Single high dose of liposomal amphotericin B in human immunodeficiency virus/AIDS-related disseminated histoplasmosis: A randomized trial

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (\u3e4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access

A case of spotted fever group rickettsiosis imported into the United Kingdom and treated with ciprofloxacin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spotted fever group rickettsioses are an interesting group of infections, which are increasing in incidence worldwide.</p> <p>Case presentation</p> <p>Here we describe an imported case to the United Kingdom occurring in a patient who had recently visited Kruger National Park in South Africa – a highly endemic area for <it>Rickettsia </it>infections. Initial treatment with doxycycline failed but the patient made a prompt recovery after commencement of ciprofloxacin.</p> <p>Conclusion</p> <p>This finding raises the possibility that there are resistant strains of <it>Rickettsia </it>present.</p

Candida guilliermondii como agente de candidose

Candida guilliermondii is one of the components of human microbiota. This yeast has been infrequently associated with human infections, which may be related to its low pathogenicity. The aim of this study was to provide clinical and epidemiological data for patients infected with C. guilliermondii at Santa Casa Complexo Hospitalar, Brazil. From October 1997 to October 2003, C. guilliermondii was isolated from clinical samples from 11 patients. Three patients were excluded because the isolation of the yeast represented colonisation. Specimens from the eight patients included in the study corresponded to blood (n = 5), ascitis fluid (n = 2), and oesophagus biopsy (n = 1). Three patients (37.5%) had major immunosuppressed conditions, including solid organ transplantation, AIDS, and leukaemia. Previous use of antibiotics occurred in 87.5%. Main invasive medical procedures were central venous catheter (50.0%), abdominal surgery (25.0%), and peritoneal dialysis (50.0%). No susceptibility data was obtained. Although risk factors for candidaemia were similar amongst patients infected by with C. guilliermondii or other Candida species, mortality associated with C. guilliermondii was significantly lower.Candida guilliermondii é um dos componentes da microbiota humana e infecções associadas com esta levedura têm sido incomuns, o que pode ser atribuído a sua baixa patogenicidade. O objetivo deste trabalho foi documentar aspectos clínico-epidemiológicos em pacientes que tiveram C. guilliermondii isolada a partir de amostras biológicas. O estudo foi conduzido na Santa Casa Complexo Hospitalar, Brasil. Durante outubro de 1997 e outubro de 2003, C. guilliermondii foi isolada de 11 pacientes, três dos quais foram excluídos por se apresentarem apenas colonizados. Espécimes clínicos corresponderam a sangue (n = 5), líquido de ascite (n = 2) e biópsia de esôfago (n = 1). Três pacientes eram imunodeprimidos, incluindo transplante de órgãos sólidos, SIDA e leucemia. Uso prévio de antimicrobianos ocorreu em 87,5% dos casos. Procedimentos médicos invasivos incluíram o uso de cateteres venosos centrais (50,0%), cirurgia abdominal (25,0%) e diálise peritonial (50,0%). Testes de susceptibilidade não foram realizados. Embora fatores de risco para candidemia tenham sido semelhantes entre pacientes infectados por C. guilliermondii ou outras espécies de Candida, a mortalidade associada com C. guilliermondii foi significativamente menor

Anfotericina B: uma revisão sobre suas diferentes formulações, efeitos adversos e toxicidade

A incidência de infecções fúngicas invasivas tem aumentado, como consequência do contingente cada vez maior de pacientes com imunossupressão. O tratamento de infecções fúngicas com anfotericina B (AmB) está associado a efeitos adversos importantes, como nefrotoxicidade e toxicidade hematológica. Nesta revisão buscou-se abordar os estudos sobre AmB nas diferentes formulações, focando em suas características farmacológicas e toxicidade. Formulações lipídicas de AmB estão associadas a um risco menor de nefrotoxicidade, entretanto ainda há controvérsia sobre diferenças entre as duas formulações lipídicas de AmB disponíveis. Diferenças em relação ao perfil imunomodulatório e ligação a lipoproteínas podem explicar parte das diferenças clínicas existentes entre as formulações de AmB. A maioria dos estudos clínicos que avaliou a nefrotoxicidade associada à AmB em diferentes formulações não utilizou critérios validados para classificação do dano renal, o que dificulta sua comparação. A toxicidade hematológica relacionada ao uso de AmB é um fenômeno descrito desde os primórdios do seu uso clínico, entretanto poucos dados existem sobre sua frequência, fatores de risco e impacto nos desfechos clínicos. Dados precisos, e adequados ao contexto local, sobre a toxicidade de AmB nas suas diferentes formulações são necessários para uma adequada avaliação dos aspectos de farmacoeconomia e custo-efetividade

