Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis

Xue, Li; Qi, Hui; Jin, Fei; Yao, Bu‐Fan; Wu, Yue‐E; Qi, Yuan; Kou, Chen; Wu, Xirong; Luo, Xiao-Jing; Shen, Yifan; Zheng, Xu; Wang, Yonghong; Xu, Fang; Jiao, Weiwei; Li, Jieqiong; Xiao, Jing; Dong, Yining; Du, Bin; Shi, Haiyan; Xu, Bin; Shen, Adong; Zhao, Wei

doi:10.1016/j.ejps.2021.105868

Cited by 8 publications

(8 citation statements)

References 36 publications

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“…Since ceftazidime is predominantly cleared via glomerular filtration, functional end-organ maturation is also expected to have an influence (20). In line with our findings, the above-mentioned PK studies by Li et al and Wang et al found age and PNA to be predictors of ceftazidime CL (11,12). Additionally, the latter study also identified GA and PMA as significant covariates for CL (12).…”

Section: Discussionsupporting

confidence: 91%

“…Also, asphyxiated neonates are more at risk for multiorgan failure due to resuscitation, and this could also have a negative impact on ceftazidime CL (16). This may partially explain the low CL of 0.03 L/ h/kg that we found compared to those in two recent studies on the PK of ceftazidime in nonhypothermic and nonasphyxiated Chinese term neonates (0.27 L/h/kg and 0.11 L/h/kg) (11,12). Older neonates and infants (aged 1 to 81 days) were also included in those two studies, making their population and ours (neonates aged up to 5 days) difficult to compare.…”

Section: Discussionmentioning

confidence: 49%

“…Despite its widespread clinical use, the optimal dosage of ceftazidime for suspected or proven neonatal P. aeruginosa infections remains largely unknown, with studies suggesting a large range of different dosing regimens (10)(11)(12). Studies describing its PK in neonates during controlled TH are lacking.…”

mentioning

confidence: 99%

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Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Veer

Haan

Franken

et al. 2023

Antimicrob Agents Chemother

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Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 49%

See 1 more Smart Citation

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Veer

Haan

Franken

et al. 2023

Antimicrob Agents Chemother

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“…We identified two population pharmacokinetics studies with ceftazidime ( 24 , 25 ). Li et al set the target to 70% f T> MIC to test PTA of initial doses in neonates against pathogens with MIC up to 8 mg/L.…”

Section: Resultsmentioning

confidence: 99%

“…Simulations with the initial dose of 25 mg/kg twice daily achieve the target only for newborn with postnatal age ≤ 3 days. They proposed higher initial doses of 30–40 mg/kg every 8 h for optimal PTA ( 25 ). Bui et al studied older patients (up to 12 years) and considered the targets of 60 and 90% f T> MIC.…”

Section: Resultsmentioning

confidence: 99%

Beta-Lactams Therapeutic Monitoring in Septic Children–What Target Are We Aiming for? A Scoping Review

et al. 2022

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The antimicrobial therapy of sepsis and septic shock should be individualized based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to deliver effective and timely treatment of life-threatening infections. We conducted a literature scoping review to identify therapeutic targets of beta-lactam antibiotics in septic pediatric patients and the strategies that have been applied to overcome sepsis-related altered pharmacokinetics and increase target attainment against susceptible pathogens. A systematic search was conducted in the MEDLINE, EMBASE and Web of Science databases to select studies conducted since 2010 with therapeutic monitoring data of beta-lactams in septic children. Last searches were performed on 02 September 2021. Two independent authors selected the studies and extracted the data. A narrative and qualitative approach was used to summarize the findings. Out of the 118 identified articles, 21 met the eligibility criteria. Population pharmacokinetic modeling was performed in 12 studies, while nine studies reported data from bedside monitoring of beta-lactams. Most studies were conducted in the United States of America (n = 9) and France (n = 5) and reported PK/PD data of amoxicillin, ampicillin, azlocillin, aztreonam, cefazolin, cefepime, cefotaxime, ceftaroline, ceftazidime, doripenem, meropenem and piperacillin/tazobactam. Therapeutic targets ranged from to 40% fT> MIC to 100% fT> 6 × MIC. Prolonging the infusion time and frequency were most described strategies to increase target attainment. Monitoring beta-lactam serum concentrations in clinical practice may potentially maximize therapeutic target attainment. Further studies are required to define the therapeutic target associated with the best clinical outcomes.

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Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction

et al. 2021

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Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis

Cited by 8 publications

References 36 publications

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Beta-Lactams Therapeutic Monitoring in Septic Children–What Target Are We Aiming for? A Scoping Review

Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction

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