Objective-To test the safety, tolerability, and pharmacokinetics of the anti-TNF-α monoclonal antibody, infliximab, in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).Study design-We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever following initial treatment with IVIG. Primary outcome measures were infliximab safety, tolerability, and pharmacokinetics. Secondary outcome measures were duration of fever and changes in markers of inflammation.Results-Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were © 2008 Mosby, Inc. All rights reserved.Corresponding author: Jane C. Burns, M.D. Dept of Pediatrics 9500 Gilman Dr. La Jolla, CA 92093-0830 Tel. 619-543-5326 FAX 619-543-3546 jcburns@ucsd.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. NIH Public AccessConclusion-Both infliximab and a second IVIG infusion were safe and well-tolerated in subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined. KeywordsTNF-α; cytokine; monoclonal antibody; coronary artery aneurysm; infliximab; Kawasaki disease Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms in up to 25% of untreated children. Administration of high-dose intravenous immunoglobulin (IVIG) in combination with aspirin (ASA) results in dramatic clinical improvement and reduced incidence of coronary artery aneurysms in the majority of patients with KD (1). However, a subset of patients has persistence or recrudescence of fever following IVIG treatment (2). Common practice is to administer a second dose of IVIG (2 g/kg) to patients who fail to become afebrile within 24 to 48 hours after completion of the first infusion, even though the benefits of this approach have never been formally evaluated (3). Fever persists in approximately half of the patients treated with a second dose of IVIG (2 g/kg) (2). Because KD is a self-limited illness from which most children eventually recover with no specific therapy, it is unclear whether retreated patients become afebrile as a result of the addition...

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The purpose of this study was to describe the maturation of vancomycin (V) clearance and the influence of altered renal function in infants on vancomycin using population pharmacokinetic methods. A population pharmacokinetic model was developed using NONMEM from clinical data obtained from 374 newborns and infants < 2 years of age (median age = 27 days) from four institutions. A total of 1103 serum V concentrations were used in the model development, including 311 with elevated serum creatinine (CR) (> 0.8 mg/dl) and more than 104 evaluations in infants older than 2 months of age. The final model was evaluated against a second data set of 160 concentrations from 67 infants at one of the institutions and then used to develop dosing guidelines. The data were best described by a two-compartment model. Weight and CR greatly influenced vancomycin elimination, while postnatal age and prematurity (< 28 weeks) were significant but less important predictors of V elimination. For the typical study infant (age = 27 days, CR = 0.6, WT= 1.8 kg, gestational age = 33.5 weeks), this results in VdSS = 0.79 l/kg and Cl = 0.066 l/h/kg. The validation data set showed the model to be unbiased. Dosing guidelines from this model, based on serum creatinine and gestational age at birth, performed better than published guidelines based on postconceptional age. Vancomycin clearance is initially reduced in premature infants and increases with postnatal age. Most of the age-related changes could be predicted by the concomitant fall in serum creatinine. Dosing guidelines that incorporate these factors are more likely to produce therapeutic V concentrations in infants.

In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.