Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug–target interactions, stability, and others, and points out the most relevant aspects for clinical practice.

Highlights Thirteen different neoplasms were shown to be susceptible to the antidepressant drug sertraline. The mechanisms of action through which sertraline can kill tumor cells are apoptosis, autophagy, and drug synergism. Sertraline inhibits TCTP, a tumor protein involved in cell survival pathways, responsible for reducing p53 levels. The testing of sertraline in vitro and in vivo resulted in reduced cell counting, shrinking of tumoral masses and increased survival rates. Dose extrapolation from animals to humans has shown a therapeutic index of sertraline that could support future clinical trials.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. Three hundred eighty-four patients were included; the median age was 39 years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplanted (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). Two hundred and seventy-one (70.6%) patients were discharged home and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional AMB mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories (P = 0.017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death [odds ratio (OR), 1.03; 95% Confidence Interval (CI), 1.01 to 1.05; P = 0.008 and OR, 1.84; 95% CI, 1.01 to 3.53; P = 0.048, respectively]. Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

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Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background Deoxycholate amphotericin B (D-AMB) remains an antifungal of great therapeutic value in pediatrics. It is generally accepted that its use in neonates is safer than in older children. However, childhood presents different periods of development which deserves to be evaluated more precisely. Our goal was to assess the usage profile of D-AMB in stratified pediatric age groups, adapted according to the National Institute of Child Health and Human Development (NICHD) classification. Methods We conducted a retrospective cross-sectional observational study at a Brazilian tertiary children's hospital. 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 in contingency tables. Results A total of 127 medical records were stratified as preterm neonatal (birth <37 weeks postmenstrual age), term neonatal (birth 27 days), infants (28 days-12 months), toddler (13 months-2 years), early childhood (3-5 years), middle childhood (6-11 years) and early adolescence (12-18 years). Very few acute infusion-related side effects were observed during administration of D-AMB in pediatrics. We found an unfavorable impact of D-AMB from 13 months onward, suggesting this group as a turning point for a greater chance of adverse events, and not soon after the neonatal period as is conventionally known (Fig. 1). Conclusions Clinical or observational studies based on age stratification are essential to precisely elucidate whether drugs with toxicity potential can be used safely in the pediatric population. Searching for a turning point has been shown to contribute to the accuracy of the study, while providing more substantial information on the impact of D-AMB on different pediatric age groups.