Fungal meningitis medical therapy

(Induction/consolidation):

• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg PO QID for at least 2 weeks

THEN fluconazole 400 mg/day PO/IV (6 mg/kg/day);

• Lipid formulations of amphotericin B may be substituted for Amphotericin B deoxycholate if necessary: liposomal amphotericin B 3-4 mg/kg/day IV and amphotericin B lipid complex 5 mg/kg/day IV.

(Maintenance):

• Fluconazole 200 mg/day

Solid organ transplant:

• Lipid formulations of amphotericin B (liposomal amphotericin B 3-4 mg/kg/day IV or amphotericin B lipid complex 5 mg/kg/day IV) plus flucytosine 25 mg/kg PO QID for at least 2 weeks

THEN fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day) for 8 weeks THEN fluconazole 200-400 mg/day for 6-12 months

Non-HIV, non-organ transplant:

• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg QID for at least 4 weeks

THEN fluconazole 200 mg/day (3 mg/kg) for 6-12 months

(Induction/consolidation):

• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day IV or lipid formulations of amphotericin B (liposomal Amphotericin B 3-4 mg/kg/day IV and amphotericin B lipid complex 5 mg/kg/day IV) monotherapy for 4-6 weeks;
• Amphotericin B deoxycholate 0.7 mg/kg/day IV plus fluconazole 800 mg/day PO/IV for 2 weeks THEN fluconazole 800 mg/day for a minimum of 8 weeks;
• fluconazole (≥800 mg/day) PO/IV plus flucytosine 25 mg/kg PO QID for 6 weeks

(Maintenance):

• Itraconazole 200 mg PO BID

Solid organ transplant:

• If flucytosine not used, then consider extension of induction with lipid formulations of amphotericin B for at least 4-6 weeks.

Non-HIV, non-organ transplant:

• Lipid formulations of amphotericin B (liposomal amphotericin B 3-4 mg/kg/day IV or amphotericin B lipid complex 5 mg/kg/day IV) can be substituted in those unable to tolerate Amphotericin B deoxycholate;
• if flucytosine not used, then consider extension of Amphotericin B deoxycholate or lipid formulations of amphotericin B induction for at least 2 additional weeks.

• Voriconazole 6 mg/kg IV q12h on day 1

THEN 4 mg/kg q12h; further conversion to oral therapy may be considered.

• Typical oral dosing is 200 mg q12h but is dependent on therapeutic drug monitoring.
• Total duration of therapy has not been defined. Multiple factors must be considered, including extent of disease, response to therapy, and underlying immune status of the host.

• Liposomal amphotericin B 3-5 mg/kg/day IV, amphotericin B lipid complex 5 mg/kg/day IV, itraconazole 200 mg PO BID, or posaconazole 200 mg PO q6h.
• Combination therapy with voriconazole and an echinocandin such as caspofungin 70 mg IV on day 1 and 50 mg/day IV thereafter may be considered.

• Lipid formulations of Amphotericin B 3-5 mg/kg/day +/− Flucytosine 25 mg/kg QID for ∼3 weeks

THEN Fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day)

• Treatment continued until clinical signs and symptoms resolved and CNS and radiographic abnormalities have normalized.

• Fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day)

• Lipid formulations of Amphotericin B 5 mg/kg/day for 4-6 weeks

THEN Fluconazole 800 mg/day PO/IV

• Treatment for at least 12 months and until resolution of CSF abnormalities

• Alternative azole considerations include itraconazole 200 mg PO BID to TID and voriconazole 200-400 mg PO BID.

• Fluconazole 400 mg/day PO/IV. Some use higher doses of Fluconazole, up to 1,000 mg/day up-front.
• Azole therapy is typically continued indefinitely.

• Itraconazole 200 mg PO BID to TID
• The addition of Intrathecal amphotericin B deoxycholate to azole therapy may be considered in those not responding to azoles.
• Intrathecal amphotericin B deoxycholate. dosing ranges from 0.1 to 1.5 mg per dose given daily to weekly.

• Voriconazole 6 mg/kg IV every 12h with assessment of voriconazole trough concentrations on day 5 of therapy with adjustment to achieve trough of 2-5 mcg/ml.
• IV therapy should be initiated in most cases with transition to PO therapy once improving and clinically stable.
• Total duration of therapy is unknown and will depend on extent of infection, response to therapy, and underlying immune status of the host.
• Minimum duration of 3-6 months.

• The addition of liposomal amphotericin B 5-6 mg/kg/day IV should be considered in patients with severe disease and/or not responding appropriately to voriconazole monotherapy.
• Doses of liposomal amphotericin B up to 7.5 mg/kg/day IV may be considered in patients who continue to do poorly.

• Liposomal amphotericin B 5 mg/kg/day IV for 4-6 weeks

THEN itraconazole 200 mg BID to TID for at least 1 year and until resolution of CSF abnormalities including Histoplasma antigen levels.

• Amphotericin B deoxycholate 0.7-1.0 mg/kg/day is an alternative to liposomal amphotericin B in patients at low risk of nephrotoxicity.

IV, intravenous;

PO, per os, oral administration;

BID, twice daily;

TID, three times daily;

QID, four times daily;