Contemporary management and clinical outcomes of mucormycosis: A systematic review and meta-analysis of case reports

Highlights

• Mucormycosis-associated 90-day mortality remains high (41%) despite the advent of newer antifungals.

• First-line antifungals with good efficacy and safety remain an urgent unmet need.

• i.v. lipid-based AmB did not confer a survival advantage over i.v. C-AmB but was associated with fewer adverse effects.

• Initial combination antifungal therapy was not associated with reduced mortality compared with initial AmB monotherapy.

• Surgery is fundamental to improving survival and must be accessible to all patients.

ABSTRACT

With the advent of newer antifungals, optimum treatment of mucormycosis remains to be fully elucidated. This study systematically evaluated the contemporary management and outcomes of mucormycosis. Mucormycosis cases in patients aged ≥18 years published between January 2000 and January 2017 were identified through Ovid MEDLINE and Embase. Of the 3619 articles identified, 600 (851 individual patient cases) were included in the review. Of the 851 patient cases, antifungal treatment details were available for 785. Intravenous (i.v.) amphotericin B formulations remained the most commonly prescribed first-line antifungals (760/785; 96.8%): 88.2% (670/760) were initiated as monotherapy and 11.8% (90/760) as combination antifungal therapy. Posaconazole oral suspension monotherapy was prescribed as an initial antifungal in 11 cases. It was also administered as maintenance or salvage therapy in 39 and 25 cases, respectively. Itraconazole capsule monotherapy (n = 10) was prescribed primarily for cutaneous disease in patients not receiving any immunosuppressive therapy. All-cause 90-day mortality was 41.0% (349/851). Initial treatment with combination antifungals did not reduce 90-day mortality compared with i.v. conventional amphotericin B or i.v. liposomal amphotericin B monotherapy [35/90 (38.9%) vs. 146/369 (39.6%) vs. 91/258 (35.3%), respectively; P = 0.541]. Concomitant surgical and antifungal therapy was associated with significantly lower 90-day mortality compared with treatment with antifungals alone (OR = 0.23, 95% CI 0.13–0.41; P < 0.001). The findings suggest that first-line antifungals with good efficacy remain an urgent unmet need. Whilst surgery is fundamental to improving survival, the clinical utility of combination antifungal therapy or posaconazole monotherapy requires further investigation.

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.