Background: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015.Methods: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System.Results: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions.Conclusions: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

Objective Because pharmacokinetic data are limited, continuous infusions of vancomycin in neonates are administered using different dosing regimens. The aim of this work was to evaluate the results of vancomycin therapeutic drug monitoring (TDM) under three different dosing regimens and to optimise vancomycin therapy. Methods Vancomycin TDM concentrations were noted and compared prospectively in three hospitals. Population pharmacokinetic analysis was performed to optimise dosing using NONMEM software. Patient-tailored optimised dosing regimens were evaluated in a prospective study. Results Two hundred and seven serum vancomycin concentrations from 116 neonates were analysed. Only 48 neonates (41%) had serum vancomycin concentrations within the therapeutic range of 15–25 mg/l using a current dosing regimen. Concentrations ranged from 5.1 to 61.5 mg/l. Loading doses were required to decrease the risk of sub-therapeutic levels during early treatment. An optimised dosing regimen, taking into account birth weight, current weight, postnatal age and serum creatinine, was developed based on a one-compartment pharmacokinetic model. A prospective validation study in 58 neonates demonstrated a higher percentage of neonates (70.7%, n=41) reaching the therapeutic range and early dosage adaptation (6–12 h post-dose) using an optimised dosing regimen. Conclusions A patient-tailored optimised dosing regimen should be used routinely to individualise vancomycin continuous infusion therapy in neonates.

Aims: Vancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study‐related factors influencing the transferability of pharmacokinetic models to different clinical settings.Method: Published neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of six models was evaluated using an independent dataset (112 concentrations from 78 neonates). The evaluation procedures used simulation‐based diagnostics [visual predictive check (VPC) and normalized prediction distribution errors (NPDE)].Results: Differences in predictive performances of models for vancomycin pharmacokinetics in neonates were found. The mean of NPDE for six evaluated models were 1.35, −0.22, −0.36, 0.24, 0.66 and 0.48, respectively. These differences were explained, at least partly, by taking into account the method used to measure serum creatinine concentrations. The adult conversion factor of 1.3 (enzymatic to Jaffé) was tested with an improvement in the VPC and NPDE, but it still needs to be evaluated and validated in neonates. Differences were also identified between analytical methods for vancomycin.Conclusion: The importance of analytical techniques for serum creatinine concentrations and vancomycin as predictors of vancomycin concentrations in neonates have been confirmed. Dosage individualization of vancomycin in neonates should consider not only patients' characteristics and clinical conditions, but also the methods used to measure serum creatinine and vancomycin.