Heteroresistance to piperacillin-tazobactam in Klebsiella pneumoniae is mediated by increased copy number of multiple beta-lactamase genes

Piperacillin-tazobactam is a betalactam/betalactamase inhibitor combination with a broad spectrum of activity that is often used as empirical and/or targeted therapy among hospitalized patients. Heteroresistance, a form of antibiotic resistance where a minor cell population of resistant cells coexist within a major susceptible cell population. The heteroresistance phenotype is known to cause antibiotic treatment failure in murine models. In this project we want to understand the implications of heteroresistance in clinical settings by determining the prevalence and mechanisms of heteroresistance to TZP among clinical Klebsiella pneumoniae bloodstream infection isolates.