Defining the impact of severity of illness on time above the MIC threshold for cefepime in Gram-negative bacteraemia: a 'Goldilocks' window

•Patients with modified APACHE II scores of 9-22 may have improved outcomes when fT>MIC is optimised.•Patients with modified APACHE II scores <9 and >22 may not experience as significant a benefit when fT>MIC goals are met.•fT>MIC goals may need be higher in patients with APACHE II scores >22.

The quantitative impact of severity of illness on pharmacodynamic thresholds is poorly defined. We used a robust cefepime outcomes cohort and previously identified pharmacodynamic breakpoints of 68% [pharmacokinetic (PK) model 1] and 74% (PK model 2) to probe interactions and relationships with modified Acute Physiology and Chronic Health Evaluation (mAPACHE) II scores. When the time that serum concentration remains above the minimum inhibitory concentration during the dosing interval (fT>MIC) was optimised, mortality was improved between mAPACHE II scores of 9-23 and 9-22 in models 1 and 2, respectively. No significant interactions were identified. These results suggest that mAPACHE II scores of 9-22 may fall within a 'Goldilocks' window in which hospital survival is improved among patients achieving goal fT>MIC thresholds.