Clinical audit of gentamicin use by Bayesian pharmacokinetic approach in critically ill children

Sridharan, Kannan; Daylami, Amal Al

doi:10.1016/j.jiac.2020.01.007

Cited by 8 publications

(9 citation statements)

References 27 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%

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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%

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Scoping review of augmented renal clearance in critically ill pediatric patients

2021

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“…Aminoglycosides are also commonly monitored in clinical practice, which is reflected by several studies describing the PK of gentamicin [73][74][75][76] and amikacin [77][78][79]. For gentamicin, higher initial doses and longer dosing intervals have been suggested for neonates and (young) infants in two studies to compensate for an (age-related) increase in Vd and decrease in CL, respectively [74,75].…”

Section: Critical Illness Related Pharmacokinetic Alterations In Children and Infantsmentioning

confidence: 99%

“…Interestingly, even for concentration-dependent antibiotics like gentamicin, ARC has been shown to contribute to subtherapeutic exposure. A recent study demonstrated decreased exposure (AUC 0-24 ) and target attainment for gentamicin in critically ill children with ARC vs. those without ARC [76]. As the bactericidal activity has been reported to correlate well with the AUC of gentamicin in preterm neonates, the authors recommend measuring the AUC of gentamicin in critically ill children with ARC.…”

Section: Subpopulations Of Critically Ill Children and Neonates At Increased Risk Of Pharmacokinetic Alterations 41 Augmented Renal Clearmentioning

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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Is fat‐free mass‐based gentamicin dosing regimen preferable than whole‐body weight in neonates?

Sridharan,

Al Jufairi,

Al Ansari

et al. 2023

Pediatric Investigation

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Importance: Body fluid dynamics and renal maturation status vary during the neonatal period. We hypothesized that differences in peak and trough gentamicin concentrations could be expected. Objective: To predict the peak and trough gentamicin concentrations in critically ill neonates and to predict the changes in the predicted peak plasma concentrations of gentamicin following fat-free mass dosing. Methods: Critically ill neonates that received gentamicin and have gentamicin concentration measured were recruited. Fat mass was estimated using skinfold thicknesses. Changes in the peak plasma concentrations (C max ) using whole-body weight (estimated using the current dosing regimen) and predicted concentrations following the fat-free mass-based dosing were the outcome measures. Results: Eighty-nine critically ill neonates were recruited. Sub-therapeutic C max was estimated using the current dosing regimen in 32.6%, and 22.5% neonates following the first and second doses of gentamicin. Preterm neonates had significantly higher fat mass compared to term neonates. All except one had C max above 12 µg/ml after the first dose and all had after the second gentamicin dose following the predicted fat-free massbased gentamicin dosing. The recommended doses are as follows: extreme preterm: 7.95 mg/kg every 48 h; very preterm: 7.30 mg/kg every 36-48 h; late preterm: 5.90 mg/kg every 36-48 h; and term neonates at 5.10 mg/kg every 24 h. Interpretation: Fat-free mass dosing may be considered for obtaining optimal therapeutic effects in the neonatal population.

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Clinical audit of gentamicin use by Bayesian pharmacokinetic approach in critically ill children

Cited by 8 publications

References 27 publications

Scoping review of augmented renal clearance in critically ill pediatric patients

Scoping review of augmented renal clearance in critically ill pediatric patients

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

Is fat‐free mass‐based gentamicin dosing regimen preferable than whole‐body weight in neonates?

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