Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represent an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top ten signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.
23 June 2020 in Antimicrobial Agents and Chemotherapy
Tedizolid has demonstrated its efficacy and safety in clinical trials; however, data concerning its tolerability in long-term treatments are scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid. A multicentric retrospective study of patients who received tedizolid for more than 6 days was conducted. Adverse events (AEs) were identified from patients’ medical records and laboratory data. The World Health Organization causality categories were used to discern AEs that were probably associated with tedizolid.