Antibiotic efficacy in the complex infection environment

•The infection environment influences antibiotic susceptibility.•Clinical susceptibility assays frequently fail to predict drug efficacy in patients.•Host interactions and microbial interactions alter antibiotic susceptibility.•Environmental factors may potentiate or antagonize antibiotic activities.•Consideration of these factors may improve antibiotic treatment of patients.

Accurate prediction of antimicrobial efficacy is essential for successful treatment of bacterial infection. Beyond genetically encoded mechanisms of antibiotic resistance, the determinants of antibiotic susceptibility during infection remain poorly understood, and treatment failure is common. Traditional antibiotic susceptibility testing fails to account for extrinsic determinants of antibiotic susceptibility present in the complex infection environment and is therefore a poor predictor of antibiotic treatment outcome. Here we discuss how host-pathogen interaction, microbial interspecies interaction, and metabolic heterogeneity contribute to the success or failure of antibiotic therapy. Consideration of these factors during the treatment of disease will improve our ability to successfully resolve recalcitrant bacterial infection and improve patient health.