Evaluation of Vancomycin Use in Late-Onset Neonatal Sepsis Using the Area Under the Concentration-Time Curve to the Minimum Inhibitory Concentration ≥400 Target.

AIM: To develop a vancomycin population pharmacokinetic model and assess the probability of attaining a pharmacodynamic target associated with clinical and microbiological success, a ratio of the 24-hour area under the concentration-time curve to the minimum inhibitory concentration (MIC) ≥ 400, in a 5-year clinical cohort of preterm and term neonatal patients with late-onset staphylococcal sepsis. METHODS: Therapeutic drug monitoring data were obtained from septic neonates with ≥1 vancomycin concentration(s) from January 2006 to September 2011. Only neonates with a postnatal age of >72 hours and a positive microbiological culture were included. Population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM 7.2). Eleven demographic characteristics were evaluated as covariates. Probabilities of achieving the pharmacodynamic target were evaluated. RESULTS: A 1-compartment model with first-order elimination was constructed from 528 vancomycin concentrations collected from 152 preterm and term neonates. Body weight, creatinine clearance (CL), and postmenstrual age were identified as significant covariates. Estimated vancomycin CL and volume of distribution for typical neonates were 0.068 ± 0.03 L·h·kg and 0.62 ± 0.13 L/kg, respectively. Coagulase-negative staphylococci (85.5%) and Staphylococcus aureus (14.5%) were the common pathogenic organisms. The distribution of vancomycin MIC breakpoints was composed of approximately 70% MIC breakpoint of ≤2 mcg/mL. Approximately 54% of neonates, with a median serum creatinine concentration of 0.44 mg/dL, achieved the target ratio of 24-hour area under the concentration-time curve to the MIC ≥ 400 with a median daily dose of 30 (interquartile range, 21-42) mg/kg. CONCLUSIONS: Body weight, creatinine CL, and postmenstrual age significantly influenced vancomycin CL. The current vancomycin doses are acceptable at MICs ≤1 mcg/mL because they are likely to achieve the pharmacodynamic target in the majority of neonatal patients, although higher doses may be considered for more resistant staphylococcal infections.

Clinical practice, resource utilization, and outcomes of device closure of patent foramen ovale in pediatrics.

BACKGROUND: There are few data on patent foramen ovale closure and its outcome in children. In this study, we evaluated the current clinical practice, resource utilization, and outcome of device closure of patent foramen ovale in children. We hypothesized that patent foramen ovale closure would not result in a demonstrated benefit in children. METHODS: We undertook a prospective survey of all consecutive patients (<20 years) who underwent patent foramen ovale closure in our metropolitan area between 1995 and 2010. Differences in proportions were tested using the chi-square test or Fisher's exact test where appropriate. Differences in group medians were tested using Wilcoxon signed-rank test. RESULTS: A total of 153 patients (104 girls), median age 16 years (range 7-19) were studied. Indications for patent foramen ovale closure included: (1) migraine headache (104; 68%), (2) nonmigraine headache (24; 16%), (3) visual symptoms (110; 72%), (4) transient ischemic attack symptoms (42; 28%), and (5) stroke-like symptom (24; 16%). Patent foramen ovale was closed with an Amplatzer septal occluder in 115 (75%) and a Helex septal occluder in 47 (30%). The mean length of hospital stay was 18 ± 11 hours; the mean hospital charge was $24,126 ± $5808. The median duration of follow-up was 12 months, and 80 patients responded to the study survey. On follow-up, symptoms improved in 143 (93%), of which 29 (19%) had a residual shunt. None of the patient or treatment parameters predicted lack of improvement on follow-up. CONCLUSIONS: Despite the lack of proven benefit, children undergo closure of the patent foramen ovale for a variety of reasons, with the vast majority (92%) of patients reporting significant improvement in their symptoms. However, patent foramen ovale closure is an expensive procedure with serious potential complications. Symptomatic improvement even in the presence of a residual shunt suggests a strong placebo effect.

Outcome and resource utilization of infants born with hypoplastic left heart syndrome in the Intermountain West.

