Meningite criptocócica na gravidez: revisão de aspectos terapêuticos / Cryptococcal meningitis in pregnancy: review of the therapeutic aspects

A criptococose é uma infecção fúngica, cujo envolvimento do sistema nervoso central é caracteristicamente insidioso, apresentando sinais de irritação meníngea, sequelas neurológicas e alta mortalidade. A gestação, condição que leva a certo grau de imunossupressão, pode dificultar a resposta ao tratamento. Objetivando determinar a estratégia de tratamento mais efetiva para meningite criptocócica em grávidas sem outras condições de imunossupressão, o presente trabalho realizou um levantamento bibliográfico acerca do tema. Foram revisados cinco artigos, os quais evidenciaram ampla utilização de anfotericina B em monoterapia ou associada à flucitosina, inclusive no primeiro, segundo e terceiro trimestre de gestação. Também foi relatada a utilização de fluconazol e itraconazol. Em todos os relatos, os resultados foram favoráveis tanto para mãe quanto para a criança. Existem poucos dados disponíveis na literatura acerca do tema proposto. Preferencialmente, a conduta a ser realizada envolve internação da gestante como gravidez de alto risco e administração de anfotericina B. Embora os resultados apresentados tenham sido favoráveis tanto para a monoterapia com anfotericina B quanto para sua associação com flucitosina, ou para monoterapia com fluconazol ou itraconazol, são necessários estudos prospectivos, controlados e randomizados para determinar o esquema terapêutico significativamente mais eficaz para o tratamento da criptococose em gestantes

Cryptococcosis is an infection caused by a fungus, whose involvement in the central nervous system is characteristically insidious, presenting signs of meningitis, neurological sequelae, and high mortality. The pregnancy, a condition that leads to a certain degree of immunosupression, may hinder the response to treatment. With the aim of determining the most effective treatment for cryptococcal meningitis in pregnant women without other causes of immunodeficiency, this paper carried out a survey about the subject. Five articles were analyzed and they showed a wide utilization of amphotericin B as monotherapy or associated with flucytosine in the treatment of cryptococcal meningitis in pregnant women, which includes the usage during the first, second and third trimesters of pregnancy. It was also reported the usage of itraconazole and fluconazol. The results were positive in all articles for both mother and fetus. There are few data available in the literature about this theme. Preferably, the physician should proceed with the admission of the patient as a high-risk pregnancy and should administer amphotericin B. Although the presented results were favorable to monotherapy with amphotericin B and to its association with flucytosine, as well as to monotherapy with fluconazole or itraconazole, only randomized controlled trials will be able to determine the best significantly effective therapeutics for cryptococcosis in pregnant women

Fatal cerebral abscess caused by Cladophialophora bantiana.

Primary cerebral phaeohyphomycosis is caused by pigmented fungi that exhibit distinct neurotropism often in immunocompetent individuals. A 20-yr-old male presented with multiple brain abscess which was subsequently proven microbiologically to be due to Cladophialophora Bantiana. In spite of near total excision and appropriate antifungal agents succumbed to his illness. We report this case to highlight its rarity and high mortality in an immunocompetent host. There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation.

Tratamiento de las micosis profundas. Estado actual / Treatment of deep mycosis. Present state

Se hace una revisión de los antifúngicos disponibles en el mercado internacional en la actualidad, se profundiza más en el anfotericín B, con sus virtudes y reacciones adversas, así como de otros antifúngicos, sobre todo los derivados azoles, imidazólicos y los triazoles, como compuestos con buenos resultados y menos reacciones secundarias, en particular el fluconazol y el itraconazol y sus características

Comparison of amphotericin B, flucytosine and itraconazole with amphotericin B and flucytosine in the treatment of cryptococcal meningitis in AIDS.

