IDSA Endemic Mycoses Guidelines Guidelines Ryan Bariola, MD - PowerPoint PPT Presentation

IDSA Endemic Mycoses Guidelines Guidelines Ryan Bariola, MD

Endemic Mycoses Endemic Mycoses • Prior Guidelines Issued in 2000 Prior Guidelines Issued in 2000 • Updated in 2007/2008 Updated in 2007/2008 – Sporotrichosis Sporotrichosis – Blastomycosis y – Histoplasmosis

Common Themes Common Themes • Increased role for lipid formulations of Increased role for lipid formulations of Amphotericin B • Step down therapy with AmB followed by azoles • Possible role of voriconazole and posaconazole o e o e o o co o e po co o e • Therapeutic drug monitoring Therapeutic drug monitoring

Sporotrichosis Sporotrichosis • Sporothrix schenckii p • Usual inoculation is cutaneous • Manifestations – Cutaneous/lymphocutaneous disease C t /l h t di – Osteoarticular disease – Pulmonary – Disseminated – Meningitis

Unchanged Recommendations Unchanged Recommendations • Cutaneous/Lymphocutaneous Disease Cutaneous/Lymphocutaneous Disease – Itraconazole preferred – 2-4 weeks after lesions resolve (3-6 months) 2 4 weeks after lesions resolve (3 6 months) – Local hyperthermia therapy – Terbinafine T bi fi – SSKI

Unchanged Recommendations Unchanged Recommendations • Osteoarticular Osteoarticular – Itraconazole x 12 months • Mild to moderate pulmonary disease – Itraconazole x 12 months – Surgical resection in select cases

Changes in Guidelines: Sporotrichosis 2000 2000 2007 2007 • Cutaneous • Cutaneous – Itraconazole 100-200 mg – Itraconazole 200 mg g – Fluconazole 2 nd line – Fluconazole only if itra, SSKI, or terbinafine are ineffective • Osteoarticular • Osteoarticular – Fluconazole not – Fluconazole 3rd line recommended

Changes in Guidelines: Sporotrichosis 2000 2000 2007 2007 • Severe disease • Severe disease – Amphotericin B p – Lipid AmB followed by p y deoxycholate itraconazole • Meningitis • Meningitis • Meningitis Me i iti – Lipid AmB 4-6 weeks – AmB deoxycholate 1-2 gm followed by itraconazole

Changes in Guidelines: Sporotrichosis • Role of voriconazole and posaconazole Role of voriconazole and posaconazole – No published data – Voriconazole has no in vitro activity Voriconazole has no in vitro activity

Blastomycosis Blastomycosis • Blastomyces dermatitidis y • Inhalational inoculation • Manifestations – Pulmonary u o a y – Cutaneous – Osteoarticular – Genitourinary Genitourinary – CNS – Virtually any organ

Unchanged Recommendations Unchanged Recommendations • Mild to moderate pulmonary disease Mild to moderate pulmonary disease – Itraconazole x 6-12 months • Mild to moderate disseminated disease – Itraconazole x 6-12 months • Osteoarticular – Itraconazole x 12 months Itraconazole x 12 months

Changes in Guidelines: Blastomycosis 2000 2000 2008 2008 • Severe Disease • Severe Disease – AmB deoxycholate y – Lipid AmB 1-2 weeks, Lipid AmB 1 2 weeks, followed by itraconazole 1.5-2.5 gm total • Immunosuppressed I d • Immunosuppressed I d – Lipid AmB 1-2 weeks, – AmB deoxycholate 1.5-2.5 followed by oral azole gm, followed by oral azole th therapy at least 12 months t l t 12 th th therapy indefinitely i d fi it l

Changes in Guidelines: Blastomycosis 2000 2000 2008 2008 • CNS Disease • CNS Disease – Lipid AmB 4-6 weeks, – AmB deoxycholate followed by itraconazole, 2 gm total voriconazole, or high dose fluconazole

Changes in Guidelines: Blastomycosis • Ketoconazole and fluconazole largely removed g y from guidelines • Voriconazole and posaconazole have activity • Voriconazole and posaconazole have activity against B. dermatitidis • Clinical reports of successful treatment with voriconazole, especially CNS disease • No reports yet of posaconazole use for B. dermatitidis

Changes in Guidelines: Blastomycosis • Therapeutic Drug Monitoring Therapeutic Drug Monitoring – Itraconazole levels 2 weeks after starting therapy therapy • 1.0-10.0 μ g/mL – Voriconazole levels? Voriconazole levels?

Histoplasmosis Histoplasmosis • Histoplasma capsulatum p p • Inhalational exposure • Manifestations – Asymptomatic infection sy pto at c ect o – Pulmonary/Mediastinal disease – Disseminated – CNS CNS – Visceral involvement, especially mucosal involvement – Rheumatologic manifestations Rh t l i if t ti

Unchanged Recommendations Unchanged Recommendations • No indication for antifungal therapy No indication for antifungal therapy – Localized pulmonary disease • Symptoms < than 4 weeks • Symptoms < than 4 weeks – Rheumatologic complications – Pericarditis Pericarditis • Unless steroids given for severe pericarditis – Histoplasmoma – Histoplasmoma – Broncholithiasis – Asymptomatic granulomatous mediastinitis Asymptomatic granulomatous mediastinitis

Unchanged Recommendations Unchanged Recommendations • Treatment recommended Treatment recommended – Acute pulmonary disease, > 4 wks symptoms – Severe pulmonary disease • Antifungal therapy + steroids – Chronic cavitary pulmonary disease – Mild to moderate disseminated disease • Itraconazole

Changes in Guidelines: Histoplasmosis 2000 2000 2007 2007 • Severe disease • Severe disease – Amphotericin B, p – Lipid AmB, followed by p y sometimes for entire itraconazole course • CNS disease • CNS disease – Liposomal AmB 4-6 weeks, – Amphotericin B 3 months, then itraconazole then itraconazole then fluconazole then fluconazole

Changes in Guidelines: Histoplasmosis • Antifungal discontinuation in AIDS patients Antifungal discontinuation in AIDS patients – At least 1 year of itraconazole – Negative blood cultures g – Serum and urine antigen levels <2 ng/mL – CD4 >150 cells/mm 3 – On HAART

Changes in Guidelines: Histoplasmosis • Voriconazole and posaconazole have Voriconazole and posaconazole have activity against H. capsulatum • Decreased voriconazole sensitivity in patients that have failed fluconazole patients that have failed fluconazole therapy • After itraconazole, all other azoles are considered second-line alternatives considered second line alternatives

Changes in Guidelines Changes in Guidelines • Therapeutic Drug Monitoring Therapeutic Drug Monitoring – Itraconazole • 1 0-10 0 μ g/mL • 1.0-10.0 μ g/mL – Voriconazole • Trough at least 0 5 μ g/mL Trough at least 0.5 μ g/mL • Peak at least 2 μ g/mL – Posaconazole Posaconazole • Random level at least 0.5 μ g/mL

Thank You Thank You