-based ART regimen is unnecessary.

Signs and symptoms

Slow onset severe headache; confusion; convulsions; +/- fever; +/- neck stiffness

Investigations

Lumbar puncture (LP) feasible / not contraindicated Cryptococcal antigen (CrAg) rapid test or India Ink stain on CSF.

LP not feasible CrAg rapid test on serum, plasma or whole blood.

Note: start CM treatment without delay for patients with acute meningitis signs + positive serum CrAg test, even if confirmation through CSF CrAg is not immediately possible.

Treatment

Admit Daily therapeutic spinal tap if high intracranial pressure, severe headache or vomiting is present (up to 30 ml per puncture).

Do NOT give adjunctive corticosteroids during CCM treatment.

If not already on ART, start ART only 5 weeks after antifungal treatment initiation.

Do not interrupt ART if already on ART.

Before giving Liposomal Amphotericin B: Pre-hydrate and supplement electrolytes: 1000ml normal saline solution (weight-based for children) + Potassium 2 tabs 12- hourly + Magnesium trisilicate 1 tab 24-hourly. Give Magnesium trisilicate in the evening to avoid absorption interactions with DTG.

Pharmacological

How to prepare liposomal amphotericin B (Ambisome) for infusion

• Based on the patient weight, calculate how many mg and how many vials are needed in total.
• Inject 12ml of water for injection in each vial and shake vigorously for 30 sec until all powder

is dissolved and the solution is clear.

• The solution in each vial will contain 4mg /ml
• Calculate the total volume (ml of solution) needed for the total dose to be given.
• Remove the equivalent volume of dextrose 5% or 10% from the infusion bag to make room for

the total Ambisome solution to be added.

• Do not use saline or Ringer’s lactate instead of dextrose solution because the Ambisome

solution may clot.

• Attach a needle to the filter included with the Ambisome and inject the solution through the

filter into the dextrose bag. Use a new filter for each vial of Ambisome solution.

• Shake the dextrose bag gently to mix when all Ambisome has been added.

Recommended regimen: if all meds are available Adults Liposomal amphotericin B 10 mg/kg IV over 3 hours, single dose.

+ Flucytosine tabs 100mg/kg/day divided into 4 doses (6-hourly) for 14 days + Fluconazole tabs/IV 1200mg/day (24-hourly) for 14 days Children Liposomal amphotericin B 6mg/kg IV over 6 hours 24-hourly for 7 days.

+ Flucytosine tabs 100mg/kg/day divided into 4 doses (6-hourly) for 7 days + Fluconazole tabs Start after the 7-day course of Liposomal amphotericin B + flucytosine is completed 12mg/kg (max 800mg) 24-hourly for 7 days Alternative regimen 1: if liposomal amphotericin B is not available Requires FBC monitoring: at baseline and 2-3 times in the second week of treatment.

Fluconazole tabs Adult: 1200mg 24-hourly for 14 days Child: 12mg/kg (max 800mg) 24-hourly for 14 days + Flucytosine tabs 100mg/kg/day divided into 4 doses (6-hourly) for 14 days HIV-related diseases 25 Alternative regimen 2: if flucytosine not available Requires FBC, Creatinine and K+ monitoring: at baseline and 2-3 times in the second week of treatment.

Liposomal Amphotericin B 3-4 mg/kg IV over 6 hours 24-hourly for 14 days Give up to 6 mg/kg for treatment failure or serious disease.

+ Fluconazole tabs Adult: 1200mg 24-hourly for 14 days Child: 12mg/kg (max 800mg) 24-hourly for 14 days

Pharmacological

Fluconazole tabs for 8 weeks Adult: 800mg 24-hourly Child: 12mg/kg (max 800mg) 24-hourly

Pharmacological

Fluconazole tabs, lifelong Adult: 200mg 24-hourly Child: 6mg/kg 24-hourly