We compared amphotericin B (0.3 mg/kg/d) plus flucytosine (150 mg/kg/d) plus itraconazole (400 mg/d) (study group) with amphotericin B plus flucytosine (control group) by an open-randomized trial. In the study group, after CSF mycological cultures disclosed nothing, itraconazole was administrated alone through six weeks of treatment. Treatment was considered successful if the patient had two consecutive negative CSF cultures by the end of the 6-week treatment period. Fifty patients were enrolled in each group. There were significant differences between the study group and the control group in the successful treatment (100% vs 90%; P = 0.03), the mean length of time until normal body temperature after treatment (5.9 +/- 3.7 days vs 8.8 +/- 5.1 days; P = 0.02) and the adverse effects. The mean length of time to the first negative CSF culture was 13.9 +/- 6.1 days in the study group and 13.3 +/- 6.5 days in the control group (P = 0.66). Relapse rate with itraconazole 200 mg/day was higher in the study group.

Amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS.

Eighteen consecutive AIDS patients with a first episode of cryptococcal meningitis were enrolled in the study to evaluate the efficacy and tolerability of amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS. The treatment consisted of intravenous amphotericin B 0.6 mg/kg daily with or without flucytosine (150 mg/kg d in four divided doses) for 2 weeks which was then followed by oral fluconazole 400 mg daily for 8 weeks. After completion of primary therapy, all patients received a maintenance dose of oral fluconazole 200 mg daily. The primary therapy was successful in 17 (94%) of the 18 patients. The median length of time to the first negative cerebrospinal fluid culture for Cryptococcus neoformans in the 17 patients with successful treatment was 3 (range 2 to 6) weeks. No patient had to discontinue the treatment due to adverse drug reactions. During a mean observation period of 26.94 weeks, no relapse case was documented among the 17 patients. Our results indicate that this regimen as primary therapy for cryptococcal meningitis in AIDS patients is effective and well tolerated.

Resolution of cryptococcal meningitis and associated granuloma lung with antifungal therapy: report of a case.

A 49-year-old diabetic male had been unsuccessfully treated with antitubercular therapy for a granulomatous lesion of the left lung detected elsewhere nine months ago. He presented with evidence of meningitis which was found to be due to infection with Cryptococcus neoformans. Both the meningeal and lung lesions resolved after 6 weeks of combined therapy with amphotericin B and flucytosine. The report of the case along with a brief review of the relevant literature is presented.

Treatment of cryptococcal meningitis with combination itraconazole and flucytosine.

The results of an open study of the efficacy of itraconazole and flucytosine in 10 patients with cryptococcal meningitis are reported. The outcome revealed eight responding cases (cure in 4 cases and improvement in 4 cases), and two failure cases. One patient had a relapse which responded to amphotericin B and flucytosine. No toxicity was observed.

Cura biológica de la criptococosis experimental murina con la asociación de anfotericina B y 5 fluorocitosina / Biological cure of murine experimental cryptococcosis with the association of anphotericin B and 5 fluorocytosine

Se evaluó la capacidad de la asociación de anfotericina B (AMB) (6mg/kg/día por medio) con 5-fluorocitosina (5FC)(300mg/kg/día), durante 2 semanas, para producir la cura biológica de la criptococosis esperimental murina. Nueve de 12 (75 por ciento) ratones Balb/C tratados, sacrificados a los 90, 180 y 210 días de evolución (3 en cada oportunidad), presentaron hepatosplenomegalia en forma inconstante y macro, microscopia, histopatología y siembra masiva de cerebro negativas. Los 3 ratones restantes (25 por ciento) murieron espontáneamente a los 81, 148 y 150 días post infección, con presencia, en la mayor parte de ellos, de macro, microscopia, histopatología y siembra masiva de cerebro positivas. Según lo apreciado en este modelo experimental, estudiado hasta los 210 días postinfección, la asociación de AMB con 5FC logró la cura biológica de esta infección experimental por lo menos a nivel de su localización más importante, el sistema nervioso central

Cryptococcal meningitis in pregnancy: a case report.

We report a pregnant woman with cryptococcal meningitis. She experienced symptoms of meningitis before gestation which worsened during pregnancy. Combined treatment of amphotericin B and flucytosine, including ventriculo-peritoneal shunt gave a favorable outcome for both the patient and her child. We suggest that pregnant women with cryptococcal meningitis should continue their pregnancy and prefer to use combination of both drugs in standard doses because of the effectiveness, shorter duration of treatment and less toxicity than amphotericin B alone.

