RESUMEN
BACKGROUND: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. METHODS: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. RESULTS: Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). CONCLUSIONS: High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.
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Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Mucormicosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Preescolar , Desbridamiento , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mucormicosis/cirugía , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit (D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial ß -tubulin II (TUB2); iv) γ-actin (ACT); v) translation elongation factor 1-α (TEF1α); and vi) the second largest subunit of RNA-polymerase II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP; iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1α. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding a single PCR-product. Barcode gap and multi-dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections, a novel high fidelity primer pair for TEF1α, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2 are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail.
RESUMEN
We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. This case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.
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Antifúngicos/farmacología , Aspergillus fumigatus/aislamiento & purificación , Emericella/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aspergilosis Pulmonar Invasiva/microbiología , Adulto , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Azoles/farmacología , Sistema Enzimático del Citocromo P-450/genética , ADN de Hongos/genética , Farmacorresistencia Fúngica , Resultado Fatal , Femenino , Proteínas Fúngicas/genética , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: Mucormycosis are rare fungal infections occurring chiefly in the lung or the rhinocerebral compartment, particularly in patients with immunodeficiency or mellitus diabetes. We report the case of an elderly patient with cutaneous mucormycosis caused by Rhizopus microsporus. PATIENTS AND METHODS: An 89-year-old man presented a skin lesion of the forearm rapidly becoming inflammatory and necrotic. The patient had been treated for 2months with oral corticosteroids for idiopathic thrombocytopenia. Histological and mycological examination of the skin biopsy revealed the presence of a filamentous fungus, R. microsporus. The outcome was unfavorable, despite prescription of high-dose liposomal amphotericin B. DISCUSSION: Mucormycosis are infrequent opportunistic infections caused by angio-invasive fungi belonging to the Mucorales order. Cutaneous presentations are rare, and in rare cases the species R. microsporus is isolated in clinical samples. Diagnosis is based on histological examination highlighting the characteristic mycelium within infected tissue, together with ex vivo mycological identification using morphological and molecular methods. Treatment consists of liposomal amphotericin B combined with debridement surgery. CONCLUSION: R. microsporus is a marginal fungal species rarely isolated in clinical practice, and even less in dermatology departments. This clinical case report highlights the severity of infection with this fungus, particularly in the absence of early surgery.
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Dermatomicosis/diagnóstico , Dermatomicosis/microbiología , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Rhizopus , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Anciano de 80 o más Años , Anfotericina B/administración & dosificación , Biopsia , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/patología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Mucormicosis/tratamiento farmacológico , Mucormicosis/patología , Necrosis , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/patología , Cuidados Paliativos , Rhizopus/ultraestructura , Piel/patología , Trombocitopenia/tratamiento farmacológicoRESUMEN
BACKGROUND: Mucormycosis is a deadly invasive fungal infection whose characteristics are only partially understood. METHODS: Data on mucormycosis obtained in France between 2005 and 2007 from 2 notification systems were merged. The 2008 European Organisation for Research and Treatment of Cancer/Mycoses Study Group definition criteria were applied and risk factors for death were analyzed by hazard ratios (HRs) calculated from the Cox proportional hazards regression model. RESULTS: A total of 101 cases (60 proven, 41 probable), mostly in men (58%) >50 years (mean age, 50.7 ± 19.9) were recorded. Hematological malignancies represented 50% (median time for occurrence, 8.8 months after disease onset), diabetes 23%, and trauma 18% of cases. Sites of infection were lungs (28%; 79% in hematology patients), rhinocerebral (25%; 64% in diabetic patients), skin (20%), and disseminated (18%). Median time between first symptoms and diagnosis was 2 weeks. The main fungal species were Rhizopus oryzae (32%) and Lichtheimia species (29%). In cases where the causative species was identified, R. oryzae was present in 85% of rhinocerebral forms compared with only 17% of nonrhinocerebral forms (P < .001). Treatment consisted of surgery in 59% and antifungals in 87% of cases (liposomal amphotericin B in 61%). Ninety-day survival was 56%; it was reduced in cases of dissemination compared with rhinocerebral (HR, 5.38 [2.0-14.1]; P < .001), pulmonary (HR, 2.2 [1.0-4.7]; P = .04), or skin localization (HR, 5.73 [1.9-17.5]; P = .002); survival was reduced in cases of hematological malignancies compared with diabetes mellitus (HR, 2.3 [1.0-5.2]; P < .05) or trauma (HR, 6.9 [1.6-28.6], P = .008) and if ≥2 underlying conditions (HR, 5.9 [1.8-19.0]; P = .004). Mucormycosis localization remained the only independent factor associated with survival. CONCLUSIONS: This 3-year study performed in one country shows the diverse clinical presentation of mucormycosis with a high prevalence of primary skin infection following trauma and a prognosis significantly influenced by localization.
