Vancomycin Dosing in Children and Young Adults: Back to the Drawing Board

Camaione, Lauren; Elliott, Kimberly Ann; Steele, Amy Mitchell-Van; Lomaestro, Ben M.; Pai, Manjunath P.

doi:10.1002/phar.1345

Cited by 25 publications

(14 citation statements)

References 19 publications

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“…In contrast, most pediatric studies reported no clinically significant differences in the PK parameters between obese and nonobese children . Based on Bayesian PK analysis, Vd is strongly correlated with TBW and Cl, with ALW and BSA …”

Section: Methodsmentioning

confidence: 93%

“…Vancomycin is perhaps the most studied antimicrobial agent in obese children and adults . PK studies suggest a strong correlation between Vd and Cl with TBW in obese adults .…”

Section: Methodsmentioning

confidence: 99%

“…Based on a Monte Carlo simulation, dosing the maintenance regimen of 60 mg/kg/day by TBW, as compared with other weight measures, resulted in the highest achievement of an AUC:MIC ratio of 400 or higher in obese children . One study recommended future evaluations of BSA‐based vancomycin dosing that necessitates establishing a different dosing regimen . Current literature supports dosing obese children at 60 mg/kg/day by TBW to provide the highest achievement of pharmacodynamic targets.…”

Section: Methodsmentioning

confidence: 99%

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Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

et al. 2017

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Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.

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Section: Methodsmentioning

confidence: 93%

“…Vancomycin is perhaps the most studied antimicrobial agent in obese children and adults . PK studies suggest a strong correlation between Vd and Cl with TBW in obese adults .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing

et al. 2017

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“…Clearance was best described using TBW to the power of 0.75, also known as allometric weight (37). In another analysis of 115 children and adolescents over a wide spectrum of body sizes, Camaione and colleagues (38) speculated that defining a desired target range for area‐under‐the‐concentration‐time curve (AUC) might be worth exploring as an alternative to target drug concentrations (i.e., peak and trough). They also proposed body surface area as an alternative to body weight.…”

Section: Findings and Discussion By Therapeutic Categorymentioning

confidence: 99%

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Ameer

Weintraub

2020

Obesity

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Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight‐based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.

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“…The fourth article by Dr. Lauren Camaione and colleagues evaluated vancomycin dosing and pharmacokinetics in 115 children and young adults who each had 2–9 serum concentration measurements . These investigators employed a previously described one‐compartment pharmacokinetic model to derive individual maximum a posteriori probability (MAP)‐Bayesian pharmacokinetic parameter estimates and to evaluate covariate relationships of body size descriptors (weight, height, and body surface area [BSA]).…”

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confidence: 99%