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Piperacillin/tazobactam treatment in children: evidence of subtherapeutic concentrations
Panpan Ye1, Jinyi Shi1, Zixuan Guo2
1Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
Insights
The current piperacillin/tazobactam (PIP/TAZ) dosage for pediatric lower respiratory tract infections is insufficient, resulting in low drug concentrations. Optimized dosing or alternative treatments are needed for effective bacterial infection management.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacokinetics and Pharmacodynamics
- Antimicrobial Stewardship
Background:
- Piperacillin/tazobactam (PIP/TAZ) is a critical antibiotic for treating bacterial infections in children.
- Current dosing regimens aim to achieve therapeutic drug levels, but their efficacy in pediatric lower respiratory tract infections is not well-established.
Purpose of the Study:
- To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets of current piperacillin/tazobactam (PIP/TAZ) dosing in children with lower respiratory tract bacterial infections.
- To assess the probability of target attainment (PTA) for key PK/PD parameters.
Main Methods:
- Intravenous PIP/TAZ administration was studied in 57 pediatric patients.
- Piperacillin (PIP) concentrations were measured using high-performance liquid chromatography.
- PK/PD targets (70% fT > MIC and 50% fT > 4x MIC) were evaluated using Bayesian methods.
Main Results:
- The probability of attaining therapeutic PK/PD targets for common pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae was 0%.
- Median trough concentrations (Cmin) of PIP were higher in infants than older children.
- q8h dosing resulted in higher median Cmin than q12h dosing.
Conclusions:
- Current PIP/TAZ dosing regimens result in sub-therapeutic piperacillin concentrations in most children with lower respiratory tract bacterial infections.
- There is a critical need to explore optimized dosing strategies or alternative antimicrobial therapies for this patient population.
Objective:
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.
Patients And Methods:
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 (fT > MIC) and (2) 50% fT > 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.
Results:
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% fT > MIC and 50% fT > 4× MIC for Pseudomonas aeruginosa and Klebsiella pneumoniae, the PTA was all 0. The median Cmin of PIP was significantly higher in infants than in children, and the median Cmin after administration in q8h was significantly higher than that after administration in q12h.
Conclusion:
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.
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