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Enfermedades Cerebelosas/microbiología , Mucormicosis/epidemiología , Rhizopus/patogenicidad , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Enfermedades Cerebelosas/complicaciones , Enfermedades Cerebelosas/patología , Enfermedades Cerebelosas/cirugía , Niño , Recolección de Datos , Dermatomicosis/complicaciones , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/microbiología , Diabetes Mellitus/microbiología , Femenino , Francia/epidemiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/microbiología , Humanos , Pulmón/microbiología , Pulmón/patología , Masculino , Persona de Mediana Edad , Mucormicosis/complicaciones , Mucormicosis/tratamiento farmacológico , Mucormicosis/microbiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Heridas y Lesiones/complicaciones , Heridas y Lesiones/microbiología , Heridas y Lesiones/cirugía , Adulto JovenRESUMEN
Saksenaea is a monotypic genus belonging to the order Mucorales and capable of producing severe human infections. Through a polyphasic study based on analysis of the sequences of the internal transcribed spacer (ITS) region, domains D1 and D2 of the 28S rRNA gene, and the elongation factor 1α (EF-1α) gene, as well as by evaluation of relevant morphological and physiological characteristics of a set of clinical and environmental strains, we have demonstrated that Saksenaea vasiformis is a complex of species. We propose as new species Saksenaea oblongispora, characterized by oblong sporangiospores and unable to grow at 42°C, and Saksenaea erythrospora, characterized by large sporangiophores and sporangia and by ellipsoid sporangiospores, biconcave in the lateral view. Itraconazole, posaconazole, and terbinafine were active against all isolates included in the study, while amphotericin B, voriconazole, and the echinocandins showed low activity.
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Mucorales/clasificación , Mucorales/genética , Antifúngicos/farmacología , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Microbiología Ambiental , Proteínas Fúngicas/genética , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Mucorales/citología , Mucorales/fisiología , Mucormicosis/microbiología , Técnicas de Tipificación Micológica , Naftalenos/farmacología , Factor 1 de Elongación Peptídica/genética , Filogenia , Análisis de Secuencia de ADN , Esporas Fúngicas/citología , Esporas Fúngicas/crecimiento & desarrollo , Temperatura , Terbinafina , Triazoles/farmacologíaAsunto(s)
Ascomicetos/aislamiento & purificación , Absceso Encefálico/diagnóstico , Absceso Encefálico/microbiología , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Anciano , Antifúngicos/uso terapéutico , Biopsia con Aguja , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/patología , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Fúngicas del Sistema Nervioso Central/patología , Francia , Humanos , Masculino , SobrevidaRESUMEN
OBJECTIVES: Fungal keratitis is rare in France, but could be a severe sight-threatening condition. Here, we aimed to describe the epidemiology of fungal keratitis in Réunion Island. METHODS: In a retrospective study, we analyzed 13 culture-proven keratitis episodes, occurred between January 2013 and July 2017 in the ophthalmology ward of a University Hospital, Saint-Pierre. Twelve isolates were genotyped and antifungal susceptibility testing was performed. RESULTS: Corneal abrasion caused by vegetable matter was the main predisposing factor. Stromal infiltration was observed in 12 patients. Six patients did not response to medical treatment, requiring surgical care, including two enucleations surgery. Fusarium solani (n = 6) and Fusarium dimerum (n = 4) were the main fungal species involved in fungal keratitis. Clinical failures were more prevalent with F. solani infections. The lowest minimal inhibitory concentrations for Fusarium sp. were observed with voriconazole and amphotericin B. CONCLUSION: In Reunion Island, the epidemiology of fungal keratitis is characterized by the predominance of Fusarium species, potentially involved in visual loss. This pattern is consistent with the epidemiology usually observed in tropical areas.
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Infecciones Fúngicas del Ojo/epidemiología , Queratitis/epidemiología , Adulto , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Lesiones de la Cornea/complicaciones , Lesiones de la Cornea/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Femenino , Fusariosis/tratamiento farmacológico , Fusariosis/epidemiología , Fusariosis/microbiología , Hospitales Universitarios/estadística & datos numéricos , Humanos , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Reunión/epidemiología , Voriconazol/uso terapéutico , Infección de Heridas/epidemiología , Infección de Heridas/microbiologíaRESUMEN
The case is reported of a patient with cavitary sarcoidosis complicated by an aspergilloma caused by an itraconazole-resistant strain of Aspergillus fumigatus, who was treated with voriconazole. The authors suggest that susceptibility testing of A. fumigatus strains is of value during long-term therapy with itraconazole, and that voriconazole may be a good option for treatment of patients infected with itraconazole-resistant strains of A. fumigatus.
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Antifúngicos/farmacología , Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/efectos de los fármacos , Itraconazol/farmacología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Adulto , Aspergilosis/etiología , Aspergilosis/microbiología , Farmacorresistencia Fúngica , Humanos , Hidroxicorticoesteroides/uso terapéutico , Enfermedades Pulmonares Fúngicas/etiología , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Sarcoidosis/complicaciones , Sarcoidosis/tratamiento farmacológico , Resultado del Tratamiento , VoriconazolRESUMEN
The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p <10-6). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.
