Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

OBJECTIVES: To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). DESIGN: Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. SETTING: Tertiary children's hospital. PATIENTS: Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. INTERVENTIONS: Retrospective measurement of VTL, eGFR, and clinical variables. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. CONCLUSIONS: Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Clonidine for the Treatment of Agitation After Dexmedetomidine Discontinuation in Pediatric Patients: A Retrospective Cohort Study.

OBJECTIVE: Dexmedetomidine has become a widely used drug in PICUs for sedation. We aim to determine the effects of clonidine on pediatric patients after dexmedetomidine use. METHODS: This was a retrospective cohort study that evaluated all pediatric patients admitted to a tertiary PICU who received dexmedetomidine infusion for >48 hours. Outcomes in patients exposed to clonidine (CLON) were compared with those of patients who were not exposed (NoCLON). RESULTS: A total of 216 patients were included in this study (43 CLON and 173 NoCLON). The primary outcome, agitation, was less in the CLON cohort (9.3%) than in the NoCLON cohort (9.3% versus 29.5%, respectively; p < 0.01). Hospital LOS was longer in the CLON group (59 versus 20 days, p < 0.01), as was PICU LOS (37.4 versus 11.1 days, p < 0.01). There was no significant difference in the occurrence of increased heart rate or blood pressure between the 2 cohorts. Patients exposed to concurrent midazolam and opioid infusions had higher incidence of agitation when they did not receive clonidine (CLON 8% versus NoCLON 37%, OR 0.15; 95% CI, 0.05-0.51; p < 0.01). In contrast, there was no difference in the incidence of agitation for the CLON group versus the NoCLON group when dexmedetomidine was administered alone (25% versus 19%, OR 1.4; p = 0.99). CONCLUSIONS: Our study confirms the importance and effectiveness of clonidine to treat agitation after dexmedetomidine discontinuation. A validated withdrawal scoring tool can help better define dexmedetomidine withdrawal in pediatric patients.

Pediatric Antiviral Stewardship: Defining the Potential Role of Ribavirin in Respiratory Syncytial Virus-Associated Lower Respiratory Illness.

OBJECTIVES: Although no longer included in the American Academy of Pediatrics guideline, ribavirin was shown to be beneficial in a subset of adult patients with severe respiratory syncytial virus (RSV)-associated bronchiolitis. This study aimed to investigate risk factors for progression to severe acute respiratory tract infections in hospitalized pediatric patients with RSV-associated bronchiolitis to identify which patients may benefit from inhaled ribavirin therapy, despite its substantial cost, diffcult administration, and potential complications. METHODS: Patients were identified by ICD-9 codes for RSV bronchiolitis and were only included if they had a confirmed positive result for RSV via polymerase chain reaction for detection and typing of respiratory viruses. Patient characteristics, including underlying conditions and comorbidities, were analyzed for the risk of severe acute respiratory tract infection. RESULTS: A total of 299 patients were included in the study population. Ninety-six patients (32%) were admitted to the pediatric intensive care unit, and almost half of those patients (46%) required mechanical ventilation. Weight and presence of atrial septal defect were the only factors significantly associated with the need for mechanical ventilation, as identified by univariate analysis. Two patients required extracorporeal membrane oxygenation (ECMO), and a total of 5 patients, including one who received ECMO, died with RSV infection as the primary cause. Of these patients, all were less than 1 year of age. Two had a history of prematurity; however, no variables were associated with mortality. CONCLUSIONS: Given the side effect profile and expense of ribavirin therapy, it is prudent to limit use to patients at risk for significant morbidity and mortality from RSV disease. Because we were unable to identify patients who would most likely benefit from ribavirin antiviral therapy, we cannot recommend the routine use of ribavirin to prevent mechanical ventilation, ECMO, or death from RSV bronchiolitis in our institution.

Adrenocorticotropic hormone for the treatment of West Syndrome in children.

