The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists have recently published revised guidelines for the therapeutic monitoring of vancomycin. Previous iterations of the guideline largely focused on targeting vancomycin trough concentrations (VTCs) in the range of 15 to 20 mg/L for therapeutic efficacy. The revised guidelines shift the focus of therapeutic monitoring directly to AUC/MIC-based therapeutic monitoring for children, with a suggestion of a goal AUC/MIC 400 to 800. The primary hesitation in applying these recommendations to children stems from the absence of pediatric clinical data demonstrating correlations with clinical outcomes and either VTC or AUC and no benefit in other secondary outcomes (e.g., recurrence, duration of bacteremia). One can glean indirectly from this that such aggressive dosing and monitoring strategies are unnecessary to achieve therapeutic success in the majority of children with serious methicillin-resistant Staphylococcus aureus infections. Providers should carefully weigh the potential unknown benefits of targeting vancomycin AUC 400 to 800 mg*hr/L in children with the known risks of acute kidney injury associated with increasing the dose of vancomycin as well as the substantial time, effort, and costs of this process.
Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ≥400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ≥400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.
The first plant-derived, purified pharmaceutical-grade cannabidiol (CBD) medication, Epidiolex, was approved in the United States by the FDA on June 25, 2018. Its approval for patients ≥ 2 years of age with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) markedly altered the treatment of medically refractory seizures in these disorders. This state-of-the-art review will discuss the history of CBD, its current pharmacology and toxicology, evidence supporting its use in a variety of epileptic syndromes, common side effects and adverse effects, and pharmacokinetically based drug-drug interactions. Owing to the importance in considering side effects, adverse effects, and drug-drug interactions in patients with medically refractory epilepsy syndromes, this review will take a deeper look into the nuances of the above within a clinical context, as compared to the other antiepileptic medications. Furthermore, despite the limited data regarding clinically significant drug-drug interactions, potential pharmacokinetic drug-drug interactions with CBD and other antiepileptics are theorized on the basis of their metabolic pathways. The article will further elucidate future research in terms of long-term efficacy, safety, and drug interactions that is critical to addressing unanswered questions relevant to clinical practice.
To evaluate the incidence and causes of infusion alarms in a NICU/PICU setting. We conducted a 90-day prospective analysis of event logs downloaded daily from infusion pumps (syringe and volumetric pumps). The details about conditions surrounding alarm events were described daily by bedside nurses on a standardized form. The occlusion pressure alarm was set at 300 mm Hg on each device. Forty-one pediatric patients including 12 neonates, mean weight 11.0 ± 11.3 kg (minimum–maximum, 0.48–50), were included for a total infusion time of 2164 hours. Eight hundred forty-three infusion alarms were documented (220 [26.1%] occlusion; 273 [32.4%] infusion completed; 324 [38.4%] door open/syringe disengagement; 26 [3.1%] air-in-line) resulting in an incidence of 4.7 infusion (1.2 occlusion) alarms per patient per day. Detailed conditions surrounding occlusion alarm events were documented in only 22.7% (50/220) of the cases. Of these, 36% (18/50) were related to closed or clamped lines, 4% (2/50) to syringe change, 16% (8/50) to drug injection, and 8% (4/50) to patient-related factors. The remaining 36% (18/50) occurred without any apparent external cause during ongoing infusion, among these drug incompatibilities were a potential cause for 12 events. Alarms from infusion pumps were frequent in the NICU/PICU setting, a quarter of them resulting from line occlusion. Other than well-known triggers (mechanical and patient factors), drug incompatibilities were identified as a potential cause for occlusion alarms in this pilot study.OBJECTIVES
