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.

Management of hepatitis C infection with direct action antiviral drugs (DAA)

Several new direct action antiviral drugs (DAA) against the HCV virus (HCV) are approved and marketed. The combination of DAA with pegylated interferon and ribavirin (PR) is only recommended to patients with tolerance to interferon (IFN). IFN-free treatments are now considered elective drugs for patients with chronic HCV. More than 90% of patients infected with HCV genotype 1 or 4 (fewer with other genotypes) show sustained virological response, when treated with sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the combination of paritaprevir with ritonavir, ombitasvir and dasabuvir, with or without ribavirin. The safety and efficacy of DAA therapy in HIV-HCV confection is now comparable with HCV monoinfection. DAA drugs are also efficient in patients with previous interferon/ribavirin, or protease inhibitors, treated patients as well as with hepatic transplanted patients. The goal of this review is to clarify the current stage of DAA drugs already approved and available by January-2016. Another objective is to discuss the main drugs regimen recommended by international medical associations and drugs regulatory agencies, including Brazil's Health Ministry. In this review, the authors make an approach about: adverse effects of DAA; interactions with other drugs, efficacy in patients with compensated cirrhosis or comorbidities, different genotypes or subtypes, as well as the development of resistance associated to viral mutants and their possible clinical importance