The Fungal Invasion of the ICU- A Catastrophe Waiting to Happen

Dr. Devang Patel currently serves as Chief of Infectious Disease for the MICU here at the University of Maryland. Today he was was gracious enough to speak on invasive fungal infections not only here in the continental US, but also reliant on his experience working at the University of Zambi HIV program, where being severely immunocompromised is the norm. Over the next hour, he will describe what the modern intensivist needs to know to avoid disasters and even attempt to dispel some myths along the way.

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Infections you need to know:

1) Candida

•  Fungal infections are 15% of HAI, 70-90% due to Candida
  • 4th most common blood stream infection in USA; 40-60% mortality (NEVER a contaminant)
  • Neutropenic pts are susceptible to gut translocation
  • Candida on BAL is useless, need a lung biopsy to diagnosis Candida PNA (very rare)
  • No need to tx cystitis, just remove the catheter
• Affects all hosts: immunocompetent or -compromised
  • 30-80% colonized (↑ w/ HIV infection)
• Treatment: Echinocandins until speciation (then Fluconazole is often appropriate); Ampho B reserved for immunocompromised
  • Daily blood cx until negative, with an additional 14 days past that date
  • Remove central lines (when able)
  • Eye Exam! 
    • 20% of fungemic pts will develop Candida ophthalmitis
• Prophylaxis: No data to defend prophylaxis treatment
  • 3 criteria have been suggestive of a need for empiric treatment:
    1. Persistant fever
    2. Risk factors (ab surgery, persisitant lines, TPN, neutropenia)
    3. Colonization of non-sterile sites: urine, sputum, skin

2) Pneumocystis jiroveci 

• Risks: CD4<200 (ie: development of oral thrush), long term steroid use, transplant (↑ with Alemtuzumab use)
• Pathogenesis: Inflammatory effect (hence tx with steroids) and can be subacute in nature
  • fever (80-90%), 2-4 wks of dry cough, DOE, chest tightness/pain
• Complications: thin walled cavitations →  PTX; (Pneumo-cyst-is)
• Exam: Hypoxia w/o crackles
• Imaging:
  • CXR- bat-wing pattern; CT: patchy ground glass opacities
• Diagnosis:
  • LDH- high NPV, low specificity
  • BAL: 90-100% sensitive (compared to 50-80% sensitive for sputum)
• Treatment: Bactrim (if allergic- Desensitize!) + 21 days of steroids

3) Cryptococcus 

• Inhalation of propagules → PNA is first manifestation (negative serum crypto antigen)
  • CXR: calcified nodules
• Meningitis develops in immunocompromised population (90% of HIV population w/ CD4<100)
  • Sub-acute development: 2-4 weeks → meningitis/meningoencephalitis
  • S/S: memory loss, confusion, CN palsy
  • CSF:
    • Extremely ↑ ICP
    • Profile nl in 25-30%, but LOW WBC in HIV population = worse prognosis
    • Serum crypto- useful only in AIDS population
    • India Ink can be diagnostic
• Treatment: Ampho B and serial LPs to decrease ICP (Goal: 20% decrease)
  • No gain from combination: Ampho B and Flucytosine
    • Will clear CSF faster, but no change to morbidity and mortality
    • Leads to increased side effects
  • Maintenance: Fluconazole

4) Aspergillus 

• Risk factors: Neutropenia, SCT, transplants: lung, liver, heart
• Aspergilloma can develop in any existing cavity- not invasive
• Invasive Pulmonary Aspergillosis (IPA)
  • Progressive dry cough, SOB, fever, and pleuritic CP despite abx
  • Hemoptysis (angio-invasive), PTX
  • Diagnosis is difficult: can be colonized
    • 50% of sputum samples are falsely negative
    • Galactomannan assay in BAL- 90% sensitive and 94% specific
      • False positive: You may have a false positive assay if patient is being treated with Pip/Tazo
• Treatment: Voriconazole > Ampho B; Echinocandins are not preferred

5) Regional Fungal Infections: Histoplasmosis and Coccidioidomycosis

• Histoplasmosis: Mississippi River valley
  • Acute Pulmonary Histoplasmosis: 90% are asymptomatic
    • Incubation: 7-21 days, can have reactivation
    • Symptoms: mild flu-like (weakness, fatigue, dry cough) with nl PE
    • Imaging:
      • CXR: Hilar LAN, patchy pneumonitis
      • CT: Ghon complex (#1 cause in America is Histo)
  • Acute Progressive Disseminated Histoplasmosis 
    • Increased LFTs with hepatosplenomegaly, LAN
    • Symptoms: fever, wt loss
  • Treatment: Itraconazole (out patient) or Ampho B for inpatient (disseminated pts)
  • Prophylaxis: CD4<150 + endemic area: Itraconazole
• Coccidiomycosis: SW (AZ, CA)
  • 50% of pts have reactivation
  • African and Filipino descent leaads to a greater risk of dissemination
  • Signs/Symptoms: similar to CAP
  • Treatment: Ampho B then fluconazole for long term therapy

References