The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses

Moriyama, Hiromu; Tsutsuura, Moeko; Kojima, Nana; Mizukami, Yukiko; Tashiro, Syoichi; Osa, Sumika; Enoki, Yuki; Taguchi, Kazuaki; Oda, Kazutaka; Fujii, Satoshi; Takahashi, Yoshiko; Hamada, Yukihiro; Kimura, Toshimi; Takesue, Yoshio; Matsumoto, Kazuaki

doi:10.1016/j.jiac.2021.01.015

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…The dosing interval 8 h achieved similar AUC/MIC target as for the dosing interval 6 h. However, the longer time interval reduces the C trough [132]. Meta-analysis performed by Moriyama et al [133] proved that incidence of nephrotoxicity increased in the trough concentration ≥15 mg/L. The concentrations >10 mg/L allowed to attain of AUC values higher than 400 µg•h /mL.…”

Section: The Optimal Dosage Regimenmentioning

confidence: 91%

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

2021

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The review includes studies dated 2011–2021 presenting the newest information on voriconazole (VCZ), mycophenolic acid (MPA), and vancomycin (VAN) therapeutic drug monitoring (TDM) in children. The need of TDM in pediatric patients has been emphasized by providing the information on the differences in the drugs pharmacokinetics. TDM of VCZ should be mandatory for all pediatric patients with invasive fungal infections (IFIs). Wide inter- and intrapatient variability in VCZ pharmacokinetics cause achieving and maintaining therapeutic concentration during therapy challenging in this population. Demonstrated studies showed, in most cases, VCZ plasma concentrations to be subtherapeutic, despite the updated dosages recommendations. Only repeated TDM can predict drug exposure and individualizing dosing in antifungal therapy in children. In children treated with mycophenolate mofetil (MMF), similarly as in adult patients, the role of TDM for MMF active form, MPA, has not been well established and is undergoing continued debate. Studies on the MPA TDM have been carried out in children after renal transplantation, other organ transplantation such as heart, liver, or intestine, in children after hematopoietic stem cell transplantation or cord blood transplantation, and in children with lupus, nephrotic syndrome, Henoch-Schönlein purpura, and other autoimmune diseases. MPA TDM is based on the area under the concentration–time curve; however, the proposed values differ according to the treatment indication, and other approaches such as pharmacodynamic and pharmacogenetic biomarkers have been proposed. VAN is a bactericidal agent that requires TDM to prevent an acute kidney disease. The particular group of patients is the pediatric one. For this group, the general recommendations of the dosing may not be valid due to the change of the elimination rate and volume of distribution between the subjects. The other factor is the variability among patients that concerns the free fraction of the drug. It may be caused by both the patients’ population and sample preconditioning. Although VCZ, MMF, and VAN have been applied in pediatric patients for many years, there are still few issues to be solve regarding TDM of these drugs to ensure safe and effective treatment. Except for pharmacokinetic approach, pharmacodynamics and pharmacogenetics have been more often proposed for TDM.

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Section: The Optimal Dosage Regimenmentioning

confidence: 91%

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

2021

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“…The guidelines committee members, Moriyama et al, conducted a systematic review and meta-analysis to investigate optimal trough-guided monitoring of vancomycin in children. They found that the treatment failure for MRSA infection in pediatric patients was significantly lower with vancomycin trough ≥10 µg/mL, but that nephrotoxicity was higher in patients with vancomycin trough ≥15 µg/mL 13 ; therefore, the guidelines in Japan recommend vancomycin trough within 10–15 µg/mL for pediatric patients with MRSA infection. For initial vancomycin dosing in children, the guidelines suggest age-based dosing (Table 1).…”

Section: Clinical Aspects Of the Application Of Pediatric Pk/pd Infor...mentioning

confidence: 99%

“…11 Before the last revision, the guidelines committee members conducted thorough systematic reviews and meta-analyses, or single/multiple center PK studies, to establish evidence to cite in the guidelines. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] These guidelines included the antimicrobials which TDM is commonly performed in Japan, described previously.…”

