Mycoses

When to consider systemic mycoses?

• • Normal host with unexplained chronic pulmonary pathology, chronic meningitis, lytic bone lesions, chronic skin lesions, FUO, or cytopenias.

  • Immunocompromised patients, with pulmonary, cutaneous, funduscopic, or head-neck signs and symptoms, or persistent or unexplained fever.

Consider geographic predisposition of the mycoses, site of infection, inflammatory response, microscopic fungal appearance.

Candidiasis

• • Often associated with ABx use, OCP, immuosuppressant and cytotoxic therapy, and indwelling FB.

  • Candidemia leading to skin lesions, ocular disease, and OM can occur.

  • Dx: mucocutaneous candidiasis is usually based on clinical findings, but can be confirmed by a KOH preparation of exudates. Culture can be obtained in refractory cases to exclude non-albican Candidia spp. Invasive candidiasis is Dx by positive BC or tissue cultures.

Tx:

• • Mucocutaneous candidiasis: Clotrimazole troches, 10 mg dissolved PO x 5 time daily for 14 days

    • Esophageal candidiasis: Fluconazole 100 - 200 mg PO qd x 14 d.

    • Vaginal: topical azole x 1 - 14 d or fluconazole150 mg PO x 1

      • Suppressive therapy is not indicated in HIV unless severe recurrences.

    • Neutropenia and candidiasis: Fluconazole, 400 mg PO qd or itraconazole, 200 mg PO q12h. Continue prophylaxis until ANC >500 or 3 mo post solid organ transplant.

  • Invasive Candidiasis: Fluconazole, 800 mg loading dose, then 400 mg IV/PO qd x 7 d, then PO x 14 d.

    • Severe dz, recent azole exposure, suspicion of non-albicans species: Amphotericin B (AmpB doxycholate: 0.7 - 1 mg/kg. AmpB liposomal 3 - 5 mg/kg) or anidulafungin 200 mg IV x 1, then 100 mg daily.

    • Treat all +ve BC as invasive dz, with at least 14-d therapy. Catheters must be removed. Treat for 14-d beyond last +ve BC. C. parapsilosis should not be initially treated with an echinocandin.

Cryptococcus neoformans

• • Ubiquitous yeast associated with soil and pigeon excrement.

  • Disease is mainly meningitis (HA and mental status) and pulmonary ( ASx nodular dz to fulminant respiratory failure).

  • Dx: detection of encapsulated yeast in tissue or body fluid (India ink stain) with confirmation by culture. Latex agglutination test for cryptococcal antigen (CrAg) in serum or CSF is helpful, and a +ve Sr. CrAg titer is highly suggestive of disseminated disease.

Tx:

• • Nonmeningeal disease: Fluconazole, 400 mg PO or IV qd x 8 wk - 6 mo.

  • Immunosuppressed: Fluconazole, 200 mg PO qd

  • Isolated pulmonary disease in immunocompetent patients can be followed expectantly.

  • Meningitis:

    • Immunocompetent: AmpB liposomal 3 - 5 mg/kg + flucytosine 25 mg/kg q6h IV x 2 wk, then fluconazole 400 mg PO qd x 8 wk

      • Always check OP and reduce by 50% if elevated above 25 cm H2O by removing upto 30 cc CSF. Serial LPs to reduce pressure are required as long as CSF is elevated.

    • Immunosuppressed: AmpB liposomal 3 - 5 mg/kg + flucytosine 25 mg/kg q6h IV x 2 wk, then fluconazole 400 mg PO qd x 8 wk

      • Suppressive Tx: Fluconazole, 200 mg PO qd. Continue prophylaxis until immunocompetent or CD4 count sustained >200 for 6 mo.

    • Amphotericin is associated with renal failure, hypokalemia, and hypomagnesemia; and flucytosine may cause hematologic abnormalities

    • C/w HAART

Histoplasma capsulatum. Clinical manifestations vary from acute flu like or chronic granulomatous pulmonary dz, or fulminant multiorgan failure in the immunocompromised patient.

• • H. capsulatum is prevalent in the Ohio and Mississippi River Valleys of the US and in Latin America, and grows best in soil contaminated by bat or bird droppings.

