Vol.67 No.3 May 2019
Safety analysis of teicoplanin trough concentrations of over 15 μg/mL, and evaluation of the recommended loading dose regimen to rapidly achieve optimal concentrations in pediatric patients
1)Department of Pharmacy, University Hospital Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
2)Department of Pediatrics, University Hospital Kyoto Prefectural University of Medicine
Abstract
Teicoplanin (TEIC) is widely used for the treatment of gram-positive infections in pediatric patients. However, not enough is known about the optimal loading dose regimens and the safety and effectiveness of the target serum trough concentrations of ≥15 μg/mL. The aims of this study were (i) to evaluate the safety of serum TEIC trough concentrations of ≥15 μg/mL, (ii) to evaluate the serum TEIC levels after administration of the loading dose, and (iii) to investigate factors that cause serum TEIC concentrations to fluctuate in pediatric patients.
This retrospective study was conducted between January 2012 and March 2017. A total of 78 pediatric patients between 2 and 15 years of age with at least one serum TEIC concentration measurement were included in this study. The patients were divided by the serum TEIC concentrations into the low trough group (<15 μg/mL; LTG) and high trough group (≥15 μg/mL; HTG).
The incidence of abnormal laboratory values in the LTG vs. HTG were as follows: serum creatinine (Scr; 0% vs. 0%), aspartate aminotransferase (AST; 13.8% vs. 14.3%), alanine aminotransferase (ALT; 20.7% vs. 24.5%), platelet count (PLT; 20.7% vs. 16.3%), white blood cell count (WBC; 27.6% vs. 26.5%), and hematocrit (Hct; 13.8% vs. 6.1%). The incidence of adverse reactions did not differ between the LTG and HTG.
In this study, the recommended TEIC loading dose yielded target serum concentrations of ≥15 μg/mL in 45% of all patients (n=51). In contrast, the target concentration was reached in only 26% of children with hematologic malignancies. Multivariate logistic regression revealed that the factors influencing the likelihood of achievement of the target TEIC levels were age [odds ratio (OR)=1.346; 95% confidence interval (CI): 1.015-1.654; P=0.005] and neutrophil count (OR=1.349; 95% CI: 1.118-1.628; P=0.002).
Our results suggest that it is possible to safely set the target trough concentrations at ≥15 μg/mL in pediatric patients. However, TEIC loading doses of 10 mg/kg were inadequate for rapidly achieving trough concentrations of ≥15 μg/mL. Individualization of regimens taking into consideration the age and pathology (e.g., febrile neutropenia) is required.
Key word
teicoplanin, therapeutic drug monitoring, adverse effect, child
Received
May 11, 2018
Accepted
November 19, 2018
Jpn. J. Chemother. 67 (3): 376-384, 2019
