Hospital-acquired pneumonia (HAP), often caused by Pseudomonas aeruginosa, poses a significant health threat. Meropenem, a common therapeutic agent, faces emergent resistance during treatment. Using a rabbit HAP model, we assessed meropenem’s pharmacodynamics. Dose-response and emergent resistance displayed an inverted U relationship. Combining amikacin with meropenem suppressed resistance. Mechanisms included porin loss, efflux upregulation, and increased AmpC expression. Simulations identified meropenem 2 g i.v. q8h as an optimal regimen to suppress resistance. This innovative platform allows pre-clinical assessment, informing strategies to mitigate emergent resistance during HAP treatment with meropenem.