Estudio comparativo de 7 tratamientos antifungicos en un modelo experimental de criptococosis murina (1* parte) / Comparative study of 7 antifungal treatment in experimental model of murine cryptococcosis

Se realizó un estudio comparativo de 7 tratamientos antifúngicos en un modelo experimental de criptococosis murina. Fueron inoculados por vía intraperitoneal con 10 células de Cryptococcus neoformans var. neoformans, 100 ratones Balb C, divididos en 10 grupos de 10 animales cada uno. Cinco días después de la infección, 7 grupos recibieron los siguientes tratamientos, durante 2 semanas: anfotericina B (6 mg/kg%día por medio, por vía intraperitoneal), itraconazol, fluconazol y Sch 39.304 (todos ellos a razón de 16 mg/kg/día por gastrocisis), 5-fluorocitosina sola (300 mg/kg/día) y en combinación con anfotericina B y con fluconazol, en iguales dosis y por iguales vías que cuando fueron administradas solas. Los 3 grupos restantes fueron usados como control y recibieron los solventes de las drogas. El tiempo de sobrevida, el aspecto macroscópico de cerebro, higado, pulmones y bazo, la presencia de levaduras capsuladas en el examen microscópico de estos mismos órganos y la siembra masiva de pulmones y cerebro, fueron tomados como parámetros de efectividad de las drogas. La combinación de anfotericina B y 5-fluorocitosina fue el tratamiento más efectivo, ya que produjo la negativización de los exámenes macro y microscópicos como también del 90%de las siembras masivas y prolongó el tiempo de sobrevida más allá de 60 días en todos los animales. La anfotericina B sola fue superior a los compuestos azólicos; con tiempos de sobrevida similares a los de la combinación de anfotericina B con 5-fluorocitosina y negativizó los exámenes macroscópicos, en el 60%de los ratones tratados. El Sch 39.304 mostró los tiempos de sobrevida más largos entre los derivados azólicos. Ninguno de los componentes de este grupo modificó los restantes parámetros estudiados. La asociación de 5-fluorocitosina con fluconazol no mostró mayor efectividad que cuando ambas drogas se administraron separadamente

Anfotericina B no tratamento da neurocriptococose em pacientes submetidos a transplante renal / Amphotericin B in the treatment of neurocryptococcosis in patients subjected to renal transplantation

Foram estudados 35 casos de neurocriptococose, 17 dos quais em pacientes submetidos a transplante renal. O objetivo foi avaliar a resposta terapêutica observada no grupo de pacientes transplantados renais neurocriptococose, com ênfase à funçäo renal, submetidos a esquema medicamentoso que inclui a anfotericina B. A resposta observada foi comparada aos resultados obtidos no grupo dos demais pacientes com a mesma infecçäo, submetidos ao mesmo esquema medicamentoso, porém sem insuficiência renal prévia. Dos 35 paciente, 10 faleceram nos primeiros dias do tratamento e, assim, 25 foram efetivamente tratados para neurocriptococose. Destes 25, 18 apresentavam outra condiçäo clínica associada, sendo esta transplante renal em 15 deles. Os medicamentos utilizados basicamente foram a anfotericina B intravenosa e intra-raqueana associada à 5-fluorocitosina via oral. Sete pacientes faleceram durante o tratamento. Assim, dos 35 pacientes que inicialmente compunham a casuística, 17 faleceram, (48,57%) e 18 foram tratados com sucesso, nenhum deles apresentado recidiva. As intercorrências observadas durante o tratamento säo discutidas e é feita correlaçäo dos dados obtidos neste estudo aos disponíveis na literatura. A análise dos resultados obtidos permite ressaltar: a necessidade do surgimento de medicamentos mais eficazes e menos tóxicos para a terapêutica da neurocriptococose, sendo até o momento a anfotericina B o principal medicamento existente; o esquema terapêutico atualmente indicado consiste na associaçäo anfotericina B e 5-fluorocitosina, havendo vantagens na utilizaçäo simultânea da anfotericina B pelas vias intravenosa e intra-raqueana. A análise dos resultados permite concluir por näo haver contra-indicaçäo ao uso da anfotericina B por via intravenosa em tranpslante renais com neurocriptococose