Chronic Histoplasma capsulatum Infection of the Central Nervous System Successfully Treated with Fluconazole

Tiraboschi, Iris Nora; Parera, Ignacio Casas; Pikielny, R.; Scattini, G.; Micheli, Fabrizio

doi:10.1159/000116794

Cited by 26 publications

(12 citation statements)

References 10 publications

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“…Favorable outcomes have been reported in 4 patients with Histoplasma meningitis who were treated with Flu [20][21][22]. Prior therapy with AmB had been unsuccessful for all 4, and therapy with Itra had also been unsuccessful for 1 patient [20].…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

et al. 2000

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To investigate the efficacy of combined treatment with fluconazole (Flu) and amphotericin B (AmB) for Histoplasma capsulatum meningitis, MICs were determined for 10 clinical isolates, following National Committee for Clinical Laboratory Standards guidelines. Weak synergy was observed for 6 of the 10 isolates. For the in vivo models, mice either were sham treated or were given Flu (75 mg/kg/day), AmB (2 mg/kg every other day), itraconazole (Itra; 75 mg/kg/day), AmB+Flu, or AmB+Itra. Following infection with 5x105 yeasts, Flu antagonized AmB's reduction of fungal burden without reducing its effect on survival. When in vivo antagonism was reproduced following infection with 1x104 yeasts, a higher fungal burden was observed in the lungs. Itra had no effect on AmB's activity and was more effective than Flu for clearance of fungal burden. These findings caution against use of AmB+Flu for treatment of histoplasmosis, but studies of the effect of treatment on the fungal burden in the brain are needed to assess combination therapy for meningitis.

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Section: Discussionmentioning

confidence: 99%

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

et al. 2000

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“…The failure of fluconazole in a murine model of CNS histoplasmosis has been noted (53,75). Both azoles have been used successfully for secondary treatment following induction therapy with amphotericin B (1,70,126). The dosage suggested for itraconazole is 200 mg twice or thrice daily, and that for fluconazole is 800 mg daily.…”

Section: Central Nervous System Histoplasmosismentioning

confidence: 99%

Histoplasmosis: a Clinical and Laboratory Update

2007

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SUMMARY Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

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“…A primeira paciente chegou a nós relativamente bem, confirmando a afirmação de Machado e col. 11 de ser o quadro clínico por ocasião do diagnóstico em geral relativamente benigno. Tiraboschi e col. 12 ressaltam que o acometimento do SNC, embora ocorra em 10 a 25% dos pacientes com doença disseminada, pode não ser diagnosticado caso não haja procura ativa nesse sentido. Já o caso da criança se apresentou de forma mais grave, caracterizado por quadro de instalação subaguda com sintomas gerais e alteração de marcha seguido de importante quadro álgico lombar, sem alterações do sensório, crises convulsivas ou sinais e sintomas de hipertensão intracraniana, manifestações essas mais tipicamente encontradas em quadros de meningite.…”

Section: Discussionunclassified

“…Embora o itraconazol tenha ação contra o H. capsulatum superior à do fluconazol 5 , preferiu-se este último (bem como para a manutenção do segundo caso) devido a sua melhor penetração no LCR 20 . Essa opção foi também embasada em alguns relatos de sucesso terapêutico na literatura nesta forma da doença 12,[21][22][23] . Embora esperássemos obter resposta favorável, como costuma ocorrer na maioria dos pacientes sem imunosupressão 2 , fomos agradavelmente surpreendidos pela rapidez da melhora clínica e laboratorial, em particular por ter nossa paciente adulta respondido a dose diária de 400 mg, sendo esta a dose mínima preconizada na literatura, preferindo a maioria dos autores iniciar posologias diárias mais elevadas, na faixa de 600 a 800 mg 2,21,24,25 .…”

Section: Discussionunclassified

Histoplasmose do sistema nervoso central como única manifestação da doença em pacientes imunocompetentes: apresentação de dois casos

Levi

Pozzi²,

Hirschheimer³

et al. 2003

Arq. Neuro-Psiquiatr.

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RESUMO -Apresentamos dois casos de histoplasmose em que o acometimento do sistema nervoso central foi a única manifestação clínica da doença. Revisão da literatura permitiu confirmar a raridade dessa forma de patologia, em particular em crianças, sendo o segundo caso aqui apresentado o de mais baixa idade na literatura nacional. São feitos comentários sobre a variedade das apresentações clínicas e os principais diagnósticos diferenciais da doença. São discutidos os resultados laboratoriais, tanto em relação às alterações liquóricas quanto aos resultados sorológicos. Finalmente, é analisada a terapêutica dessa forma de infecção fúngica tanto em relação aos medicamentos utilizáveis quanto à duração prolongada aconselhável para o tratamento específico.PALAVRAS-CHAVE: histoplasmose cerebral, meningite crônica, terapêutica antifúngica. C C C C Central nervous system involvement by histoplasmosis as the unique manifestation of this disease in entral nervous system involvement by histoplasmosis as the unique manifestation of this disease in entral nervous system involvement by histoplasmosis as the unique manifestation of this disease in entral nervous system involvement by histoplasmosis as the unique manifestation of this disease in entral nervous system involvement by histoplasmosis as the unique manifestation of this disease in immunocompetent patients: presentation of two cases immunocompetent patients: presentation of two cases immunocompetent patients: presentation of two cases immunocompetent patients: presentation of two cases immunocompetent patients: presentation of two cases ABSTRACT -We present two patients with central nervous system involvement as the unique clinical manifestation of histoplasmosis. A clinical review confirmed the infrequency of this form of the disease, overall in childhood, being one of these cases the youngest in Brazilian reports. Comments about the diversity of clinical presentation and main differential diagnosis are presented. We analyze the serologic and cerebrospinal fluid results and, finally, discuss the drugs and duration of treatment.KEY WORDS: cerebral histoplasmosis, chronic meningitis, antifungal therapy. A infecção pelo Histoplasma capsulatum é relativamente comum em nosso meio. Lacaz e col.1 , empregando o teste cutâneo da histoplasmina, verificaram positividade de 16,0% no Rio de Janeiro, 19,0% em São Paulo, 19,2% em Goiás e 27,5% no Pará. A maioria dessas infecções, no entanto, é oligo ou assintomática, sendo os casos com manifestação clí-nica franca uma pequena minoria (menos que 5% nas exposições de baixo nível, porém mais comum após exposições mais intensas 2 ). As formas mais frequentemente descritas da histoplasmose são basicamente de dois tipos: 1.Doença progressiva grave, em geral disseminada, em indivíduos com comprometimento da imunidade. Nos anos mais recentes a maioria desses casos foi descrita em pacientes com a síndrome da imunodeficiência adquirida 3 , havendo também relatos em pacientes com lupus eritematoso 4,5 e com a síndrome da linfopenia CD 4 idiop...

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Chronic Histoplasma capsulatum Infection of the Central Nervous System Successfully Treated with Fluconazole

Cited by 26 publications

References 10 publications

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

Histoplasmosis: a Clinical and Laboratory Update

Histoplasmose do sistema nervoso central como única manifestação da doença em pacientes imunocompetentes: apresentação de dois casos

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