Pathogen-Specific Architectures of Carbapenem Resistance: Hydrolysis, Transport and Target Engagement

This is the authors' abstract. We don't add key points for this paper.

Although Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are all classified as carbapenem-resistant, they differ in how they control antibiotic access to its targets. This narrative review concerns resistant clinical isolates. It compares β-lactamases, drug uptake and efflux, and penicillin-binding proteins (PBPs), including their implications for β-lactam treatment. We use enzyme–transport–target architecture to describe functional relationships among these components in a specified organism and drug context. Evidence from the examined systems links protein homeostasis to enzyme stability, transport alterations to drug-specific responses, and treatment to changes in resistance determinants and bacterial population composition. For example, a PBP3 substitution increased the sulbactam–durlobactam MIC eightfold in an Acinetobacter baylyi model, whereas another substitution altered purified-protein reactivity without increasing the MIC. Clinical treatment evidence is assessed separately from these mechanistic findings. The review distinguishes pathogen-focused trials, observational outcomes and in vitro activity, and relates treatment options to carbapenemase class, susceptibility and infection site. It helps explain why shared resistance determinants can produce different susceptibility profiles by linking enzyme activity, drug access and target engagement to the response to specific β-lactams.