biostudies-literatureErsoy SCNHLBI NIH HHS173-181https://www.ebi.ac.uk/biostudies/studies/S-EPMC5478264biostudies-literatureUnknown20The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic efficacy. This assay fails to incorporate environmental factors normally present during host-pathogen interactions in vivo that significantly impact antibiotic efficacy. Here we report that standard antimicrobial susceptibility testing (AST) failed to detect antibiotics that are in fact effective in vivo; and frequently identified antibiotics that were instead ineffective as further confirmed in mouse models of infection and sepsis. Notably, AST performed in media mimicking hosEBioMedicineCorrecting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.PMC5478264P01 HL131474R01 HL125352Smith JWHouse JKMahan MJBarnes LErsoy SCHeithoff DMMarth JDTripp GKfalseCorrecting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic efficacy. This assay fails to incorporate environmental factors normally present during host-pathogen interactions in vivo that significantly impact antibiotic efficacy. Here we report that standard antimicrobial susceptibility testing (AST) failed to detect antibiotics that are in fact effective in vivo; and frequently identified antibiotics that were instead ineffective as further confirmed in mouse models of infection and sepsis. Notably, AST performed in media mimicking hos2017-01-01T00:00:00Z2017 Jun2025-04-19T19:05:06.584Z2019-03-27T02:48:05ZS-EPMC54782642857930010.1016/j.ebiom.2017.05.026