Journal of Pediatric Pharmacology and Therapeutics最新文献

Objective: Given the limited data on the use of ibuprofen arginine for the closure of patent ductus arteriosus (PDA), this study aims to retrospectively assess PDA closure rates and the safety profile of ibuprofen arginine as compared with ibuprofen lysine and indomethacin in neonates across a multicenter hospital system.

Methods: This retrospective cohort study included neonates with symptomatic PDA admitted between July 2021 and August 2023, who received at least 1 dose of injectable indomethacin, ibuprofen lysine, or ibuprofen arginine. The primary aim was to compare closure rates of the PDA during the initial course of pharmacologic therapy. Secondary outcomes included the failure of therapy necessitating a repeat course or surgical ligation and adverse effects such as gastrointestinal bleeding, acute kidney injury, necrotizing enterocolitis, chronic lung disease, and intraventricular hemorrhage.

Results: A total of 54 patients were included in the analysis; 26 received indomethacin, 13 received ibuprofen lysine, and 15 received ibuprofen arginine. There was no significant difference among groups in terms of closure rates after 1 course (53% indomethacin, 39% ibuprofen lysine, and 47% ibuprofen arginine; p = 0.66). Similarly, no differences were found in the need for a repeat course (35% indomethacin, 54% ibuprofen lysine, and 53% ibuprofen arginine; p = 0.29) or surgical ligation. Adverse effects rates were comparable across the groups.

Conclusions: Indomethacin, ibuprofen lysine and ibuprofen arginine can all be considered viable options for pharmacologic closure of PDA in this population. Future prospective studies are needed to confirm these results and optimize patient outcomes.

Objective: This study compares the efficacy of starting with low-dose vs high-dose enteral clonidine for the treatment of pain, agitation, and opioid withdrawal in high-risk infants admitted to the neonatal intensive care unit (NICU).

Methods: This was a retrospective chart review study of infants admitted to a level IV NICU between September 2014 and December 2022 who were started on enteral clonidine before 50 weeks post-menstrual age (PMA) for pain, agitation, or opioid withdrawal. Data were collected over the first 30 days of clonidine treatment. Infants started on low-dose (LDC: <4 mcg/kg/day) and high-dose clonidine (HDC: ≥4 mcg/kg/day) were compared using SPSS V29.0 (IBM) for statistical analyses.

Results: Ninety-five infants met the inclusion criteria; 41 received LDC, and 54 received HDC. There were no statistically significant differences in any demographic parameter between the groups before starting clonidine. There was no difference in reduction in Neonatal-Pain, Agitation, and Sedation Scale (N-PASS) scores during the 30-day treatment period, despite the LDC group having a lower maximum clonidine dose (4 vs 8 mcg/kg/day, p ≤ 0.01) than the HDC group.

Conclusion: Our observational study suggests that starting with LDC may be as effective as HDC in treating pain, agitation, and opioid withdrawal in infants admitted to the NICU.

Objective: Central venous catheter (CVC) thrombosis is a serious complication in pediatric intestinal failure (IF) patients who require long-term parenteral nutrition. Alteplase is commonly used to restore patency in catheter-related thrombosis. Dispensing practices may vary and include constitution of 2-mg ready-to-use vials by nursing staff or thawing of batched frozen syringes from previously cryopreserved larger alteplase vials, which requires pharmacy involvement. Objectives included comparing time to administration, CVC patency restoration rates, and cost between dispensing methods.

Methods: Single-center retrospective study evaluating patients with IF who presented with catheter-related thrombosis and received alteplase between 2011 and 2017. Patients were consecutively enrolled from the Pediatric Intestinal Rehabilitation program's institutional database. Data included IF-related care during outpatient visits, emergency department (ED) visits, and hospitalizations, including thrombosis events. CVCs were placed by either a pediatric surgeon or the vascular access team, depending on catheter type. Removal occurred if patients were weaned off parenteral nutrition, had an irreparable line break, or a nonsalvageable infection. We reported the efficacy of the intervention in restoring CVC patency using a weight-based alteplase dosing. Cost analysis included assessment of medication cost, pharmacy technician, pharmacist, and nursing time.

Results: We recorded 83 alteplase administrations in 16 patients. Most (81.9%) were instilled in tunneled single-lumen silicon catheters. Alteplase installation was performed in the outpatient clinic (35%), inpatient (59%), and the ED (6%). Ready-to-use 2-mg vials were used in 31% of cases. Median time to administration was significantly shorter with ready-to-use 2-mg vials compared with thawed frozen syringes, at 15 and 71 minutes, respectively (p < 0.0001). The success of restoring patency was noted in 65% and 70% of cases after 1 and 2 doses of alteplase, respectively. Cost was similar between dispensing thawed frozen syringes and ready-to-use 2-mg vials, at $189.0 and $190.4, respectively (based on 2023 expense data).