Amphotericin B : a review on different formulations, side effects, and toxicity

A incidência de infecções fúngicas invasivas tem aumentado, como consequência do contingente cada vez maior de pacientes com imunossupressão. O tratamento de infecções fúngicas com anfotericina B (AmB) está associado a efeitos adversos importantes, como nefrotoxicidade e toxicidade hematológica. Nesta revisão buscou‑se abordar os estudos sobre AmB nas diferentes formulações, focando em suas características farmacológicas e toxicidade. Formulações lipídicas de AmB estão associadas a um risco menor de nefrotoxicidade, entretanto ainda há controvérsia sobre diferenças entre as duas formulações lipídicas de AmB disponíveis. Diferenças em relação ao perfil imunomodulatório e ligação a lipoproteínas podem explicar parte das diferenças clínicas existentes entre as formulações de AmB. A maioria dos estudos clínicos que avaliou a nefrotoxicidade associada à AmB em diferentes formulações não utilizou critérios validados para classificação do dano renal, o que dificulta sua comparação. A toxicidade hematológica relacionada ao uso de AmB é um fenômeno descrito desde os primórdios do seu uso clínico, entretanto poucos dados existem sobre sua frequência, fatores de risco e impacto nos desfechos clínicos. Dados precisos, e adequados ao contexto local, sobre a toxicidade de AmB nas suas diferentes formulações são necessários para uma adequada avaliação dos aspectos de farmacoeconomia e custo-efetividade.Invasive fungal infections have emerged in recent years, as a consequence of increasing numbers of immunosuppressed patients. Treatment of these conditions with amphotericin B (AmB) has been associated with important side effects, such as nephrotoxicity and hematological toxicity. In this review we aimed to assess studies about different formulations of AmB, focusing on pharmacological properties and toxicity. Lipid formulations of AmB have been linked to a lower risk of nephrotoxicity; however, there is still controversy about differences between the two available lipid formulations. Differences in immunomodulatory profile and lipoprotein binding could partly explain clinical inequalities among AmB formulations. Most clinical trials that evaluated AmB-associated nephrotoxicity did not use validated criteria for renal injury classification, impairing comparability. Hematological toxicity associated with AmB treatments is an occurrence described since the beginning of its clinical use; nevertheless, few data exist about its frequency, risk factors, and clinical impact. Clear and more precise information, derived from local studies, is needed to an adequate evaluation about pharmacoeconomic aspects of AmB treatment and cost-effectiveness of lipid formulations

Candidaemia and cancer: patients are not all the same

BACKGROUND: Most of the studies about invasive Candida infections in cancer patients have focused on haematological patients. The aim of this study was to provide information about risk factors for candidaemia in patients with solid tumours. METHODS: Retrospective cohort study. During a 9-year period (1995–2003) we reviewed all cases of candidaemia that affected cancer patients in Santa Casa Complexo Hospitalar, Brazil. RESULTS: During the period of study, 210 patients had the diagnosis of candidaemia in our medical centre, and 83 of these patients had cancer (39.5%). The majority of patients with cancer had solid tumours (77.1%), mostly in the alimentary tract. Most of solid cancers were non-metastatic (71.9%). Major diagnoses in patients with haematological neoplasia were acute leukaemia (n = 13), high grade non-Hodgkin lymphoma (n = 5) and Hodgkin's disease (n = 1). Non-Candida albicans species caused 57.8% of the episodes of candidaemia in patients with cancer, mainly in patients with haematological malignancies (p = 0.034). Neutropenia and treatment with corticosteroids were more frequent in the haematological group, in comparison with patients with solid tumours. Only 22.2% of patients with solid tumours were neutropenic before candidaemia. Nonetheless, the presence of ileus and the use of anaerobicides were independent risk factors for candidaemia in patients with solid cancers. The overall mortality in cancer patients with candidaemia was 49.4%. We then compared 2 groups of adult patients with candidaemia. The first was composed of non-neutropenic patients with solid tumours, and the second group included patients without cancer. We found that central venous catheters and gastrointestinal surgery were independently associated with candidaemia in patients with solid tumour. CONCLUSION: Cancer patients with candidaemia seem to have very different predisposing factors to acquire the infection when stratified according to baseline diseases. This study provides some useful clinical information regarding risk for candidaemia in patients with solid tumours

Esofagite por Candida: distribuição da espécie e fatores de risco para a infecção

