Fungal meningitis medical therapy: Difference between revisions

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* 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.
* 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.
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* [[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. 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.
* [[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.
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|''Candida''
|''Candida''
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* Lipid formulations of [[amphotericin B]] 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)
* 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.
* 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)
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* [[Fluconazole]] 400-800 mg/day PO/IV (6-12 mg/kg/day)
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|''Blastomyces''
|''Blastomyces''
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* Lipid formulations of [[amphotericin B]] 5 mg/kg/day for 4-6 weeks followed by [[fluconazole]] 800 mg/day PO/IV
* 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
* 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.
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* Alternative [[azole]] considerations include [[itraconazole]] 200 mg PO BID to TID and [[voriconazole]] 200-400 mg PO BID.
|-
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|''Coccidioides''
|''Coccidioides''
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* [[Fluconazole]] 400 mg/day PO/IV. Some use higher doses of [[fluconazole]], up to 1,000 mg/day up-front.
* [[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.
* [[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.
* [[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 [[Azole|azoles]].  
* [[Intrathecal]] [[amphotericin B]] [[deoxycholate]]. dosing ranges from 0.1 to 1.5 mg per dose given daily to weekly.
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|''Cryptococcus''
|''Cryptococcus''
|'''HIV-infection'''
|'''HIV-infection'''
'''''(Induction/consolidation)''''':
'''''(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 followed by [[fluconazole]] 400 mg/day PO/IV (6 mg/kg/day);  
* [[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.
* 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):'''''
'''''(Maintenance):'''''
* Fluconazole 200 mg/day
* Fluconazole 200 mg/day
'''''Solid organ transplant:'''''
'''''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  
* 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
{{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:'''''
'''''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 '''followed by''' [[fluconazole]] 200 mg/day (3 mg/kg) for 6-12 months
* [[Amphotericin B]] [[deoxycholate]] 0.7-1.0 mg/kg/day IV plus [[flucytosine]] 25 mg/kg QID for at least 4 weeks  
|HIV-infection
{{then}}  [[fluconazole]] 200 mg/day (3 mg/kg) for 6-12 months
(Induction/consolidation):
|'''HIV-infection'''
 
'''(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 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
* [[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;
(Maintenance):
* [[fluconazole]] (≥800 mg/day) PO/IV '''plus''' [[flucytosine]] 25 mg/kg PO QID for 6 weeks
 
[[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.
'''(Maintenance):'''
* [[Itraconazole]] 200 mg PO BID


Non-HIV, non-organ transplant:
'''Solid organ transplant:'''
* If [[flucytosine]] not used, then consider extension of induction with  lipid formulations of [[amphotericin B]] for at least 4-6 weeks.


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 AmBd; if [[flucytosine]] not used, then consider extension of [[Amphotericin B]] [[deoxycholate]] or  lipid formulations of [[amphotericin B]] induction for at least 2 additional 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.
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|''Exserohilum''
|''Exserohilum''
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* Total duration of therapy is unknown and will depend on extent of infection, response to therapy, and underlying immune status of the host.  
* 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.
* 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.
|
* 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.
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|''Histoplasma''
|''Histoplasma''
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* [[Liposomal amphotericin B]] 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 capsulatum|Histoplasma]]'' antigen levels.
* [[Liposomal amphotericin B]] 5 mg/kg/day IV for 4-6 weeks  
|[[Amphotericin B]] [[deoxycholate]] 0.7-1.0 mg/kg/day is an alternative to [[liposomal amphotericin B]] in patients at low risk of [[nephrotoxicity]].
{{then}} [[itraconazole]] 200 mg BID to TID for at least 1 year and until resolution of [[CSF]] abnormalities including ''[[Histoplasma capsulatum|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]].
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Revision as of 15:22, 2 February 2017

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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

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.
Candida

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.
Blastomyces

THEN fluconazole 800 mg/day PO/IV

  • Treatment for at least 12 months and until resolution of CSF abnormalities
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.
Cryptococcus HIV-infection

(Induction/consolidation):

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

(Maintenance):

  • Fluconazole 200 mg/day

Solid organ transplant:

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:

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

HIV-infection

(Induction/consolidation):

(Maintenance):

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:

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.
Histoplasma

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

KEY:

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. ↑ 1.0 1.1 Bicanic T, Harrison TS (2004). "Cryptococcal meningitis". Br Med Bull. 72: 99–118. doi:10.1093/bmb/ldh043. PMID 15838017.
  2. ↑ Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Seminars in Neurology. 20 (3): 307–22. doi:10.1055/s-2000-9394. PMID 11051295.

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