Protection of children from medication toxicity and providing evidence of effectiveness have long been the goals of studies of drugs in infants, children and adolescents. Ideally, the first child studied with a newly approved medication will receive that drug in dosages based on well-controlled studies with well-studied appropriate formulations in similar aged patients with similar disorders that established efficacy similar to what was required in adults. With motivation to achieve what is best for children, we have come a long way, but the progress is incomplete. In the 1800's, the beginning of modern pharmacopeia's emerged in the U.S. and Europe.
Azithromycin has been explored as a treatment option for eradication of Ureaplasma and prevention of bronchopulmonary dysplasia (BPD) in preterm neonates. However, there is debate about the need for eradication of Ureaplasma and whether azithromycin is safe and efficacious for this indication. This literature review provides an overview of the evidence for use of azithromycin for eradication of Ureaplasma and prevention of BPD, including dosing and duration of azithromycin used in these studies. The literature search included articles published in the English language in Medline and PubMed from 1946 to January 2022. Relevant citations within identified articles were also reviewed. A total of 9 studies representing 388 neonates were included. The percentage of neonates that tested positive for Ureaplasma in these studies ranged from 18.6% to 57.1%. Azithromycin was initiated at <3 days of life in 8 studies (88.9%). Dosing was variable and ranged from 5 to 20 mg/kg/dose administered once daily, and the duration of treatment ranged from 1 to 35 days. Most studies used intravenous azithromycin. Overall, azithromycin was more efficacious than placebo at Ureaplasma eradication; however, most of these studies did not find a difference in the incidence of BPD between patients receiving azithromycin versus placebo. No adverse effects, specifically pyloric stenosis or QT interval prolongation, were noted in these studies.
Acetaminophen is one of the oldest medications commonly administered in children. Its efficacy in treating fever and pain is well accepted among clinicians. However, the available evidence supporting the use of acetaminophen's different modes of administration remains relatively scarce and poorly known. This short report summarizes the available evidence and provides a framework to guide clinicians regarding a rational use of acetaminophen in children.
To evaluate the effects of dietary eicosapentaenoic acid (EPA) in children with atopic dermatitis. Forty-eight children with atopic dermatitis were randomly allocated to receive either 250 mg twice daily EPA (n = 24) or placebo (n = 24) for 4 weeks. The absolute improvement in the SCORing Atopic Dermatitis (SCORAD) index and the necessity to use topical corticosteroids was evaluated. Based on an intention-to-treat analysis, after 2 weeks the scores decreased to 30.50 ± 8.91 and 38.34 ± 10.52 in the EPA and placebo groups, respectively (p = 0.015). Per-protocol analysis showed a decrease in scores to 18.01 ± 10.63 in the EPA group and to 30.11 ± 9.58 in the placebo group (p = 0.001). After 2 weeks, corticosteroid was needed in 11 (50.0%) patients in the EPA group and 14 (58.3%) patients in the placebo group (p = 0.571), and after 4 weeks, it was needed in 7 (33.3%) patients in the EPA group and 14 (63.6%) patients in the placebo group, respectively (p = 0.047). Our results show significant favorable effects of EPA on the SCORAD scale and with regard to the necessity for corticosteroid readministration. Few adverse effects were reported in the 2 groups. We conclude that EPA supplementation is a well-tolerated and effective add-on strategy for reducing the severity of atopic dermatitis in children.OBJECTIVE
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To evaluate the clinical effect and estimate cost avoidance attributed to a pharmacist-led admission medication reconciliation service at a children's hospital. This was a prospective observational cohort study that measured pharmacist interventions for pediatric patients over a 90-day period. Pharmacists logged all interventions identified during medication reconciliation in real time. Patient demographic data were collected retrospectively. Cost avoidance from prevented adverse drug events (ADEs) was estimated based on previously published literature. Pharmacists completed 283 admission medication reconciliations during the study period. Of those, 69% of medication reconciliations required intervention. Interventions affected care during the hospital admission in 21.9% of patients and 8 medication reconciliations resulted in prevention of a major ADE. This pharmacist-led service resulted in an estimated cost avoidance of $46,746.65 in the 3-month period. Implementation of a pharmacist-led admission medication reconciliation service for pediatric patients improved medication safety and resulted in significant cost avoidance, which justifies investment in these pharmacist resources.OBJECTIVE
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This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity. This was a retrospective chart review comparing the absolute neutrophil counts (ANCs) of neonates administered 2 doses of subcutaneous darbe 10 mcg/kg to that of a randomly selected comparator group of neonates not administered the drug. Neonates <34 weeks gestational age, gestational age between 23w1d and 33w4d, born between July 2016 and June 2019, were included in the study. The ANCs of 45 darbe-treated neonates compared with those of 45 randomly selected comparator control neonates revealed no difference in the rate of occurrence of neutropenia (ANC ≤1000/μL) between the darbe-treated neonates (26.7%) and comparator neonates (24.4%) (p > 0.99). There was also no difference in the rate of occurrence of severe neutropenia (ANC ≤500/μL) between the darbe-treated neonates (11.1%) and comparator neonates (6.7%) (p = 0.70). Darbepoetin alfa did not lead to differences in rates of resolution of neutropenia or severe neutropenia. Short-term administration of darbe did not affect the ANCs of preterm neonates treated for anemia of prematurity. There was no difference in the rates of occurrence of neutropenia, severe neutropenia, or resolution of either between the darbe-treated neonates and comparator neonates.OBJECTIVE
