Coccidioidomycosis medical therapy: Difference between revisions

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===Antimicrobial Regimen===
===Antimicrobial Regimen===
:* 1. '''Primary pulmonary infection''' <ref name="pmid16206093">{{cite journal| author=Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA et al.| title=Coccidioidomycosis. | journal=Clin Infect Dis | year= 2005 | volume= 41 | issue= 9 | pages= 1217-23 | pmid=16206093 | doi=10.1086/496991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16206093  }} </ref>
:* '''1. Primary pulmonary infection''' <ref name="pmid16206093">{{cite journal| author=Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA et al.| title=Coccidioidomycosis. | journal=Clin Infect Dis | year= 2005 | volume= 41 | issue= 9 | pages= 1217-23 | pmid=16206093 | doi=10.1086/496991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16206093  }} </ref>
::* 1.1 '''Indications for antifungal therapy'''
::* 1.1 '''Indications for antifungal therapy'''
::::* Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
::::* Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
Line 22: Line 22:
::::* Prominent or persistent hilar adenopathy
::::* Prominent or persistent hilar adenopathy
::::* Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16
::::* Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16
::* 1.2 '''Patients with low risk of complications or dissemination'''
::* '''1.2 Patients with low risk of complications or dissemination'''
::::* For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.
::::* For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.
::* 1.3 '''Patients with high risk of complications or dissemination'''
::* '''1.3 Patients with high risk of complications or dissemination'''
:::* 1.3.1 '''Mild to moderate pneumonia'''
:::* '''1.3.1 Mild to moderate pneumonia'''
::::* Preferred regimen (1): [[Itraconazole]] solution 200 mg PO bid or IV q12h
::::* Preferred regimen (1): [[Itraconazole]] solution 200 mg PO bid or IV q12h
::::* Preferred regimen (2): [[Fluconazole]] 400 mg PO q24h for 3–12 months
::::* Preferred regimen (2): [[Fluconazole]] 400 mg PO q24h for 3–12 months
:::* 1.3.2 '''Locally severe or disseminated pneumonia'''
:::* '''1.3.2 Locally severe or disseminated pneumonia'''
::::* Preferred regimen: ([[Amphotericin B]] 0.6–1 mg/kg PO qd every 7 days {{then}} 0.8 mg/kg PO every other day {{or}} [[Liposomal Amphotericin B]] 3-5 mg/kg IV q24 hrs {{or}} [[Amphotericin B lipid complex]] 5 mg/kg IV q24 hrs until clinical improvement) followed by [[Itraconazole]] {{or}} [[Fluconazole]] for at least 1 year.
::::* Preferred regimen: ([[Amphotericin B]] 0.6–1 mg/kg PO qd every 7 days {{then}} 0.8 mg/kg PO every other day {{or}} [[Liposomal Amphotericin B]] 3-5 mg/kg IV q24 hrs {{or}} [[Amphotericin B lipid complex]] 5 mg/kg IV q24 hrs until clinical improvement) followed by [[Itraconazole]] {{or}} [[Fluconazole]] for at least 1 year.
::::* Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
::::* Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
::::* Note (2): Consultation with specialist recommendation, surgery may be required.
::::* Note (2): Consultation with specialist recommendation, surgery may be required.


:* 2. '''Meningitis'''<ref name="pmid16206093">{{cite journal| author=Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA et al.| title=Coccidioidomycosis. | journal=Clin Infect Dis | year= 2005 | volume= 41 | issue= 9 | pages= 1217-23 | pmid=16206093 | doi=10.1086/496991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16206093  }} </ref>
:* '''2. Meningitis'''<ref name="pmid16206093">{{cite journal| author=Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA et al.| title=Coccidioidomycosis. | journal=Clin Infect Dis | year= 2005 | volume= 41 | issue= 9 | pages= 1217-23 | pmid=16206093 | doi=10.1086/496991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16206093  }} </ref>
::* 2.1 '''Adult'''
::* '''2.1 Adult'''
::::* Preferred regimen: [[Fluconazole]] 400–1,000 mg PO q24h indefinitely.
::::* Preferred regimen: [[Fluconazole]] 400–1,000 mg PO q24h indefinitely.
::::* Alternative regimen: [[Amphotericin B]] 3-5 mg/kg IV q24 hrs {{plus}} 0.1–0.3 mg qd intrathecal (intraventricular) via reservoir device {{or}} [[Itraconazole]] 400–800 mg q24h {{or}} [[Voriconazole]]
::::* Alternative regimen: [[Amphotericin B]] 3-5 mg/kg IV q24 hrs {{plus}} 0.1–0.3 mg qd intrathecal (intraventricular) via reservoir device {{or}} [[Itraconazole]] 400–800 mg q24h {{or}} [[Voriconazole]]
::::* Note: Some use combination of [[Amphotericin B]] and [[Fluconazole]] for progressive severe disease; controlled series lacking.
::::* Note: Some use combination of [[Amphotericin B]] and [[Fluconazole]] for progressive severe disease; controlled series lacking.
::* 2.2 '''Child'''
::* '''2.2 Child'''
::::* Preferred regimen: [[Fluconazole]] PO (Pediatric dose not established, 6 mg per kg q24h used)
::::* Preferred regimen: [[Fluconazole]] PO (Pediatric dose not established, 6 mg per kg q24h used)
::::* Alternative regimen: [[Amphotericin B]] 3-5 mg/kg IV q24 hrs {{plus}} 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device {{or}} itra 400–800 mg q24h {{or}} [[Voriconazole]]
::::* Alternative regimen: [[Amphotericin B]] 3-5 mg/kg IV q24 hrs {{plus}} 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device {{or}} [[Itraconazole]] 400–800 mg q24h {{or}} [[Voriconazole]]