OBJECTIVE: To review the current literature on the efficacy and safety of low- versus high-dose adrenocorticotropic hormone (ACTH) regimens, low-dose ACTH regimens, and comparison of ACTH with oral corticosteroids or vigabatrin for the treatment of West syndrome. DATA SOURCES: A literature search was performed using MEDLINE, PubMed, and Inter national Pharmaceutical Abstracts (1975-November 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: infantile spasms, West syndrome, adrenocorticotropic hormone, corticotropin, symptomatic West syndrome, cryptogenic West syndrome, pediatric, children, infant, adolescent, and neonate. STUDY SELECTION AND DATA EXTRACTION: Studies included in this article evaluated low-dose versus high-dose ACTH, low-dose ACTH, and ACTH compared with vigabatrin and oral corticosteroids. Data reporting the efficacy and adverse effects of ACTH, vigabatrin, and oral corticosteroids were extracted from each publication. Only English-language publications were included. We initially reviewed 20 studies, and 14 were included: 5 prospective randomized clinical trials and 9 chart reviews. DATA SYNTHESIS: West syndrome is an age-specific epileptic disorder that occurs in infancy and early childhood. It is characterized by the triad of infantile spasms, neurodevelopmental regression or delay, and hypsarrhythmia on electroencephalogram (EEG). The efficacy and adverse events of ACTH with different dosage regimens were reviewed and analyzed. ACTH compared with vigabatrin and oral corticosteroids was also evaluated. Based on this review, low-dose ACTH is probably as effective as high-dose ACTH. Compared with other agents, ACTH is suggested to be more effective than oral corticosteroids, and compared with vigabatrin, it has improved outcomes in the cessation of spasms. However, studies evaluating the efficacy of ACTH are limited by small sample size, inconsistent dosage regimens, and the use of synthetic or natural ACTH products. Serious adverse events, including intracranial hemorrhage, brain atrophy, Cushing syndrome, infection, weight gain, and hypertension, may deter the use of ACTH. Short-term therapy is recommended to reduce the risk of adverse effects. CONCLUSIONS: The current literature suggests that short-term, low-dose ACTH should be considered first-line treatment of infantile spasms.

Continuous and extended infusions of ß-lactam antibiotics in the pediatric population.

OBJECTIVE: To conduct a systematic review of available data on the use of extended or continuous infusion of ß-lactam and monobactam therapy in the pediatric population (aged 0-18 years). DATA SOURCES: A literature search was performed using PubMed (1975-May 2012), International Pharmaceutical Abstracts (1970-May 2012), and Web of Science (1977-May 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: pediatric, children, neonate, infant, adolescent, ß-lactam, cephalosporin, carbapenem, penicillin, monobactam, continuous infusion, extended infusion, and/or prolonged infusion. Individual names of drugs in each class of antibiotics were also included in the search. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled clinical trials, pharmacokinetic/pharmacodynamic studies, observational studies, and case reports involving pediatric patients who received extended or continuous infusion of ß-lactam or monobactam antibiotics were reviewed. Only English-language publications were included. DATA SYNTHESIS: One randomized controlled clinical trial, 5 pharmacokinetic studies, 2 pharmacodynamic studies using Monte Carlo simulation, 1 case series, and 7 case reports were included in the analysis. The cephalosporin class has been studied the most and currently represents the only clinical trial using a continuous infusion dosing strategy in pediatric patients. There is limited clinical evidence available to support the use of extended or continuous infusion of ß-lactam antibiotics in the pediatric population. Pharmacodynamic studies conducted in this population mirror the current evidence in adults for cefepime and meropenem. The single prospective clinical trial using continuous infusion of ceftazidime failed to demonstrate any clinical benefit over traditional dosing; however, there was equal efficacy. CONCLUSIONS: More well-designed prospective clinical trials are required to determine the role of extended or continuous infusion of ß-lactam antibiotics in treatment of pediatric patients.