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Febrile #69 – Investigating IFI

69 Cover Art OPT

Summary

Drs. Ralph Tayyar and Jessica Ferguson discuss the challenges of investigating invasive fungal infections in immunocompromised hosts and interpreting noninvasive fungal markers!

Table of Contents

Credits

Host(s): Ralph Tayyar, Sara Dong

Guest: Jessica Ferguson

Writing: Ralph Tayyar, Jessica Ferguson, Sara Dong

Producing/Editing/Cover Art/Infographics: Sara Dong

Our Guests

Guest Co-Host

Ralph Tayyar, MD

Dr. Ralph Tayyar is currently a transplant or immunocompromised ID fellow at Stanford in Palo Alto CA, where he also completed his ID fellowship. 

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Guest Discussant

Jessica Ferguson, MD

Dr. Jessica Ferguson is a Clinical Assistant Professor in the Division of Infectious Diseases at Stanford University School of Medicine in Palo Alto, CA. She completed a one-year Transplant Infectious Disease fellowship at Stanford University in 2021 and joined the Stanford clinical faculty in August 2021. Her academic interests include medical education, transplant protocol development, CMV, antimicrobial resistance, and antibiotic stewardship.

Culture

Ralph was watching the World Cup games at the time of the recording, and Jessica was getting caught up on the TV show Billions

Consult Notes

Consult Q

What is the differential and diagnostic work-up for pulmonary nodules in an immunocompromised patient?

Case Summary

77 year old female with myelodysplastic syndrome transformed to AML who developed cough, neutropenic fever, and new pulmonary nodules – found to have invasive pulmonary aspergillosis due to A.fumigatus

Key Points

Risk factors for invasive fungal infections

Jessica discussed the differential for pulmonary nodules in immunocompromised patients, here is a brief summary of some of the typical causes:

  • Infectious
    • Fungal – Aspergillus, Mucormycoses, Scedosporium, Lomentosporium, Cryptococcus, Dimorphic fungi, nodular form of Pneumocystis jiroveci (rare) and others
    • Mycobacterial – M. tuberculosis and nontuberculous mycobacteria
    • Bacterial – bacterial abscess, septic emboli 
    • Parasitic – Paragonimiasis 
    • Viral – less likely
  • Inflammatory
    • Sarcoidosis
    • Granulomatosis with polyangiitis 
    • Cryptogenic organizing pneumonia 
  • Malignancy – primary malignancy, metastases 

Check out this paper and the figures (Fig 1 & 2 noted below): Azoulay E, Russell L, Van de Louw A, et al. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med. 2020;46(2):298-314. doi:10.1007/s00134-019-05906-5

The episode also discussed radiographic features that are suggestive of invasive pulmonary fungal infections. Here are a few notes:

  • Halo sign: CT finding of ground-glass opacity surrounding a pulmonary nodule or mass
    • Most commonly associated with invasive pulmonary aspergillosis (25-95% incidence in neutropenic patients)
  • Reverse halo (atoll) sign: focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation
    • Most commonly associated with pulmonary mucormycosis cases (19%)
  •  
  • Calcification can be a sign of prior granulomatous infection and would need to consider dimorphic fungi (Coccidioides, Histoplasma, Blastomyces – depending on where you practice)
  • Jessica also discussed the non-ID differential, such as rheumatologic (sarcoidosis, granulomatosis with polyangiitis), cryptogenic organizing pneumonia, malignancy

 

Some resources for further reading (in addition to those in the prior section):



Non-invasive evaluation for pulmonary nodules

Here is a chart that Ralph and Jessica provided for the Consult Notes:

Test

Sensitivity

Specificity

Comments

1,3-B-D-glucan

33-100%

36-94%

  • Cross-reacts with other fungi
  • High false positivity

Aspergillus galactomannan (serum)

61-79%

81-95%

  • Cross-reacts with other fungi
  • Can be falsely positive with B-lactams
  • Higher sensitivity and specificity in neutropenic patients or heme malignancies
  • Lower sensitivity in non-neutropenic patients or those on antifungals

Aspergillus galactomannan (BAL)

58-90%

84-96%

  • Can be positive in aspergillus colonization

Mold PCR plasma/whole blood

84% (Aspergillus 79%)

76% (Aspergillus 79.6%)

  • Specificity significantly increases with two consecutive positive test results

BAL PCR

77.2%

93.5%

  • Lower sensitivity (58%) on antifungals
  • PMID: 22952268

Biopsy PCR

89%

100%

  •  
  •  

Blood Aspergillus Antibody by EIA

67%-84% 

52%-67%

  • PMID: 22824184

As mentioned on the show, don’t forget to send specific testing in patients where relevant (such as Cryptococcal antigen or endemic fungi Ab/Ag testing)

Another quick reference would be the Febrile fungal markers chart (which is just focused on BDG and GM)

There are a ton of readings for fungal markers, and many references for the two tables above:

Here is a webpage of fungal testing publications

Jessica also discussed invasive diagnostics (BAL with or without biopsy) as well as the criteria for proven/probable invasive fungal disease

Episode Art & Infographics

Infographics

Find all the Febrile infographics here!

Goal

Listeners will be able to discuss the use of noninvasive fungal markers when investigating suspected pulmonary fungal infection.

Learning Objectives

After listening to this episode, listeners will be able to:

  • Recognize radiographic features that are suggestive of invasive fungal infection
  • Compare and contrast 1,3-beta-D-glucan, Aspergillus galactomannan, and mold-specific PCR

Disclosures

Our guests as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Ferguson, J., Tayyar, R., Dong, S. “#69: Investigating IFI”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/11924671-c113-4193-a686-7de383b3cb6c

Transcript

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