Accuracy and actionability of mold PCR on bronchoalveolar lavage fluid for diagnosis of invasive mold disease

ABSTRACT Bronchoalveolar lavage fluid (BAL) is commonly obtained for diagnosing invasive mold disease (IMD) in immunocompromised patients. This study investigated the accuracy, turnaround time, and clinical actionability of mold polymerase chain reaction (PCR) on BAL. All BAL tested with mold PCR and fungal culture during the study period were included in this study. The mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium spp./ Lomentospora prolificans . Cases were classified per the EORTC/MSGERC definitions. The sensitivity, specificity, turnaround time, and actionability of the mold PCR were measured. Out of 1,958 BAL samples tested, mold PCR was positive in 160 (8.2%) and culture in 75 (3.8%). Mold PCR was most commonly positive for Aspergillus species (77.5%), followed by Scedosporium spp./ L. prolificans (20.0%), Mucorales agents (8.3%), and Fusarium species (1.2%). The sensitivity and specificity of the mold PCR using culture as the reference standard were 92.0% (69/75, 95% CI 83.4–97.1) and 95.2% (1794/1883, 95% CI 94.2–96.2), respectively. In 32 proven IMD cases, the sensitivity of mold PCR panel and culture was 90.6% (29/32, 95% CI 74.9–98.1) and 56.3% (18/32, 95% CI 37.7–73.7) ( P < 0.001), respectively. The median time to positivity for mold PCR and culture was 1 day (interquartile range [IQR] 1–2) and 3 days (IQR 2–4) ( P < 0.001), respectively. Among positive mold PCR results that provided a new finding ( n = 91), 65.9% were clinically actionable. Mold PCR performed on BAL was more sensitive and rapid compared with fungal culture, and positive results were highly actionable. IMPORTANCE Invasive mold disease (IMD) in immunocompromised patients is associated with high morbidity and mortality. Bronchoalveolar lavage fluid (BAL) is commonly obtained for diagnosing pulmonary IMD, but rapid and accurate diagnosis of IMD is challenging with conventional diagnostics. The aim of this study was to investigate the accuracy, turnaround time, and clinical actionability of a BAL mold PCR assay detecting the five most common genera causing IMD. The BAL mold PCR was highly sensitive and specific compared to BAL fungal culture used as the reference method. In patients with proven pulmonary IMD, the BAL mold PCR was highly sensitive and significantly more sensitive compared with fungal culture. The BAL mold PCR was significantly more rapid than fungal culture, and the results were highly actionable. Overall, findings indicate the BAL mold PCR is highly accurate, rapid, and actionable for diagnosis of pulmonary IMD.