Cystatin C-Guided Dosing Nomogram Improves Target Attainment for Cefepime in the Critically Ill

OBJECTIVES: Estimated glomerular filtration rate is more accurate with combined creatinine and cystatin C equations (eGFR_cr-cys) than creatinine alone. This study created and evaluated a cefepime dosing nomogram based on eGFR_cr-cys for initial dosing in the critically ill. DESIGN: Pharmacokinetic modeling and simulation study. SETTING: Academic medical center. PATIENTS: Critically ill adults treated with cefepime. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 120 patients with baseline cystatin C and follow-up cefepime levels were used to develop a nomogram based on eGFR_cr-cys and weight for initial cefepime dosing. The predicted proportion of patients who achieved a free cefepime concentration above the minimum inhibitory concentration of the organism for 100% of the dosing interval in the first 24 hours (100% T > MIC at 24 hr) was compared between administered doses and those predicted by the nomogram doses. Overall drug exposure was estimated with the free area under the concentration time curve from 0 to 24 hours (AUC_0-24) and compared between administered and nomogram doses. Achievement of 100% T > MIC at 24 hours was predicted to be significantly better with the nomogram compared with the administered dose (76% vs. 38%; p < 0.001). The median AUC_0-24 as predicted by the nomogram (666 mg·hr/L) was slightly higher than the actual AUC_0-24 with administered doses (612 mg·hr/L; p = 0.01), but the nomogram led to fewer AUC_0-24 values which were either too high (> 900) or too low (< 300) (7% vs. 20%; p = 0.004). CONCLUSIONS: Use of a cystatin C-inclusive dosing nomogram for cefepime could improve target attainment without increasing the risk of potentially toxic levels in the critically ill.