Conclusions: In this population with long-term CVC dependence, dispensing alteplase using ready-to-use 2-mg vials was associated with a significantly shorter time to administration and comparable cost compared with batching and dispensing thawed frozen syringes.

Objective: Escherichia coli is a leading cause of Gram-negative rod bacteremia in infants. Cerebrospinal fluid (CSF) evaluation is often deferred, and guidance on antibiotic duration is lacking in these circumstances. We evaluated whether treatment duration is associated with infection recurrence or mortality.

Methods: This cohort study included infants discharged from Pediatrix Medical Group neonatal intensive care units (NICUs) from 1997 to 2022 with first instance of E coli bacteremia. Infants with CSF evaluation, delayed antimicrobial initiation (>2 days), or death/discharge during therapy were excluded. Antibiotic duration was categorized as <14, 14-21, or >21 days. Associations between treatment duration and 30-day and in-hospital mortality and the combined outcome of recurrence of infection or death within 30 days were evaluated by using 2-way tabulations and inverse probability weighted regression adjustment (IPWRA) models. Sensitivity analysis excluded courses <5 days.

Results: We included 1125 infants with E coli bacteremia. After adjusting for gestational age, postnatal age, number of positive cultures, and severe disease, shorter courses were associated with higher 30-day and in-hospital mortality and the combined outcome. IPWRA modeling confirmed lower risks among infants treated for longer durations. The results were similar in the sensitivity analysis.

Conclusions: While the optimal duration of therapy for infants with E coli bacteremia without CSF evaluation requires further evaluation, our data suggest that infants should receive antibiotic therapy for at least 14 days and that longer durations (21 days) can be considered.

Objective: Meropenem is commonly used to treat bloodstream and central nervous system (CNS) infections in preterm and term infants; however, the optimal dosage of meropenem in infants <3 months is not known, and its cerebrospinal fluid (CSF) pharmacokinetics (PK) are not well established in this age group.

Methods: We externally evaluated a previously developed meropenem population PK model using opportunistic plasma and CSF PK samples collected in infants and children <2 years of age who received intravenous meropenem per standard of care. We evaluated model performance, and simulated age-dependent dosing regimens (20 and 40 mg/kg every 8 hours [12 hours if gestational age <32 weeks and postnatal age <2 weeks]) to estimate the reduction in CSF bacterial burden.

Results: Clinical and PK data from 10 children were used to externally evaluate the NeoMero model; model predictive performance was satisfactory with the addition of NeoMero (n = 167) data. Visual predictive check of combined data showed reasonable concordance between predictions and observed concentrations for plasma and CSF. Dosing simulations adjusted for population minimum inhibitory concentration distributions for Pseudomonas aeruginosa estimated that a 20 mg/kg intravenous bolus dose reduced CSF bacterial burden by a weighted mean 5.13 (SD 1.51) log colony forming unit (CFU), while a 40 mg/kg intravenous bolus dose resulted in a weighted mean 5.48 (SD 1.14) log CFU reduction in CSF.

Conclusions: The original NeoMero model performed reasonably well, and the proposed dosing regimens, that is, 20 or 40 mg/kg every 8 hours (12 hours if gestational age <32 weeks and postnatal age <2 weeks), depending on target MIC are estimated to achieve substantial bacterial killing in the CNS.

Introduction: Avoiding residual neuromuscular blockade in the postoperative period sparked interest in the use of sugammadex as a reversal agent. However, because sugammadex was considered more expensive than other commonly used medications for this purpose, it was crucial to investigate potential disparities in its use.

Methods: A retrospective cohort study of children (<18 years) was performed, who underwent general anesthesia and received neuromuscular blockade, in hospitals reporting to the Pediatric Health Information System between January 1, 2018, and December 31, 2023 was performed. Multivariable log-binomial regression was used to estimate the adjusted relative risk (RRAdj) of sugammadex administration across racial and ethnic groups, while adjusting for baseline covariates.

Results: The study included 246,171 children. The overall use of sugammadex steadily increased among all groups throughout the study period from 2018 to 2023. The adjusted rate of sugammadex administration trended consistently lower for Black children compared with White children throughout the study period (54.5% vs 62.7%, RRAdj: 0.86 [95% CI, 0.84-0.87]), p < 0.01). A less pronounced lower rate of receiving sugammadex was noted for Hispanic children compared with White children (60.7% vs 62.7%, RRAdj 0.97 [95% CI, 0.95-0.98], p < 0.01). Asian children were also less likely to receive sugammadex, compared with White children (58.7% vs 62.7%, RRAdj 0.94 [95% CI, 0.91-0.96], p < 0.01). Within insurance group comparisons mirrored the disparities observed in the main model.

