Repurposing of the Tamoxifen Metabolites to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli

The development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating innate immune system cell traffic. main objective this study was to analyze the activity N-desmethyltamoxifen, 4-hydroxytamoxifen, endoxifen, three major metabolites tamoxifen, these pathogens. We showed immunosuppressed mice infected with A. P. or E. peritoneal sepsis treated at 80 mg/kg/d for days still reduced bacterial load tissues blood. Moreover, it increased survival 66.7% (for baumannii coli) 16.7% aeruginosa) when compared immunocompetent mice. Further, susceptibility time-kill assays endoxifen exhibited minimum inhibitory concentration 90% isolates (MIC90) values 16 mg/L, were bactericidal clinical coli. This paralleled membrane permeability without affecting their outer proteins profiles. Together, data presented antibacterial MDR coli, may be a potential alternative treatment infections caused two