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The primary objective was to evaluate the effect of parenteral potassium chloride (KCl) supplementation on potassium (K+) concentrations in a non-cardiac pediatric population. Secondary outcomes were to identify variables that may influence response to KCl supplementation (i.e., change in K+ concentration after KCl administration) and assess the incidence of hyperkalemia. This single-center, retrospective study evaluated infants and children who received parenteral KCl supplementation of 0.5 or 1 mEq/kg between January 2017 and December 2019. The study included 102 patients with a median age of 1 year (IQR, 0.4–3.9) and weight of 9.1 kg (IQR, 4.9–14.2) who received 288 parenteral KCl administrations. One hundred seventy-three administrations were in the 1 mEq/kg group, and 115 administrations were in the 0.5 mEq/kg group. The median changes in K+ were 0.8 and 0.5 mEq/L in the 1 mEq/kg and 0.5 mEq/kg groups, respectively. Patients who had a repeat K+ concentration within 4 hours of the end of a 1 to 2–hour infusion had a higher median change in K+ compared with those who had a concentration drawn after this time frame (0.8 vs 0.6 mEq/L; p < 0.01). There is a paucity of data on the correlation between parenteral KCl supplementation and change in K+ concentrations in pediatric patients. Our study demonstrated an association between KCl supplementation doses of 1 and 0.5 mEq/kg and changes in K+ of 0.8 and 0.5 mEq/L, respectively, in non-cardiac pediatric patients, with low observed incidence of hyperkalemia.OBJECTIVE
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Sepsis causes morbidity and mortality in pediatric patients, but timely antibiotic administration can improve sepsis outcomes. The pharmacy department can affect the time from order to delivery of antibiotics. By evaluating the pharmacy process, this study aimed to decrease the time from antibiotic order to delivery to within 45 minutes. All antibiotic orders placed following a positive sepsis screen for acute care patients at a freestanding children's hospital from April 1, 2019, to December 31, 2019, were reviewed. Lean Six Sigma methodology including process mapping was used to identify and implement improvements, including educational interventions for providers. Outcome measures included time from antibiotic order placement to delivery and to administration. Additional assessment of process measures included evaluation of order priority, PowerPlan (an internally created order set) use, and delivery method. Ninety-eight antibiotic orders for 85 patients were evaluated. In an individual chart of antibiotic delivery time, a trend towards faster delivery time was observed after interventions. Stat orders (40.5 minutes [IQR, 19.5–48]) were delivered more quickly than routine orders (51 minutes [IQR, 45–65]; p < 0.001). Orders using the PowerPlan (20.5 minutes [IQR, 18.5–38]) were delivered more quickly than those that did not (47 minutes [IQR, 34–64]; p < 0.01). Shorter time to administration was observed with pneumatic tube delivery (41 minutes [IQR, 20–50]) than with direct delivery to a health care provider (51 minutes [IQR, 31–83]; p < 0.05) or to the automated dispensing cabinet's refrigerator (47 minutes [IQR, 41–62]; p < 0.0001). Multifactorial coordinated interventions within the pharmacy department improve medication delivery time for pediatric sepsis antibiotic orders.OBJECTIVE
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An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated. Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety. Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7–49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04–2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07–1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2–15.5) and 80.7% (95% CI, 74.3–87.1), respectively. Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals.OBJECTIVE
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Neonatal gentamicin dosing algorithms are not designed to achieve serum trough concentrations ≤1 mcg/mL. The purpose of our study was to evaluate a new gentamicin algorithm based on serum creatinine (SCr) and gestational age (GA) designed to achieve serum gentamicin trough concentrations ≤1 mcg/mL. A retrospective cohort study was conducted in a level IIIB neonatal intensive care unit. The incidence of elevated serum gentamicin troughs for this study was compared with the center's previously published results to evaluate the proposed dosing algorithm. Patients were included if gentamicin was administered within the first 7 days of life and a serum gentamicin trough concentration and a baseline SCr concentration were obtained. Patients were further subdivided into groups based on GA for data analysis: ≤30 weeks (group 1), 30–34 weeks (group 2), and ≥35 weeks (group 3). The SCr was considered mildly elevated (0.81–0.99 mg/dL) or elevated (≥1 mg/dL). The respective outcomes between the post-algorithm and control groups were examined using intention-to-treat analysis and Bayesian modeling to calculate rate differences. Of the 2377 patients evaluated, 366 met the inclusion criteria. Significantly lower percentages of elevated serum gentamicin troughs were noted in groups 2 and 3 subsequent to the implementation of the dosing algorithm with 16% and 15% lower rate differences, respectively. Regardless of GA, there were significantly fewer elevated serum troughs in the post-implementation groups than in the control with mildly elevated and elevated SCr p < 0.001. Using a dosing algorithm based on SCr significantly reduced the number of elevated serum trough rates in neonates with a GA greater than 30 weeks.OBJECTIVE
