Vancomycin Treatment Failure in Children With Methicillin-Resistant Staphylococcus aureus Bacteremia.

OBJECTIVES: Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC24/MIC) ratio ≥400. It is unknown if this relationship is useful in children. METHODS: Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC24/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality. RESULTS: There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC24/MIC ratios (R 2 = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC24/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure. CONCLUSIONS: Treatment failure was lower than previously reported in children. AUC24/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.

Premixed Parenteral Nutrition Solution Use in Children.

OBJECTIVES: In response to national drug shortages, our institution established criteria for the use of commercial premixed parenteral nutrition (PN) solutions in select pediatric patients. Although these solutions have been marketed for use in children, there are no data in this patient population. The objective of this study was to review our use of commercial premixed PN solutions in children. METHODS: This was a retrospective review of patients ≤18 years of age who received a premixed PN solution from October 2010 to April 2012. All premixed PN courses were assessed for incidence of premixed PN discontinuation due to laboratory abnormalities. Estimated goal and actual protein and total caloric intake were evaluated for premixed PN courses that were continued for >48 hours. RESULTS: Sixty-nine patients received 74 courses of premixed PN solutions for a mean duration of 5.6 ± 6.2 (range, 1-31) days. Fifteen courses (20%) required discontinuation of premixed PN as a result of mild laboratory abnormalities. No changes in clinical status were observed in patients and all abnormalities were corrected after switching to individualized PN. In patients receiving PN for >48 hours, premixed PN solutions provided goal protein in 48/49 (98%) courses and goal calories in 33/49 (67%) courses. CONCLUSIONS: Premixed PN solutions were used in a wide range of pediatric patients and provide a potential option for PN support in pediatric patients when drug shortages limit PN product supply. Close monitoring for electrolyte abnormalities and protein and caloric intake is recommended when using premixed PN solutions in children.

Bumetanide continuous infusions in critically ill pediatric patients.

OBJECTIVE: Limited data exist for the use of bumetanide continuous infusions in children. The purpose of this study was to evaluate the use of bumetanide continuous infusions in critically ill pediatric patients. DESIGN: This study was an institutional review board approved, single-center, retrospective chart review of 95 patients. Dosing practices were described by rate (µg/kg/hr), duration (days), and previous diuretic use. Efficacy, determined by ability to achieve negative fluid balance and time to reach negative fluid balance, was assessed at 12, 24, and 48 hours. Safety was evaluated based on prevalence of adverse drug reactions. Adverse drug reactions were predefined as serum potassium concentration less than 3 mEq/L, serum chloride concentration less than 90 mEq/L, serum carbon dioxide concentration greater than 35 mEq/L, and serum creatinine increased greater than 1.5 times baseline and above patient-specific normal range. SETTING: Le Bonheur Children's Hospital, Memphis, TN. PATIENTS: Critically ill patients who are 18 years old or younger and received bumetanide continuous infusions. A total of 95 patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean dose of bumetanide was 5.7 ± 2.2 µg/kg/hr (1-10 µg/kg/hr) with a median duration of 3.3 days (0.3-18.5). The total percentage of patients achieving negative fluid balance by 48 hours was 76% with 54% of patients reaching negative fluid balance within 12 hours. CONCLUSIONS: This study showed that a bumetanide dose of 5.7 µg/kg/hr was effective in achieving negative fluid balance in the majority of critically ill pediatric patients. Additionally, bumetanide appears to be a safe loop diuretic for use as a continuous infusion at the doses described in critically ill pediatric patients.

Ethanol lock therapy: a pilot infusion study in infants.

BACKGROUND: Ethanol lock therapy (ELT) has emerged as an effective method for the prevention and treatment of central line-associated bloodstream infections (CLABSIs), but the safety of ELT in infants has not been established. OBJECTIVE: The objective of this study was to determine blood alcohol concentration (BAC) and evidence of hepatic injury in infants after infusing a small one-time dose of ethanol, equivalent to the volume that would be flushed through the central venous catheter (CVC) after ELT is completed. METHODS: This was a prospective pilot study in infants weighing ≤6 kg with and without liver dysfunction who had a CVC. The primary end points were 5-minute and 1-hour BACs after a 0.4-mL dose of 70% ethanol was flushed through the CVC. Acceptable BACs were defined as <0.025% at 5 minutes and <0.01% at 1 hour. The secondary end point was evidence of hepatic injury, defined as a change of greater than 2 times the upper limit of normal of any component in the hepatic panel in patients with a normal baseline panel or doubling of any component in the hepatic panel in patients with an abnormal baseline panel (aspartate aminotransferase, alanine transaminase, total or direct bilirubin, gamma-glutamyl transferase, or alkaline phosphatase). RESULTS: A total of 10 patients were included for analysis, with a mean age and weight of 3.5 ± 2.4 months and 4.5 ± 0.9 kg, respectively. All patients had acceptable BACs and no evidence of hepatic injury. In 8 patients, 5-minute BACs were undetectable; BACs of the other 2 patients were 0.011%. One-hour BACs in all patients were undetectable. CONCLUSIONS: Flushing ELT resulted in acceptable BACs and no evidence of hepatic injury in this patient cohort. Further studies are needed to investigate the long-term safety and efficacy of ethanol infusion after ELT in this patient population for the prevention and treatment of CLABSIs.

Glomerular filtration rate equations do not accurately predict vancomycin trough concentrations in pediatric patients.

BACKGROUND: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. OBJECTIVE: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. METHODS: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. RESULTS: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r (2) = 0.028) and Bedside CKiD equation (r (2) = 0.028). A weak relationship between serum creatinine and troughs was observed (r (2) = 0.132). Limitations include small sample size and retrospective design. CONCLUSIONS: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications.

Recent new drug approvals, part 2: drugs undergoing active clinical studies in children.

The objective of this 2-part review is to provide information about drugs that have been recently approved by the US Food and Drug Administration. Part 1 reviewed recently approved drugs with pediatric indications. Part 2 reviews drugs recently approved only in adults and have published or ongoing studies in children.

Vancomycin Dosing Practices, Trough Concentrations, and Predicted Area Under the Curve in Children With Suspected Invasive Staphylococcal Infections.

Recent guidelines recommend empiric vancomycin dosing of 60 mg/kg per day and consideration of higher trough concentrations (15-20 mcg/mL) in children with invasive infections. In this study, we report a retrospective review evaluating the dose/trough relationship and predicted area under the curve in pediatric patients receiving vancomycin for invasive staphylococcal infections.

Recent new drug approvals. Part 1: drugs with pediatric indications.

This two-part review provides information about drugs that have been recently approved by the Food and Drug Administration and focuses on drugs approved with pediatric indications or approved in adults with active pediatric studies. Information was obtained from the product labeling and selected published studies. Part 1 reviews recently approved drugs with labeled pediatric indications, and Part 2 will review recent drug approvals in adults that have potential use in pediatrics and have active studies.