The American Thoracic Society (ATS) has published a new clinical practice guideline detailing recommendations for various microbiologic laboratory testing approaches for the diagnosis of fungal infections in pulmonary and critical care, with a particular focus on immunocompromised patients. The full guideline was published in the American Journal of Respiratory and Critical Care Medicine.

A panel of experts in fungal infections representing pulmonary medicine, critical care, and infectious diseases physicians convened for the review. The panel performed a comprehensive literature review of articles published from 1980 to April 14, 2016. Articles on the diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses were included in the review, and meta-analysis was occasionally performed. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to develop recommendations for this guideline.

Galactomannan Testing for Fungal Infection Diagnosis

Based on their review, the panel recommended serum galactomannan testing in patients with severe immunocompromise (eg, neutropenia or hematologic malignancy) for identifying and diagnosing aspergillosis (strong recommendation, high-quality evidence). Patients with strong risk factors for invasive aspergillosis but negative serum galactomannan or patients with confounding factors for false-positive galactomannan, bronchoalveolar lavage testing with galactomannan is recommended to identify invasive fungal infections (strong recommendation, high-quality evidence).

The Role of Polymerase Chain Reaction

The guideline also recommended the use of polymerase chain reaction (PCR) in the diagnosis of invasive pulmonary aspergillosis. Aspergillus PCR in bronchoalveolar lavage testing integrated into an evaluation is recommended for patients who are severely immunocompromised and are suspected of having invasive pulmonary aspergillosis (strong recommendation, high-quality evidence). Blood or serum Aspergillus PCR is also recommended for severely immunocompromised patients who are also suspected of having invasive pulmonary aspergillosis (strong recommendation, high-quality evidence).

Utility of β-D-glucan Assays

With regard to critically ill patients with suspected invasive candidiasis, the panel does not believe that β-D-glucan assays alone are sufficient for diagnostics (conditional recommendation, low-quality evidence). The β-D-glucan assay may hold diagnostic utility in combination with clinical risk determination and microbiologic data to identify patients at highest risk for invasive candidiasis.

Serology and Antigen Testing in Endemic Mycoses

In patients who are immunocompetent and have suspected pulmonary histoplasmosis, the ATS panel recommended the use of Histoplasma serologies, with the addition of Histoplasma antigen to serologic testing potentially improving diagnostic yield (conditional recommendation, moderate-quality evidence). The use of Histoplasma antigen in urine or serum is also recommended for rapid diagnosis of suspected disseminated and acute pulmonary histoplasmosis (strong recommendation, high-quality evidence).

A conditional recommendation, based on low-quality evidence, for patients with suspected blastomycosis is to use serum antibody testing directed against anti-Blastomyces adhesin 1 antigen. Urinary antigen testing for blastomycosis plus clinical and epidemiologic data are also recommended to establish a diagnosis of blastomycosis in immunocompromised patients (conditional recommendation, moderate-quality evidence).

For the diagnosis of coccidioidomycosis, the panel also recommends performing urinary and serum antigen testing, particularly in immunocompromised patients (conditional recommendation, moderate-quality evidence). The use of >1 diagnostic test for patients with geographic exposure and illness associated with infection or pneumonia caused by blastomycosis that is tailored to illness severity and the clinical context is also recommended (conditional recommendation, moderate-quality evidence). These tests could include direct visualization and culture of sputum bronchoalveolar lavage or other biopsy material, urine antigen testing, and serum antibody testing. Serologic testing plus close clinical follow-up and serial testing is recommended in patients with suspected community-acquired pneumonia from the endemic area for coccidioidomycosis.

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“With the rising incidence of invasive fungal infections in both immunocompromised and immunocompetent patients,” the panel committee wrote, “the clinician should become familiar with the application of relevant laboratory testing outlined in this guideline to confirm the diagnosis of these important infections.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Hage CA, Carmona EM, Epelbaum O, 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 Respir Crit Care Med. 2019;200(5):535-550.