Fungal meningitis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor(s)-in-Chief: Rim Halaby
Overview
Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungals. In addition, frequent lumbar punctures are recommended in order to relieve the increased intracranial pressure[1].
Medical Therapy
- The treatment of fungal meningitis, such as cryptococcal meningitis, is a long course of high dose antifungals. The most commonly administered antifungals are amphotericin B and flucytosine[2]. Other antifungals that can be used are miconazole and fluconazole.
- Increased intracranial pressure is a common finding in fungal meningitis. Therefore, it is recommended to do frequent, ideally daily, lumbar punctures to relieve the intracranial pressure.[1]
| ANTIFUNGAL THERAPY IN FUNGAL MENINGITIS | ||
|---|---|---|
| Type of fungal meningitis | Preferred therapy | Alternate therapy |
| Aspergillus | Voriconazole 6 mg/kg IV q12h on day 1 followed by 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 AmB 3-5 mg/kg/day IV, ABLC 5 mg/kg/day IV, itraconazole 200 mg PO BID, or posaconazole 200 mg PO q6h. Note that 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. |
| Candida | LFAmB 3-5 mg/kg/day +/− flucytosine 25 mg/kg QID for ∼3 weeks followed by 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) |
| Blastomyces | LFAmB 5 mg/kg/day for 4-6 weeks followed by 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. |
| Coccidioides | 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 AmBd to azole therapy may be considered in those not responding to azoles. Intrathecal AmBd dosing ranges from 0.1 to 1.5 mg per dose given daily to weekly. |
| Cryptococcus | HIV-infection
(Induction/consolidation): AmBd 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg PO QID for at least 2 weeks followed by fluconazole 400 mg/day PO/IV (6 mg/kg/day); LFAmB may be substituted for AmBd if necessary: liposomal AmB 3-4 mg/kg/day IV and ABLC 5 mg/kg/day IV. (Maintenance): Fluconazole 200 mg/day[null b] Solid organ transplant: LFAmB (liposomal AmB 3-4 mg/kg/day IV or ABLC 5 mg/kg/day IV) plus flucytosine 25 mg/kg PO QID for at least 2 weeks followed by fluconazole 400-800 mg/day PO/IV (6-12 mg/kg/day) for 8 weeks followed by fluconazole 200-400 mg/day for 6-12 months Non-HIV, non-organ transplant: AmBd 0.7-1.0 mg/kg/day IV plus flucytosine 25 mg/kg QID for at least 4 weeks followed by fluconazole 200 mg/day (3 mg/kg) for 6-12 months |
HIV-infection
(Induction/consolidation): AmBd 0.7-1.0 mg/kg/day IV or LFAmB (liposomal AmB 3-4 mg/kg/day IV and ABLC 5 mg/kg/day IV) monotherapy for 4-6 weeks; AmBd 0.7 mg/kg/day IV plus fluconazole 800 mg/day PO/IV for 2 weeks followed by 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[null b] Solid organ transplant: If flucytosine not used, then consider extension of induction with LFAmB for at least 4-6 weeks. Non-HIV, non-organ transplant: LFAmB (liposomal AmB 3-4 mg/kg/day IV or ABLC 5 mg/kg/day IV) can be substituted in those unable to tolerate AmBd; if flucytosine not used, then consider extension of AmBd or LFAmB induction for at least 2 additional weeks. |
| Exserohilum | 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 AmB 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 AmB up to 7.5 mg/kg/day IV may be considered in patients who continue to do poorly. |
| Histoplasma | Liposomal AmB 5 mg/kg/day IV for 4-6 weeks followed by itraconazole 200 mg BID to TID for at least 1 year and until resolution of CSF abnormalities including Histoplasma antigen levels. | AmBd 0.7-1.0 mg/kg/day is an alternative to liposomal AmB in patients at low risk of nephrotoxicity. |
| IV, intravenous; AmB, amphotericin B; ABLC, amphotericin B lipid complex; PO, per os, oral administration; BID, twice daily; LFAmB, lipid formulations of amphotericin B; TID, three times daily; QID, four times daily; AmBd, amphotericin B deoxycholate. | ||
References
- ↑ 1.0 1.1 Bicanic T, Harrison TS (2004). "Cryptococcal meningitis". Br Med Bull. 72: 99–118. doi:10.1093/bmb/ldh043. PMID 15838017.
- ↑ Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Seminars in Neurology. 20 (3): 307–22. doi:10.1055/s-2000-9394. PMID 11051295.