Section: Antimicrobials Tdm Guidelines In Japanmentioning

confidence: 99%

Current Aspects of Pediatric Pharmacokinetics and Pharmacodynamics of Antimicrobials in Japan: Importance of the Promotion of Population PK/PD Analysis

Shoji¹,

Saito²,

Nakamura

et al. 2022

Pediatric Infectious Disease Journal

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Pharmacologic knowledge is important for pediatricians conducting feasible pharmacokinetic or pharmacodynamic (PK/PD) studies or applying effective antimicrobial therapies in children. Because of the difficulties in conducting PK/PD studies in children, antimicrobial PK/PD data in children are still limited. To fill in the lack of knowledge, promotion of population PK/PD analysis, which allows us to handle sparse sampling data from individual patients, is important because it is considered a suitable methodology to conduct PK/PD studies in children with limited blood drug concentration data for PK/PD analysis. Population PK/PD analysis is also useful in the clinical setting to provide individualized optimal dosage for each patient with various conditions. Here we summarized the current aspects of pediatric PK/PD studies of antimicrobials in Japan from clinical and research perspectives, specifically focusing on the importance of population PK/PD analysis.

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“…7 A recent systematic review and meta-analysis recommended 10–15 mcg/mL as the target vancomycin trough levels in pediatric patients. 8…”

Section: Introductionmentioning

confidence: 99%

“…7 A recent systematic review and meta-analysis recommended 10-15 mcg/mL as the target vancomycin trough levels in pediatric patients. 8 Elevated vasopermeability along with inflammation in febrile neutropenia results in increased distribution of watersoluble drugs. Furthermore, this condition augments cardiac output with a subsequent increase in renal blood flow, which leads to augmented renal clearance (ARC), a phenomenon associated with increased renal drug excretion.…”

Section: Introductionmentioning

confidence: 99%

Association of Vancomycin Trough Concentration and Clearance With Febrile Neutropenia in Pediatric Patients

Amano

Tanaka

Ono

et al. 2022

Therapeutic Drug Monitoring

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Background: Febrile neutropenia promotes renal drug excretion. Adult and pediatric patients with febrile neutropenia exhibit a lower vancomycin concentration/dose (relative to bodyweight) ratio than those with other infections. In pediatric patients, renal function relative to bodyweight varies depending on age, and vancomycin clearance is age dependent. This study aimed to analyze the effects of febrile neutropenia on the pharmacokinetics of vancomycin in age-stratified pediatric patients. Methods: This retrospective, single-center, observational cohort study analyzed 112 hospitalized pediatric patients who met the selection criteria and intravenously received vancomycin at the Department of Pediatrics of the Oita University Hospital between April 2011 and October 2019. Results: The febrile neutropenia (n = 46) cohort exhibited a significantly higher estimated glomerular filtration rate than the nonfebrile neutropenia (n = 66) cohort. Compared with those in the nonfebrile neutropenia cohort, the daily vancomycin dose relative to bodyweight and vancomycin clearance were significantly higher, and the vancomycin trough concentration and vancomycin concentration/dose ratio were significantly lower in the febrile neutropenia cohort. In the age groups of 1–6 and 7–12 years, compared with those in the nonfebrile neutropenia cohort, the vancomycin concentration/dose ratio was significantly lower, and vancomycin clearance was significantly higher in the febrile neutropenia cohort. Univariate and multivariate analyses identified febrile neutropenia as the independent factor influencing vancomycin concentration/dose ratio and clearance only in pediatric patients aged 1–6 years. Conclusions: Increased initial dosage and therapeutic drug monitoring-guided dose optimization are critical for the therapeutic efficacy of vancomycin in pediatric patients with febrile neutropenia, especially in those aged 1–6 years.

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The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses

Cited by 5 publications

References 15 publications

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

Current Aspects of Pediatric Pharmacokinetics and Pharmacodynamics of Antimicrobials in Japan: Importance of the Promotion of Population PK/PD Analysis

Association of Vancomycin Trough Concentration and Clearance With Febrile Neutropenia in Pediatric Patients

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