Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients
Abstract
Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr) and cumulative fluid balance (CFB) on PK/PD target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB).
Assuming that the positive correlation between CFB and Vd exists for piperacillin in the pathological setting, then CFB should predict Vd across subjects at each and every time point. The authors recommend to use two times higher starting dose of piperacilin/tazobactam and 100 %f T > 4 MIC for PK/PD target attainment in critically ill patient undergoing aggressive fluid resuscitation than in standard type of patient.