Salerno S, et al. – The physicians applied electronic health record (EHR) data, in order to evaluate the safety of piperacillin–tazobactam in infants with nosocomial infections. They found no associations between predicted piperacillin exposures and the occurrence of adverse events (AEs). These findings approved the feasibility of using population pharmacokinetics and EHR to relate drug exposure with safety.

Methods

• This study consisted of infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012.
• Using a previously published population pharmacokinetic model in the target population, the physicians simulated piperacillin steady state area under the concentration versus time curve from zero to τ (AUC_{ss,0– τ}) and steady state maximal drug concentration (Cmax_ss).
• They applied multivariable logistic regression to determine the association between simulated AUC_ss,0–τ and Cmax_ss with clinical AEs (seizure and rash) and laboratory AEs controlling for gestational age.
• The odds ratios (95% confidence intervals) comparing the third versus the first tertiles for AUC_ss,0–τ and Cmax_ss were reported.

Results

• 746 infants with a median (interquartile range) gestational age of 30 weeks (26–33) and postnatal age of 11 days (6–25) were included.
• 225 mg/kg/d (176–300) was the median (interquartile range) piperacillin dose.
• No significant associations were found between simulated piperacillin exposure (AUC_ss,0–τ and Cmax_ss) and clinical and laboratory AEs.