  • Dx is based or histopathology, antigen assay (urine, blood, or CSF), or complement fixation assay (>1:16 or 4-fold rise). Urine antigen assay is good for detecting disseminated disease and is helpful in following response to therapy.

Tx:

• • Chronic forms, mild dz, immunompetent: Itraconazole, 200 - 400 mg PO daily for >6 mo. Goal Sr. itraconazole level >1 mcg/mL.

  • Acute dissemination; severe disease; immunocompromised: AmpB liposomal 3 - 5 mg/kg x 2 wk or until clinically improved, then itraconazole, 200 mg PO bid >12 mo

    • Suppressive therapy: Itraconazole, 200 mg PO daily.

    • Continue prophylaxis until sustained CD4 count >200 for 6 months.

Blastomyces dermatitidis. Commonly disseminates even in immunocompetent patients, and tends to affect the lungs, skin, bone, and GU tract. Aggressive pulmonary and CNS disease can occur in immunocompromised patients.

• • B. dermatitidis is endemic in the upper midwestern, south-central, and south-eastern U.S

  • Dx requires isolation of the organism by culture or histopathology. Serologic tests cross-react with tests for Histoplasma and Cryptococcus sp and are unreliable for Dx, but can be used to assess early response to therapy if positive.

Tx:

• • Nonmeningeal disease; mild to moderate disease; immunocompetent. Itraconazole, 200 - 400 mg/d PO x 6 mo

  • Acute dissemination; severe disease; immunocompromised. AmpB x 2 wks or until clinically improved, then itraconazole 200-400 mg PO qd x 6 mo.

    • Suppressive: Itraconazole, 200-400 mg PO qd.

Coccidioides immitis

• • Nonmeningeal disease: Itraconazole, 200 mg PO bid or fluconazole, 400 mg PO qd x 12 mo.

    • Suppressive: Fluconazole, 400 mg PO qd (lifelong suppression required if disseminated).

    • Follow serum CF titers after treatment. Rising titers suggest recurrence.

  • Meningitis: Fluconazole, 400 - 800 mg IV/PO q24h. Intrathecal AmpB deoxycholate, 0.1 - 1.5 mg qd to qwk may be added to azole therapy for severe meningeal disease.

    • Suppressive: Fluconazole, 400 mg PO qd indefinetly.

    • For pulmonary nodules and ASx cavitary dz, no therapy indicated. Consider surgery if cavitary dz persists >2 yr, progresses >1 yr, or is located near pleura.

Aspergillus

• • Aspergilloma: surgical resection in case of severe hemoptysis

  • Invasive aspergillosis: Voriconazole 6 mg/kg q12h PO/IV x 2 doses, then 4 mg/kg q12h, then 200 mg O bid. Continue for at least 6 - 12 wk, as long as immunosuppression continues, and until lesions resolve.

    • Immunosuppression: Continue or restart therapy.

    • AmpB to cover mucormycosis as initial therapy for sinus disease pending confirmation of Dx.

Sporothrix

• • Itraconazole, 100 - 200 mg PO qd x 3 - 12 mo.

    • Alternative: Saturated solution of K iodide, 5 gtt PO tid, increased to 40 gtt tid as tolerated.

    • Follow levels of itraconazole.

  • Severe meningeal dz: AmpB for initial 6 wks of therapy.

Mucormycosis

• • AmpB at upper dose range x 6 mo

Nocardia

• • Pulmonary. TMP/SMX, 5 - 10 mg/kg/d IV in divided doses x 3 - 6 wk, then 1 - 2 DS PO bid.

  • Less serious: TMP/SMX, 1 - 2 DS bid up to 2 DS tid or minocycline 100 mg PO bid.

    • Suppressive: TMP/SMX, 1 - 2 DS bid or dapsone 100 mg PO qd or minocycline 100 mg PO bid.

    • Initially treat for 6 mo if immunocompetent or >12 mo if immunocompromised.

  • CNS. TMP/SMX, 15 mg/kg/d, IV x 3 - 6 wk, then 3 DS PO bid.

Actinomyces

• • PCN G, 18 - 24 million units IV/d or clindamycin, 600 mg IV q8h x 2 - 6 wk, then doxycyline 100 mg PO bid x 6 - 12 mo.