Genetic basis for in vivo piperacillin-tazobactam resistance

Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. While in vitro experiments have shown that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in vivo study could confirm the role of blaTEM and other genes. Thereby, we aimed to identify the P/T resistance mechanisms through the follow-up of patients with intraabdominal E. coli infections (IAI) and P/T treatment failure. Here, we found a higher copy number of blaTEM gene in P/T-R isolates, generated by three different genetic events: (1) IS26-based duplication of blaTEM gene; (2) generation of a small multicopy plasmid (ColE-like) harboring blaTEM; and (3) adaptative evolution through the reduction of the plasmid size, leading to a higher plasmid copy number. Moreover, OmpC expression was affected in two P/T-R strains. Thus, P/T treatment might generate resistance in patients with IAI by E. coli, through three mechanisms blaTEM-dependent and OmpC downregulation.