ArticleAntimicrobial agents and chemotherapy2014
Developmental pharmacokinetics of piperacillin and tazobactam using plasma and dried blood spots from infants.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Assessment of Piperacillin-Tazobactam Population Pharmacokinetic Models in Neonates: An External Validation.European journal of drug metabolism and pharmacokinetics · 2025Pooled it
- Scaling beta-lactam antimicrobial pharmacokinetics from early life to old age.British journal of clinical pharmacology · 2019Pooled it
- Blood kinetics of Ebola virus in survivors and nonsurvivors.The Journal of clinical investigation · 2015Trial
- Antibiotic Therapy for the Prevention and Treatment of Neonatal Sepsis.Clinics in perinatology · 2026Review
- Population pharmacokinetic modeling and simulation-informed ceftazidime dosing in Chinese neonates using quantitative dried blood spot micro-sampling.Antimicrobial agents and chemotherapy · 2026Article
- Population pharmacokinetics and dose optimization of piperacillin-tazobactam in premature and term neonates with severe infections.Antimicrobial agents and chemotherapy · 2026Article
- Population Pharmacokinetics and Dose Optimization of Piperacillin in Infants and Children with Pneumonia.Paediatric drugs · 2025Article
- A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.Clinical pharmacokinetics · 2025Article
- External Evaluation of Population Pharmacokinetic Models of Piperacillin in Preterm and Term Patients from Neonatal Intensive Care.European journal of drug metabolism and pharmacokinetics · 2024Article
- Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.European journal of pediatrics · 2024Article
- Dried Blood Spots-A Platform for Therapeutic Drug Monitoring (TDM) and Drug/Disease Response Monitoring (DRM).European journal of drug metabolism and pharmacokinetics · 2023Review
- Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review.Molecules (Basel, Switzerland) · 2023Review
- Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants.Biomedicines · 2023Review
- A Validated UHPLC-MS/MS Method to Quantify Eight Antibiotics in Quantitative Dried Blood Spots in Support of Pharmacokinetic Studies in Neonates.Antibiotics (Basel, Switzerland) · 2023Article
- Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.British journal of clinical pharmacology · 2022Review
- Use of Antibiotics in Preterm Newborns.Antibiotics (Basel, Switzerland) · 2022Review
- Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction.Clinical pharmacokinetics · 2021Article
- Infection control and other stewardship strategies in late onset sepsis, necrotizing enterocolitis, and localized infection in the neonatal intensive care unit.Seminars in perinatology · 2020Article
- Barriers and Challenges in Performing Pharmacokinetic Studies to Inform Dosing in the Neonatal Population.Pharmacy (Basel, Switzerland) · 2020Review
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Piperacillin-tazobactam is often given to infants with severe infection in spite of limited pharmacokinetics (PK) data. We evaluated piperacillin-tazobactam PK in premature and term infants of ages <61 days with suspected systemic infection. Infants received intravenous piperacillin-tazobactam (80 to 100 mg/kg of body weight every 8 h [q 8 h]) based on gestational and postnatal age. Sparse plasma samples were obtained after first and multiple doses. Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effect modeling. Target attainment rates for the time unbound piperacillin concentrations remained above the MIC for 50% and 75% of the dosing interval at steady state were evaluated. Bias in population PK parameter estimates was assessed for dried blood spot (DBS) samples, and a comparability analysis was performed for DBS and plasma drug concentrations using linear regression. We obtained 128 plasma samples from 32 infants, median gestational age of 30 weeks (range, 23 to 40 weeks) and postnatal age of 8 days (range, 1 to 60). Piperacillin and tazobactam PK models included body weight (WT) and postmenstrual age (PMA) as covariates for clearance and WT for volume of distribution and were used to optimize dosing in infants. DBS drug concentrations were 50 to 60% lower than those in plasma, but when combined with plasma concentrations and a matrix effect, the data generated PK model parameters similar to those for plasma alone. With PMA-based dosing (100 mg/kg q 8 h, 80 mg/kg q 6 h, and 80 mg/kg q 4 h for PMA of ≤30, 30 to 35, and 35 to 49 weeks, respectively), 90% of simulated infants achieved the surrogate therapeutic target of time above the MIC (≤32 mg/liter) for 75% of the dosing interval.
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