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.

Reconhecimento de lesões de pele suspeitas de malignidade por médicos da atenção primária de Curitiba-PR / Identification of skin lesions suspected of malignity by primary care physitians in Curitiba-PR

Este estudo teve por objetivo analisar o desempenho de médicos atuantes na atenção primária frente ao reconhecimento de lesões suspeitas de câncer de pele. Trata-se de um estudo de campo exploratório descritivo com abordagem quantitativa. Médicos generalistas, médicos de família e residentes em Medicina de Família e Comunidade atuantes nas 66 unidades de saúde de Curitiba-PR, foram entrevistados. O conhecimento em dermatologia foi considerado mínimo para 61,5% dos participantes. A sensibilidade média (S) no reconhecimento das lesões suspeitas foi de 63,92% (IC95% 60,5-67,34). O desempenho foi considerado satisfatório na identificação do melanoma cutâneo (S=83%) e do carcinoma espinocelular (S=97%) e insatisfatório nos casos de ceratose actínica (S=54%), nevo melanocítico displásico (S=51%) e carcinoma basocelular (S=32%). Lesões de pele prevalentes podem estar sendo diagnosticadas tardiamente ou subdiagnosticadas. Salienta-se a importância de atualizações e treinamentos profissionais para aprimoramento da percepção e capacidade de reconhecimento precoce na atenção primária. (AU)

The aim of this study was to analyze the performance of primary care doctors in recognizing suspected skin cancer lesions. This is an exploratory-descriptive field study with a quantitative approach. General practitioners, family doctors, and family and community medicine residents working in the 66 health units in Curitiba-PR were interviewed. Knowledge in dermatology was considered basic for 61.5% of the participants. The mean sensitivity (S) in recognizing suspected lesions was 63.92% (CI95% 60.5-67.34). The performance was considered satisfactory in the identification of cutaneous melanoma (S=83%) and squamous cell carcinoma (S=97%) and unsatisfactory in cases of actinic keratosis (S=54%), dysplastic melanocytic nevus (S=51%) and basal cell carcinoma (S=32%). Prevalent skin lesions may be diagnosed late or underdiagnosed. The importance of professional updates and training is emphasized to improve perception and the ability to recognize early in primary care. (AU)