Cryptococcosis medical therapy: Difference between revisions

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{{CMG}}
__NOTOC__
{{Cryptococcosis}}
{{Cryptococcosis}}
{{CMG}} {{AE}} {{SSK}}; {{YD}}


==Overview==
==Overview==
The standard regimen of treatment in non-[[AIDS]] patients is [[Intravenous therapy|intravenous]] [[amphotericin B]] combined with [[oral]] [[flucytosine]]. [[HIV AIDS|AIDS]] patients often have a reduced response to [[amphotericin B]] and [[flucytosine]], therefore after initial treatment as above, [[oral]] [[fluconazole]] can be used.


==Medical Therapy==
==Medical Therapy==
The standard regimen of treatment in non-AIDS patients [[intravenous]] [[Amphotericin B]] combined with [[Wiktionary:oral|oral]] [[flucytosine]].
The standard regimen of treatment in non-[[HIV AIDS|AIDS]] patients is [[intravenous]] [[amphotericin B]] combined with [[oral]] [[flucytosine]]. [[AIDS]] patients often have a reduced response to [[amphotericin B]] and [[flucytosine]], therefore after initial treatment as above, [[oral]] [[fluconazole]] can be used.
===Antimicrobial Regimens===
* '''1. ''Cryptococcus neoformans'''''
:* '''1.1 Meningoencephalitis in HIV infected patients'''<ref name="pmid20047480">{{cite journal| author=Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ et al.| title=Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. | journal=Clin Infect Dis | year= 2010 | volume= 50 | issue= 3 | pages= 291-322 | pmid=20047480 | doi=10.1086/649858 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20047480  }} </ref>
::* '''1.1.1 Induction and consolidation'''
:::*Preferred regimen: ([[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h for 2 weeks {{and}} [[Flucytosine]] 100 mg/kg/day PO/IV q6h for 2 weeks) {{then}} [[Fluconazole]] 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
:::*Preferred regimen ([[Renal impairment|renally impaired]]): ([[Liposomal AmB]] 3-4 mg/kg IV q24h {{and}} [[Flucytosine]] 100 mg/kg/day PO/IV q6h for 2 weeks) {{then}} [[Fluconazole]] 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
:::*Preferred regimen ([[Renal impairment|renally impaired]]): ([[Amphotericin B]] lipid complex (ABLC) 5 mg/kg IV q24h {{and}} [[Flucytosine]] 100 mg/kg/day PO/IV q6h for 2 weeks) {{then}} [[Fluconazole]] 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
:::*Alternative regimen (1): [[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h {{or}} [[Liposomal AmB]] 3-4 mg/kg IV q24h {{or}} [[Amphotericin B]] lipid complex 5 mg/kg IV q24h for 4-6 weeks
:::*Alternative regimen (2): ([[Amphotericin B]] deoxycholate 0.7 mg/kg IV q24h {{and}} [[Fluconazole]] 800 mg PO qd for 2 weeks) {{then}} [[Fluconazole]] 800 mg PO qd for ≥ 8 weeks
:::*Alternative regimen (3): [[Fluconazole]] 800-1200 mg PO qd {{and}} [[Flucytosine]] 100 mg/kg/day PO qid for 6 weeks
:::*Alternative regimen (4): [[Fluconazole]] PO 800-2000 mg PO qd for 10-12 weeks


AIDS patients often have a reduced response to Amphotericin B and flucytosine, therefore after initial treatment as above, oral [[fluconazole]] can be used.
::* '''1.1.2 Maintenance and prophylactic therapy'''
:::*Preferred regimen: [[Fluconazole]] 200 mg PO qd {{and}} [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|HAART]] 2-10 weeks after initiation of [[Antifungal medication|antifungal therapy]]
:::*Alternative regimen (1): [[Itraconazole]] 200 mg PO bid
:::*Alternative regimen (2): [[Amphotericin B]] deoxycholate 1 mg/kg IV qw
:::* Note (1): Consider discontinuing therapy if [[CD4]] count is higher than 100 cells/uL {{and}} undetectable {{or}} very low [[HIV]] [[RNA]] level for > 3 months
:::* Note (2): Consider reinstitution of maintenance therapy if [[CD4]] count <100 cells/uL
 
