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A vancomycin steady-state trough concentration (C min ) of 15-20 mg/L is recommended for achieving a ratio of the 24-hour area under the curve to the minimum inhibitory concentration (AUC 0-24 /MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between C min and AUC 0-24 /MIC in paediatric patients. Population-based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between C min and the calculated AUC 0-24 /MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body-weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, C min ranges of 5.0-5.9 and 9.0-12.9 mg/L were associated with AUC 0-24 /MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a C min of 5.0-5.9 mg/L and AUC 0-24 /MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved C min of 9.0-12.9 mg/L and AUC 0-24 /MIC ≥400 in 2.0- and 1.6-fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin C min values of 5.0-12.9 mg/L were strongly predictive of achieving AUC 0-24 /MIC ≥400, and rational dosing regimens of 10-15 mg/kg q6h were required in paediatric patients, depending on the pathogen., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

This study used high-performance liquid chromatography to measure 202 teicoplanin plasma trough concentrations (C min ) in 114 haematological malignancy patients with febrile neutropenia. Patients were divided into two groups according to the mean initial dose (MID) over the first 3 days of treatment: (i) MID = 533.33 mg/day (loading dose group, 400 mg q12h for three doses followed by 400 mg qd, n = 62) and (ii) MID < 533.33 mg/day (unloaded or underloaded group, n = 52). During the first 3 days after treatment, the overall C min was higher in group 1 than in group 2 (10.96 ± 5.44 mg/L versus 6.31 ± 3.73 mg/L, mean ± S.D.; p = 0.002), as was the qualifying rate of C min > 10 mg/L (54.5% versus 11.1%, p = 0.001), and the probability of C min < 5 mg/L was lower in group 1 than in group 2 (13.6% versus 40.7%, p = 0.037). After 3 days, the average C min and qualifying rates did not differ significantly between the two groups, and the average C min was <10 mg/L in both groups. Binary logistic regression analysis revealed that creatinine clearance (p = 0.004) and MID (p = 0.010) could affect C min during the first 3 days of treatment and that age (p = 0.022) only could affect C min after 3 days. In conclusion, it is necessary to apply loading dose to achieve teicoplanin C min > 10 mg/L rapidly and, from a pharmacokinetic/pharmacodynamic perspective, 600 mg is recommended as loading and maintenance dose for these patients when AUC 24 /minimum inhibitory concentration > 345., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)