For a fungus, this thing attracts a lot of attention from the college. Question 9  from the second paper of 2014 asked for a substantial amount of detail regarding the diagnosis of aspergillosis.

As with many of these, the Manual offers little help. Instead, one should turn to LITFL's CCC entry on this subject, which is precise and brief. However if one is not into brevity and precision, one can enjoy several hours submerged in the reference swamp listed below. Selected reading could be limited to the following exceptional articles:

Risk factors for aspergillus infection

One of the articles referenced by LITFL contains within it Table 2 (p.207) which lists the risk categories for invasive aspergillosis among ICU patients. In a contorted form, those data are displayed below:

Low risk

Intermediate risk

High risk

  • Heart, kidney, liver transplant
  • Burns
  • Stay in ICU > 21 days
  • Malnutrition
  • Cardiac surgery
  • Short term steroids
  • Bone marrow transplant (auto)
  • COPD
  • Cirrhosis
  • Solid malignancy
  • HIV
  • Lung transplant
  • Chronic steroids
  • Chronic immunesuppression
  • Bone marrow transplant (allo)
  • Neutropenia
  • Haem malignancy

It should be noted (from the same article) that merely being intubated places one at an increased risk of forming Aspergillus colonies in one's respiratory tract. This has the effect of causing positive test results, but no actual invasive disease.

Diagnosis of aspergillosis

An old 1977 article (from before PCRs and whatnot) and a new 2002 article describe the clinical picture. Their suggestions can be compiled into a table:

Clinical Features and Associated Findings in Aspergillosis

Pulmonary:

  • An asthma-like clinical picture
  • Haemoptysis
  • Chronic cough

Extrapulmonary: immunocompromised host

  • endopthalmitis
  • endocarditis
  • Eosinophilia
  • Elevated serum IgE
  • Spherical lesions on CXR
  • Incidental lesions on CT

Difficulty of identifying aspergillosis in the ICU

This answers Question 9 from the second paper of 2014.

Why the diagnosis is not straightforward:

  • ICU patients will have nonspecific signs, buried under other signs, and often no history.
  • Radiological diagnosis may be obscured by othr pathology, or may be logistically difficult
  • Biopsy is frequently impossible
  • Immunocompetent individuals are not suspected, yet may still develop the disease
  • Clinically insignificant colonisation is common, but will yield the same positive diagnostic results as active invasive disease.
  • Diagnostic test accuracy may be confounded by many factors, eg. concurrent β-lactam therapy.

Laboratory tests

Aspergillus galactomannan: blood

Aspergillus galactomannan: bronchoalveolar lavage

Aspergillus PCR on bronchoalveolar lavage specimens

Aspergillus hyphae identified

  • The gold standard
  • Again, as all of these tests, it cannot discriminate among those who have invasive aspergillosis and those who are merely colonised.

Radiological identification

LITFL link to an excellent Radiopedia page which has some lovely fungus balls. A definitive journal reference would have to be this 2001 article.

In brief, the radiological features are:

  • Pulmonary nodule on CXR
  • A "halo" of ground-glass opacity surrounds the nodules on CT
  • Wedge-like haemorrhagic pulmonary infarcts
  • Air crescents following resolution (necrotic lung separating from the rest of the parenchyma)

Tissue biopsy

Open lung biopsy is not to be taken lightly. Furthermore, it is not always helpful. In one 2001 study the authors claim that they could histopathologically confirm invasive fungal infections only in 53.1% by open lung biopsy. Generally speaking these days people rely on laboratory data and radiology. The open biopsy remains at the hopeless end of the diagnostic algorithm flowcharts. Its only benefit is to spare the patient from a course of amphotericin therapy.

Management of Aspergillosis

The Sanford Guide recommends the following:

  • Voriconazole (loading dose of 6mg/kg, followed by 4mg/kg)

Alternatives include

  • Amphotericin B
  • Posaconazole
  • Caspofungin
  • Itraconazole

References

ROSENBERG, MICHAEL, et al. "Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis." Annals of Internal Medicine 86.4 (1977): 405-414.

Soubani, Ayman O., and Pranatharthi H. Chandrasekar. "The clinical spectrum of pulmonary aspergillosis." CHEST Journal 121.6 (2002): 1988-1999.

Sherif, Rami, and Brahm H. Segal. "Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications." Current opinion in pulmonary medicine 16.3 (2010): 242.

Meersseman, Wouter, et al. "Invasive aspergillosis in the intensive care unit."Clinical Infectious Diseases 45.2 (2007): 205-216.

Trof, R. J., et al. "Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients." Intensive care medicine 33.10 (2007): 1694-1703.

Mennink-Kersten, Monique ASH, J. Peter Donnelly, and Paul E. Verweij. "Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis." The Lancet infectious diseases 4.6 (2004): 349-357.

Musher, Benjamin, et al. "Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid." Journal of Clinical Microbiology 42.12 (2004): 5517-5522.

Pfeiffer, Christopher D., Jason P. Fine, and Nasia Safdar. "Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis." Clinical Infectious Diseases 42.10 (2006): 1417-1727.

Patmore, J. V., H. D. Goff, and S. Fernandes. "Cryo-gelation of galactomannans in ice cream model systems." Food Hydrocolloids 17.2 (2003): 161-169.

Wald, Anna, et al. "Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation." Journal of Infectious Diseases 175.6 (1997): 1459-1466.

Escuissato, Dante L., et al. "Pulmonary infections after bone marrow transplantation: high-resolution CT findings in 111 patients." American Journal of Roentgenology 185.3 (2005): 608-615.

Nucci, Marcio, et al. "Early diagnosis of invasive pulmonary aspergillosis in hematologic patients: an opportunity to improve the outcome." haematologica98.11 (2013): 1657-1660.

Acosta, J., et al. "A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→ 3)–β–d‐glucan chromogenic assay in serum samples." Clinical Microbiology and Infection 17.7 (2011): 1053-1060.

Izumikawa, Koichi, et al. "Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis." Medical mycology 50.8 (2012): 811-817.

Boonsarngsuk, Viboon, et al. "False-positive serum and bronchoalveolar lavage Aspergillus galactomannan assays caused by different antibiotics."Scandinavian journal of infectious diseases 42.6-7 (2010): 461-468.

Digby, Justin, et al. "Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients." Clinical and diagnostic laboratory immunology 10.5 (2003): 882-885.

Hage, Chadi A., et al. "Plasmalyte as a cause of false-positive results for Aspergillus galactomannan in bronchoalveolar lavage fluid." Journal of clinical microbiology 45.2 (2007): 676-677.

Buess, Michael, et al. "Aspergillus-PCR in bronchoalveolar lavage for detection of invasive pulmonary aspergillosis in immunocompromised patients." BMC infectious diseases 12.1 (2012): 237.

Heng, Siow-Chin, et al. "Clinical utility of Aspergillus galactomannan and PCR in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies." Diagnostic microbiology and infectious disease 79.3 (2014): 322-327.

Franquet, Tomás, et al. "Spectrum of Pulmonary Aspergillosis: Histologic, Clinical, and Radiologic Findings 1." Radiographics 21.4 (2001): 825-837.

Kim, Kihyun, et al. "Importance of open lung biopsy in the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies." American journal of hematology 71.2 (2002): 75-79.

Blot, Stijn I., et al. "A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients." American journal of respiratory and critical care medicine 186.1 (2012): 56-64.