Cefepime pharmacodynamics in patients with extended spectrum β-lactamase (ESBL) and non-ESBL infections

SummaryObjectiveThis study was designed to compare cefepime exposures with microbiological outcomes in ESBL and non-ESBL infections and determine the pharmacodynamic profiles associated with successful outcome.MethodsCefepime pharmacodynamic exposures of unbound drug [time above MIC (fT > MIC), minimal concentration over MIC (fCmin/MIC), and area under the curve over MIC (fAUC/MIC)] for 18 patients with ESBL and non-ESBL infections were determined by using a published population pharmacokinetic model. Classification and regression tree analysis was used to identify pharmacodynamic breakpoints that predicted eradication. A 5000-patient Monte Carlo Simulation was conducted to estimate the probability of target attainment for the goal pharmacodynamic exposures.ResultsEradication was 80% when fT > MIC was 50% compared with 0% when T > MIC was less than 50% (p < 0.05). The median fCmin/MIC ratio for ESBL group was statistically lower than that for the non-ESBL group (1.54 versus 138, p < 0.001). Regardless of ESBL production, all pathogens were eradicated when fCmin/MIC > 7.6 and only 33.3% were eradicated when fCmin/MIC ≤ 7.6 (p < 0.05). Pharmacodynamic exposures of 50% fT > MIC and fAUC/MIC > 1654 were also predictive of eradication. While conventional dosage regimens of 2 g q 12 h and q 8 h failed to achieve adequate target attainment, 4 g continuous infusion and 2 g q 6–8 h prolonged infusion could attain more than 90% of target attainment at the MIC of 2 μg/ml for the breakpoint of fCmin/MIC = 7.6.ConclusionMicrobiological eradication in patients receiving cefepime was best predicted by fCmin/MIC ratio greater than 7.6 regardless of the presence of an ESBL. Continuous or prolonged infusion regimens provided the greatest probability of attaining this exposure.