Data were identified by searches of PubMed for articles published from 1950 to 2010, with the terms “zygomycetes”, “mucormycosis”, “Mucorales” and “breakthrough”, “voriconazole”, “posaconazole”, “echinocandins”, “caspofungin”, “micafungin”, “anidulafungin”, “hematological malignancy”, “transplant”, “polyene”, “amphotericin B deoxycholate”, “liposomal amphotericin B”, “amphotericin B lipid complex”, “calcineurin inhibitors”, “tacrolimus”, “cyclosporine”, “mammalian target of rapamycin”,
ReviewMucormycosis: its contemporary face and management strategies
Introduction
With the advent of effective antifungal agents against Candida and Aspergillus spp, a growing population of immunocompromised hosts, improved diagnostic tools, and possible selection pressure from widespread use of broad-spectrum antifungal agents, mucormycosis has emerged as an important infection. Mucormycosis and entomophthoramycosis were previously encompassed by the term zygomycosis.1 Changes in high-level taxonomy in reference to molecular phylogenetic analyses have, however, led to the class name Zygomycota being replaced by Glomeromycota.2 In this new classification, all the agents of mucormycosis have been placed under the subphylum Mucormycotina and the agents of entomophthoramycosis are now in the subphylum Entomophthoramycotina. Since the phylum Zygomycota no longer exists, the disease name zygomycosis has become obsolete.3
Mucormycotina are characterised by large, ribbon-like hyphae with only occasional septae (aseptate fungi). These fungi cause mucormycosis, which comprises severe and potentially life-threatening infections, particularly in immunocompromised hosts. Improvements in culture-based morphological and molecular identification of fungi in the past two decades have led to expansion of the number of species known to cause mucormycosis. Infections are, however, primarily caused by those in the order Mucorales and the family Mucoraceae.4
Mucormycosis was reported in the Transplant Associated Infectious Surveillance Network study to occur in 9% of haemopoietic stem-cell transplant (HSCT) recipients and 2·1% of solid-organ transplant recipients.5, 6 Increases in incidence of mucormycosis have been reported in several countries in the past few years.7, 8, 9, 10, 11, 12, 13, 14 In developed countries, such as the USA, France, and Austria, mucormycosis mainly occurs in transplant recipients and neutropenic patients, although in France the frequency is rising among patients with diabetes mellitus.10, 11, 12, 13 In India the frequency has risen from 13 cases per year in 1990–99 to 36 cases per year in 2000–04, and 50 cases per year in 2006–07,7, 8, 9 and the highest-risk group is patients with uncontrolled diabetes.15
In immunocompetent patients, Apophysomyces elegans has emerged as an important pathogen for mucormycosis, leading to primarily cutaneous and rhino-orbital-cerebral disease with infections and generally occurring after traumatic inoculation.16, 17, 18 Additionally, several studies from India have reported isolated renal mucormycosis due to A elegans, mostly in immunocompetent young adults.7, 8, 9 Although rare, mucormycosis outbreaks—defined as more than two cases in 2–6 months—have been reported to occur in hospitals.19
In this Review we summarise the current state of knowledge about features of and risk factors for mucormycosis, and provide updates on potential therapeutic options and strategies for the management of this infection.
Section snippets
Clinical manifestations
Invasive mucormycosis is characterised by the rapid development of tissue necrosis as a result of vascular invasion and subsequent thrombosis. Disease may manifest as rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, or disseminated forms.1 In a review of 929 patients with mucormycosis assessed in 1940–2003, diabetes was the most frequent underlying condition (36%).20 The predominant clinical manifestations differ from host to host. Patients with diabetes most frequently present
Treatment
Successful treatment of mucormycosis requires early diagnosis, reversal of underlying risk factors, reduction, if possible, of immunosuppression, prompt administration of antifungal therapy, and surgical debridement when applicable.43 Delayed initiation of an amphotericin-B-based regimen (>6 days after diagnosis) has been reported to be associated with doubled mortality at 12 weeks.44 In patients with diabetes, with or without ketoacidosis, efforts should be made to restore euglycaemia and
Preventive strategies
In patients with GVHD who are receiving immunosuppressive therapy, and in patients with neutropenia due to chemotherapy for acute myelogenous leukaemia and myelodysplastic syndrome, prophylaxis with posaconazole substantially decreases the incidence of invasive fungal infections, particularly invasive aspergillosis.78, 79 In two studies mortality associated with invasive fungal infections was lowered,78, 79 although overall mortality was only lowered in one.78 These findings, along with the
Conclusions
Mucormycosis is an important opportunistic fungal infection, particularly in patients with haematological disorders, malignancy, and diabetes mellitus, and in those undergoing transplantation. Whether the rising rates in certain populations are related to evolving characteristics of patients or to antimicrobial selection pressure from prescription practices for current antifungal agents deserves further investigation. Liposomal amphotericin B is the preferred therapeutic agent for mucormycosis.
Search strategy and selection criteria
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