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.