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1.
Eur J Clin Microbiol Infect Dis ; 30(4): 551-3, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21107627

RESUMO

The galactomannan assay to diagnose invasive aspergillosis is recommended and clinically utilized, yet the mechanism of galactomannan release from Aspergillus fumigatus is unknown. We used an A. fumigatus strain lacking calcineurin A (cnaA), already shown to be critically important for pathogenicity, to evaluate galactomannan kinetics. During the logarithmic growth phase when glucose was consumed, ß-D-galactofuranoside (galf)-antigens were released in the culture. However, after glucose became limited, GM release further increased in the supernatants of the wild type strain while there was no further increase of GM release in the ΔcnaA strain. ß-Galactofuranosidase activity was also decreased in the ΔcnaA mutant, and the amount of galf-antigen in the cell wall fraction of the ΔcnaA mutant was approximately ten-fold higher. This suggests the possibility that the antigen is unable to be released due to a cell wall abnormality. This and previous work suggest a dynamic calcineurin-dependent cell wall during periods of growth, with galactomannan release from the cell wall possibly calcineurin-dependent and reflected in the decreased GM release and greatly increased cell wall fraction of galf in the ΔcnaA mutant.


Assuntos
Aspergillus fumigatus/crescimento & desenvolvimento , Calcineurina/metabolismo , Mananas/metabolismo , Aspergilose/diagnóstico , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/genética , Calcineurina/genética , Parede Celular/metabolismo , Meios de Cultura/química , Galactose/análogos & derivados , Glucose/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Humanos , Mutação
2.
Transpl Infect Dis ; 12(3): 220-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20113459

RESUMO

Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.


Assuntos
Micoses/epidemiologia , Micoses/mortalidade , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergilose/mortalidade , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Candidíase/mortalidade , Criptococose/tratamento farmacológico , Criptococose/epidemiologia , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus/efeitos dos fármacos , Cryptococcus/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/microbiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
3.
J Perinatol ; 27(2): 127-9, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17262048

RESUMO

Candidemia is common in extremely low birth weight infants and is associated with substantial mortality and morbidity. Treatment options have traditionally been limited to amphotericin B deoxycholate or fluconazole. We present a case of a premature infant with persistent candidemia despite antifungal treatment that responded to therapy with caspofungin, an echinocandin antifungal. The infant's Candida isolate developed resistance to azoles during fluconazole administration and also suffered from severe hypercalcemia during the initiation of caspofungin therapy.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Doenças do Prematuro/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Caspofungina , Resistência Microbiana a Medicamentos , Equinocandinas , Humanos , Hipercalcemia/induzido quimicamente , Recém-Nascido , Recém-Nascido Prematuro , Lipopeptídeos , Masculino , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol
4.
J Perinatol ; 27(2): 97-100, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17080094

RESUMO

OBJECTIVE: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. STUDY DESIGN: We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate. RESULTS: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. CONCLUSION: Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.


Assuntos
Candidíase/sangue , Candidíase/líquido cefalorraquidiano , Meningites Bacterianas/sangue , Meningites Bacterianas/líquido cefalorraquidiano , Sepse/microbiologia , Glicemia/análise , Feminino , Humanos , Recém-Nascido , Contagem de Leucócitos , Masculino , Meningites Bacterianas/microbiologia , Sepse/líquido cefalorraquidiano
5.
Bone Marrow Transplant ; 36(7): 621-9, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16044133

RESUMO

Invasive fungal infections (IFI) are the leading cause of infectious mortality in adult patients undergoing hematopoietic cell transplantation (HCT) after myeloablative conditioning, but the extent of this problem in the pediatric population is unclear. We retrospectively examined risk factors for IFI among 120 consecutive pediatric patients undergoing allogeneic HCT at a single center. The incidence of proven or probable IFI in pediatric patients during the first year after allogeneic HCT was 13%, comparable to the rate reported in adult patients; however, unlike IFI in adult patients, the majority of IFI in children occurred within the first month after transplantation. The primary risk factors for IFI were duration of neutropenia, age greater than 10 years, transplant for severe aplastic anemia or Fanconi anemia, and high-dose corticosteroid administration for 10 days or longer. IFI were more likely to be successfully treated (42%, 5/12 patients) in pediatric HCT recipients when compared to previous reports of adult recipients. Nonrelapse mortality was estimated at 17% (20/120 patients) after allogeneic HCT, of which 35% (seven patients) were directly attributed to IFI. Thus, IFI is a significant cause of nonrelapse mortality in children undergoing allogeneic HCT and more effective strategies are needed to prevent and treat IFI.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Micoses/diagnóstico , Micoses/etiologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Adolescente , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Condicionamento Pré-Transplante , Resultado do Tratamento
6.
J Chemother ; 15 Suppl 2: 16-27, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14708963

