Vancomycin Monitoring in Children Using Bayesian Estimation

Lê, Jennifer; Ngu, Becky; Bradley, John S.; Murray, William S.; Nguyen, Austin Huy; Nguyen, Lyn; Romanowski, Gale L.; Vo, Tiana; Capparelli, Edmund V.

doi:10.1097/ftd.0000000000000039

Cited by 36 publications

(22 citation statements)

References 28 publications

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“…In addition, using these studies, Bayesian pharmacokinetic models may be developed to estimate individual pharmacokinetic parameters using only a few concentration values [118]. Bayesian models for TDM have been developed for immunosuppressant [119,120], anticancer [121], and antimicrobial [122,123] drugs. However, the benefit of anti-TNF-a biopharmaceutical TDM has not been fully established yet.…”

Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis

et al. 2015

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Monoclonal antibodies (mAbs) are increasingly used to treat rheumatoid arthritis (RA). At present, anti-tumor necrosis factor-α drugs (infliximab, adalimumab, certolizumab pegol, and golimumab), rituximab, and tocilizumab are approved for RA treatment. This review focuses on the pharmacokinetics and pharmacodynamics of mAbs approved in RA. Being large proteins, mAbs exhibit complex pharmacokinetic and pharmacodynamic properties. In particular, owing to the interactions of mAbs with their antigenic targets, the pharmacokinetics of mAbs depends on target turnover and exhibits non-specific (linear) and target-mediated (often nonlinear) clearances. Their volume of distribution is low (3-4 L) and their elimination half-life usually ranges from 2 to 3 weeks. The inter-individual pharmacokinetic variability of mAbs is usually large and is partly explained by differences in antigenic burden or by anti-drug antibodies, which accelerate mAb elimination. The inter-individual variability of clinical response is large and influenced by the pharmacokinetics. The analysis of mAbs concentration-effect relationship relies more and more often on pharmacokinetic-pharmacodynamic modeling; these models being suitable for dosing optimization. Even if adverse effects of mAbs used in RA are well known, the relationship between mAb concentration and adverse effects is poorly documented, especially for anti-tumor necrosis factor-α mAbs. Overall, RA patients treated with mAbs should benefit from individualized dosing strategies. Because of the complexity of their pharmacokinetics and mechanisms of action, the current dosing strategy of mAbs is not based on sound knowledge. New studies are needed to assess individual dosing regimen, adjusted notably to disease activity.

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Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis

et al. 2015

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“…17,18 Optimal strategies for monitoring vancomycin in children remain controversial. 19 Vancomycin has traditionally been viewed as a nephrotoxic agent, and recent reviews are available discussing potential explanations for the physiologic basis of vancomycin-associated nephrotoxicity, including continued presence of fermentation by-products, direct oxidative stress, or allergic interstitial nephritis. 12,20 Adult patients experiencing initial vancomycin serum trough concentrations ≥15 mg/L or receiving therapy durations ≥7 days may be at higher AKI risk.…”

Section: Discussionmentioning

confidence: 99%

Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy

et al. 2015

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Abstract:Background: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥8 days of vancomycin therapy.Methods: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy and within 48 hours following vancomycin discontinuation. The primary outcome was incidence of late AKI as determined by modified pRIFLE criteria. Results: One-hundred sixty-seven patients were included, with a median (interquartile range) age (years) and weight (kg) of 2 (1-7) and 12.5 (8.9-23.8). Late AKI was identified in 12.6% (21/167). A higher percentage of late AKI patients received concomitant treatment with intravenous acyclovir, amphotericin products, or piperacillin-tazobactam. Age <1 year was the only factor independently associated with late AKI development (odds ratio = 4.4; 95% confidence interval = 1.3-15.4). Conclusions: Late AKI occurred in nearly 13% of children receiving ≥8 days of vancomycin therapy. This study suggests that vancomycin trough concentrations are not associated with late AKI, but that age <1 year and concomitant administration of certain nephrotoxins may be factors associated with increased risk.

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“…In our study, more than 80% of our study population was less than 24 months old and no very appropriate model for calculating AUC was available in this age group; estimation of an AUC using vancomycin clearance and creatinine clearance based on the model developed by Frymoyer et al (16), was originally developed to predict vancomycin AUC 24 /MIC in children aged 2 to 12 years. Although a Bayesian model employing the serum creatinine value and one set of trough and peak vancomycin concentrations has been developed to estimate a PK model for vancomycin in young children (1718), our study was conducted retrospectively and the standard of care in our institute involves checking only trough levels during vancomycin therapy.…”

Section: Discussionmentioning

confidence: 99%

Impact of Initial Vancomycin Trough Concentration on Clinical and Microbiological Outcomes of Methicillin-ResistantStaphylococcus aureusBacteremia in Children

2017

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It is important to use vancomycin in a proper manner to ensure optimal drug exposure. Despite extensive use of vancomycin in children, studies on its optimal trough concentration (Ctrough) in the pediatric population remained rare. This retrospective study included children < 18 years old with culture-confirmed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who were hospitalized in our institute from January 2010 to April 2014. Clinical characteristics, initial vancomycin dose, Ctrough and clinical/microbiological outcomes were retrospectively collected from medical records. Forty-six MRSA bacteremia cases occurring to the patients with a mean age of 22.0 ± 46.9 months were included and all of them were healthcare-associated. Severe diseases requiring intensive care unit (ICU) stay, mechanical ventilation and/or resulting in death were observed in 57.8% (26/45); all-cause 30-day fatality was 11.1% (5/45). An initial Ctrough ≥ 15 μg/mL was achieved in only 4 (8.7%) cases with an average vancomycin dosage of 40.6 ± 7.9 mg/kg/day. Persistent bacteremia at 48 hours after initiation of vancomycin was observed more frequently in children with initial Ctrough < 10 μg/mL than in those with Ctrough ≥ 10 μg/mL (P = 0.032). However, there was no statistically significant difference between the two groups in terms of 30-day mortality and recurrent bacteremia (P = 0.899, and P = 0.754, respectively). Although initial Ctrough may be a useful parameter for minimizing early microbiological failure, it does not predict 30-day fatality or recurrence in pediatric MRSA bacteremia. Further prospective data on vancomycin dosing are needed to find the optimal drug exposure and clarify its impact on clinical outcomes in pediatric populations.

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Vancomycin Monitoring in Children Using Bayesian Estimation

Cited by 36 publications

References 28 publications

Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis

Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis

Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy

Impact of Initial Vancomycin Trough Concentration on Clinical and Microbiological Outcomes of Methicillin-ResistantStaphylococcus aureusBacteremia in Children

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