AUTHOR=Ye Panpan , Shi Jinyi , Guo Zixuan , Yang Xinmei , Li Qian , Chen Keguang , Zhao Furong , Zhou Haiyan , Zhang Yehui , van den Anker John , Song Linlin , Zhao Wei 

TITLE=Piperacillin/tazobactam treatment in children: evidence of subtherapeutic concentrations

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1254005

DOI=10.3389/fphar.2024.1254005

ISSN=1663-9812

ABSTRACT=<sec><title>Objective</title><p>Piperacillin/tazobactam (PIP/TAZ) is used for the treatment of lower respiratory tract bacterial infections in children. This study was performed to evaluate if the current dosing regimen results in therapeutic drug concentrations.</p></sec><sec><title>Patients and methods</title><p>Patients suspected or proven to have lower respiratory tract bacterial infection and administrated PIP/TAZ intravenously for a duration of no less than 0.5 h, q6h–q12h daily, were enrolled. Blood samples were collected, and PIP concentrations were determined by high-performance liquid chromatography. The individual predicted concentration of PIP was evaluated using the individual empirical Bayesian estimate method. The evaluated PK/PD targets included (1) 70% time when the predicted free drug concentration exceeds the minimum inhibitory concentration (<italic>f</italic>T &gt; MIC) and (2) 50% <italic>f</italic>T &gt; 4× MIC. Probability of target attainment (PTA) was assessed by the proportion of patients who reached the PK/PD targets. The PIP concentrations between different groups of patients were compared.</p></sec><sec><title>Results</title><p>A total of 57 samples were collected from 57 patients with a median age of 2.26 years (0.17–12.58). For the PK/PD targets of 70% <italic>f</italic>T &gt; MIC and 50% <italic>f</italic>T &gt; 4× MIC for <italic>Pseudomonas aeruginosa</italic> and <italic>Klebsiella pneumoniae</italic>, the PTA was all 0. The median C<sub>min</sub> of PIP was significantly higher in infants than in children, and the median C<sub>min</sub> after administration in q8h was significantly higher than that after administration in q12h.</p></sec><sec><title>Conclusion</title><p>The current dose regimen of PIP/TAZ leads to extremely low plasma concentrations in most children with lower respiratory tract bacterial infections. More optimized dosing regimens or better alternative therapies need to be further explored.</p></sec>