Case Commentary: When one target is not enough-PBP3 insertions and target redundancy in Escherichia coli.

This challenging clinical case highlights the impact of PBP3 insertions in Escherichia coli, which reduce susceptibility to key β-lactam agents and complicate treatment, particularly in the setting of NDM production (C. Fabrizio, F. Valzano, S. Giuliano, E. Morelli, et al., Antimicrob Agents Chemother 70:e00887-25, 2026, https://doi.org/10.1128/aac.00887-25). Clinical improvement was achieved with imipenem-relebactam plus aztreonam, supporting the idea that targeting multiple penicillin-binding proteins can overcome functional redundancy. These findings emphasize the clinical relevance of PBP3-mediated resistance and the need for treatment strategies that address complex β-lactam resistance in Gram-negative pathogens.