Fungal Infections¶

Ally Glover

Evaluation¶

Bacterial BCx can detect candidemia but low sensitivity (50%). Fungal blood cultures also with low sensitivity.
Beta-d-glucan: note will not be elevated in mucormycosis, cryptococcosis, and blastomycosis.
Aspergillus galactomannan: BAL > serum.
Pts with risk factors for candidemia (TPN, chronic line, GI disease, persistent neutropenic fever) with concerning clinical syndrome can be treated empirically with micafungin.

Part of normal flora of human GI and GU tract
Broad range of associated diseases from vaginal candidiasis to candidemia
Pts at highest risk of severe / invasive candida infection (candidemia):
- Burn / surgical ICU pts
- Solid organ recipients
- Chemo pts / malignant heme pts
- TPN dependent / central access pts (especially in ICU)

Oropharyngeal: white plaques/patches in mouth ± erythema, painful when eating
Esophageal: dysphagia/odynophagia, chest pain w/ swallowing
Vulvovaginitis: white, thick discharge; pruritus/erythema
Balanitis: white patches on penis with severe burning/itching
Mastitis: breast feeding pts with nipple injury
Invasive focal infections
- UTI: ascending infection (can often be unilateral) vs. hematologic source (micro abscesses)
- Peritonitis: often in peritoneal dialysis pts
- Mediastinitis: often post thoracic surgery
- Hepatosplenic: often in pts who just recovered from neutropenia in setting of heme malignancy
Candidemia: sepsis, often in setting of critical illness, think about when above risk factors present

Blood: candida is NEVER a contaminant in blood cultures
Urine: culture is standard method of identification but RARELY a urinary pathogen

Candidemia / critical illness: start micafungin 100mg daily, consult ID
Vulvovaginitis: fluconazole 150mg x1 if mild, 150mg every 72 hrs for 2-3 doses if severe
Oropharyngeal: nystatin oral suspension if mild thrush, if moderate – severe candidiasis then fluconazole 100-200mg qday for 7-14 days
Esophageal candidiasis (AIDS defining illness): fluconazole 200-400mg qday or micafungin 150mg daily for 14-21 days as an alternative agent

Remember to check susceptibilities (C krusei has intrinsic azole resistance and C glabrata has high rates of fluconazole resistance)

Most often in pts who have prolonged neutropenia, high dose steroids, or other immunosuppressive drug regimen or condition
Take thorough hx: farming, occupational exposure where pt might have inhaled conidia

Classic pulmonary aspergillosis presentation: neutropenic pt with fever, pleuritic chest pain and hemoptysis
Tracheobronchitis: can occur in lung transplant pts

Aspergillus galactomannan Ag
Lung imaging if concerned for pulmonary aspergillosis
Differentiate possible vs probable vs proven (tissue) aspergillosis as it can reflect colonization without proper clinical syndrome or host

Consult ID. Usually treat with voriconazole or other triazole (posaconazole, isavuconazole). Preferred over amphotericin based on clinical trials.
Fluconazole is NOT active against aspergillus

Endemic in midwest, southeast, southern central US, and parts of Canada that border the Great Lakes
Mostly pulmonary manifestations, 25-40% of infections w/ extrapulmonary involvement (skin, bone, GU, and CNS presentations)

Pulmonary blastomycosis
- Mild to Moderate: itraconazole 6-12 months
- Moderate to Severe: ampho followed by itraconazole for 6-12 months
Disseminated extrapulmonary blastomycosis: ampho followed by itraconazole for a year
- Note: in anyone who is immunosuppressed, especially pts with AIDS, start with amphotericin
CNS blastomycosis: 4-6 weeks of ampho followed by a year of itraconazole

The most common endemic mycosis in the US. Endemic to Ohio and Mississippi river valley.
Most infections are not clinically significant / do not require treatment.
At risk for disseminated disease (HIV, transplant recipients, immunocompromised, TNF- alpha inhibitors, elderly)
Differential diagnosis: TB, malignancy, sarcoidosis, other fungal infection

Pulmonary histo: pna w/ mediastinal or hilar LND or masses, pulmonary nodules, cavitation
Disseminated histo: fever, mediastinal LND, diffuse pulm interstitial infiltrates, HSM, liver involvement, popular rash, cytopenias, mucosal lesions,  LDH, ferritin, adrenal involvement, colonic involvement.

Send BOTH Urine and Serum antigens. Requires attending name to order.
Antibody testing less useful in acute disease (interpret with caution)
Other diagnostics to consider: peripheral smear/buffy coat, fungal blood cultures, LDH, ferritin, BAL with cultures and cytology
Remember histo Ag has high cross reactivity with blasto Ag

Amphotericin and Itraconazole- discuss with ID, pharmacy about dosing, duration.
Pulmonary histo:
- Mediastinal granuloma, fibrosis, broncholithiasis: usually no tx.
- Mild-moderate acute pulmonary histo: itraconazole if persistent symptoms > 1mo
- Chronic cavitations: itraconazole, likely 1 to 2 years
- Severe acute pulmonary histo: amphotericin for 1-2 weeks ± methylprednisolone followed by itraconazole for 12 weeks
Disseminated histo:
- Mild-moderate disseminated disease: itraconazole for ~12 months
- Severe disseminated disease: ampho for 1-2 weeks followed by itraconazole for ~12 mo

Disseminated histoplasmosis can be associated with secondary HLH. Follow CBC closely.
If concerned for sarcoidosis, need to rule out histo prior to starting treatment for sarcoidosis
Urine antigen can be used to trend response to treatment