:* 3. '''Special considerations for HIV/AIDS patients'''<ref>{{ cite web | title = Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents | url = https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultOITablesOnly.pdf }}</ref>
:* '''3. Special considerations for HIV/AIDS patients'''<ref>{{ cite web | title = Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents | url = https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultOITablesOnly.pdf }}</ref>
::* 3.1 '''Clinically mild infections (e.g., focal pneumonia)'''
::* '''3.1 Clinically mild infections (e.g., focal pneumonia)'''
:::* Preferred regimen: [[Fluconazole]] 400 mg PO daily {{or}} [[Itraconazole]] 200 mg PO bid
:::* Preferred regimen: [[Fluconazole]] 400 mg PO daily {{or}} [[Itraconazole]] 200 mg PO bid
:::* Alternative regimen (unresponsive to Fluconazole or Itraconazole): [[Posaconazole]] 200 mg PO bid {{or}} [[Voriconazole]] 200 mg PO bid
:::* Alternative regimen (unresponsive to Fluconazole or Itraconazole): [[Posaconazole]] 200 mg PO bid {{or}} [[Voriconazole]] 200 mg PO bid
:::* Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional
:::* Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional
::* 3.2 '''Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)'''
::* '''3.2 Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)'''
:::* 3.2.1 Preferred regimen: [[Amphotericin B]] deoxycholate 0.7–1.0 mg/kg IV q12hrs {{or}} Lipid formulation [[Amphotericin B]] 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
:::*Preferred regimen: [[Amphotericin B]] deoxycholate 0.7–1.0 mg/kg IV q12hrs {{or}} Lipid formulation [[Amphotericin B]] 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
:::* 3.2.2 Alternative regimen: Some specialists will add a triazole ([[Fluconazole]] or [[Itraconazole]], with [[Itraconazole]] (preferred for bone disease) 400 mg per day to [[Amphotericin B]] therapy and continue triazole once [[Amphotericin B]] is stopped
:::*Alternative regimen: Some specialists will add a triazole ([[Fluconazole]] or [[Itraconazole]], with [[Itraconazole]] (preferred for bone disease) 400 mg per day to [[Amphotericin B]] therapy and continue triazole once [[Amphotericin B]] is stopped
:::* Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
:::* Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
:::* Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL
:::* Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL
::* 3.3 '''Meningeal Infections'''
::* '''3.3 Meningeal Infections'''
:::* Preferred regimen: [[Fluconazole]] 400–800 mg IV or PO daily
:::* Preferred regimen: [[Fluconazole]] 400–800 mg IV or PO daily
:::* Alternative regimen: [[Itraconazole]] 200 mg PO tid for 3 days {{then}} 200 mg PO bid {{or}} [[Posaconazole]] 200 mg PO bid {{or}} [[Voriconazole]] 200–400 mg PO bid {{or}} Intrathecal [[Amphotericin B]] deoxycholate when triazole antifungals are ineffective.
:::* Alternative regimen: [[Itraconazole]] 200 mg PO tid for 3 days {{then}} 200 mg PO bid {{or}} [[Posaconazole]] 200 mg PO bid {{or}} [[Voriconazole]] 200–400 mg PO bid {{or}} Intrathecal [[Amphotericin B]] deoxycholate when triazole antifungals are ineffective.
Line 58: Line 58:
:::* Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
:::* Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
:::* Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy
:::* Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy
::* 3.4 '''Chronic Suppressive Therapy'''
::* '''3.4 Chronic Suppressive Therapy'''
:::* Preferred regimen (1): [[Fluconazole]] 400 mg PO qd
:::* Preferred regimen (1): [[Fluconazole]] 400 mg PO qd
:::* Preferred regimen (2): [[Itraconazole]] 200 mg PO bid
:::* Preferred regimen (2): [[Itraconazole]] 200 mg PO bid

