RESUMEN
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergillus/aislamiento & purificación , Manejo de la Enfermedad , Anticuerpos Antifúngicos/sangre , Antifúngicos/farmacología , Aspergilosis/complicaciones , Aspergilosis/inmunología , Aspergillus/efectos de los fármacos , Aspergillus/inmunología , Biopsia/métodos , Lavado Broncoalveolar , Diagnóstico Precoz , Flucitosina/farmacología , Flucitosina/uso terapéutico , Galactosa/análogos & derivados , Humanos , Huésped Inmunocomprometido , Pruebas Inmunológicas , Aspergilosis Pulmonar Invasiva/diagnóstico , Itraconazol/farmacología , Itraconazol/uso terapéutico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Imagen por Resonancia Magnética , Mananos/análisis , Pruebas de Sensibilidad Microbiana , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/terapia , Nitrilos/farmacología , Nitrilos/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Tomografía Computarizada por Rayos X , Triazoles/farmacología , Triazoles/uso terapéutico , Voriconazol/farmacología , Voriconazol/uso terapéuticoRESUMEN
The AsperGenius® assay detects several Aspergillus species and the A. fumigatus Cyp51A mutations TR34/L98H/T289A/Y121F that are associated with azole resistance. We evaluated its contribution in identifying A. lentulus and A. felis, 2 rare but intrinsically azole-resistant sibling species within the Aspergillus section Fumigati. Identification of these species with conventional culture techniques is difficult and time-consuming. The assay was tested on (i) 2 A. lentulus and A. felis strains obtained from biopsy proven invasive aspergillosis and (ii) control A. fumigatus (n=3), A. lentulus (n=6) and A. felis species complex (n=12) strains. The AsperGenius® resistance PCR did not detect the TR34 target in A. lentulus and A. felis in contrast to A. fumigatus. Melting peaks for L98H and Y121F markers differed and those of the Y121F marker were particularly suitable to discriminate the 3 species. In conclusion, the assay can be used to rapidly discriminate A. fumigatus, A. lentulus and A. felis.
Asunto(s)
Antifúngicos/farmacología , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/clasificación , Aspergillus fumigatus/efectos de los fármacos , Azoles/uso terapéutico , Sistema Enzimático del Citocromo P-450/genética , Proteínas Fúngicas/genética , Anciano , Aspergilosis/microbiología , Aspergillus fumigatus/genética , Farmacorresistencia Fúngica/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana EdadRESUMEN
Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 µg/ml, those for M. circinelloides were 1 and 2 µg/ml, those for R. arrhizus were 2 and 4 µg/ml, and those for R. microsporus were 2 and 2 µg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 µg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica Múltiple/efectos de los fármacos , Itraconazol/uso terapéutico , Mucorales/efectos de los fármacos , Mucormicosis/tratamiento farmacológico , Triazoles/uso terapéutico , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 µg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 µg/ml for C. glabrata, and 0.063 to 1 µg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
Asunto(s)
Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Equinocandinas/uso terapéutico , Anidulafungina , Candida/crecimiento & desarrollo , Candida/aislamiento & purificación , Candidiasis/microbiología , Caspofungina , Farmacorresistencia Fúngica , Europa (Continente) , Humanos , Lipopéptidos/uso terapéutico , Micafungina , Pruebas de Sensibilidad Microbiana/normas , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , América del Norte , Variaciones Dependientes del Observador , América del Sur , Especificidad de la EspecieRESUMEN
Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 µg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 µg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 µg/ml (VGII); itraconazole, 0.25 µg/ml (VNI), 0.5 µg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 µg/ml (VGIV); posaconazole, 0.25 µg/ml (C. neoformans nontyped and VNI) and 0.5 µg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 µg/ml (VNIV), 0.25 µg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 µg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Asunto(s)
Antifúngicos/uso terapéutico , Criptococosis/tratamiento farmacológico , Criptococosis/epidemiología , Cryptococcus gattii/efectos de los fármacos , Fluconazol/uso terapéutico , Itraconazol/uso terapéutico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Antifúngicos/farmacología , Australia/epidemiología , Criptococosis/microbiología , Cryptococcus gattii/crecimiento & desarrollo , Cryptococcus gattii/aislamiento & purificación , Farmacorresistencia Fúngica/efectos de los fármacos , Europa (Continente)/epidemiología , Fluconazol/farmacología , Humanos , India/epidemiología , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , América del Norte/epidemiología , Pirimidinas/farmacología , Sudáfrica/epidemiología , América del Sur/epidemiología , Triazoles/farmacología , VoriconazolRESUMEN
A 71-year-old male with mild steroid-induced hyperglycaemia was diagnosed with a lethal invasive Rhizopus microsporus infection. Disseminated zygomycosis is a rare entity and is most frequently found in neutropenic patients with haematological malignancies, post-transplants or in patients on deferoxamine therapy. Infection is characterised by tissue infarction and necrosis due to angioinvasive hyphae. Culture of Zygomycetes is necessary for species determination but histology is a must to prove the infection. Ante-mortem diagnosis and culture is challenging and therefore mortality approaches 100%. Apart from amphotericine B, most anti-fungals have no activity against Zygomycetes but posaconazole might offer new possibilities as a first-line agent. Timely diagnosis, rapid surgery of infected tissue, correction of underlying disorders and correct anti-fungal therapy might be life-saving. Due to the increasing use of potent immunosuppression, stem cell and organ transplants and possibly selection for Zygomycetes by prior treatment with broad-spectrum antifungal therapy, the incidence of zygomycosis is rising. Therefore, clinicians might encounter an increasing number of zygomycosis cases in the near future.