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In preterm infants, the standard pharmacologic treatment for a hemodynamically significant patent ductus arteriosus (hsPDA) is either ibuprofen or indomethacin. However, these medications may be less effective after 2 weeks of age. We investigated the use of acetaminophen in hsPDA closure beyond 2 weeks of age. An observational study of 11 infants, <30 weeks' gestation at birth and postnatal age > 2 weeks, who received acetaminophen treatment for their hsPDA. Echocardiograms (ECHOs), B-type natriuretic peptide (BNP) levels, and the fraction of inspired oxygen (FiO2) were obtained before and after treatment to analyze ductal characteristics. Renal and liver functions were monitored pretreatment and posttreatment to look for potential medication side effects. Of the 10 infants with ECHO data for before and after acetaminophen treatments, 4/10 (40%) had a decrease in PDA size, with no infants having complete closure immediately posttreatment. Eight of 11 (73%) infants had a decreased FiO2 requirement after treatment. Of the 5 infants with pretreatment and posttreatment BNP data, 2/5 (40%) infants had a decrease in BNP level. One infant received an additional course of acetaminophen. Four infants underwent a surgical ligation. Two infants died. No medication side effects occurred with regard to hepatic and renal function. Acetaminophen is a safe and effective pharmacologic treatment to reduce the significance of the hsPDA in some infants beyond 2 weeks of age, as shown by ECHO and BNP data.OBJECTIVE
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Children admitted to the ICU are commonly treated with opioids for postoperative pain. We hypothesized that administration of IV acetaminophen in the immediate postoperative period is effective in lowering cumulative opioid use leading to other benefits. This was a retrospective chart review of patients admitted to the PICU between December 2016 and April 2019. For each patient, data including demographics, cumulative opioid usage per kilogram, oral or rectal acetaminophen, x-ray findings, hospital costs, and surgical procedure were collected. Cumulative opioid usage was determined by converting all opioids to morphine equivalents (MEs) per kg. Standard descriptive and comparative analyses were conducted using SAS 9.4 (SAS Institute, Inc, Cary, NC). A total of 200 patients met inclusion and exclusion criteria (N = 92 in IV acetaminophen group and N = 108 in no IV acetaminophen group). There was no significant difference in ME per kilogram between the groups (0.3 ME/kg in IV acetaminophen group, IQR 0.5 ME/kg versus 0.4 ME/kg in no IV acetaminophen group, IQR 0.5 ME/kg, adjusted p = 0.38). Rate of atelectasis was not significant between the groups (47.8% in IV acetaminophen versus 45.4% in no acetaminophen group, p = 0.28). There was a significant difference in median total hospital costs between the groups ($22,456 in IV acetaminophen group, IQR $18,650 versus $18,552 in no IV acetaminophen group, IQR $13,361, adjusted p = 0.04). IV acetaminophen in the immediate postoperative period did not lead to a decrease in cumulative opioid usage or rate of atelectasis. IV acetaminophen usage was associated with increase in overall hospital costs per patient.OBJECTIVE
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To determine whether combination therapy with vancomycin and TZP is associated with a higher incidence of acute kidney injury (AKI) compared with vancomycin with cefepime in infants admitted to the NICU. This retrospective cohort study included infants in the NICU who received vancomycin/cefepime or vancomycin/TZP for at least 48 hours. The primary outcome was incidence of AKI, which was defined by the neonatal modified Kidney Disease Improving Global Outcomes AKI criteria. Forty-two infants who received vancomycin with cefepime and 58 infants who received vancomycin with TZP were included in the analysis. The median gestational age at birth, birth weight, and dosing weight were lower in the TZP group, but other baseline characteristics were comparable, including corrected gestational age. Two patients (3%) receiving vancomycin/TZP versus 2 patients (5%) receiving vancomycin/cefepime met criteria for AKI during their antibiotic course (p = 1.00). There were no clinically significant changes in serum creatinine or urine output from baseline to the end of combination antibiotic treatment in either group. Among infants admitted to our NICU, AKI incidence associated with vancomycin and either TZP or cefepime therapy was low and did not differ by antibiotic combination.OBJECTIVES
