Invasive fungal infections
Risk: neutropenia, transplant, high-dose steroids, biologics, HIV with low CD4, liver failure, TPN, broad abx, central lines.
Nick Peterson5 min6 questions1 trials
Who is at risk, and what the markers mean
Candida, Aspergillus, and Pneumocystis account for >80% of fungal infections diagnosed in hospital (:ofab593). Risk: heme malignancy and HSCT more than solid-organ transplant, selected biologics, HIV/AIDS, prolonged neutropenia, prolonged glucocorticoids, liver disease, burns, severe lung disease / prolonged intubation. Call ID for invasive disease.
Gold standard remains tissue with culture. PCR / Karius for odd pathogens with ID guidance.
| Test | Detects | Lies |
|---|---|---|
| 1,3-β-D-glucan () | Candida, Aspergillus, PJP, Fusarium, Trichosporon, Histo, Coccidioides. Not Mucor, Rhizopus, Blastomyces, Cryptococcus. | False positive: IVIG, albumin, dialysis, pip-tazo, amp-sulbactam, Streptococcus, Pseudomonas. False negative possible in candidemia. |
| Galactomannan | Aspergillus cell wall. Serum Sn 65–80%, BAL 90–95%, Sp ~88%. | False positive: some TPN, IVIG, blood products. Trend serum on treatment; BAL beats serum. |
| CrAg | Cryptococcus. Serum Sn/Sp >90% if disseminated; less for isolated pulmonary disease (better in HIV). | Positive serum + negative CSF = cryptococcal antigenemia — still LP. |
| Histo / Blasto Ag | Urine Ag more sensitive than serum. Histo urine Ag Sn ~90% if disseminated. Blasto urine Ag Sn ~80% for pulmonary disease. | Cross-reactivity between histo and blasto. Blasto is never a colonizer. |
Candida and Cryptococcus
Candida (CID 2016;62:e1)
- Risk: neutropenia, transplant, HIV, TPN, PWID, CVC, recent abdominal surgery, ICU.
- Spectrum: sepsis (~25% mortality), macronodular skin lesions (~10%), endophthalmitis, endocarditis, osteomyelitis, UTI.
- Yeast in blood is never a contaminant. Repeat cultures daily. TTE. Dilated eye exam in non-neutropenic patients (in neutropenia, once ANC recovers). CT A/P if abdominal symptoms, rising LFTs, or persistent fever. Skin biopsy if lesions.
- Candidemia: echinocandin first, then step down to an azole. Pull the line. Amphotericin for resistant strains. Uncomplicated BSI: 2 weeks after first negative culture and no dissemination.
Cryptococcus (Lancet Infect Dis 2024)
- HIV/AIDS, malignancy, transplant, ESLD — and immunocompetent hosts (C. gattii > C. neoformans).
- Asymptomatic antigenemia → meningoencephalitis, pulmonary failure, skin nodules, liver abscess. Often subacute.
- LP: opening pressure often >20 cm H2O, low glucose, high protein, lymphocytes. MRI brain, CT chest. Screen serum CrAg if CD4 <200, then LP if positive.
- Meningitis: amphotericin + flucytosine × 2 weeks, then fluconazole ≥8 weeks. Serial LPs if OP ≥20 or pressure symptoms. Fluconazole for mild pulmonary disease / antigenemia.
Aspergillus, Mucor, PJP, endemic
| Pathogen | Clues | Treatment |
|---|---|---|
| Aspergillus () | Neutropenia, steroids, transplant, COPD in a long ICU stay, anti-TNF, cannabis, COVID ARDS. Invasive pulmonary disease, aspergilloma, sinus, tracheobronchitis, CNS, eye, necrotic skin. CT halo / crescent. BAL wet prep / culture ± biopsy. | Voriconazole (trough and interactions) or isavuconazole / posaconazole. Debride necrosis. Pulmonary disease often >6–12 weeks. Prophylaxis: vori or posa in prolonged neutropenia / GVHD (). Voriconazole + micafungin is not better than vori alone. |
| Mucorales () | DKA, iron overload, heme malignancy, prolonged neutropenia. Rhino-orbital-cerebral, pulmonary, GI, renal. Black eschars, reverse-halo on CT, rapidly progressive. Broad non-septate hyphae — tell the lab. | Debridement plus amphotericin. Posaconazole or isavuconazole for salvage or renal failure. Voriconazole does not cover Mucor and can select for it. |
| PJP | HIV, heme malignancy, transplant, prednisone ~20 mg/day × 4 weeks. Subacute dyspnea, pneumothorax, hypoxemia out of proportion to the film, diffuse GGO. LDH >500 (sensitive, not specific). BAL > induced sputum (silver / DFA); BDG supportive. | TMP-SMX 8–20 mg/kg/day of the trimethoprim component, divided q6–12h × 21 days (adjust for GFR). Steroids if PaO2 <70 or A-a ≥35 (best evidence in HIV): prednisone 40 mg BID then taper. Alts: TMP + dapsone, clinda + primaquine, atovaquone, pentamidine. Prophylaxis: TMP-SMX DS daily or SS daily or DS MWF; atovaquone; dapsone (G6PD); inhaled pentamidine. |
Endemic mycoses — geography first
- Histoplasma (CID 2025): central/eastern US (not only Ohio/Mississippi valleys), Latin America, Asia, Africa. Pneumonia, mediastinal disease, meningitis, dissemination, pericarditis. Urine + serum Ag. Itraconazole or none if mild; amphotericin then itra if severe.
- Blastomyces (): eastern US and Canada. Pneumonia ± ARDS, ulcerated skin, osteomyelitis, prostatitis, CNS. Broad-based budding yeast. Itra if mild–moderate; amphotericin then itra if severe. 6–12 months.
- Coccidioides (): deserts of the Southwest, Mexico, Central/South America. 40% symptomatic; 5–10% chronic pulmonary; 1% disseminated. Erythema nodosum, eosinophilia, meningitis, osteomyelitis. Spherules; alert the lab (biohazard). Often no therapy if mild and immunocompetent; fluconazole / itra, amphotericin if severe. Meningitis prophylaxis may be lifelong.