Asunto(s)
Corticoesteroides/efectos adversos , Mucormicosis/tratamiento farmacológico , Rhizopus , Anciano , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiinflamatorios/efectos adversos , Antifúngicos/uso terapéutico , Ciprofloxacina/uso terapéutico , Resultado Fatal , Humanos , Itraconazol/uso terapéutico , Masculino , Mucormicosis/etiología , Mucormicosis/microbiología , Prednisolona/efectos adversos , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , VoriconazolRESUMEN
BACKGROUND: To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS: Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L emulsions containing long-chain- (LCT), medium-chain- (MCT), mixed LCT/MCT-, alpha-tocopherol-enriched LCT/MCT (LCT/MCT-E), or structured lipids (SL). After washing, the neutrophils were incubated with C. albicans. Phagocytosis was measured as the number of yeast-associated neutrophils relative to the total neutrophil count. Killing was expressed as the percentage of Candida survival relative to the initial yeast cell count. RESULTS: No significant differences in yeast-neutrophil association could be demonstrated after neutrophil incubation in various lipid emulsions or medium, after correction for non-specific adhesion. However, although Candida survival after 1 hour incubation with non-lipid-exposed neutrophils amounted to 53% +/- 11% and was not influenced by LCT (60% +/- 11%), LCT/MCT (78% +/- 7%), LCT/MCT-E (72% +/- 12%), and SL (67% +/- 6%), pure MCT (70% +/- 13%) significantly impaired the killing capacity of neutrophils. CONCLUSIONS: The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsions influence the elimination of C. albicans depending on the triglyceride chain length.
Asunto(s)
Candida albicans/inmunología , Emulsiones Grasas Intravenosas/farmacología , Neutrófilos/fisiología , Fagocitosis , Adyuvantes Inmunológicos/farmacología , Adulto , Candida albicans/fisiología , Candidiasis/inmunología , Candidiasis/microbiología , Recuento de Colonia Microbiana , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacosRESUMEN
A polymerase chain reaction (PCR)-mediated genotyping assay for Candida albicans has been developed. By amplification of genomic regions bordered by eukaryotic or prokaryotic repeat-like motifs, differences between C. albicans isolates can be determined. The resolution of this typing procedure is at least as good as that of other genotypic assays. To ascertain the epidemiologic and clinical usefulness of this PCR genotyping, a retrospective analysis of serial C. albicans isolates from neutropenic adults treated with fluconazole was done. By PCR genotyping, 40 strains were detected in 24 patients. Eighteen C. albicans strains were found on multiple samplings in individual patients. It appears that most patients remain colonized with a C. albicans strain of constant genotypic characteristics. However, exceptions were observed. In 7 (29%) of 24 patients, strains deviating from the most frequently encountered type could be identified. All but 1 strain remained susceptible to fluconazole in vitro after treatment in vivo. It was not possible to demonstrate a relation of genotypic variation and antifungal susceptibility changes.
Asunto(s)
Candida albicans/genética , Candidiasis/tratamiento farmacológico , Fluconazol/uso terapéutico , Neutropenia/microbiología , Adulto , Secuencia de Bases , Candida albicans/efectos de los fármacos , Candidiasis/inmunología , Candidiasis/microbiología , ADN de Hongos , Electroforesis en Gel de Campo Pulsado , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Neutropenia/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos Nucleicos , Estudios RetrospectivosRESUMEN
We present a 45-year-old male patient with chronic obstructive lung disease treated with low-dose corticosteroids, who developed a chronic septic polyarthritis due to Pseudomonas aeruginosa following a surgical wound infection. Due to the mild synovitis and the absence of systemic signs of infection the diagnosis was delayed for nearly 2 years and resulted in severe joint destruction.