Evaluation of an Unfractionated Heparin Pharmacy Dosing Protocol for the Treatment of Venous Thromboembolism in Nonobese, Obese, and Severely Obese Patients.

BACKGROUND: Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting. OBJECTIVE: The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol. METHODS: This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese (BMI < 30 kg/m2), obese (BMI = 30-39.9 kg/m2), and severely obese (BMI ≥ 40 kg/m2). Data on height, weight, initial bolus dose, initial infusion rate, time to therapeutic aPTT, and therapeutic infusion rate were collected. Dosing body weight (DBW) was utilized for patients 20% over their ideal body weight (IBW). The primary outcome was time to therapeutic aPTT. RESULTS: Analysis included 298 patients. Median times to therapeutic aPTT (hours:minutes) in the nonobese, obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21), 15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54-23:40), respectively ( P = 0.506). There was no difference in bleeding among the nonobese (14%), obese (13.9%), or severely obese groups (7.9%; P = 0.453). No adverse thrombotic events occurred during hospitalization. CONCLUSION: Using a DBW for heparin dosing in patients 20% over their IBW resulted in similar times to therapeutic aPTT and adverse events in the nonobese, obese, and severely obese.

Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support.

OBJECTIVES: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary »-inch extracorporeal life support circuit with a Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC, Wayne, NJ). DESIGN: Retrospective medical record review. SETTING: Two free-standing tertiary/quaternary pediatric children's hospitals. PATIENTS: Neonates receiving either veno-arterial or veno-venous extracorporeal life support and vancomycin for empiric or definitive therapy with resulting serum concentrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve patients with a median gestations age of 39 weeks (range 36-41 wk) and a median postnatal age of 9.5 days (range 0-28 d) accounted for 14 courses of vancomycin therapy while on extracorporeal life support and were included in the analysis. The median weight was 3.1 kg (range 2.2-4.41 kg) with five of 12 patients (41.7%) being female. Vancomycin concentrations were best described by an one-compartment model incorporating allometric scaling of estimated glomerular filtration rate on clearance. The mean total body clearance (mL/min/kg) for the population was 3.48 ± 1.31 mL/min/kg, and the mean total volume of distribution (L/kg) for the population was 1.2 ± 0.4 L/kg. The intermittent and continuous infusion dosing regimens that provided for the highest percentage of trough concentrations in the range of 10-20 mg/L were the 10 mg/kg/dose IV q8h, 12.5 mg/kg/dose IV q8-12h, 15 mg/kg/dose IV q12h, and 20 mg/kg/dose IV q12h, and the 20, 25, and 30 mg/kg/d continuous infusion regimens, respectively. All regimens allowed for an area under the concentration:minimum inhibitory concentration ratio of 400:1 for minimum inhibitory concentrations of less than or equal to 0.5 mg/L for a 90% PTA. None of the simulated regimens had a greater than 90% probability of achieving an area under the concentration:minimum inhibitory concentration ratio of 400:1 for vancomycin minimum inhibitory concentrations greater than or equal to 1 mg/L while maintaining trough concentrations in the range of 10-20 mg/L. CONCLUSIONS: To our knowledge, this is the first pharmacokinetic and pharmacodynamic study of neonates receiving vancomycin with a contemporary »-inch extracorporeal life support circuit including the Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC). The data suggest differences in vancomycin pharmacokinetics compared with previous extracorporeal life support data, notably a more rapid clearance, which could result in lower vancomycin concentrations. Considering this, a more aggressive initial dosing regimen may need to be employed in infants on extracorporeal life support.

Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children.

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.

Optimizing Guideline-Recommended Antibiotic Doses for Pediatric Infective Endocarditis.

The American Heart Association recently published an updated scientific statement on the management of infective endocarditis in childhood. The recommendations included for vancomycin, aminoglycoside, and ß-lactam dosing and monitoring are based primarily on expert opinion and do not consider available evidence for dose optimization based on pharmacokinetic and pharmacodynamic principles in pediatric patients. This is concerning because even when clinically necessary, some practitioners may be hesitant to deviate from guideline-recommended doses. In this perspective, we highlight potential areas for improvement in the statement-recommended doses and summarize evidence supporting antibiotic dosing optimization. The addition of a pediatric clinical pharmacist with expertise in antibiotic dosing to the panel would be beneficial for future updates.

Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy.

