Contemporary management and clinical outcomes of mucormycosis: A systematic review and meta-analysis of case reports
Introduction
The management of mucormycosis is challenging given its aggressive nature and difficulty in diagnosing the infection [1]. In addition, the choice of antifungal therapy is limited given the reduced susceptibility of the Mucorales to many antifungal agents [2], [3], [4]. Owing to its broad-spectrum antifungal activity, traditionally amphotericin B (AmB) formulations have been the antifungal of choice for the treatment of mucormycosis [5], [6], [7], [8]. However, with the advent of newer triazoles, specifically posaconazole and isavuconazole, clinicians now have access to a wider range of therapeutic options.
Of importance, optimal management strategies for mucormycosis and associated patient outcomes remain to be fully elucidated. Prospective clinical studies evaluating the safety and efficacy of mucormycosis treatment are scarce; only three clinical trials have been reported to date [9], [10], [11] and evidence surrounding the treatment of mucormycosis has been extrapolated primarily from case reports or small case series [5], [6], [7], [8]. Roden et al. performed a comprehensive review of approaches to managing mucormycosis, but this was conducted more than 10 years ago in the absence of the newer antifungals [12]. This prompted a timely review of the current literature to generate up-to-date evidence required to support and optimise the management of this difficult-to-treat infection.
Section snippets
Methods
This was a systematic review of published case reports and case series of proven and probable mucormycosis, as defined by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria [13], in patients aged ≥18 years. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines [14] were adopted to guide the undertaking and reporting of this review.
Study inclusion and selection
A total of 3619 articles were identified in the initial search, of which 600 (comprising 851 individual patient cases) were included. Appendix B lists the articles included in the review. Details of patient characteristics, underlying conditions/risk factors, disease manifestations and causative pathogens have been described recently [17].
Treatment modalities
Treatment data were reported for 815 of the 851 cases. Antifungal therapy in combination with surgery was the most commonly prescribed treatment (476/815;
Discussion
To our knowledge, this is the most comprehensive systematic review to date investigating the management strategies and outcomes of mucormycosis, a critical therapeutic area that is relatively evidence-poor. This review has provided important insights into the clinical utility of the newer antifungals such as posaconazole in the management of mucormycosis. Pivotal data associated with adjunctive therapy are presented. Furthermore, the treatment outcomes and clinical variables influencing 90-day
Funding
This was an investigator-initiated study supported by internal funding.
Competing interests
MAS and SCAC have received grants from Pfizer, Merck Sharp & Dohme (MSD) and Gilead Sciences; DCMK has sat on advisory boards for Pfizer and MSD, and has received financial/travel support unrelated to the current work from Roche, Pfizer and MSD. All other authors declare no competing interests.
Ethical approval
Not required.
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Preliminary data from this work were presented at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 22–25 April 2017, Vienna, Austria [poster 2078].