Study Objective To evaluate the impact of a hospital-wide increase in the recommended vancomycin starting dose in children from 45 to 60 mg/kg/day on vancomycin trough concentrations. Design Retrospective chart review. Setting Dedicated children's hospital located within a tertiary care, academic medical center. Patients Children aged 1 month-12 years with normal renal function who were treated with vancomycin during two one-year periods: July 2006-June 2007 (low dose [LD]; 45 mg/kg/day divided q8 hour; n=88) and July 2008-June 2009 (high dose [HD]; 60 mg/kg/day divided q6 hour; n=94). Measurement and Main Results Patient demographics along with vancomycin dose and initial vancomycin trough concentration were collected. No significant demographic differences existed in patients between the two periods. The mean initial vancomycin trough level increased from 7 ± 5 μg/ml to 9 ± 5 μg/ml (LD vs HD; p<0.001). The percentage of patients with an initial trough <5 μg/ml declined from 39% to 17% (LD vs HD; p<0.001) while the percentage of patients with an initial trough concentration in the potentially adverse range (>20 μg/ml) was unchanged between the two periods (2% vs 2%; p=0.9). Less than 15% achieved a trough level between 15-20 μg/ml in the HD period of our study. Conclusions This is the first report of a hospital-wide increase in the recommended vancomycin starting dose to 60 mg/kg/day in children. The use of a vancomycin starting dose of 60 mg/kg/day decreased the likelihood of an initial low vancomycin trough < 5 μg/ml with no increase in the proportion of patients with trough levels in a potentially toxic range. The 60 mg/kg/day dose does not consistently achieve a vancomycin trough of 15-20 μg/ml, a goal suggested by some experts.

R ISK OF INFECTION, AND ANTIBIOTIC PROPHYLAXIS, are topics that have been debated for decades by those involved in the care of children undergoing cardiac surgery. In this review we attempt to analyse what is known and what has been postulated about this subject. Suggestions regarding the best strategies for treatment have been formulated, based on published reports, as well as current practices worldwide. The burden of infection of the site of cardiac surgery Cardiac surgery is clean surgery, and should be associated with an incidence of infection less than 5%. Recent studies in adults have demonstrated an incidence of 2 to 6.4% for superficial infections of sternal wounds, 1-3 and an incidence of deep infections or mediastinitis that ranges from 0.77 to 3.3%. 1-5 The National Cardiac Surgical Database of the Society of Thoracic Surgeons revealed an incidence of deep sternal infections of 0.4% in 2002. Lu et al. 6 demonstrated a significantly higher mortality in patients with infected sternal wounds compared to those without such infection during a 4-year follow-up period after coronary arterial bypass grafting. Postoperative mediastinitis is associated with a mortality of up to 16%. 7 This complication is

OBJECTIVE To evaluate the accuracy of a neonatal gentamicin nomogram to achieve therapeutic gentamicin serum concentrations without further adjustment, allowing for decreased serum drug monitoring METHODS Retrospective single center review of all gentamicin pharmacokinetic evaluations in patients ≤ 30 days of life from July 2005 – June 2007. Patients were evaluated for postnatal age, gestational age, weight, serum creatinine, dose/interval, serum drug peaks and troughs, results of discharge hearing test and recent use of indomethacin. Logistic regression was utilized to determine potential factors impacting overall dosing accuracy, potentially allowing for decreased therapeutic drug monitoring. Factors found to be significant were incorporated into new guidelines which were evaluated through pharmacokinetic modeling. RESULTS Overall accuracy rate was 84% when empiric dosing guidelines were utilized; 16% of all doses were changed due to supratherapeutic troughs and 1% were changed due to subtherapeutic peaks. Variables found to impact the necessity for dose changes incuded gestational age (p≤0.001), weight (p≤0.001), indomethacin use (p≤0.001), number of indomethacin doses used (p≤0.001 and p=0.009 for 1–3 and 4–6 doses, respectively), and SCr in patients ≥ 7 days old (p=0.028); however, only gestational age remained a significant predictor when all other factors were considered (p=0.008). The current guidelines were changed to account for increased troughs in patients ≤ 28 weeks gestation and examined through pharmacokinetic modeling. Pharmacokinetic modeling of the new guidelines predicted an overall accuracy of 94%. CONCLUSIONS From the data gathered regarding the accuracy in patients ≥ 35 weeks gestation, we recommend to decrease therapeutic drug monitoring within this cohort. Utilizing the results of regression analysis, the current guidelines have been adjusted to allow for increased clearance in patients ≤ 28 weeks gestation, although they still need to be prospectively evaluated.

Talwar and colleagues raise very valid points, and we agree with all of them. The need for worldwide trials of antibiotics is obvious, as we suggested in our manuscript. Adjustment for local epidemiologic and demographic conditions will be important for making informed and useful recommendations. A recent visit we made to the very impressive home institution of the authors confirms that they will be well positioned to contribute to future studies of this type.