Comparison of histopathological analysis, culture, and polymerase chain reaction assays to detect invasive mold infections from biopsy specimens

Background. With the advent of new antifungal agents, the identification of a causative pathogen is crucial to guide the antifungal treatment of invasive mold infection. However, tissue cultures often fail to grow a fungal pathogen in cases of suspected mold infection. Methods. In a prospective multicenter study, we compared the results of histopathological analysis, culture, and 2 seminested polymerase chain reaction assays identifying Aspergillus species and Zygomycetes as causative agents of invasive mold infections using respiratory tract biopsy samples obtained from 56 immunocompromised patients who had suspected mold infection. Results. Mold hyphae were detected histopathologically in 27 (48%) of the tissue specimens. Hyphae corresponded to either aspergillosis (n=18) or zygomycosis (n=6) or could not be further specified (n=3). A mold was cultured from 14 of 18 samples with aspergillus hyphae, 2 of 6 samples with Zygomycetes hyphae, and 1 of 3 samples with unspecified hyphae. Polymerase chain reaction was superior to culture in detecting the infecting mold (26 of 27 samples vs. 17 of 27 samples, respectively; P=.006) from histopathologically positive samples. Pp. 006 Genus or species identification by sequencing of the polymerase chain reaction products were in accordance with culture results in 16 of 18 culture-positive samples. Both polymerase chain reaction assays failed to detect fungal DNA in 1 sample that had unspecified hyphae and negative culture results. Conclusion. The PCR assays offer a reliable etiologic diagnosis that is superior to culture in patients with proven invasive mold infection. This may improve patient management through tailored antifungal therapy when cultures fail to grow a pathogen.