Article
Non-aspergillus mold diseases – update on epidemiology and management
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Authors
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Andreas H. Groll
- Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Germany
| Published: | October 8, 2018 |
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Outline
Text
Invasive fungal infections are an important cause for morbidity and mortality in immuno-compromised and severely ill patient populations. During the past decade, there has been a steady increase in infections by previously unusual filamentous fungi including hyaline and dematiaceous molds and the mucorales.
Clinical manifestations of these infections range from colonization to acute or chronic localized lesions to acute invasive and/or disseminated diseases. Clinical manifestations and results of imaging are unspecific and diagnosis usually requires isolation of the infecting pathogen from the infected site and definite identification by molecular typing; polymerase chain reaction (PCR) based diagnostics can be helpful but does not allow for resistance testing that may be critical for treatment decisions. Principles of management include the prompt initiation of antifungal chemotherapy, evaluation of the patients for further sites of infection, stabilization of the infection during the period of compromised host defenses, reconstitution of host defenses, if feasible, surgical interventions as appropriate, and treatment until the resolution of all attributable symptoms and findings. With the exception of mucormycosis, there are no uniformly accepted first-line standard therapies, and recommendations are based on case series or the cumulative experience of individual case reports. Treatment recommendations are limited by the fact that the non-Aspergillus molds encompass a large number of biologically diverse pathogens, the lack of standardized in vitro resistance testing, little data from preclinical animal studies and the virtual absence of phar-macokinetic/pharmacodynamic models, and lack of correlation of preclinical data with clinical outcomes. Therapeutic options are restricted to amphotericin B and the triazoles: Whereas liposomal amphotericin B remains the first choice for initial treatment of mucormycosis with isavuconazole being the first alternative, voriconazole and posaconazole can be effective and are recommended against infections by Fusarium spp., Scedosporium and most phaeohyphomycetes; the relative role of liposomal amphotericin B in treatment of the hyalohyphomycetes and the phaeohyphomycetes is unclear at present. Among the current investigational agents, APX001 that targets the attachment of essential fungal adhesion proteins holds promise for clinical development against non-Aspergillus molds.
As we enter the next decade, it is to be expected that emergent fungal infections will continue to develop in the settings of permissive environmental conditions, selective antifungal pressure, and an expanding population of immunocompromised hosts.
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