Utility of Mucorales polymerase chain reaction to diagnose Rhizomucor infections in neutropenic patients

Abstract

Mucormycoses are life-threatening infections related to fungi from the Mucorales order. Based on fungal culture, the most frequently involved genera are Rhizopus spp., Mucor spp., or Lichtheimia spp. However, since the introduction of Mucorales polymerase chain reaction (PCR), many diagnoses have been made without positive fungal culture, biasing mucormycosis epidemiology. We conducted a single-centre retrospective observational study on invasive mucormycosis cases diagnosed between April 2020 and December 2022. Cases were classified according to EORTC/MSGERC definitions, adding a 'PCR-only' category for patients with a positive Mucorales PCR as the only mycological evidence. Genus/species identification was obtained by sequencing the Mucorales 18S rDNA directly on Mucorales PCR-positive samples. We identified 35 cases of mucormycosis, including 6 proven, 7 probable, and 22 'PCR-only'. Genus/species identification was achievable in 34 cases and surprisingly revealed the genus Rhizomucor as the main aetiological agent (n = 14, 41.2%). Interestingly, all the Rhizomucor infections, except one, were classified as 'PCR-only', while fungal culture was positive in 11/20 (55%) for other Mucorales genera (P <.001). Moreover, in comparison with other genera, the genus Rhizomucor was significantly more associated with neutropenia (11/14 [78.6%] vs. 2/20 [10%], P < .0001) and pulmonary localizations (11/14 [78.6%] vs. 6/20 [30%], P = .01). Our study reveals the changing epidemiology of mucormycosis in our centre with the use of Mucorales PCR and underlines the importance of the genus Rhizomucor, especially in neutropenic patients. This highlights the benefits of using Mucorales PCR in clinical practice for mucormycosis diagnosis in high-risk patients and the need to include it in diagnostic criteria.

Keywords: Mucorales; Rhizomucor; DNA sequencing; molecular diagnosis; mucormycosis.