Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk

Kato, Hideo; Hagihara, Mao; Okudaira, Masami; Asai, Nobuhiro; Koizumi, Yusuke; Yamagishi, Yuka

doi:10.1016/j.ijantimicag.2021.106393

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…In our review, three of four patients who developed toxicity showed a Cmin above 10 mg/L. Recently, some meta-analyses have been reported in order to establish the evidence of PK/PD [ 40 , 41 ]. There is one meta-analysis regarding the Cmin of amikacin for reducing the risk of toxicity in adults [ 42 ].…”

Section: Discussionmentioning

confidence: 96%

Amikacin Therapy in Japanese Pediatric Patients: Narrative Review

Kato

Hamada

2022

IJERPH

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Children show a very wide range of physical development processes. These changes impact pharmacokinetic (PK) variability in pediatric patients. Most PK studies have been conducted on the Caucasian population. Therefore, whether current evidence of how developmental change affects PK and exposure–response relationships applies to Japanese pediatric patients remains unclear. This narrative review focuses on amikacin therapy in Japanese pediatric patients and shows the relationship between amikacin concentrations and efficacy/toxicity. Ten relevant articles were identified. Of these, nine articles were published in the 1980s. All studies reported a maximum concentration (Cmax) and minimum concentration (Cmin) of amikacin. Overall, articles reporting PK/pharmacodynamic (PD) indices and minimum inhibitory concentration (MIC) of isolated bacteria in Japanese pediatric patients is lacking, whereas all patients recovered from an infection state and showed negative cultures. Five of the included studies reported the association between Cmin and toxicity. The Cmin in three of four patients who developed toxicity was above 10 mg/L. This narrative review shows that further PK study of amikacin in Japanese pediatric patients is necessary. In particular, the pursuit of knowledge of Cmax/MIC ratio is vital. On the other hand, this review demonstrates that the optimal Cmin for Japanese pediatric patients is below 10 mg/L as a candidate concentration. However, it is noted that the number of patients who developed toxicity is very small.

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Section: Discussionmentioning

confidence: 96%

Amikacin Therapy in Japanese Pediatric Patients: Narrative Review

Kato

Hamada

2022

IJERPH

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“…The previous IDSA guidelines published in 2011 recommend that vancomycin trough concentrations are closely related to clinical outcomes in adults and can predict adverse reactions as well as the clinical efficacy of vancomycin ( 3 ). Several studies have shown that vancomycin trough concentration monitoring can improve clinical efficacy and reduce nephrotoxicity in children infected with Gram-positive pathogens, similar to adults ( 6 , 45 – 47 ). Therefore, it is necessary to monitor the serum trough concentrations in children.…”

Section: Discussionmentioning

confidence: 99%

“…Vancomycin is a common cause of serious hepatotoxicity, nephrotoxicity, and ototoxicity and especially occurs in treatment with higher trough concentrations and longer durations of therapy ( 1 , 2 ). According to the previous recommendations of the Infectious Diseases Society of America (IDSA), vancomycin serum trough concentrations ranging from 10 to 20 μg/mL (MIC ≤1 μg/mL) can achieve the target area under the concentration-time curve (AUC)/MIC ratio of >400, which is a suitable target to attain successful clinical efficacy in adults ( 3 – 6 ). Although the latest IDSA guidelines note that the AUC-guided administration strategy based on the Bayesian method may be the best method for individualized vancomycin therapy ( 7 ), it is still necessary and feasible to use the trough concentrations for medication guidance owing to the relative difficulty in calculating and evaluating the AUC 24 for individual patients in many hospitals in developing countries.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis

Cao

Zhang

et al. 2022

Antimicrob Agents Chemother

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To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov , the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021.

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“…The patients was seriously ill, and the proportion of treatment failure and subsequent death in the hospital was 23.6% in present study. However, one systematic review and meta-analysis indicated that vancomycin trough concentrations of 10–15 mg/L was associated with significantly lower mortality in pediatric patients infected with Gram-positive pathogens ( 38 ). This finding seemed to be inspiring, while the high trough concentrations may incur serious adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit

Zhang

Xiong²,

Bai

et al. 2022

Front. Pediatr.

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ObjectiveTo explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity.MethodsThe medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected. Univariate analysis was used to assess the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity. Binary logistic regression was used to analyze the risk factors for vancomycin-related nephrotoxicity. The vancomycin area under the concentration-time curve over 24 h (AUC0–24) threshold was determined by receiver operating characteristic (ROC) curve analysis.ResultsOne hundred and 10 patients were included in this study. Seventy-six patients (69.1%) exhibited clinically effective response, while the rest exhibited clinically ineffective response. There were no significant differences in APACHE II score, steady-state trough concentration, peak concentration or AUC0–24 of vancomycin between the effective and ineffective groups. Among the 110 patients, vancomycin-related nephrotoxicity occurred in 15 patients (13.6%). Multivariate analysis showed that vancomycin treatment duration, trough concentration, and AUC0–24 were risk factors for vancomycin-related nephrotoxicity. The ROC curve indicated that AUC0–24 < 537.18 mg.h/L was a suitable cutoff point for predicting vancomycin-related nephrotoxicity.ConclusionNo significant correlations were found between the trough concentration or AUC0–24 of vancomycin and therapeutic efficacy when the daily dose of vancomycin was approximately 40 mg/kg d, while the trough concentration and AUC0–24 were both closely related to vancomycin-related nephrotoxicity. The combination of AUC0–24 and trough concentration for therapeutic drug monitoring may reduce the risk of nephrotoxicity.

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Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk

Cited by 9 publications

References 18 publications

Amikacin Therapy in Japanese Pediatric Patients: Narrative Review

Amikacin Therapy in Japanese Pediatric Patients: Narrative Review

Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis

Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit

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