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

Salvador, E.; Oualha, Mehdi; Bille, Emmanuelle; Béranger, Agathe; Moulin, F.; Benaboud, Sihem; Boujaafar, Sana; Gana, Inès; Urien, Saı̈k; Zheng, Yi; Toubiana, Julie; Briand, C.; Bustarret, Olivier; Geslain, Guillaume; Renolleau, Sylvain; Tréluyer, Jean Marc; Hirt, Déborah

doi:10.1016/j.cmi.2020.04.022

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…Review of titles and abstracts led to the retrieval of 215 potentially relevant full‐text citations. After full‐text review, 25 citations met the criteria for inclusion 16–41 . The most common reason for exclusion was non‐pediatric population studies (190 citations), followed by lack of ARC data (24 citations).…”

Section: Resultsmentioning

confidence: 99%

“…Table 1 summarizes the characteristics of the studies included based upon their primary objective 16–41 . The first articles related to ARC in pediatrics were published in 2015 and were pharmacokinetic objective studies 20,36 .…”

Section: Resultsmentioning

confidence: 99%

“…In 2019, the first articles were published that evaluated general information related to ARC in pediatric patients 16,28,34 . Most of the published work (84%) has described the impact of ARC on pharmacokinetic/pharmacodynamic alterations in antimicrobial agents 18–22,24–27,29–33,35–41 . The 25 citations, representing a total of 2102 patients, were published across 22 different journals, with only two journals having more than one published article related to ARC: Pediatric Nephrology and Antimicrobial Agents and Chemotherapy .…”

Section: Resultsmentioning

confidence: 99%

“…Table 4 summarizes the 21 studies that evaluated the impact of ARC on pharmacokinetic and pharmacodynamic parameters 18–22,24–27,29–33,35–41 (see Table for full extraction of pharmacokinetic and pharmacodynamic data). Most of the studies evaluated glycopeptides (42.9%), 22,24,25,30,32,33,36,37,41 followed by aminoglycosides (19%), 21,31,38,40 penicillins (14.3%), 18–20 and carbapenems (9.5%) 27,39 .…”

Section: Resultsmentioning

confidence: 99%

“…Most of the studies evaluated glycopeptides (42.9%), 22,24,25,30,32,33,36,37,41 followed by aminoglycosides (19%), 21,31,38,40 penicillins (14.3%), 18–20 and carbapenems (9.5%) 27,39 . Cefazolin, 29 colistin, 26 and acyclovir/valacyclovir 35 were evaluated individually in three other publications. The most common pharmacokinetic parameters reported were drug clearance ( n = 10), minimum or trough concentration ( n = 8), volume of distribution ( n = 6), and area under the curve ( n = 5).…”

Section: Resultsmentioning

confidence: 99%

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Scoping review of augmented renal clearance in critically ill pediatric patients

2021

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Augmented renal clearance (ARC), a phenomenon of enhanced elimination of renal solutes, has been described in adult critically ill patients, but little is known about the phenomenon in children. The aim of this scoping review was to gather and summarize all evidence on ARC in pediatric patients to examine its breadth and depth including prevalence, risk factors, and pharmacokinetic alterations and identify any gaps for further areas of inquiry. PubMed, Embase, and Web of Science were searched for titles, abstracts, or keywords that focused on ARC. Non‐English studies, reviews, and nonhuman studies were excluded. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews (PRISMA‐ScR) guidelines. Data were extracted on article type, study details, patient population, ARC definition and prevalence, methods of renal function assessment, and study results. A total of 215 citations were found with 25 citations meeting the criteria for inclusion in pediatrics (2102 total patients); the majority of studies (84%) focused on pharmacokinetics (PK) of antimicrobial agents. The median/mean age range was 1.25–12 years. There were a total of 10 different definitions of ARC. The prevalence of ARC ranged from 7.8% to 78%. The most common method for documenting creatinine clearance (CrCl) was the modified Schwartz equation (64%). Only 20% of studies reported risk factors for ARC including low serum creatinine, increasing age, febrile neutropenia, male, septic shock, and treatment with antibiotics. Glycopeptide antimicrobials were the most evaluated class (42.9%) among the 21 antimicrobial drug studies. All studies reported increased drug clearance and/or poor probability of achieving target concentrations of the agents studied. ARC showed variable prevalence in pediatric patients likely due to the lack of a standard definition and many studies not considering age‐related changes in CrCl with pediatric intensive care unit (PICU) patients. ARC was shown to impact PK of antibiotics commonly administered to pediatric patients, which may necessitate changes in standard dosing regimens.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Scoping review of augmented renal clearance in critically ill pediatric patients

2021

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International consensus recommendations for the use of prolonged‐infusion beta‐lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists

Hong,

Downes,

FakhriRavari

et al. 2023

Pharmacotherapy

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Intravenous β‐lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β‐lactams are well established to display time‐dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β‐lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β‐lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug‐monitoring considerations, and the use of PI β‐lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β‐lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

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Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

Gebreyesus,

Dresner,

Wiesner

et al. 2024

CPT Pharmacom & Syst Pharma

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Cefazolin is an antibiotic used to prevent surgical site infections. During cardiac surgery with cardiopulmonary bypass (CPB), its efficacy target could be underachieved. We aimed to develop a population pharmacokinetic model for cefazolin in children and optimize the prophylactic dosing regimen. Children under 25 kg undergoing cardiac surgery with CPB and receiving cefazolin at standard doses (50 mg/kg IV every 4–6 h) were included in this analysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) for efficacy and toxicity with the standard regimen and an alternative regimen of continuous infusion, where loading and maintenance doses were calculated from model‐derived individual parameters. Twenty‐two patients were included, with median (range) age, body weight, and eGFR of 19.5 (1–94) months, 8.7 (2–21) kg, and 116 (48–159) mL/min, respectively. Six patients received an additional dose in the CPB circuit. A two‐compartment disposition model with an additional compartment for the CPB was developed, including weight‐based allometric scaling and eGFR. For a 10 kg patient with eGFR of 120 mL/min/1.73 m2, clearance was estimated as 0.856 L/h. Simulations indicated that the standard dosing regimen fell short of achieving the efficacy target >40% of the time within a dosing duration and in patients with good renal function, PTA ranged from <20% to 70% for the smallest to the largest patients, respectively, at high MICs. In contrast, the alternative regimen consistently maintained target concentrations throughout the procedure for all patients while using a lower overall dose.

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

Cited by 12 publications

References 30 publications

Scoping review of augmented renal clearance in critically ill pediatric patients

Scoping review of augmented renal clearance in critically ill pediatric patients

Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

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