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Impact of attaining an aggressive PK/PD target with continuous infusion beta-lactams on the clinical efficacy of targeted therapy of early post-transplant Gram-negative infections in critically ill OLT recipients. An interim analysis of a 3-year prospective, observational, study.
J Infect Dis
January 2025
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy.
Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections.
Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured.
Impact of COVID-19 vaccination on hospitalization, hospital utilization and expenditure for COVID-19: A retrospective cohort analysis of a South African private health insured population.
PLoS One
January 2025
Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
This study quantifies the impact of COVID-19 vaccination on hospitalization for COVID-19 infection in a South African private health insurance population. This retrospective cohort study is based on the analysis of demographic and claims records for 550,332 individuals belonging to two health insurance funds between 1 March 2020 and 31 December 2022. A Cox Proportional Hazards model was used to estimate the impact of vaccination (non-vaccinated, partly vaccinated, fully vaccinated) on COVID-19 hospitalization risk; and zero-inflated negative binomial models were used to estimate the impact of vaccination on hospital utilization and hospital expenditure for COVID-19 infection, with adjustments for age, sex, comorbidities and province of residence.
View Article and Find Full Text PDFSecondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials.
PLoS One
January 2025
Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells.
View Article and Find Full Text PDFStructure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.
Proc Natl Acad Sci U S A
January 2025
Cellular and Structural Physiology Laboratory, Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo-ku, Tokyo 113-8510, Japan.
Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).
View Article and Find Full Text PDFLong COVID and gut microbiome: insights into pathogenesis and therapeutics.
Gut Microbes
December 2025
Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome.
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