:* '''1.2. Cerebral cryptococcomas'''
:::*Preferred regimen for induction and consolidation: ([[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with [[renal dysfunction]]) {{or}} [[Liposomal AmB]] 3-4mg/kg IV qd {{or}} [[Amphotericin B]] lipid complex (ABLC) 5mg/kg IV qd) {{plus}} [[Flucytosine]] 100mg/kg/day PO or IV qid for at least 2 weeks followed by [[fluconazole]] 400mg (6mg/kg) PO qd for at least 8 weeks
:::*Note: Consider surgery if [[lesions]] are larger than 3cm, accessible [[lesions]] with [[mass effect]] or [[lesions]] that are enlarging and not explained by [[Immune reconstitution inflammatory syndrome|IRIS]]
 
:* '''1.3. ''Cryptococcus neoformans'' meningitis in HIV negative patients'''
:::*Preferred regimen: [[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV qd {{plus}} [[Flucytosine]] 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any [[neurological]] complication) followed by [[fluconazole]] 400mg PO qd for 8 weeks. If there's toxicity to  [[amphotericin B]] deoxycholate, consider changing to [[liposomal AmB]] in the second 2 weeks
:::*Note (1): After induction and consolidation therapy, start [[fluconazole]] 200mg (3mg/kg) PO qd for 6-12 months
:::*Note (2): If [[flucytosine]] is not given, consider lengthening the induction therapy for at least 2 weeks
 
:* '''1.4. ''Cryptococcus neoformans'' pulmonary disease - immunosupressed'''
:::*Mild-moderate symptoms, without severe [[immunosupression]] and absence of diffuse [[pulmonary]] infiltrates:
::::*Preferred regimen: [[Fluconazole]] 400 mg PO qd for 6-12 months
:::*Severe [[pneumonia]], [[disseminated disease]], or [[CNS]] infection:
::::*Preferred regimen: treat like [[CNS]] [[cryptococcosis]]
:::*Note (1): In [[Human Immunodeficiency Virus (HIV)|HIV]]-infected patients, treatment should be stopped after 1 year if [[CD4]] count is > 100 and a [[Cryptococcal infection|cryptococcal]] [[antigen]] [[titer]] is < 1:512 and not increasing.
:::*Note (2): Consider [[corticosteroid]] if [[ARDS]] is present in a context which it might be attributed to [[Immune reconstitution inflammatory syndrome|IRIS]]
 
:* '''1.5 ''Cryptococcus neoformans'' pulmonary disease - non-immunosupressed'''
:::*Mild-moderate symptoms, without severe [[immunosupression]] and absence of diffuse [[pulmonary]] infiltrates:
::::*Preferred regimen: [[Fluconazole]] 400 mg PO qd for 6-12 months
::::*Alternative regimen: If [[fluconazole]] is unavailable or contraindicated, [[Itraconazole]] 200mg PO bid, [[voriconazole]] 200 mg PO bid, and [[posaconazole]] 400mg PO BID
:::*If the patient has severe [[pneumonia]], [[disseminated disease]], or [[Central nervous system infection|CNS infection]]:
::::*Preferred regimen: Treat like [[CNS]] [[cryptococcosis]] for 6-12 months
 
:* '''1.6 ''Cryptococcus neoformans'' non-lung, non-CNS infection'''
:::*Cryptococcemia or disseminated cryptococcic disease  (involvement of at least 2 noncontiguous sites or [[Cryptococcal infection|cryptococcal]] [[antigen]] [[titer]] > 1:512):
::::*Preferred regimen: treat like [[Central nervous system infection|CNS infection]]
:::*If infection occurs at a single site and no [[Immunosuppressive drug|immunosupressive]] risk factors
::::*Preferred regimen: [[Fluconazole]] 400mg PO qd for 6-12 months
 
:* '''1.7. Cryptococcosis in children'''
::::*Preferred regimen for induction and consolidation: [[Amphotericin B]] deoxycholate 1.0 mg/kg qd IV {{plus}} [[Flucytosine]] 100mg/kg PO or IV qid for 2 weeks followed by [[fluconazole]] 10-12mg/kg PO qd for 8 weeks
::::*Alternative regimen ([[Renal impairment|renally impaired]]): Change [[amphotericin B]] deoxycholate by [[liposomal AmB]] 5mg/kg IV qd or [[amphotericin B]] lipid complex (ABLC) 5mg/kg IV qd
::::*Preferred regimen for maintenance: [[Fluconazole]] 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized
:::*[[Cryptococcal infection|Cryptococcal]] [[pneumonia]]:
::::*Preferred regimen: [[Fluconazole]] 6-12mg/kg PO qd for 6-12 months
 
:* '''1.8. Cryptococcosis in pregnant women'''
:::*Preferred regimen for induction and consolidation: [[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with [[renal dysfunction]] - [[liposomal AmB]] 3-4mg/kg IV qd {{or}} [[amphotericin B]] lipid complex (ABLC) 5mg/kg IV qd). Consider using [[flucytosine]] in relationship to benefit risk basis, since it is a category C drug for pregnancy
:::*Start [[fluconazole]] after delivery
:::*Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy
:::*Note: If [[pulmonary]] [[cryptococcosis]], perform close follow-up and administer [[fluconazole]] after delivery.
 
