Diagnosis ofInvasive Aspergillosis using Galactomannan nd (1-3)-Beta-D-Glucan Assays
Invasive Aspergillosis is an opportunistic mycotic infection witha mortality rate of 15-30% depending on when the infection isdiagnosed and type of therapy elected.
While therequirement for a diagnosis of proven invasive pulmonaryaspergillosis remains a lung biopsy for histopathology andculture, these patients are immunocompromised by definitionand such an invasive procedure is often not recommended.
Empiric treatment, likewise, is not ideal because the antifungalsrequired to treat invasive aspergillosis are expensive withtreatment of IA in the hospital reaching almost $2900 per dayand antifungals are notoriously toxic. Therefore,diagnosticians increasingly rely on alternative, less invasivetesting.
The problem with Aspergillus testing is that while the biopsy hassensitivity and specificity nearing 100% each, the less invasiveoptions are extremely variable in their sensitivities andspecificities. The current assays are: Galactomannan (GM)serum, GM bronchoalveolar lavage (BAL), Fungitell Beta-D-Glucan (BDG) serum, and Fungitell BDG BAL, with additionalassays in development. GM serum has been cited as having asensitivity of 68-74% and a specificity of 88-90%. GM BALhas a reported sensitivity of 55-87% and specificity of 70-78%. BDG serum has sensitivity of 67-84% and specificity of80-90% . BDG BAL has a sensitivity of 71% and specificity of67%.
To complicate the use of non-biopsy testing for Aspergillus, thecross-reactivity of the broad-spectrum antibiotic piperacillin-tazobactam (Zosyn) due to the presence of galactomannan in theformulation can lead to false positive tests . While morerecent formulations of piperacillin-tazobactam have been shownto decrease the incidence of these false positives, misdiagnosesstill occur . Additionally, solid organ transplants, in particularlung transplants, present a diagnostic challenge becausecolonization without invasion can lead to false positiveAspergillus test results. 25-30% of all lung transplant patientsare colonized with Aspergillus; therefore, leading to over-diagnosis and treatment of IA in this cohort and, as a reactionto this finding, this test result can be incorrectly dismissed as afalse positive, leading to delayed diagnosis and treatment inthese patients as well.
Journal of Infectious Diseases and Diagnosis