Although histoplasmosis is highly endemic in certain regions of the Americas, disease may be seen globally and should not be overlooked in patients with unexplained pulmonary or systemic illnesses. Most patients exhibit pulmonary signs and symptoms, accompanied by radiographic abnormalities, which often are mistaken for community-acquired pneumonia caused by bacterial or viral agents. Once a diagnosis is considered, a panel of mycologic and non-culture-based assays is adequate to establish a diagnosis in a few days to a week in most patients. Once diagnosed, the treatment is highly effective even in immunocompromised patients.

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.

Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors. We examined the impact of the multiplexed, semiquantitative BioFire FilmArray Pneumonia panel (PN panel) test on laboratory reporting for 259 adult inpatients submitting bronchoalveolar lavage (BAL) specimens for laboratory analysis. The PN panel demonstrated a combined 96.2% positive percent agreement (PPA) and 98.1% negative percent agreement (NPA) for the qualitative identification of 15 bacterial targets compared to routine bacterial culture. Semiquantitative values reported by the PN panel were frequently higher than values reported by culture, resulting in semiquantitative agreement (within the same log10 value) of 43.6% between the PN panel and culture; however, all bacterial targets reported as >105 CFU/ml in culture were reported as ≥105 genomic copies/ml by the PN panel. Viral targets were identified by the PN panel in 17.7% of specimens tested, of which 39.1% were detected in conjunction with a bacterial target. A review of patient medical records, including clinically prescribed antibiotics, revealed the potential for antibiotic adjustment in 70.7% of patients based on the PN panel result, including discontinuation or de-escalation in 48.2% of patients, resulting in an average savings of 6.2 antibiotic days/patient.

Histoplasmosis is a global disease endemic to regions of all six inhabited continents. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. As a result of climate change and anthropogenic land utilization, the conditions suitable for Histoplasma capsulatum are changing, leading to a corresponding change in epidemiology. The clinical manifestations of histoplasmosis are protean, variably resembling other common conditions such as community-acquired pneumonia, tuberculosis, sarcoidosis, Crohn's disease, or malignancy. Making a successful diagnosis is contingent on a thorough understanding of epidemiology, common clinical presentations, and best testing practices for histoplasmosis. While most subclinical or self-limited diseases do not require treatment in immunocompetent patients, all immunocompromised patients and those with progressive disseminated disease or chronic pulmonary disease should be treated. Liposomal amphotericin B is the preferred agent for severe or disseminated disease, while itraconazole is adequate for milder cases and “step-down” therapy following response to amphotericin B. In this review, we discuss the current evidence-based approaches to the epidemiology, diagnosis, and management of histoplasmosis.