Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics.

OBJECTIVE: Vancomycin dosing requirements to achieve a target area under curve/minimum inhibitory concentration (AUC/MIC) of 400 to 600 mg•hr/L have not been established in pediatrics. Dose modeling studies and recent guidelines suggest dosing higher than historical recommendations. This study examines dosing requirements to achieve target AUC/MIC in human pediatric patients. METHODS: This retrospective study includes 77 patients, aged 1 month to 18 years, at a single center, who received at least 2 days of intravenous vancomycin with a pharmacokinetic monitoring note and calculated AUC/MIC. Dosing to achieve target AUC/MIC was evaluated by age and indication. Nephrotoxicity was also assessed. RESULTS: The mean dose required to achieve target AUC/MIC for all patients was 67.7 mg/kg/day. Adjusting for age, the mean dose required to achieve target AUC/MIC of 400 to 600 mg•hr/L was found to be statistically significantly different among 3 age cohorts: 1 month to 5 years, 6 to 12 years, and 13 to 18 years [F(2,74) = 15.32, p < 0.001], with mean requirements of 79 ± 14.1, 65.6 ± 21.1, and 53.9 ± 17.1 mg/kg/day, respectively. Dosing requirements were also found to be statistically significantly different across indications [F(6,70) = 4.84, p < 0.001]. Acute kidney injury was identified in 5 patients (6.5%). CONCLUSIONS: The vancomycin dose required to achieve target AUC/MIC in pediatrics was significantly higher in younger pediatric patients and ranged from 53.9 to 79 mg/kg/day, confirming recent guideline recommendations. Doses can be further adjusted for indication. Nephrotoxicity rates remain low compared with historical rates with single trough monitoring.

Oral Targeted Therapies and Central Nervous System (CNS) Metastases.

The purpose of our review is to summarize the clinical activity of oral targeted agents against brain metastases. This includes BRAF inhibitors (dabrafenib and vemurafenib), human epidermal growth factor receptor inhibitors (lapatinib, gefitinib, erlotinib, and afatinib), multi-kinase angiogenesis inhibitors (sorafenib, sunitinib, pazopanib, and vandetanib), and ALK/c-MET (crizotinib) and ALK/IGF-1 (ceritinib) inhibitors. Effective systemic therapies are needed for long-term benefit in brain metastases and documentation of intracranial activity for many therapies is poor. Our review provides a summary of the literature with pertinent data for clinicians. This is needed as subjects with brain metastases are often prevented from enrolling in clinical trials and investigations focused on systemic therapies for brain metastases are rare.