Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis: A Pre and Post-Intervention Analysis

• Main Authors: Malene Risum, Jannik Helweg-Larsen, Søren Lykke Petersen, Peter Kampmann, Ulrik Malthe Overgaard, Daniel El Fassi, Ove Juul Nielsen, Mette Brabrand, Niclas Rubek, Lars Munksgaard, Marianne Tang Severinsen, Bendt Nielsen, Jan Berg Gertsen, Åsa Gylfe, Ulla Hjort, Angeliki Vourtsi, Rasmus Krøger Hare, Maiken Cavling Arendrup
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Journal of Fungi
• Subjects: Mucorales; mucormycosis; haematology; neutropenia and mortality
• Online Access: https://www.mdpi.com/2309-608X/6/4/268

Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016–2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012–2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012–2015 and 2016–2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; <i>p</i> = 0.039). Initial systemic AFT was liposomal amphotericin B (<i>n</i> = 12) or posaconazole (<i>n</i> = 1) given as monotherapy (<i>n</i> = 4) or in combination with isavuconazole/posaconazole (<i>n</i> = 3/6) and terbinafine (<i>n</i> = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (<i>n</i> = 13). Mucormycosis related six month mortality was 3/5 in 2012–2015 and 0/7 patients in 2016–2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.