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Aprepitant is effective for the prevention of chemotherapy-induced or postoperative nausea and vomiting (CINV/PONV). The aim of this study was to develop a population pharmacokinetic (PK) model of aprepitant in pediatric patients and to support dosing recommendations for oral aprepitant in pediatric patients at risk of CINV. A population PK model was constructed based on data from 3 clinical studies in which children (6 months to 12 years) and adolescents (12–19 years) were treated with a 3-day regimen of oral aprepitant (capsules or suspension), with or without intravenous fosaprepitant on day 1 (CINV), or a single dose of oral aprepitant (capsules or suspension; PONV). Nonlinear mixed-effects modeling was used for model development, and a stepwise covariate search determined factors influencing PK parameters. Simulations were performed to guide final dosing strategies of aprepitant in pediatric patients. The analysis included 1326 aprepitant plasma concentrations from 147 patients. Aprepitant PK was described by a 2-compartment model with linear elimination and first-order absorption, with allometric scaling for central and peripheral clearance and volume using body weight, and a cytochrome P450 3A4 maturation component for the effect of ontogeny on systemic clearance. Simulations established that application of a weight-based (for those <12 years) and fixed-dose (for those 12–17 years) dosing regimen results in comparable exposures to those observed in adults. The developed population PK model adequately described aprepitant PK across a broad pediatric population, justifying fixed (adult) dosing for adolescents and weight-based dosing of oral aprepitant for children.OBJECTIVES
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Postoperative bleeding is a common cause of morbidity and mortality in cardiac patients who undergo cardiopulmonary bypass (CPB). Pediatric patients are especially at risk for adverse effects of surgery and CPB on the coagulation system. This can result in bleeding, transfusions, and poor outcomes. Excessive bleeding unresponsive to blood products can warrant the off-label use of recombinant activated clotting factor VIIa (rFVIIa) and/or anti-inhibitor coagulant complex (FEIBA). Several studies have shown the utility in these agents off-label in patients who have undergone cardiac bypass surgery with acute bleeding episodes that are refractory to blood products. However, data regarding use of these agents in pediatrics are sparse. The purpose of this study is to report the use of rFVIIa and FEIBA in pediatric cardiac surgery patients in our institution. This was a retrospective chart review of pediatric cardiothoracic surgery patients who received rFVIIa or FEIBA at Children's Healthcare of Atlanta during the study period. Thirty-three patients received rFVIIa and 9 patients received FEIBA either intraoperatively or postoperatively for bleeding related to the cardiac procedure. Approximately 13% of rFVIIa patients and 55% of FEIBA patients required repeat doses. There were decreases for all blood products administered after rFVIIa and FEIBA were given. However, the doses used did not correlate with either positive or negative outcomes. Seventeen percent (n = 7) of rFVIIa patients experienced a thrombus and 22% (n = 2) of FEIBA patients experienced a thrombus. Both rFVIIa and FEIBA reduced blood product usage in pediatric patients following cardiac procedures.OBJECTIVES
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Late-onset sepsis caused by Staphylococcus aureus is a serious and relatively common complication encountered by preterm neonates in NICUs. Typical treatment regimens for invasive methicillin-sensitive Staphylococcus aureus (MSSA) include semisynthetic beta lactam antibiotics, such as nafcillin. This report describes the first use of a combination of cefazolin and ertapenem to successfully treat persistent MSSA bacteremia in a preterm neonate who failed traditional first-line therapy.
A 19-month-old child presented with fever and acute neurological deterioration with hypertonia, tremors, and clonus 1 day after starting metoclopramide. The clinical course of the patient was suggestive of neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS), which can both be triggered by metoclopramide. This first pediatric report of an overlap between NMS and SS associated to metoclopramide highlights the importance of considering this new entity and its consequences on treatment.
As pediatric pharmacists and residency program directors, we read with interest the article by Shaddix et al1 outlining the advantages and disadvantages of pediatric-focused and traditional postgraduate year 1 (PGY1) pharmacy residencies. Which program is the right fit is a question every student needs to answer when evaluating PGY1 residencies. In addition to the points outlined in the recent article, we believe there are several other considerations when deciding which program best prepares one for a postgraduate year 2 (PGY2) pediatric pharmacy residency and a career in pediatrics. The authors group PGY1 programs into “pediatric-focused”To the Editor