The objective of the present study was to characterize the outcomes and resource utilization of all infants born with hypoplastic left heart syndrome (HLHS) in the Intermountain West. This was a retrospective cohort study of all infants born with HLHS in the Intermountain West from January 1995 and January 2010. The cohort was divided into 3 eras: era 1, 1995 to 1999; era 2, 2000 to 2004; and era 3, 2005 to 2010. Cox proportional hazards regression analysis was performed to assess mortality. The lifetime hospitalization days and charges were also determined. Of the 245 infants identified, 65% were male infants and 172 (70%) underwent Stage 1 palliation. The transplant-free survival rate for the entire cohort was 33% at 14 years. The 1-year transplant-free survival rate for the surgical cohort was 60% in era 3. The infants whose initial presentation included shock, restrictive or intact atrial septum, chromosomal defects, or multiorgan dysfunction had an increased risk of death. A recent era of birth, greater birthweight, and older gestational age were associated with improved survival. The factors associated with mortality after stage 1 included surgical procedure type (Blalock-Taussig vs Sano shunt, hazard ratio 2.1), requirement for postoperative extracorporeal membrane oxygenation (hazard ratio 4.2), postoperative renal dysfunction (hazard ratio 3.0), anomalous pulmonary venous return (hazard ratio 2.9), and moderate or greater tricuspid valve regurgitation at any point (hazard ratio 2.0). For patients who had undergone stage 1, 2, or 3 palliation, the median cumulative lifetime hospitalization was 32, 48, and 65 days, and the median cumulative lifetime charges for hospitalization were $201,812, $253,183, and $296,213, respectively. In conclusion, although hospital-based studies of HLHS have shown significantly improved survival after surgical palliation, population-based studies have shown that HLHS continues to have a high mortality and high resource utilization.

The changing epidemiology of invasive pneumococcal disease at a tertiary children's hospital through the 7-valent pneumococcal conjugate vaccine era: a case for continuous surveillance.

BACKGROUND: In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among US children. Many sites have since reported changes in invasive pneumococcal disease (IPD). We recognized an opportunity to describe the changes in epidemiology, clinical syndromes, and serotype distribution during a 14-year period including 4 years before vaccine introduction and spanning the entire PCV7 era. METHODS: Cases were defined as children <18 years of age who were cared for at Primary Children's Medical Center for culture-confirmed IPD. We defined the prevaccine period as the time frame spanning from 1997 to 2000 and the postvaccine period from 2001 to 2010. Demographics, clinical data, and outcomes were collected through electronic query and chart review. Streptococcus pneumoniae serotyping was performed using the capsular swelling method. RESULTS: The median age of children with IPD increased from 19 months during the prevaccine period to 27 months during postvaccine period (P = 0.02), with a larger proportion of IPD among children older than 5 years. The proportion of IPD associated with pneumonia increased substantially from 29% to 50% (P < 0.001). This increase was primarily attributable to an increase in complicated pneumonia (17% to 33%, P < 0.001). Nonvaccine serotypes 7F, 19A, 22F, and 3 emerged as the dominant serotypes in the postvaccine period. In children with IPD who were younger than 5 years, for whom vaccine is recommended, 67% of the cases were caused by serotypes in 13-valent PCV during 2005 to 2010. CONCLUSIONS: After PCV7 was introduced, significant changes in IPD were noted. One-third of IPD occurred in children older than 5 years, who were outside the age-group for which PCV is recommended. Continued surveillance is warranted to identify further evolution of the epidemiology, clinical syndromes, and serotype distribution of S. pneumoniae after 13-valent PCV licensure.

Evolution of the epidemiology of pneumococcal disease among Utah children through the vaccine era.

From 1996 to 2009, we analyzed changes in pneumococcal disease (PD) in Utah children aged <18 years using International Classification of Diseases, ninth revision coded hospital discharges. We observed a sustained decrease in the incidence of PD among children <5 years in 2001-2004 (-36%) and 2005-2009 (-34%) compared with 1996-2000 (pre-7-valent pneumococcal conjugate vaccine). Decreases were primarily in bacteremia, uncomplicated pneumonia, and meningitis. In contrast, significant increases in complicated pneumonia/empyema were noted in children <5 years (+95% and +85%) and 5 to 17 years (+2% and +70%). Despite decreases in PD among Utah children, complicated pneumonia/empyema has increased during the 7-valent pneumococcal conjugate vaccine era.