BACKGROUND: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥8 days of vancomycin therapy. METHODS: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy and within 48 hours following vancomycin discontinuation. The primary outcome was incidence of late AKI as determined by modified pRIFLE criteria. RESULTS: One-hundred sixty-seven patients were included, with a median (interquartile range) age (years) and weight (kg) of 2 (1-7) and 12.5 (8.9-23.8). Late AKI was identified in 12.6% (21/167). A higher percentage of late AKI patients received concomitant treatment with intravenous acyclovir, amphotericin products, or piperacillin-tazobactam. Age <1 year was the only factor independently associated with late AKI development (odds ratio = 4.4; 95% confidence interval = 1.3-15.4). CONCLUSIONS: Late AKI occurred in nearly 13% of children receiving ≥8 days of vancomycin therapy. This study suggests that vancomycin trough concentrations are not associated with late AKI, but that age <1 year and concomitant administration of certain nephrotoxins may be factors associated with increased risk.

Implementing extended-infusion cefepime as standard of care in a children's hospital: a prospective descriptive study.

BACKGROUND: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children. OBJECTIVE: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population. METHODS: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children's hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, operating, or emergency department areas. Demographic and clinical data for patients who received cefepime from April through August 2013, the period following EIC implementation, were extracted from the medical records. RESULTS: A total of 150 patients were included in the study, with a median age (interquartile range [IQR]) of 6 years (2-12.3 years) and median weight (IQR) of 20.7 kg (13.2-42.8 kg); 143 patients received cefepime via extended infusions, and 10 (7.0%) of those were changed to a 30-minute infusion during treatment. The most common reasons for infusion time change were intravenous (IV) incompatibility and IV access concerns, responsible for 50% of changes. Dosing errors and reported incidents during therapy were sparse (n = 12, 8.0%) and were most commonly related to renal dosing errors and/or initial dose error by prescriber. CONCLUSIONS: Because 93.0% of the patients who initially received EIC remained on EIC, implementation of EIC as the standard dosing strategy was feasible in this pediatric hospital.

Compatibility of Vancomycin and Oxacillin During Simulated Y-Site Delivery.

BACKGROUND: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. OBJECTIVE: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. METHODS: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) in an evacuated intravenous (IV) bag. One oxacillin sodium 2 g vial was reconstituted with 11.5 mL sterile water for injection and diluted with 88 mL sterile water for injection in an evacuated IV bag. Three mL of each vancomycin and oxacillin were mixed in 4 test tubes to simulate Y-site delivery. Spectrometry, pH evaluation, and visual examination were performed for each test tube immediately following mixing and at 30 minutes, 1 hour, and 2 hours after mixing. RESULTS: Upon visual examination with multiple backgrounds, a white precipitant was immediately evident in the test tubes with vancomycin and oxacillin combined. Spectrometry results strongly supported evidence of precipitation throughout the duration of the experiment. CONCLUSIONS: Vancomycin 10 mg/mL and oxacillin 20 mg/mL were determined to be physically incompatible for Y-site delivery in this study, despite prior evidence that the 2 medications in different concentrations were suitable for Y-site co-administration.

Measurement of Polyethylene Glycol 3350 With Standard Household Measuring Devices.

OBJECTIVE: Though standard household measuring devices (e.g., teaspoons, tablespoons) are often used in clinical practice to measure pediatric doses of polyethylene glycol 3350 (PEG-3350), no published -literature documents the accuracy of these measurements. Standard dosing for adults is 17 grams, which is 1 capful according to the manufacturer. The objective of this study was to determine the weight of household teaspoons and tablespoons of PEG-3350. METHODS: PEG-3350 measurements were performed using 5 different household measuring teaspoons and tablespoons and the cap that accompanies the bottle for 3 different brands of PEG-3350. Using an electronic balance to determine weights, 3 investigators completed 5 measurements for each of the 5 measurement devices and PEG-3350 bottle caps as follows: leveled teaspoons and tablespoons, unleveled teaspoons and tablespoons, "heaping" tablespoons, half-capfuls, and capfuls. RESULTS: A leveled teaspoonful of PEG-3350 weighed ∼3.3 grams and an unleveled teaspoonful weighed ∼3.7 grams. A leveled, unleveled, and heaping tablespoon of PEG-3350 weighed about 10, 11, and 15 grams, respectively. Heaping tablespoons, half-capfuls, and capfuls resulted in the most measurement variability. CONCLUSIONS: Use of a kitchen scale may be the most precise method of measurement, however not all patients have kitchen scales. Standard household measuring devices (teaspoons and tablespoons) may be used to conveniently measure PEG-3350 doses. Using 1 dedicated measurement device and leveling the dose may improve consistency, which could be beneficial for patients who are sensitive to dose variability.

Parenteral Beta-Lactam/Beta-Lactamase Inhibitor Ordering in Hospitals That Provide Care for Pediatric Patients.

