Linda Houhamdi Hammou1, Yvonne Benito1, André Boibieux2, Damien Dupont3, François Delahaye4, Françoise Thivolet-Bejui5, Martine Wallon3, François Vandenesch1, Coralie Bouchiat1. 1. Laboratoire de Bactériologie. Institut des Agents Infectieux. Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France. 2. Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France. 3. Laboratoire de Parasitologie-Mycologie, Institut des Agents Infectieux. Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France. 4. Service de Cardiologie, Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, France. 5. Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
Abstract
BACKGROUND: Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Currently, identification of its etiological microorganism remains unresolved in 5.2% of cases. We aimed to improve IE diagnosis using an ultra-sensitive molecular technique on cardiac samples in microbiologically nondocumented (culture and conventional polymerase chain reaction [PCR]) IE (NDIE) cases. METHODS: Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite IE over a 5-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultrasensitive molecular diagnosis was achieved using the Universal Microbe Detection kit (Molzym®). Fungal identification was confirmed using 26S-rDNA and internal transcribed spacer amplifications. Fungal infection was confirmed using Grocott-Gromori staining, auto-immunohistochemistry on cardiac samples, and mannan serologies. RESULTS: Among 88 included patients, microbial DNA was detected in all 16 NDIE cases. Bacterial taxa typical of IE etiologies were detected in 13/16 cases and Malassezia restricta in the 3 other cases. In these 3 cases, histological examination confirmed the presence of fungi pathognomonic of Malassezia that reacted with patient sera in an auto-immunohistochemistry assay and cross-reacted with Candida albicans in an indirect immunofluorescent assay. CONCLUSIONS: M. restricta appears to be an underestimated causative agent of NDIE. Importantly, serological cross-reaction of M. restricta with C. albicans may lead to its misdiagnosis. This is of major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.
BACKGROUND: Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Currently, identification of its etiological microorganism remains unresolved in 5.2% of cases. We aimed to improve IE diagnosis using an ultra-sensitive molecular technique on cardiac samples in microbiologically nondocumented (culture and conventional polymerase chain reaction [PCR]) IE (NDIE) cases. METHODS: Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite IE over a 5-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultrasensitive molecular diagnosis was achieved using the Universal Microbe Detection kit (Molzym®). Fungal identification was confirmed using 26S-rDNA and internal transcribed spacer amplifications. Fungal infection was confirmed using Grocott-Gromori staining, auto-immunohistochemistry on cardiac samples, and mannan serologies. RESULTS: Among 88 included patients, microbial DNA was detected in all 16 NDIE cases. Bacterial taxa typical of IE etiologies were detected in 13/16 cases and Malassezia restricta in the 3 other cases. In these 3 cases, histological examination confirmed the presence of fungi pathognomonic of Malassezia that reacted with patient sera in an auto-immunohistochemistry assay and cross-reacted with Candida albicans in an indirect immunofluorescent assay. CONCLUSIONS: M. restricta appears to be an underestimated causative agent of NDIE. Importantly, serological cross-reaction of M. restricta with C. albicans may lead to its misdiagnosis. This is of major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.
Authors: Alessandra Mularoni; Elena Graziano; Alice Annalisa Medaglia; Barbara Buscemi; Taylor Eddens; Lavinia Martino; Daniele Di Carlo; Antonio Cascio; Pier Giulio Conaldi; Alessandro Bertani; Paolo Antonio Grossi Journal: J Fungi (Basel) Date: 2021-12-10