Comparison of Vancomycin Trough-Based and 24-Hour Area Under the Curve Over Minimum Inhibitory Concentration (AUC/MIC)-Based Therapeutic Drug Monitoring in Pediatric Patients.

OBJECTIVES: Vancomycin 24-hour area under the curve over minimum inhibitory concentration (AUC/MIC) monitoring has been recommended over trough-based monitoring in pediatric patients. This study compared the proportion of target attainment between vancomycin AUC/MIC and trough-based methods, and identified risk factors for subtherapeutic initial extrapolated targets. METHODS: This was a retrospective, observational study conducted at KK Women's and Children's Hospital (KKH), Singapore. Patients aged 1 month to 18 years with stable renal function who received intravenous vancomycin between January 2014 and October 2017, with at least 2 vancomycin serum concentrations obtained after the first dose of vancomycin, were included. Using a pharmacokinetic software, namely Adult and Pediatric Kinetics (APK), initial extrapolated steady-state troughs and 24-hour AUC were determined by using a one-compartmental model. Statistical tests included Wilcoxon rank sum test, McNemar test, logistic regression, and classification and regression tree (CART) analysis. RESULTS: Of the 82 pediatric patients included, a significantly larger proportion of patients achieved therapeutic targets when the AUC/MIC-based method (24, 29.3%) was used than with the trough-based method (9, 11.0%; p < 0.01). Patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or with age <13 years had an increased risk of obtaining subtherapeutic targets. However, empiric vancomycin doses of 60 mg/kg/day would be sufficient to achieve serum therapeutic targets, using the AUC/MIC-based method. CONCLUSION: The AUC/MIC-based vancomycin monitoring may be preferred because a larger proportion of patients could achieve initial therapeutic targets. Future prospective studies with larger sample size will be required to determine the optimal vancomycin strategy for pediatric patients.

A Retrospective Review of the Efficiency of First-Dose Therapeutic Drug Monitoring of Gentamicin, Amikacin, and Vancomycin in the Pediatric Population.

Therapeutic drug monitoring (TDM) has become standard clinical practice for gentamicin, amikacin, and vancomycin to optimize efficacy and reduce toxicity. TDM after the first dose of antibiotic was adopted in our institution. This study aims to evaluate if target therapeutic drug concentrations could be achieved more rapidly in patients with TDM performed after the first dose of gentamicin, amikacin, or vancomycin compared to TDM at steady state. A single-center retrospective cohort study was conducted at KK Women's and Children's Hospital, Singapore. Patients aged 1 month to 18 years old who received amikacin, gentamicin, or vancomycin between October 2012 to March 2016 and had at least 2 serum drug concentrations done within the same dosing interval were included. The primary objective was to compare the time taken to achieve target serum drug concentrations between first-dose and steady-state TDM. A total of 334 patients on amikacin, 211 patients on gentamicin, and 140 patients on vancomycin were included. Using Kaplan-Meier analysis, the median number of days to optimize therapy was significantly shorter after first-dose TDM was performed for amikacin (first dose, 1.51 [95% confidence interval (CI), 1.44-1.89] days vs steady state, 2.85 [95%CI, 2.50-3.25] days; P < .01] and gentamicin (first dose, 1.66 [95%CI, 1.25-2.08] days vs steady state, 3.54 [95%CI, 2.40-4.75] days; P < .01] but not vancomycin (first dose, 1.34 [95%CI, 1.06-1.52] days vs steady state, 1.42 [95%CI, 1.26-1.59] days; P = .99]. First-dose TDM for gentamicin and amikacin resulted in faster attainment of target serum concentrations but did not for vancomycin. Further validation of its impact on actual clinical outcomes may be required.

Microneedle integrated transdermal patch for fast onset and sustained delivery of lidocaine.

Lidocaine as an analgesic is of particular interest in both acute and chronic pain conditions and is used via injections or transdermal patches. While injections are associated with problems such as patient incompliance, topical administration of lidocaine using patches is less efficient due to variability of drug absorption among individuals, slower drug permeation through the skin, and hence a resultant undesirable delay in analgesic effects. To address this clinical problem, we developed a microneedle integrated transdermal patch (MITP), using a photolithography based process, in which microneedles create micrometer-sized channels in the skin to deliver lidocaine rapidly, while the reservoir patch holding the bulk of the drug enables higher drug loading and carries on to release the drug for prolonged periods. We demonstrated a new approach of drug delivery using microneedles, where drugs diffuse out of microneedles through the porous channels left by dissolving drug particles. MITP was shown to be able to encapsulate up to 70 mg of lidocaine. In vitro permeation through rat skin demonstrated that MITP delivered a significantly higher amount of lidocaine than a commercial patch and with a faster onset of drug permeation.