Pharmacokinetics of cefazolin delivery via the cardiopulmonary bypass circuit priming solution in infants and children

Cies, Jeffrey J.; Moore, Wayne; Parker, Jason; Stevens, Randy; Al-Qaqaa, Yasir; Enache, Adela

doi:10.1093/jac/dky574

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…Previous paediatric PK cefazolin studies have focused on prophylactic use or were performed in neonates. Not surprisingly, we founddas was previously shown in prophylactic usedthat BW and eGFR were the main covariates [4,22,23]. In neonates, BW and PNA were the significant covariates; estimated CL and V were slightly different but our population differed in age (children without neonates) and in illness (curative use) [24,25].…”

Section: Discussionsupporting

confidence: 48%

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

Salvador

Oualha

Bille

et al. 2021

Clinical Microbiology and Infection

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Objectives: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. Methods: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 Â MIC . Results: Thirty-nine patients with a median (range) age of 7 (0.1e17) years and a BW of 21 (2.8e79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m 2 were the best schemes to reach the PK target of 100% fT > 4 Â MIC . Conclusions: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 Â MIC in children with normal and augmented renal function.

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Section: Discussionsupporting

confidence: 48%

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

Salvador

Oualha

Bille

et al. 2021

Clinical Microbiology and Infection

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“…One article [18] was included from the references of included articles and/or reviews regarding the subject. Additionally, two articles that did not come up during the systematic review and were not mention in references of reviews were added after the peer-review process [19,20]. Data-extraction was performed for 50 full-text articles with data on the PK of antibiotics in critically ill children.…”

Section: Resultsmentioning

confidence: 99%

“…Three cefazolin studies were included in our review, all conducted before, during or after cardiopulmonary bypass (CPB) [19,20,31]. One study included only patients under 10 kg bodyweight and up to 2.6 years of age [31] while the other 2 studies basically covered the whole pediatric age range from birth to 16 years old [19,20]. Used cefazolin doses varied between the 3 studies with de Cock et al and Cies et al both using 25 mg/kg/dose preoperatively and during CPB and Haessler et al using 40 mg/kg preoperatively and 105 mg/kg/day in 3 doses in the days after surgery.…”

Section: Cefazolinmentioning

confidence: 99%

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Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

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Background Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults. Methods Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life. Results 50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles. Conclusion The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.

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“…Therefore, a reduced dose of 2 mg/kg, with a second dose after 4 h if surgery is not yet completed, and no postoperative dose, is recommended Cies et al 2019 [154] Cefazolin…”

Section: Cies Et Al 2016 [139] Meropenemmentioning

confidence: 99%

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

et al. 2021

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Children show important developmental and maturational changes, which may contribute greatly to pharmacokinetic (PK) variability observed in pediatric patients. These PK alterations are further enhanced by disease-related, non-maturational factors. Specific to the intensive care setting, such factors include critical illness, inflammatory status, augmented renal clearance (ARC), as well as therapeutic interventions (e.g., extracorporeal organ support systems or whole-body hypothermia [WBH]). This narrative review illustrates the relevance of both maturational and non-maturational changes in absorption, distribution, metabolism, and excretion (ADME) applied to antibiotics. It hereby provides a focused assessment of the available literature on the impact of critical illness—in general, and in specific subpopulations (ARC, extracorporeal organ support systems, WBH)—on PK and potential underexposure in children and neonates. Overall, literature discussing antibiotic PK alterations in pediatric intensive care is scarce. Most studies describe antibiotics commonly monitored in clinical practice such as vancomycin and aminoglycosides. Because of the large PK variability, therapeutic drug monitoring, further extended to other antibiotics, and integration of model-informed precision dosing in clinical practice are suggested to optimise antibiotic dose and exposure in each newborn, infant, or child during intensive care.

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Pharmacokinetics of cefazolin delivery via the cardiopulmonary bypass circuit priming solution in infants and children

Cited by 11 publications

References 25 publications

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

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