Abstract

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%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 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.

Highlights

  • We investigated the survival rate before and after the intervention in a series of 13 patients with proven mucormycosis in 2012 to June 2019 and found no mucormycosis related deaths since 2015

  • The current study probably includes the vast majority of proven mucormycosis cases during the study period in Denmark, we cannot exclude that undiagnosed cases or non-proven cases in patients beyond therapeutic reach and for whom diagnostics or consultation were deemed unnecessary were missed in the current period

  • We report 13 cases with proven Mucorales infection diagnosed during 2012–18 and with an overall three, six, and 12 month survival rate of 83%, 67%, and 58%, respectively, with no mucormycosis related deaths after 2015

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Summary

Introduction

Interdisciplinary Management Approach in Haematological Patients with Mucormycosis:. 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. Mucormycosis is a rare, angio-invasive fungal infection [1]. The major predisposing factor for mucormycosis is haematological malignancy [1,4,5,6]. Pulmonary mucormycosis is the most frequent manifestation in haematological patients [7,8,9,10,11]. Predisposing risk factors are prolonged and severe neutropenia, high-dose corticosteroids, and iron overload (IOL) [12]

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