P103 Target attainment of amikacin therapy in critically ill children

• Published in: Archives of disease in childhood Vol. 104; no. 6; pp. e60 - e61
• Main Authors: Verbruggen, J, Jakipbayeva, K, Van Der Heggen, T, Dhont, E, Dhondt, L, Vande Walle, J, De Paepe, P, Herck, I, De Cock, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2019
• Subjects: Amikacin; Children; Correlation; Correlation coefficient; Dosage; Epidermal growth factor receptors; Intravenous administration; Minimum inhibitory concentration; Pathogens; Patients; Pediatrics; Pharmacokinetics; Toxicity
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2019-esdppp.141

BackgroundResearch regarding the optimal amikacin (AMI) dosing regimen in critically ill children is scarce.1 Optimal AMI efficacy has been observed with plasma peak over minimal inhibitory concentration of the suspected pathogen (peak/MIC) ratios of 8 to 10. Plasma trough levels (Cmin) >5mcg/ml are related to its toxicity.The objectives of this pilot study were to: (1) evaluate target attainment rate and occurrence of supratherapeutic concentrations in early and assumed steady-state dose conditions, and (2) investigate the correlation between AMI clearance and estimated glomerular filtration (eGFR).MethodsChildren admitted to the ICU receiving intravenous AMI (20 mg/kg once daily) were included. Serial blood samples were obtained from early (1st/2nd) and assumed steady-state (SS) doses. The evaluated target peak concentration range was 54–64 mcg/ml, assuming a Pseudomonas aeruginosa infection with Eucast MIC breakpoint of 8 mg/L, and a Cmin threshold of 5 mcg/L. eGFR was estimated using the modified Schwartz formula. AMI clearance was calculated using noncompartmental PK analysis. Correlation was assessed by means of a scatter plot and Pearson Correlation Coefficient (r).ResultsTwenty-one patients (median age1,5 years; range:0,5 months-14 year, median eGFR 162 ml/min/1,73m2 (range:107–475 ml/min/1,73m2) were included. In early dose conditions, 69% of patients had therapeutic peak concentrations (median: 60 mcg/ml; range:26–73 mcg/ml). In SS conditions, 60% of patients had therapeutic peak concentrations (median: 59 mcg/ml; range:35–83 mcg/ml). Only one supratherapeutic Cmin was observed. AMI clearance (median 0.08L/h/kg; range: 0.05–0.91 L/h/kg) was comparable to what has been previously reported but showed no correlation with eGFR (r=0.1; p=0,66) [1].ConclusionThis pilot study suggest that the current AMI dosing regimen may lead to subtherapeutic concentrations in patients infected with less susceptible pathogens. Supratherapeutic Cmin were far less of a concern. Dose adjustments of renally cleared drugs based on eGFR may not be reliable in this patient population.ReferencesIllamola SM, Sherwin CM, van Hasselt JGC. Clinical Pharmacokinetics of Amikacin in Pediatric Patients: A Comprehensive review of Population Pharmacokinetic Analysis. Clin Pharmacokinet ( 2018) 57:1217.Disclosure(s)Nothing to disclose