A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Amphotericin B in Pediatrics: Analysis by Age Stratification Suggests a Greater Chance of Adverse Events from 13 Months of Age Onwards.

BACKGROUND AND OBJECTIVE: Amphotericin B deoxycholate (AMB-D) remains an antifungal agent with great therapeutic value in pediatric patients. The currrent consensus is that its use in neonates is safer than in older children. However, childhood presents different periods of development that deserve to be evaluated more precisely. Our goal was to assess the usage profile of AMB-D in stratified pediatric age groups, adapted according to the National Institute of Child Health and Human Development classification. METHODS: This retrospective cross-sectional observational study was conducted at a Brazilian tertiary children's hospital between January 2014 and December 2019.  Data of patients who received at least two doses of intravenous AMB-D while hospitalized were extracted from electronic health files. Information on patient demographics, underlying diseases and comorbidities, laboratory examinations, fungal infection diagnosis, and AMB-D use were gathered following specific criteria. Nonparametric tests were applied, such as the chi-square test to compare proportions and Fisher's exact test to assess the association between categorical variables or contingency tables. RESULTS: One hundred and twenty-seven (127) medical records were stratified as preterm neonatal (birth <37 weeks postmenstrual age), term neonatal (birth-27 days), infants (28 days-12 months), toddlers (13 months-2 years), early childhood (3-5 years), middle childhood (6-11 years), and early adolescence (12-18 years). The criteria for the indication of AMB-D followed empirical use as the main indication (n = 74; 58.26%), proven and probable fungal infection (n = 39; 30.71%), and medical suspicion (n = 14; 11.02%). Candida spp. was the main etiologic agent isolated in cultures, with the highest frequency of C. albicans (n = 18; 40%), followed by Candida parapsilosis (n = 14; 31.11%), and Candida tropicalis (n = 6; 13.33%). Very few acute infusion-related adverse effects were observed during the administration of AMB-D in pediatric patients. We found an unfavorable impact of AMB-D use in patients from 13 months of age onwards suggesting this group as a turning point for a greater chance of adverse events, and not soon after the neonatal period. CONCLUSIONS: Clinical or observational studies based on age stratification are essential to accurately elucidate whether potentially toxic drugs can be used safely in the pediatric population. Our search for a turning point was shown to contribute to the accuracy of the study, as it provided data on the impact of D-AMB in specific pediatric age groups.

Tuberculose no Paraná: uma análise da série histórica alicerçada na epidemiologia descritiva / Tuberculosis in Paraná: an analysis of the historical series based on descriptive epidemiology

O objetivo desse estudo foi analisar os casos notificados de tuberculose no Paraná, com base em série histórica determinada pelo período de 2010 a 2019, alicerçada pela epidemiologia descritiva. Trata-se de um estudo epidemiológico descritivo observacional do tipo levantamento, com dados oriundos do Sistema de Informação de Agravos de Notificação. Resultou na análise de 25.893 casos, com característica endêmica, não cíclica ou sazonal, com prevalência na Regional de Saúde de Paranaguá, entre adultos, sexo masculino, cor/raça preta seguida da indígena, em pessoas com escolaridade baixa e associadas ao etilismo e tabagismo como risco. Predominaram notificações de casos novos, seguido pela recidiva decorrentes da tuberculose pulmonar. A cura prevaleceu seguido por abandono de tratamento. Por ser uma doença secular no Brasil, com etiologia multifatorial, são necessários investimentos além do acesso à saúde, em ações intersetoriais no âmbito da justiça social atreladas principalmente a educação, alimentação, renda e habitação.

The objective of this study was to analyze the reported cases of tuberculosis in Paraná, based on a historical series determined for the period from 2010 to 2019, on descriptive epidemiology basis. This is a descriptive observational epidemiological study of the survey type, with data from the Notifiable Diseases Information System. It resulted in the analysis of 25,893 cases, with endemic, non-cyclical or seasonal characteristics, with prevalence in the Health Area of Paranaguá, among male, black and indigenous adults, with low education, and associated with risk of alcoholism and smoking. Reports of new cases predominated, followed by recurrence of pulmonary tuberculosis. The cure prevailed, followed by treatment abandonment. As it is a secular disease in Brazil, with multifactorial etiology, investments not only for access to health but also in intersectoral actions, within the scope of social justice, mainly linked to education, food, income, and housing are required.

El objetivo fue analizar casos notificados de tuberculosis en Paraná, Brasil a partir de una serie histórica para el período de 2010 a 2019, con base en la epidemiología descriptiva. Se trata de un estudio epidemiológico observacional descriptivo del tipo encuesta, con datos del Sistema de Información de Enfermedades de Declaración Obligatoria. Resultó en el análisis de 25.893 casos, con características endémicas, no cíclicas o estacionales, prevalencia en la Regional de Salud de Paranaguá, entre adultos del sexo masculino, color/raza negra e indígenas, en personas con baja escolaridad y que están asociados al uso abusivo de alcohol y tabaco. Predominaron casos nuevos por tuberculosis pulmonar. Predominó la curación seguida del abandono del ratamiento. Por tratarse de una enfermedad secular en Brasil, con una etiología multifactorial, se necesitan inversiones además del acceso a la salud, en acciones intersectoriales en el ámbito de la justicia social, principalmente vinculadas a la educación, la alimentación, la renta y la vivienda.

Síndrome do intestino irritável: mebeverina ou óleo de hortelã-pimenta? Uma revisão crítica baseada em evidências / Irritable bowel syndrome: mebeverine or peppermint oil? An evidence-based critical review

Este estudo teve por objetivo reunir e analisar evidências científicas sobre a eficácia de duas abordagens terapêuticas disponíveis para alívio dos sintomas em pacientes com síndrome do intestino irritável (SII), o cloridrato de mebeverina e o óleo de hortelã-pimenta (Mentha x piperita L.). Uma revisão crítica sistematizada foi realizada a partir das bases de dados MEDLINE, CENTRAL e LILACS. Onze artigos referentes à ensaios clínicos randomizados abrangeram os critérios de elegibilidade. Os achados sugerem baixa evidência da mebeverina no controle dos sintomas intestinais da desordem, ainda que, apenas um dos estudos preocupou-se em relatar a ocorrência de efeitos adversos. Já o óleo de hortelã-pimenta mostrou-se eficaz e bem tolerado para a redução do quadro. Escalas de qualidade de vida também obtiveram resultados positivos com a fitoterapia. A busca por efeitos adversos durante o tratamento foi abordada em praticamente todos os ensaios. Em suma, as evidências apontam positivamente para o uso do fitoterápico no alívio dos sintomas da síndrome do intestino irritável, todavia a mebeverina permanece comercializada a um custo elevado e carece de estudos que demonstrem sua eficácia. Reforça-se a necessidade de investigações com métodos de qualidade criteriosos capazes de auxiliar boas escolhas terapêuticas na prática clínica.