Although Candida albicans is the main cause of fungal esophagitis, other species such as C. tropicalis, C. krusei and C. stellatoidea have also been implicated. Several studies have identified risk factors for C. albicans esophagitis. However, data for non-C. albicans species is still sparse. The aim of this study was to determine the etiology of Candida esophagitis in our medical centre over an 18-month period. Additionally, we aimed to investigate predisposing conditions for esophageal candidosis caused by different Candida species. A total of 21,248 upper gastroscopies were performed in Santa Casa Complexo Hospitalar between January 2005 and July 2006. The prevalence of Candida esophagitis was 0.74% (n = 158). C. albicans caused the vast majority of infections (96.2%), followed by C. tropicalis (2.5%), C. lusitaniae (0.6%) and C. glabrata (0.6%). There were 81 women (51.3%) and 77 men (48.7%). No case of mixed infection occurred. Concomitant oral candidosis was documented for 10.8% (n = 17). Most of cases (55.1%) involved outpatients. Around one fifth of patients in our cohort had no identifiable risk factors for esophageal candidosis (20.8%). Since nearly all infections were caused by C. albicans we were not able to determine risk factors for esophagitis caused by other Candida species.Embora Candida albicans seja a principal causa de esofagite fúngica, outras espécies como C. tropicalis, C. krusei e C. stellatoidea também têm sido implicadas. O objetivo desse estudo foi descrever espécies causadoras de esofagite fúngica em nosso centro durante um período de 18 meses, além de comparar condições predisponentes para candidose esofágica causadas por diferentes espécies de Candida. De janeiro de 2005 a julho de 2006, 21.248 endoscopias digestivas altas foram realizadas no Complexo Hospitalar Santa Casa (Porto Alegre, Brasil). A prevalência de esofagite por Candida foi de 0,74% (n = 158). C. albicans foi a causadora da maioria das infecções (96,2%), seguida por C. tropicalis (2,5%), C. lusitaniae (0,6%) e C. glabrata (0,6%). Candidose oral concomitante foi documentada em 10,8% (n = 17). Cerca de 21% dos pacientes não teve qualquer fator de risco identificável para candidose esofágica. Em função do pequeno número de pacientes infectados por espécies não-Candida albicans, não foi possível determinarmos fatores de risco para estas infecções

Alla “Scuola inclusiva nel Bosco”, per essere liberi di crescere assieme

Abstract – This paper aims to report the “Inclusive School in the Woods” experience, inspired by similar North European Outdoor Education camps. An investigation was carried out to determine the efficacy of a non-formal educational summer camp in creating inclusive activities for both childrenwith typical development and children with Autism Spectrum Disorder. Pragmatically, we carried on a series of outdoor life activities, such as woods explorations and play, lighting fires, river water activities, and so on. Specifically, our work focused on encouraging positive relationships among children. We adopted a “case study” research design, that allows multiple interpretationcomparisons, and for this reason fulfills our aims: reach an intersubjective and shared synthesis of the considered setting. We strongly believe that, from both an educational and therapeutic point of view, the interest of Outdoor setting lies on many tangible and mental links, e.g. vwith natural and cultural environment, and between people: educators and children, but also children between each others. Those very attractive relationships easily lead to some changes notonly in children with typical development, but also with Autism Spectrum Disorder. As a matter of fact, children have been stimulated to act autonomously, to be self-organized and to act globally. Despite the fact that that “Inclusive School in the Wood” is still a largely unexplored model of inclusiveexperience, it has undoubtedly great educational potential for all. Our recommendation is to further implement it both at an educational planning and scientific research level

Distribution of filamentous fungi causing invasive fungal disease at the Haematological Unit, Hospital de Clínicas de Porto Alegre, Brazil

AbstractVery limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7%), followed by Zygomycetes (13.8%). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced

Candidemia em hospital terciário brasileiro: distribuição das espécies e padrões de susceptibilidade aos antifúngicos

Recent studies have shown differences in the epidemiology of invasive infections caused by Candida species worldwide. In the period comprising August 2002 to August 2003, we performed a study in Santa Casa Complexo Hospitalar, Brazil, to determine Candida species distribution associated with candidemia and their antifungal susceptibility profiles to amphotericin B, fluconazole and itraconazole. Antifungal susceptibility was tested according to the broth microdilution method described in the NCCLS (M27A-2 method). Only one sample from each patient was analyzed (the first isolate). Most of the episodes had been caused by species other than C. albicans (51.6%), including C. parapsilosis (25.8%), C. tropicalis (13.3%), C. glabrata (3.3%), C. krusei (1.7%), and others (7.5%). Dose-dependent susceptibility to itraconazole was observed in 14.2% of strains, and dose-dependent susceptibility to fluconazole was found in 1.6%. Antifungal resistance was not found, probably related to low use of fluconazole. Further epidemiological surveillance is needed.Estudos realizados em diferentes países têm mostrado diferença na epidemiologia das infecções invasivas por Candida spp. No período de agosto de 2002 a agosto de 2003, foi conduzido estudo na Santa Casa Complexo Hospitalar, Porto Alegre, Brasil, para determinar a distribuição das espécies de Candida associadas a candidemia e o perfil de susceptibilidade das mesmas aos antifúngicos anfotericina B, fluconazol e itraconazol. Os testes de susceptibilidade foram realizados de acordo com a metodologia M27-A2 padronizada pelo NCCLS. Foi incluído no estudo o primeiro isolado de hemocultivo de cada paciente. A maioria dos episódios (51,6%) ocorreu por espécies outras que C. albicans, incluindo C. parapsilosis (25,8%), C. tropicalis (13,3%), C. glabrata (3,3%), C. krusei (1,7%) e outras espécies (7,5%). Não foi encontrada resistência aos antifúngicos testados, possivelmente devido ao baixo consumo de fluconazol na Instituição. Susceptibilidade dose-dependente ao itraconazol ocorreu em 14,2% e ao fluconazol 1,6%. Faz-se necessário monitoramento epidemiológico