OBJECTIVES: The purpose of this study was to define current practices related to beta-lactam/beta-lactamase inhibitor (BL/BLI) dose descriptions in hospitals that provide care for pediatric patients and to identify perceived implications of standardizing BL/BLI dose communication and ordering to a total drug-based strategy. METHODS: A 27-item electronic survey was distributed via 4 pediatric pharmacy and infectious diseases listservs. Survey questions pertained to hospital demographics, dosing communication practices, BL/BLI ordering and labeling practices, obstacles to safe BL/BLI use, and the effects of potential standardization to a total drug communication strategy. SPSS was used for quantitative analysis and MAXQDA was used for qualitative analysis. RESULTS: A total of 140 unique survey responses were analyzed after exclusion of incomplete responses and reconciliation of multiple responses from the same institution. Overall, 56.2% of institutions order BL/BLIs by BL component for pediatric patients, and 22% of institutions order by BL component for adult patients. Approximately half (51.8%) of respondents felt that standardizing to total drug would have a negative effect at their institution; perception of potential effect varied based on the institution's ordering strategy. CONCLUSION: Communication and ordering of BL/BLIs is inconsistent across institutions and between pediatric and adult patients. In the short term, the perception is that standardization would compound institutional challenges.

Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children.

OBJECTIVE: To characterize nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) in children. STUDY DESIGN: We conducted a retrospective chart review of children diagnosed with AKI through the use of International Classification of Diseases, Ninth Revision diagnosis code 584.5 or 584.9 from January 1999 to June 2010. Medical records were reviewed to confirm the diagnosis of AKI and to quantify NSAID administration. Pediatric RIFLE criteria were used to codify AKI. Patients were not classified as having NSAID-associated AKI if they had a diagnosis explaining AKI or comorbid clinical conditions predisposing to AKI development. RESULTS: Patients (N=1015) were identified through International Classification of Diseases, Ninth Revision screening. Twenty-one children had clinical, laboratory, and radiographic studies suggesting NSAID-associated acute tubular necrosis and 6 had findings suggesting NSAID-associated acute interstitial nephritis, representing 2.7% (27 of 1015) of the total cohort with AKI and 6.6% when excluding complex patients with multifactorial AKI. Children with NSAID-associated AKI had a median (range) age of 14.7 years (0.5-17.7 years); 4 patients (15%) were <5 years old. Fifteen of 20 children (75%) for whom dosing data were available received NSAIDs within recommended dosing limits. Patients<5 years old were more likely to require dialysis (100% vs 0%, P<.001), intensive care unit admission (75% vs 9%, P=.013), and a longer length of stay (median 10 vs 7 days, P=.037). CONCLUSIONS: NSAID-associated AKI accounted for 2.7% of AKI in this pediatric population. AKI typically occurred after the administration of correctly dosed NSAIDs. Young children with NSAID-associated AKI may have increased disease severity.

Y-site compatibility of vancomycin and piperacillin/tazobactam at commonly utilized pediatric concentrations.

BACKGROUND: Vancomycin and piperacillin/tazobactam are common empiric antibiotics in hospitalized pediatric patients. Studies evaluating intravenous (IV) compatibility at various concentrations show inconsistent results. OBJECTIVE: The objective of this study was to determine the Y-site compatibility of vancomycin 10 mg/mL and piperacillin/tazobactam 112.5 mg/mL. METHODS: Vancomycin (10 g vial) was reconstituted using sterile water for injection (SWFI) and diluted with 5% dextrose in water (D5W) to a final concentration of 10 mg/mL in an evacuated IV bag. Piperacillin/tazobactam (40.5 g vial) was reconstituted and diluted with SWFI to a final concentration of 112.5 mg/mL (100 mg/mL piperacillin) in an evacuated IV bag. Both antibacterial stock solutions were then stored in a refrigerator at 4°C (39.2°F). Initial solution appearances, including color, clarity, and particulates, were documented. Diluted solutions were mixed in a quantity of 3 mL of each vancomycin and piperacillin/tazobactam in glass test tubes. Subsequent evaluation included pH assessment and visual evaluation with unaided eye, magnifying glass, high-beam light, and via Spec-20 turbidimeter. Solution mixtures were evaluated upon mixing and again at 30 minutes, 1 hour, and 4 hours after mixing. RESULTS: Initial combination of vancomycin and piperacillin/tazobactam resulted in a milky precipitate, visible to the unaided eye, which dissipated 15 seconds after mixing. No precipitate was visualized via any method at any additional time point. Turbidimetry and pH readings did not demonstrate differences from baseline measurements. CONCLUSIONS: A combination of vancomycin 10 mg/mL and piperacillin/tazobactam 112.5 mg/mL demonstrated precipitation immediately upon mixing. Co-infusion of vancomycin and piperacillin/tazobactam via Y-site should be considered incompatible.

