David Speicher

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients

ABSTRACT This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0–∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Hospital Based Emergency Department Visits Attributed to Child Physical Abuse in United States: Predictors of In-Hospital Mortality

Objectives To describe nationally representative outcomes of physical abuse injuries in children necessitating Emergency Department (ED) visits in United States. The impact of various injuries on mortality is examined. We hypothesize that physical abuse resulting in intracranial injuries are associated with worse outcome. Materials and Methods We performed a retrospective analysis of the Nationwide Emergency Department Sample (NEDS), the largest all payer hospital based ED database, for the years 2008–2010. All ED visits and subsequent hospitalizations with a diagnosis of “Child physical abuse” (Battered baby or child syndrome) due to various injuries were identified using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes. In addition, we also examined the prevalence of sexual abuse in this cohort. A multivariable logistic regression model was used to examine the association between mortality and types of injuries after adjusting for a multitude of patient and hospital level factors. Results Of the 16897 ED visits that were attributed to child physical abuse, 5182 (30.7%) required hospitalization. Hospitalized children were younger than those released treated and released from the ED (1.9 years vs. 6.4 years). Male or female partner of the child’s parent/guardian accounted for >45% of perpetrators. Common injuries in hospitalized children include- any fractures (63.5%), intracranial injuries (32.3%) and crushing/internal injuries (9.1%). Death occurred in 246 patients (13 in ED and 233 following hospitalization). Amongst the 16897 ED visits, 1.3% also had sexual abuse. Multivariable analyses revealed each 1 year increase in age was associated with a lower odds of mortality (OR = 0.88, 95% CI = 0.81–0.96, p<0.0001). Females (OR = 2.39, 1.07–5.34, p = 0.03), those with intracranial injuries (OR = 65.24, 27.57–154.41, p<0.0001), or crushing/internal injury (OR = 4.98, 2.24–11.07, p<0.0001) had higher odds of mortality compared to their male counterparts. Conclusions In this large cohort of physically abused children, younger age, females and intracranial or crushing/internal injuries were independent predictors of mortality. Identification of high risk cohorts in the ED may enable strengthening of existing screening programs and optimization of outcomes.

Validation of a pediatric bedside tool to predict time to death after withdrawal of life support.

AIM To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS Pertinent variables for all pediatric deaths (age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit (PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support (dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min (DPT30) and within 60 min (DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated. RESULTS There were 8829 PICU admissions resulting in 132 (1.5%) deaths. Death followed withdrawal of life support in 70 patients (53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years (SD: 6.9), median time to death after withdrawal of life support was 25 min (range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients (59.6%) died within 30 min of withdrawal of life support and 52 (83.8%) died within 60 min. DPT30 scores ranged from -17 to 16. A DPT30 score ≥ -3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from -21 to 28. A DPT60 score ≥ -9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%. CONCLUSION In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.

637: Alcohol Use Necessitating ED Visits in Children in United States

Introduction: Alcohol use and abuse among children (aged ≤ 21 years) is a persistent and pervasive problem worldwide. Underage drinking is associated with high risk behaviors and significant negative societal outcomes. Hospital resource utilization and outcomes associated with alcohol use necessitat