Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive mycosis in order of importance after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients with diabetes mellitus in the Western world. Furthermore, this disease is increasingly recognized in recently developed countries, such as India, mainly in patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. Therefore, our ability to determine the burden of disease is limited. Based on anatomic localization, mucormycosis can be classified as one of 6 forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations. The underlying conditions can influence clinical presentation and outcome. This review describes the emerging epidemiology and the clinical manifestations of mucormycosis.
Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.
These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4×200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.
Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation.
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