RESUMO

Scedosporium species are now increasingly isolated from immunocompromised and immunocompetent patients. Unfortunately, Scedosporium species infections are generally resistant to amphotericin B, and S. prolificans strains are particularly resistant to presently-available antifungal agents. Here we review the microbiology, expanding epidemiology, numerous clinical presentations, and diagnostic tools available for Scedosporium species infections. Finally, we detail the available in vitro, animal model, and clinical data on the treatment of Scedosporium species infections with special emphasis on the role of newer antifungal therapies for these recalcitrant infections.


Assuntos
Antifúngicos/uso terapêutico , Micetoma/tratamento farmacológico , Micetoma/patologia , Scedosporium/patogenicidade , Resistência Microbiana a Medicamentos , Humanos , Hospedeiro Imunocomprometido , Incidência
7.
J Pediatr Endocrinol Metab ; 13(9): 1633-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11154160

RESUMO

Pancreatic exocrine insufficiency in Johanson-Blizzard syndrome (JBS) is well described but only two previous patient reports document pancreatic endocrine insufficiency manifested as diabetes mellitus, and each patient required only a modest dose of insulin to control hyperglycemia. We report a patient with JBS and new-onset diabetes mellitus with profound insulin resistance, with no clinical or laboratory evidence of pancreatic exocrine insufficiency.


Assuntos
Anormalidades Múltiplas/fisiopatologia , Cardiomegalia/complicações , Surdez/complicações , Diabetes Mellitus/etiologia , Nanismo/complicações , Resistência à Insulina , Anus Imperfurado/complicações , Cardiomegalia/congênito , Criança , Feminino , Humanos , Microcefalia/complicações , Nariz/anormalidades , Síndrome
8.
Clin Microbiol Infect ; 16(9): 1321-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20840541

RESUMO

Invasive fungal infections are major causes of morbidity and mortality in neonates and in both immunocompromised and immunocompetent children. Although these infections have been well characterized in adults, the incidence and analysis of risk factors, diagnostic tools, treatments and outcomes have not been well described for large cohorts of paediatric or neonatal patients. Paediatric exclusion has limited our knowledge of the epidemiology and pathophysiology of paediatric fungal disease, and has also resulted in a paucity of data regarding the safety and efficacy of paediatric antifungal therapy. Previous paediatric cooperative models in other disciplines have successfully advanced our understanding and treatments of childhood diseases, but in the past there has not been a similar organization for paediatric invasive fungal infections. Although there are numerous other reviews outlining the differences in paediatric antifungal dosing pharmacokinetics, there are only smaller epidemiological reports depicting the exact distribution and outcomes of paediatric invasive fungal infections treated with these antifungals. This review will highlight some of the available epidemiological data on paediatric invasive fungal infections.


Assuntos
Micoses/epidemiologia , Infecções Oportunistas/epidemiologia , Adolescente , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Micoses/diagnóstico , Micoses/mortalidade , Micoses/prevenção & controle , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/mortalidade , Infecções Oportunistas/prevenção & controle , Resultado do Tratamento
11.
Med Mycol ; 43 Suppl 1: S261-5, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16110818

RESUMO

There is a paucity of specific data on pediatric invasive aspergillosis. While the underlying predisposing patient diseases and treatments differ in children and adults, it also appears that there is a heterogeneity of invasive aspergillosis disease that extends to children. These aspects extend in some reports to the Aspergillus spp. distribution as well as the fundamental pathophysiology of the disease in different age groups. For instance, the newer diagnostic tools hold great promise for adult patients but it appears that they have limited usefulness in children. Only through dedicated pediatric study will clinicians fully discover the nuances and unique findings in children with this deadly disease.


Assuntos
Aspergilose , Aspergillus/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus/efeitos dos fármacos , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade
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