Rising Carbapenem MICs and Clinical Dose Optimization: Bridging Resistance Surveillance and Pharmacokinetic/Pharmacodynamic Strategies.

The rise in carbapenem resistance is well documented, but a less conspicuous trend has received far less attention: the gradual upward shift in minimum inhibitory concentration (MIC) values among isolates that remain phenotypically "susceptible." We propose the term carbapenem floor for this phenomenon: an intermediate zone in which standard dosing regimens become progressively less reliable at achieving target exposure, yet which remains invisible to breakpoint-based surveillance; we present this as a hypothesis-generating framework consistent with existing pharmacokinetic and epidemiological evidence rather than as an empirically established trend, since no systematic longitudinal quantification of carbapenem MIC drift has yet been undertaken. Because carbapenems exhibit time-dependent killing and their pharmacokinetic/pharmacodynamic (PK/PD) target has MIC as its denominator, even a shift within the susceptible range can substantially reduce target attainment; augmented renal clearance in critically ill patients deepens this erosion. This review integrates resistance surveillance evidence with PK/PD principles to evaluate prolonged infusion, loading doses, therapeutic drug monitoring (TDM), and empirical protocols derived from population pharmacokinetic models and local MIC distributions, examining for each the evidence and the practical constraints. We also consider the reverse relationship: failure to attain PK/PD targets appears to select for elevated MICs, suggesting that dosing practice may contribute to resistance selection and potentially influence resistance epidemiology, not only respond to it. Extending antibiogram reporting to include MIC distributions, and translating those data into dosing protocols through antimicrobial stewardship, is a feasible priority where TDM infrastructure is limited.