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Acetaminophen is a commonly administered analgesic and antipyretic medication that is generally well-tolerated. Recent studies in critically ill adults and subsets of pediatric patients with underlying cardiac disease identify an association between adverse hemodynamic effects with intravenous (IV) acetaminophen. However, the data may not be generalizable to a broader population of critically ill children. The objective of this study was to determine the incidence of hemodynamic changes associated with IV acetaminophen administration in critically ill pediatric medical-surgical patients. This was a retrospective observational study of all patients 18 years of age and younger who received at least 1 dose of IV acetaminophen in a pediatric intensive care unit at a quaternary care medical center, between July and December 2018. The primary outcome was the incidence of hypotension, defined as a decrease in mean arterial pressure (MAP) by at least 15% from baseline. Potential risk factors for IV acetaminophen-associated hypotension were assessed. A total of 212 patients received 492 doses of IV acetaminophen. The primary endpoint of hypotension occurred following 24% of doses. An intervention for hypotension, primarily fluid resuscitation, was required for 11.9% of the dose-associated hypotension events. Patients receiving vasoactive infusions had more frequent dose-associated hypotension events than those not receiving infusions; however, no other potential risk factors were identified. The incidence of hypotension observed in critically ill pediatric patients after IV acetaminophen administration is clinically relevant. Large placebo-controlled trial and further study of the risk factors and mechanism of this hemodynamic change are warranted.OBJECTIVE
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To evaluate the physical intravenous Y-site compatibility of 29 combinations of medications at commonly used pediatric concentrations using both existing and novel techniques. Medication combinations included were selected by a varied group of pediatric inpatient pharmacists, and then assessed by 3 independent reviewers for existing literature. For each combination, 2 different medications were mixed together in a 1:1 ratio and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then analyzed using the US Pharmacopeia (USP) <788> recommended analytical technique of light obscuration (LO) in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP chapter <788> large volume particle count limits for all techniques. A total of 29 different medication combinations were studied. Five combinations met criteria for compatibility by all 3 techniques. The remaining 24 combinations reached the threshold to be considered incompatible by at least 1 of the 3 techniques. Light obscuration, BMI, and FI identified 14%, 59%, and 76% of combinations as incompatible, respectively. All samples deemed incompatible by LO were also incompatible by at least 1 of the other 2 techniques. Flow imaging and BMI results agreed in 69% of samples tested. Most combinations tested were found to be incompatible by at least 1 of the 3 instruments used. Light obscuration appears to have reduced accuracy for identifying particulate resulting in physical medication incompatibility when compared with the novel techniques of FI and BMI.OBJECTIVE
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Congenitally acquired cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide and the most frequent cause of acquired sensorineural hearing loss. The burden of the disease is even more important in premature and very low birth weight infants. However, few data exist on the treatment with intravenous ganciclovir and oral valganciclovir in this vulnerable population. We report the case of twins congenitally infected with CMV and born prematurely at 27 weeks' gestation. Treatment regimens were initially individualized for their prematurity and renal function, and then adjusted with therapeutic drug monitoring (TDM) to adapt to their continuously evolving physiologic maturation. As infants were aging, the plasmatic half-life of ganciclovir slowly decreased to term infant values around 10 weeks of chronological age, or 37 weeks of postmenstrual age. Results for blood polymerase chain reaction tests became negative and long-term follow-ups were satisfactory in both twins. The limited data for infants born before 32 weeks of gestation or at less than 1200 g and evolution of ganciclovir pharmacokinetic parameters justify the use of TDM in these settings.
We report a case of a 7-year old male with idiopathic pulmonary arterial hypertension, successfully transitioned from an intravenous infusion to inhaled treprostinil during inpatient admission, after his intentional removal of multiple central venous catheters. He had no clinical, echocardiographic, or serum biomarker evidence of loss of control of pulmonary arterial hypertension during the 4-day transition. The patient was discharged home without complications, and 3 weeks after discharge the patient's pulmonary hypertension remained well controlled per clinical and echocardiographic evidence, including a significantly improved 6-minute walk distance test.