Welcome back to the tasty morsels of critical care podcast.
Today we look at everyone’s favorite mould – aspergillus. We see a number of fungal infections in the ICU, most commonly it’ll be the yeasts – forms of candida. Yeasts are single celled organisms. The moulds, of which aspergillus is a member are multicellular organisms. To continue into a brief foray of wikipedia inspired irrelevance the name aspergillus comes from the liturgical implement known as the aspergillum, more commonly known as the thing your priest man shakes to sprinkle the holy water. Apparently it was named aspergillus by the Italian priest who discovered it under his microscope and named it for the resemblance.
The biggest issue comes for us in the ICU in differentiating colonisation from active infection. Proper invasive pulmonary aspergillosis is characterised histologically by invasion across tissue planes, particularly into vessels. As you can imagine getting a lung biopsy to prove such on ICU patients can be a tad challenging so we’re stuck with the usual conundrum of trying to work it out based on probabilities and surrogate tests.
the LITFL entry has 4 types of aspergillosis described that we should be aware of:
1) allergic bronchopulm aspergillosis. This is generally an OPD condition that is rarely the cause of why the patient is in the ICU
2) the aspergilloma – the dirty great fungus ball hanging out in one of the lobes of the lung causing all kinds of bother. Surprisingly this can also often be an out patient problem
3) chronic necrotising pneumonia (described as semi-invasive in the post)
4) invasive pulmonary aspergillosis – the type we’re likely to see and most worried about.
The IBCC covers aspergillosis very well, and if this podcast does no more than refer you to the IBCC then my work is done. Josh makes an excellent point of pointing out that there is probably a different clinical pattern in the neutropaenic vs the non neutropaenic patient.
For any kind of fellowship exam you would be expected to reproduce a somewhat cogent list of risk factors for such an illness. Of note we are all exposed to aspergillus and exposure to aspergillus is a simple fact of being alive. But generally it doesn’t cause us a trouble unless something else is going on. A reasonable (but by no means complete) list of risk factors might include
- most famously stem cell and lung transplants or anyone with prolonged neutropaenia, typically >10 days (remember that haematological malignancy are the main groups to reach this level of prolonged neutropaenia)
- can also occur in much less immune suppresses people who are just really sick in ICU, or even COPD with recurrent steroids (typically at least 20mg/day of pred)
- patients post severe influenza seem to be a risk (looks like severe superinfection 3-5 days into course)
- most other solid organ transplants seem to be fairly low risk.
- COVID-19 as a risk factor is almost certainly a risk factor. However many of the studies have assumed that growth on a sputum implies invasive disease which is probably a bit of a stretch. That being said if you find that the whole airway is covered in plaques on bronch then you’ve probably established a diagnosis.
So a common clinical context might be a haematological cancer patient in the ICU as part of a neutropaenic sepsis process. They might be in a week or two with profound neutropaenia and develop recurrent fevers and a respiratory deterioation. A sequence of micro growth and adjunctive tests established a diagnosis of aspergillosis.
More recently we’ve seen it in the unfortunate chronically co morbid patient who gets a bad dose of the auld COVID and 2 weeks into their vent course they deteriorate and the bronch shows white plaques all the way down.
In terms of testing there are a number of potentially useful modalities. When it comes to radiology, CT is your friend and as always giving your radiologist a specific query might be helpful. Look for cavities, or a monod sign (air around a fungus ball). The two other signs described are the halo sign and finger in glove sign. Good examples available on radiopaedia.
In terms of blood tests we typically reach for the beta d glucan or galatcomannan. Both are cell wall compents of fungi but the galactomannan is probably more specific for aspergillus. Both have sensitivities quoted around 75% so they are by no means perfect. There are a variety of assays and types available most of which i defer to a microbiologist rather than attempt to understand. There were historical issues of false +ve with beta lactams like pip-tazo but apparently these are historical issues and not relevant to contemporary assays.
Bronchoscopy is typically performed to get a decent sample. A galactomannan on the BAL sample is something we tend to lean a lot heavier on than the serum test. In my reading i saw reports of eosinophilia and elevated serum IgE being associated with aspergillosis but have not seen that in the wild.
Ultimately making the diagnosis in the ICU is very difficult as there are lots of confounders – mainly being lots of colonisation and it can be difficult to distinguish from invasive disease. Open lung biopsy as a gold standard comes with a sensitivity of 60% so let’s just bin that idea. In general we look for it and if the patient fulfills the “sick as shit” category (which they almost always do) then we treat.
When it comes to treatment there are a few recommendations you can choose from. In general voriconazole leads the way. There have been some recent shortages of the IV form so it’s nice to know the PO version works pretty well. It does not need some monitoring of levels. Occasionally there’ll be dual antifungal cover but as always i would take advice from an expert in that type of situation.
If there’s a huge aspergilloma it’s important to note that surgical resection is a very realistic option but as you might suspect this applies to the slightly more stable population.
Since recording this one of my colleagues who does both ID and ICU pointed out this paper that looks particularly at aspergillus in the ECMO population.
- ATS 2019 Guidance: Hage, C. A. et al. Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline. Am J Resp Crit Care 200, 535–550 (2019).
- Deranged Physiology
- Fekkar, A. et al. Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU. Am J Resp Crit Care 203, 307–317 (2021).
- Verweij, P. E. et al. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis. Intens Care Med 1–16 (2021) doi:10.1007/s00134-021-06449-4.