RESUMEN
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScope® registry. For 208 Scedosporium spp. infections solid organ transplantation (n = 58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n = 28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n = 26, 46.4% versus n = 12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificans.
Asunto(s)
Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/patología , Scedosporium/aislamiento & purificación , Adulto , Anciano , Antifúngicos/uso terapéutico , Femenino , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/microbiología , Infecciones Fúngicas Invasoras/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Trasplante de Órganos/efectos adversos , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Voriconazol/uso terapéuticoRESUMEN
Rare invasive fungal diseases (IFD) are challenging for the treating physicians because of their unspecific clinical presentation, as well as the lack of standardised diagnostic and effective treatment strategies. Late onset of treatment and inappropriate medication is associated with high mortality, thus, urging the need for a better understanding of these diseases. The purpose of FungiScope™ is to continuously collect clinical information and specimens to improve the knowledge on epidemiology and eventually improve patient management of these orphan diseases. FungiScope™ was founded in 2003, and today, collaborators from 66 countries support the registry. So far, clinical data of 794 cases have been entered using a web-based approach. Within the growing network of experts, new collaborations developed, leading to several publications of comprehensive analyses of patient subgroups identified from the registry. Data extracted from FungiScope™ have also been used as the sole control group for the approval of a new antifungal drug. Due to the rarity of these diseases, a global registry is an appropriate method of pooling the scarce and scattered information. Joining efforts across medical specialities and geographical borders is key for researching rare IFD. Here, we describe the structure and management of the FungiScope™ registry.
Asunto(s)
Enfermedades Transmisibles Emergentes , Salud Global , Micosis , Enfermedades Raras , Sistema de Registros , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras , Control de Calidad , Sistema de Registros/normasRESUMEN
Saprochaete and Geotrichum spp. are rare emerging fungi causing invasive fungal diseases in immunosuppressed patients and scarce evidence is available for treatment decisions. Among 505 cases of rare IFD from the FungiScope™ registry, we identified 23 cases of invasive infections caused by these fungi reported from 10 countries over a 12-year period. All cases were adults and previous chemotherapy with associated neutropenia was the most common co-morbidity. Fungaemia was confirmed in 14 (61%) cases and deep organ involvement included lungs, liver, spleen, central nervous system and kidneys. Fungi were S. capitata (n=14), S. clavata (n=5), G. candidum (n=2) and Geotrichum spp. (n=2). Susceptibility was tested in 16 (70%) isolates. All S. capitata and S. clavata isolates with the exception of one S. capitata (MIC 4 mg/L) isolate had MICs>32 mg/L for caspofungin. For micafungin and anidulafungin, MICs varied between 0.25 and >32 mg/L. One case was diagnosed postmortem, 22 patients received targeted treatment, with voriconazole as the most frequent first line drug. Overall mortality was 65% (n=15). Initial echinocandin treatment was associated with worse outcome at day 30 when compared to treatment with other antifungals (amphotericin B ± flucytosine, voriconazole, fluconazole and itraconazole) (P=.036). Echinocandins are not an option for these infections.
Asunto(s)
Geotricosis/microbiología , Geotrichum/aislamiento & purificación , Infecciones Fúngicas Invasoras/microbiología , Sistema de Registros , Saccharomycetales/aislamiento & purificación , Adolescente , Adulto , Anciano , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Equinocandinas/farmacología , Equinocandinas/uso terapéutico , Femenino , Fluconazol/farmacología , Fluconazol/uso terapéutico , Fungemia/diagnóstico , Fungemia/tratamiento farmacológico , Fungemia/microbiología , Geotricosis/tratamiento farmacológico , Geotricosis/mortalidad , Geotrichum/clasificación , Geotrichum/efectos de los fármacos , Geotrichum/genética , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/mortalidad , Lipopéptidos/farmacología , Lipopéptidos/uso terapéutico , Masculino , Micafungina , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Neutropenia/microbiología , Saccharomycetales/clasificación , Saccharomycetales/efectos de los fármacos , Saccharomycetales/genética , Voriconazol/farmacología , Voriconazol/uso terapéutico , Adulto JovenRESUMEN
Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.
Asunto(s)
Salud Global , Guías como Asunto , Micosis , Antifúngicos/uso terapéutico , Ascomicetos , Humanos , Huésped Inmunocomprometido , Hongos Mitospóricos , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Micosis/epidemiologíaRESUMEN
Disseminated fusariosis is a rare disease, and data are scant in pediatric patients. In the FungiScope registry, we identified 10 children with disseminated fusariosis between 2006 and 2015. Our analysis of the largest pediatric case series reported to date adds pediatric-specific experience to the management of this opportunistic infection in children.