Speaker
Description
Rising antimicrobial resistance drives the search for dosing strategies that maximize bacterial eradication while minimizing unnecessary drug exposure. Standard indices, such as the minimum inhibitory concentration (MIC) or the time spent above MIC ($\%T_{>MIC}$), are static snapshots that often fail to capture the time-varying nature of periodic dosing. To address this gap, we introduce the minimum inhibitory dose (MID), a dynamic MIC analogue defined as a threshold dose size, above which bacterial populations show net negative growth from one dose to the next. Using Floquet theory on a coupled bacterial-growth and antibiotic pharmacokinetic/pharmacodynamic (PK/PD) model, we calculate the MID as a function of the dose schedule and PK/PD properties. Our framework recapitulates established clinical guidelines: minimizing the dose period-normalized MID identifies frequent dosing as optimal for time-dependent antibiotics such as ampicillin and infrequent dosing for concentration-dependent antibiotics such as rifampin. Applying this framework to N. gonorrhoeae treated with ceftriaxone, the MID accurately predicts historical dose size adjustments driven by shifts in MIC and fitness costs. These results position the MID as a unifying, mechanism aware metric to guide future rational antibiotic dosing strategies.