National Amoxicillin-Clavulanate Formulation Use Pattern: A Survey.

OBJECTIVE: Five commercially available amoxicillin-clavulanate (AMC) ratio formulations contribute to ratio selection variability with efficacy and toxicity implications. The objective of this survey was to determine AMC formulation use patterns across the United States. METHODS: A multicenter practitioner survey was distributed to multiple listservs (American College of Clinical Pharmacy pediatrics, infectious diseases, ambulatory care, pharmacy administration; American Society of Health-System Pharmacists; Pediatric Pharmacy Association members), and selected pediatric Vizient members in June 2019. Responses were screened for multiples within institutions. Repeated organization responses were identified (n = 37) and excluded if the duplicate matched another response from the same organization exactly (n = 0). RESULTS: One hundred ninety independent responses were received. Nearly 62% of respondents represented a children's hospital within an acute care hospital; remainder being from stand-alone children's hospitals. Around 55% of respondents indicated prescribers were responsible for choosing the patient-specific formulation for inpatients. Nearly 70% of respondents indicated multiple formulations were available due to clinical need (efficacy, toxicity, measurable volume), whereas over 40% responded that the number of liquid formulations were limited to decrease the potential for error. Variability was demonstrated among institutions using ≥ 2 different formulations for acute otitis media (AOM), sinusitis, lower respiratory tract infection, skin and soft tissue infection, and urinary tract infection (33.6%, 37.3%, 41.5%, 35.8%, and 35.8%, respectively). The 14:1 formulation was the most common, but not exclusive, for AOM, sinusitis, and lower respiratory tract infections with 2.1%, 2.1%, and 2.6% of respondents indicating use of the 2:1 formulation and 10.9%, 15%, and 16.6% of respondents indicating use of the 4:1 formulation. CONCLUSIONS: Significant AMC formulation selection variability exists across the United States.

Implementation of a Shared Pediatric Pharmacy Elective During the COVID-19 Pandemic.

During the COVID-19 pandemic, educators were forced to identify innovative teaching strategies to deliver high-quality learning experiences to students. In spring 2021, faculty at Butler College of Pharmacy and Health Sciences and Purdue University College of Pharmacy collaborated to successfully implement a shared pediatric pharmacy elective at both institutions.

Cefuroxime pharmacokinetics in pediatric cardiovascular surgery patients undergoing cardiopulmonary bypass.

OBJECTIVES: The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. DESIGN: A prospective study. SETTING: A tertiary pediatric teaching hospital. PARTICIPANTS: Infants and children undergoing CPB were enrolled in the study. INTERVENTION: An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. MEASUREMENTS AND MAIN RESULTS: Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) µg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. CONCLUSION: Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.

Assessment of Pharyngitis Management at a University Student Health Services Clinic.

OBJECTIVE: The objective of this study was to assess the management of students presenting with pharyngitis to a university health clinic. METHODS: This was a retrospective cohort study. Electronic medical records of undergraduate students presenting to a university health clinic from January 1, 2012, through December 31, 2014, with complaints of sore throat and a diagnosis code for pharyngitis, tonsillitis, or sore throat were reviewed. RESULTS: Records of 241 patients were screened and 197 patients were included. A rapid antigen detection test (RADT) was obtained in 145 (73.6%) patients. The incidence of group A streptococci (GAS) and non-GAS were 15.2% (30/197) and 10.1% (21/197), respectively. All patients with a positive RADT were prescribed antibiotics, with 13 (46.4%) receiving amoxicillin. Overall, 129 (65%) patients received an antibiotic prescription. CONCLUSION: Management of pharyngitis at the clinic appears inconsistent with current guidelines. Approximately 2 of every 3 students were prescribed an antibiotic with no clear indication.

Joint Statement on Pediatric Education at Schools of Pharmacy.

Providing health care for children is a unique specialty, and pediatric patients represent approximately 25% of the population. Education of pharmacy students on patients across the lifespan is required by current Accreditation Council for Pharmacy Education standards and outcomes; thus, it is essential that pharmacy students gain a proficiency in caring for children. A collaborative panel of pediatric faculty members from schools and colleges of pharmacy was established to review the current literature regarding pediatric education in Doctor of Pharmacy curricula and establish updated recommendations for the provision of pediatric pharmacy education. This statement outlines five recommendations supporting inclusion of pediatric content and skills in Doctor of Pharmacy curricula.

Sildenafil for the treatment of pulmonary hypertension in pediatric patients.

