Malassezia Restricta: An Underdiagnosed Causative Agent of Blood Culture-Negative Infective Endocarditis.

BACKGROUND Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Nowadays, 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 non-documented (culure and conventional PCR) IE (NDIE) cases. METHODS Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite-IE over a five-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultra-sensitive 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 and 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 three other cases. In these three 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 a major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.