Factors Impacting Unbound Vancomycin Concentrations in Different Patient Populations

Oyaert, Matthijs; Spriet, Isabel; Allegaert, Karel; Smits, Anne; Vanstraelen, Kim; Peersman, Nele; Wauters, Joost; Verhaegen, Jan; Vermeersch, Pieter; Pauwels, Steven

doi:10.1128/aac.01185-15

Cited by 38 publications

(40 citation statements)

References 27 publications

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“…However, it is difficult to make a simple comparison with these studies, and in addition, the aforementioned studies were conducted on adults. It is known that the protein binding faction of vancomycin is significantly lower in children than in adults [ 18 , 19 ]. Therefore, the possibility that vancomycin clearance by CVVHDF may be affected by the difference in the pharmacokinetic characteristics of vancomycin in these children compared with adults should be considered carefully.…”

Section: Discussionmentioning

confidence: 99%

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Factors affecting serum concentration of vancomycin in critically ill oliguric pediatric patients receiving continuous venovenous hemodiafiltration

et al. 2018

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Vancomycin is known to be unintentionally eliminated by continuous renal replacement therapy, and the protein bound fraction of vancomycin is also known to be different in adults and children. However, there are only a few studies investigating the relationship between the dose of continuous venovenous hemodiafiltration (CVVHDF) parameters and serum concentration of vancomycin in pediatric patients. The aim of this study was to determine clinical and demographic parameters that significantly affect serum vancomycin concentrations. This retrospective cohort study was conducted at a pediatric intensive care unit in a tertiary university children’s hospital. Data from oliguric patients who underwent CVVHDF and vancomycin therapeutic drug monitoring were collected. The correlation between factors affecting serum concentration of vancomycin was analyzed using mixed effect model. A total of 177 serum samples undergoing vancomycin therapeutic drug monitoring were analyzed. The median age of study participants was 2.23 (interquartile range, 0.3–11.84) years, and 126 (71.19%) were male patients. Serum concentration of vancomycin decreased significantly as the effluent flow rate (EFR; P < 0.001), dialysate flow rate (DFR; P = 0.009), replacement fluid flow rate (RFFR; P = 0.008), the proportion of RFFR in the sum of DFR and RFFR (P = 0.025), and residual urine output increased. The adjusted R2 of the multivariate regression model was 0.874 (P < 0.001) and the equation was as follows: Vancomycin trough level (mg/L) = (0.283 × daily dose of vancomycin [mg/kg/d]) + (365.139 / EFR [mL/h/kg])–(15.842 × residual urine output [mL/h/kg]). This study demonstrated that the serum concentration of vancomycin was associated with EFR, DFR, RFFR, the proportion of RFFR, and residual urine output in oliguric pediatric patients receiving CVVHDF.

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Section: Discussionmentioning

confidence: 99%

“…Regardless, all of these studies were conducted in adults. Since the protein bound fraction of vancomycin has been reported to be lower in children than in adults [ 18 , 19 ], there is a limit to applying the results from adult studies directly to children.…”

Section: Introductionmentioning

confidence: 99%

Factors affecting serum concentration of vancomycin in critically ill oliguric pediatric patients receiving continuous venovenous hemodiafiltration

et al. 2018

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“…The unbound concentration of vancomycin is pharmacologically active and influenced by the free fraction level of vancomycin, which shows large variability among patients. 31,47 A potential cause of the variability is changes in binding protein levels due to the disease and age of patients. The concentration of albumin, to which vancomycin predominantly binds, was influenced by inflammation and renal disease.…”

mentioning

confidence: 99%

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Emoto

Johnson

McPhail

et al. 2018

CPT Pharmacom & Syst Pharma

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Simultaneous changes in several physiological factors may contribute to the large pharmacokinetic (PK) variability of vancomycin. This study was designed to systematically characterize the effects of multiple physiological factors to the altered PK of vancomycin observed in special populations. A vancomycin physiologically based pharmacokinetic (PBPK) model was developed as a PK simulation platform to quantitatively assess the effects of changes in physiologies to the PK profiles. The developed model predicted the concentration‐time profiles in healthy adults and diseased patients. The implementation of developmental changes in both renal and non‐renal elimination pathways to the pediatric model improved the predictability of vancomycin clearance. Simulated PK profiles with a 50% decrease in cardiac output (peak plasma concentration (Cmax), 59.9 ng/mL) were similar to those observed in patients before bypass surgery (Cmax, 55.1 ng/mL). The PBPK modeling of vancomycin demonstrated its potential to provide mechanistic insights into the altered disposition observed in patients who have changes in multiple physiological factors.

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“…For example, vancomycin demonstrates partial binding to albumin, with a reported range of 30% to 60% in adults. Compared with adults, the decrease in albumin binding evident in pediatric patients results in a significant increase in the unbound vancomycin fraction, to approximately 80% . In addition, a recent study showed that the Vd of clindamycin in children who are non‐obese and children who are obese was proportional to concentrations of alpha‐1‐acid glycoprotein and albumin because it binds highly to both proteins …”

Section: Pharmacokinetics: Alterations Stemming From Growth and Develmentioning

confidence: 99%

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

Lê

Bradley

2018

The Journal of Clinical Pharma

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The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.

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Factors Impacting Unbound Vancomycin Concentrations in Different Patient Populations

Cited by 38 publications

References 27 publications

Factors affecting serum concentration of vancomycin in critically ill oliguric pediatric patients receiving continuous venovenous hemodiafiltration

Factors affecting serum concentration of vancomycin in critically ill oliguric pediatric patients receiving continuous venovenous hemodiafiltration

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

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