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This review summarizes the available data describing the use, safety, and efficacy of sildenafil for children with pulmonary hypertension.

Comparison of Antibiotic Dosing Before and After Implementation of an Electronic Order Set.

BACKGROUND: To maximize resources, the antimicrobial stewardship program at a pediatric tertiary care hospital made pediatric dosing specific guidance within the electronic health record available to all hospitals within the health system. OBJECTIVE: The objective of this study was to compare the appropriateness of antibiotic dosing before and after the implementation of an electronic intravenous (IV) antibiotic order set. METHODS: This was a retrospective cohort study evaluating orders from patients younger than 18 years who received cefepime, piperacillin-tazobactam, tobramycin, or gentamicin at 12 health-system hospitals. Antibiotic dosing regimens and order set use were evaluated in patients who received the specified antibiotics during the 6-month time frame prior to and following electronic order set availability at each hospital. RESULTS: In the before and after implementation periods, 360 and 387 total antibiotic orders were included, respectively. Most orders were gentamicin (55.8% in the before implementation period and 54.5% in the after implementation period) followed by piperacillin-tazobactam (22.5% in the before period and 22.2% in the after period). Overall, 663 orders were classified as appropriate (88.8%). Appropriateness was similar in the before or after implementation periods (87.8 vs. 89.7%, p = 0.415). There was a significant difference in appropriateness if a blank order versus the electronic IV antibiotic order set was used (82.8 vs. 90.5%; p = 0.024). CONCLUSION: No difference in antibiotic appropriateness overall was found in the before and after implementation periods. However, when specifically compared with the appropriateness of dosing when blank order forms were used, dosing was more appropriate when electronic antibiotic order sets were used.

Characterization of the Clinical Outcomes With Cefepime in a Neonatal Intensive Care Unit: A Retrospective Cohort Study.

OBJECTIVES: The objective of this study was to characterize clinical outcomes when cefepime was used in a neonatal intensive care population. METHODS: Data were extracted from the medical records of all full-term (40 weeks gestational age) patients up to 2 months of age and preterm patients up to 48 weeks postmenstrual age admitted to the neonatal intensive care unit (NICU) at a freestanding children's hospital between January 1, 2010, and December 31, 2013, who received at least 48 hours of cefepime. The primary outcome measure was a positive clinical response as defined by a normalization of white blood cell count and/or culture clearance. RESULTS: Final analysis included 74 patients. Clinical response was evaluable in 43.2% (32 of 74) of courses. Of these, positive clinical response was observed in 81.3% (26 of 32). Overall patient mortality was 16.2% (12 of 74). Adverse effects (AEs) occurred in 14.9% (11 of 74) of courses. CONCLUSIONS: Cefepime can be used safely with reasonable clinical response in a NICU population, but additional studies are needed to further determine cefepime-associated clinical outcomes.

Identification of Factors Associated With the Desire to Participate in a Pediatric Pharmacy Practice-Based Research Network.

OBJECTIVES: To evaluate the practice-based research network (PBRN) potential within the Pediatric Pharmacy Advocacy Group (PPAG) membership and to identify characteristics associated with member willingness to join a PPAG PBRN. METHODS: In October 2016, a 21-question survey was sent by email to approximately 900 PPAG pharmacist members (excluding students) using contact information contained in the PPAG membership database. The survey elucidated information regarding training, clinical and research experience, practice site information, and willingness to participate in a PPAG PBRN. Descriptive statistics described the potential PBRN and multivariate logistic regression determined respondent characteristics associated with willingness to join the PBRN. RESULTS: Of 145 survey respondents (a 16% survey response rate), 92 selected "yes" regarding their willingness to participate in the PPAG PBRN. Acute care general pediatrics was the most common area where respondents desired to perform research (44.6% of "yes" respondents), with over 2500 patients/day collectively available. The most common selected limitations to research were time and size of available patient populations (59.8% and 47.8% of "yes" respondents, respectively). Cumulative hours/week members would be willing to devote to the PBRN was approximately 77 to 206. Publication of a retrospective study (OR 10.4, 95% CI 2.1-51.9, p = 0.004), research protected time (OR 4.9, 95% CI 1.4-17.8, p = 0.015), and affiliation with an academic medical center (OR 3.32, 95% CI 1.05-10.45, p = 0.04) were independently associated with willingness (a "yes" response) to join a PPAG PBRN. CONCLUSIONS: Within the PPAG membership, there is sufficient interest, expertise, patient exposure, and member time to develop a PBRN focused on pediatric pharmacotherapy. The identified characteristics associated with willingness to join the PBRN can help focus efforts for member involvement, education, and recruitment to ensure sustainability of the PPAG PBRN.