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ADN de Hongos , Mucorales/genética , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Anciano , Anciano de 80 o más Años , Comorbilidad , ADN de Hongos/sangre , Femenino , Francia/epidemiología , Fungemia , Humanos , Masculino , Persona de Mediana Edad , Mucormicosis/epidemiología , Mucormicosis/terapia , Vigilancia de la Población , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158-804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3).
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Aspergilosis/diagnóstico , Aspergilosis/patología , Aspergillus/aislamiento & purificación , Necrosis/patología , Otitis Externa/diagnóstico , Otitis Externa/patología , Adulto , Anciano , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergillus/clasificación , Complicaciones de la Diabetes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Otitis Externa/tratamiento farmacológico , Otitis Externa/microbiología , Estudios Retrospectivos , Resultado del Tratamiento , Voriconazol/uso terapéuticoRESUMEN
Molecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae.
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Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Patología Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , ADN de Hongos/química , ADN de Hongos/genética , Humanos , Técnicas Microbiológicas/métodos , Mucorales/genética , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Análisis de Secuencia de ADN/métodos , Factores de TiempoRESUMEN
Surgery and antifungals are the reference standard for rhino-orbito-cerebral mucormycosis (ROCM) treatment. The impact of local control on survival of 22 consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively, with or without local control (p <0.0001). Hence, repeated surgical procedures are recommended to achieve local control of ROCM.
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Enfermedades Óseas Infecciosas/terapia , Desbridamiento/métodos , Mucormicosis/terapia , Enfermedades Orbitales/terapia , Enfermedades de los Senos Paranasales/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Enfermedades Óseas Infecciosas/microbiología , Enfermedades Óseas Infecciosas/mortalidad , Encefalopatías/microbiología , Encefalopatías/terapia , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucormicosis/mortalidad , Enfermedades Orbitales/microbiología , Enfermedades Orbitales/mortalidad , Enfermedades de los Senos Paranasales/microbiología , Enfermedades de los Senos Paranasales/mortalidad , Estudios Retrospectivos , Base del Cráneo/cirugía , Tasa de Supervivencia , Adulto JovenAsunto(s)
Esporotricosis , Francia , Humanos , Masculino , Persona de Mediana Edad , Esporotricosis/diagnósticoRESUMEN
Eumycetomas are chronic infectious entities characterized by presence of mycotic grains in (sub-)cutaneous tissues, after accidental inoculation of an exogenous filamentous fungus in the skin. The lesions evolve towards painless pseudotumor of the soft parts. We report the original case of a Guinean woman exhibiting eumycetoma of the right foot. Both laboratory tests identified a dematiaceous fungus, Exophiala jeanselmei, as the responsible infectious agent. A medical treatment with voriconazole alone was sufficient to notice a substantial clinical improvement. This finding is unusual as E. jeanselmei is uncommon in Guinea-Conakry, and as optimal treatment rather associate antifungal azoles and surgical excision.
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Exophiala/fisiología , Enfermedades del Pie/microbiología , Micetoma/microbiología , Adulto , Exophiala/aislamiento & purificación , Femenino , Enfermedades del Pie/diagnóstico por imagen , Guinea , Humanos , Micetoma/diagnóstico por imagen , UltrasonografíaAsunto(s)
Antifúngicos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Micosis/tratamiento farmacológico , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Fosforilcolina/análogos & derivados , Scedosporium , Anciano , Humanos , Masculino , Fosforilcolina/uso terapéutico , Terapia RecuperativaAsunto(s)
Micosis/diagnóstico , Micosis/patología , Sordariales/aislamiento & purificación , Adolescente , Adulto , Anciano , Antifúngicos/uso terapéutico , Niño , Preescolar , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Femenino , Francia , Humanos , Lactante , Masculino , Técnicas Microbiológicas , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Micosis/tratamiento farmacológico , Micosis/mortalidad , Análisis de Secuencia de ADN , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
To date, the time of acquisition of a Cryptococcus neoformans infectious strain has never been studied. We selected a primer, (GACA)(4), and a probe, CNRE-1, that by randomly amplified polymorphic DNA (RAPD) analysis and restriction fragment length polymorphism (RFLP), respectively, regrouped strains from control samples of C. neoformans var. grubii environmental isolates according to their geographical origins. The two typing techniques were then used to analyze 103 isolates from 29 patients diagnosed with cryptococcosis in France. Nine of the 29 patients lived in Africa a median of 110 months prior to moving to France; 17 of the patients originated from Europe. Results showed a statistically significant clustering of isolate subtypes from patients originating from Africa compared to those from Europe. We conclude that the patients had acquired the C. neoformans infectious strain long before their clinical diagnoses were made.