*'''2. ''Cryptococcus gatti'''''
::*[[Disseminated disease|Disseminated]] [[cryptococcosis]] or [[CNS]] disease:
:::*Preferred regimen: Treatment is the same as ''[[Cryptococcus neoformans|C. neoformans]]''
::*[[Pulmonary]] disease: Single and small cryptococcoma
:::*Preferred regimen: [[Fluconazole]] 400mg per day PO for 6-18 months
::*[[Pulmonary]] disease: Very large or multiple cryptococcomas
:::*Preferred regimen: Administer [[flucytosine]] {{and}} [[Amphotericin B]] deocycholate for 4-6 weeks, followed by [[fluconazole]] for 6-18 months
:::*Note: Surgery should be considered if there is compression of vital structures {{or}} failure to reduce the size of the cryptococcoma after 4 weeks of therapy


==References==
==References==
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[[Category:Fungal diseases]]
[[Category:Fungal diseases]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Infectious Disease Project]]
[[Category:Emergency medicine]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Pulmonology]]
[[Category:Neurology]]
[[Category:Dermatology]]

Latest revision as of 21:10, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.

Overview

The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole can be used.

Medical Therapy

The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole can be used.

Antimicrobial Regimens

  • 1. Cryptococcus neoformans
  • 1.1 Meningoencephalitis in HIV infected patients[1]
  • 1.1.1 Induction and consolidation
  • 1.1.2 Maintenance and prophylactic therapy
  • Preferred regimen: Fluconazole 200 mg PO qd AND HAART 2-10 weeks after initiation of antifungal therapy
  • Alternative regimen (1): Itraconazole 200 mg PO bid
  • Alternative regimen (2): Amphotericin B deoxycholate 1 mg/kg IV qw
  • Note (1): Consider discontinuing therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for > 3 months
  • Note (2): Consider reinstitution of maintenance therapy if CD4 count <100 cells/uL
  • 1.2. Cerebral cryptococcomas
  • 1.3. Cryptococcus neoformans meningitis in HIV negative patients
  • Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by fluconazole 400mg PO qd for 8 weeks. If there's toxicity to amphotericin B deoxycholate, consider changing to liposomal AmB in the second 2 weeks
  • Note (1): After induction and consolidation therapy, start fluconazole 200mg (3mg/kg) PO qd for 6-12 months
  • Note (2): If flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks
  • 1.4. Cryptococcus neoformans pulmonary disease - immunosupressed
  • Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months
  • Note (1): In HIV-infected patients, treatment should be stopped after 1 year if CD4 count is > 100 and a cryptococcal antigen titer is < 1:512 and not increasing.
  • Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS
  • 1.5 Cryptococcus neoformans pulmonary disease - non-immunosupressed
  • 1.6 Cryptococcus neoformans non-lung, non-CNS infection
  • Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer > 1:512):
  • Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
  • 1.7. Cryptococcosis in children
  • Preferred regimen: Fluconazole 6-12mg/kg PO qd for 6-12 months
  • 1.8. Cryptococcosis in pregnant women
  • Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - liposomal AmB 3-4mg/kg IV qd OR amphotericin B lipid complex (ABLC) 5mg/kg IV qd). Consider using flucytosine in relationship to benefit risk basis, since it is a category C drug for pregnancy
  • Start fluconazole after delivery
  • Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy
  • Note: If pulmonary cryptococcosis, perform close follow-up and administer fluconazole after delivery.
  • 2. Cryptococcus gatti
  • Pulmonary disease: Single and small cryptococcoma
  • Preferred regimen: Fluconazole 400mg per day PO for 6-18 months
  • Pulmonary disease: Very large or multiple cryptococcomas
  • Preferred regimen: Administer flucytosine AND Amphotericin B deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months
  • Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy

References

  1. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ; et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clin Infect Dis. 50 (3): 291–322. doi:10.1086/649858. PMID 20047480.