Coccidioidomycosis medical therapy

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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]Aditya Ganti M.B.B.S. [3]

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.. 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

• 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

• 2.1 Adult

• 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
• Note: Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.

• 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

• 3.1 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

• Preferred regimen (1): Fluconazole 400 mg PO qd
• Preferred regimen (2): Itraconazole 200 mg PO bid
• Alternative regimen (1): Posaconazole 200 mg PO bid
• Alternative regimen (2): Voriconazole 200 mg PO bid