Revision as of 14:03, 3 August 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2]

Treatment

The drug therapy is guided by the severity of symptoms and the immune status of the patient. Since most patients are asymptomatic or mildly affected, no treatment or a single drug azole therapy (fluconazole or itraconazole) may be sufficient in these cases. More recently resistant cases are being treated with voriconazole or posaconazole.[1]. However patients with HIV, immune-compromised, those on steroids or pregnant females need much more aggressive approach. More severe cases may require intravenous amphotericin B, with or without simultaneous oral azole therapy. Meningitis or vasculitis often need initial in-patient treatment with oral azoles plus intravenous amphotericin B with or without intrathecal amphotericin B. Untreated cases may sometimes be fatal.

Pregnant females are treated by Intravenous amphotericin B only.

Antimicrobial Regimen

  • 1. Primary pulmonary infection [2]
  • 1.1 Indications for antifungal therapy
  • Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
  • Diabetes
  • Preexisting cardiomyopathy
  • Pregnancy (third trimester)
  • Filipino or African
  • Weight loss of > 10%
  • Intense night sweats persisting longer than 3 weeks
  • Infiltrates involving more than one-half of one lung or portions of both lungs
  • Prominent or persistent hilar adenopathy
  • Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16
  • 1.2 Patients with low risk of complications or dissemination
  • For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.
  • 1.3 Patients with high risk of complications or dissemination
  • 1.3.1 Mild to moderate pneumonia
  • Preferred regimen (1): Itraconazole solution 200 mg PO bid or IV q12h
  • Preferred regimen (2): Fluconazole 400 mg PO q24h for 3–12 months
  • 1.3.2 Locally severe or disseminated pneumonia
  • Preferred regimen: (Amphotericin B 0.6–1 mg/kg PO qd every 7 days THEN 0.8 mg/kg PO every other day OR Liposomal Amphotericin B 3-5 mg/kg IV q24 hrs OR Amphotericin B lipid complex 5 mg/kg IV q24 hrs until clinical improvement) followed by Itraconazole OR Fluconazole for at least 1 year.
  • Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
  • Note (2): Consultation with specialist recommendation, surgery may be required.
  • 2. Meningitis[2]
  • 2.1 Adult
  • 2.2 Child
  • Preferred regimen: Fluconazole PO (Pediatric dose not established, 6 mg per kg q24h used)
  • Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device OR Itraconazole 400–800 mg q24h OR Voriconazole
  • 3. Special considerations for HIV/AIDS patients[3]
  • 3.1 Clinically mild infections (e.g., focal pneumonia)
  • Preferred regimen: Fluconazole 400 mg PO daily OR Itraconazole 200 mg PO bid
  • Alternative regimen (unresponsive to Fluconazole or Itraconazole): Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
  • Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional
  • 3.2 Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)
  • Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV q12hrs OR Lipid formulation Amphotericin B 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
  • Alternative regimen: Some specialists will add a triazole (Fluconazole or Itraconazole, with Itraconazole (preferred for bone disease) 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped
  • Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
  • Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL
  • 3.3 Meningeal Infections
  • Preferred regimen: Fluconazole 400–800 mg IV or PO daily
  • Alternative regimen: Itraconazole 200 mg PO tid for 3 days THEN 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid OR Intrathecal Amphotericin B deoxycholate when triazole antifungals are ineffective.
  • Note (1): Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.
  • Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
  • Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy
  • 3.4 Chronic Suppressive Therapy

References

  1. Chen, S.; Erhart, LM.; Anderson, S.; Komatsu, K.; Park, B.; Chiller, T.; Sunenshine, R. (2011). "Coccidioidomycosis: knowledge, attitudes, and practices among healthcare providers--Arizona, 2007". Med Mycol. 49 (6): 649–56. doi:10.3109/13693786.2010.547995. PMID 21247229. Unknown parameter |month= ignored (help)
  2. 2.0 2.1 Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA; et al. (2005). "Coccidioidomycosis". Clin Infect Dis. 41 (9): 1217–23. doi:10.1086/496991. PMID 16206093.
  3. "Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" (PDF).

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