Evolution of an Escherichia coli strain from a critical care patient treated with piperacillin/tazobactam

We investigated an Escherichia coli strain obtained from the bloodstream of a hospitalised patient, that evolved resistance against the antimicrobials initially used as empirical treatment. Comparing the whole-genome sequences of the susceptible isolate with the evolved, resistant isolate showed duplications of the only encoded beta-lactamase gene, blaTEM-1, resulting in increased enzyme production and resistance to TZP, a commonly prescribed BL/BLI combination antimicrobial. Despite the additional energy needed for increased enzyme production and retaining the additional copies of duplicated genes, we did not find growth differences under standard laboratory conditions. We furthermore identify phenotypic changes that indicate host adaptation and mirror phenotypic changes observed in other species of opportunistic bacterial pathogens. Our findings highlight that BL/BLI combinations can trigger the within-patient evolution of antimicrobial resistance, which is of high relevance when considering the implementation of newly developed drugs, many of which belong to the BL/BLI class.