Conclusions: Despite increased use of sugammadex among children who underwent elective surgery, racial and ethnic disparities in its use remained. These differences persisted regardless of insurance status.

Objective: Dalbavancin, a lipoglycopeptide antibiotic active against Gram-positive bacteria with a prolonged in vivo half-life, was recently approved by the Food and Drug Administration for use in pediatric skin/soft tissue infection. Although use in adult skin/soft tissue infection and off-label use in adult osteoarticular and bloodstream infection are well documented, pediatric data are limited to pharmacokinetic data, 1 clinical trial, and case reports/series. Here, we describe the clinical and microbiologic details of cases in which dalbavancin was used at 2 pediatric hospitals.

Methods: Chart review of all patients receiving dalbavancin for any indication in 2 pediatric hospitals between August 2020 and July 2025.

Results: Dalbavancin was used in 20 patients (age range 2 weeks to 18 years) in the time period. Fifteen cases had infection with either methicillin-susceptible or -resistant Staphylococcus aureus, 16 had bacteremia, 2 had endocarditis, and 11 cases had isolates available for dalbavancin susceptibility testing; all proved susceptible. Reasons for dalbavancin use included need for intravenous therapy with relative contraindications for alternative oral antibiotics or outpatient parenteral antibiotic therapy, difficulty of intravenous access, and medication nonadherence. Most cases had an uncomplicated recovery. None had microbiologic failure.

Conclusions: With the limitations of this series and prior published data, dalbavancin may be a safe and efficacious antibiotic for use in certain invasive Gram-positive infections in children. It is a reasonable alternative when faced with relative contraindications to inpatient or outpatient parenteral therapy, especially when bactericidal therapy is needed or preferred. Formal pediatric trials against the standard of care, especially beyond skin/soft tissue infection, are encouraged.

Objective: L-asparaginase is an essential component of pediatric acute lymphoblastic leukemia (ALL) treatment. However, hypersensitivity reactions can occur, necessitating a switch to alternative asparaginase formulations. In resource-limited settings, access to pegylated asparaginase and Erwinia asparaginase may be limited. This study aimed to evaluate the safety and feasibility of a premedication protocol in preventing subsequent L-asparaginase hypersensitivity reactions in children with a history of severe reactions to native Escherichia coli L-asparaginase.

Methods: A retrospective cohort study was conducted in 119 children with ALL treated with L-asparaginase at Chiang Mai University Hospital. Ten patients (8.4%) developed severe systemic hypersensitivity reactions. Subsequent intramuscular L-asparaginase doses were preceded by a standardized premedication protocol comprising oral prednisolone, cetirizine, and montelukast, along with preinfusion intravenous hydrocortisone.

Results: A total of 76 subsequent L-asparaginase doses were administered following premedication. Seven episodes (9.2%) of recurrent hypersensitivity reactions occurring within 5 to 40 minutes of L-asparaginase dosing occurred in 6 patients. Most reactions were mild and managed with additional antihistamines and corticosteroids. One episode required treatment with intramuscular epinephrine. All patients successfully completed their prescribed course of L-asparaginase therapy.

Conclusion: In resource-limited settings, our premedication protocol demonstrated potential for safely enabling continued native E. coli L-asparaginase therapy in children with a history of severe hypersensitivity reactions, thus potentially improving access to chemotherapy treatment.

Objective: The optimal antibiotic duration for infants with Escherichia coli bacteremia with reliable, normal cerebrospinal fluid (CSF) studies and without meningitis is unknown. We evaluated whether treatment duration is associated with infection recurrence or mortality in these infants.

Methods: This cohort study included infants discharged from Pediatrix Medical Group neonatal intensive care units between 2003-2022 with first instance of E coli bacteremia. Exclusion criteria included absence of CSF test results, CSF pleocytosis, positive culture or Gram stain from the CSF, delayed antimicrobial initiation (>2 days), or death/discharge during therapy. Antibiotic duration was categorized as <10, 10 to 14, or >14 days. Univariable analysis and multivariable logistic regression were used to assess associations between antibiotic duration and 30-day and in-hospital mortality, recurrence of infection, and the combined outcome of recurrence of infection or 30-day mortality. Sensitivity analysis excluded courses <5 days.

Results: In 682 infants with E coli bacteremia, recurrence of infection or death following antibiotics occurred in 3% and was not associated with antibiotic duration (p = 0.82). After adjusting for gestational age and severe disease (defined as 1 or more of the following: mechanical ventilation, inotropic administration, or extracorporeal support) on the first day of bacteremia, antibiotic durations of 10 to 14 days were associated with lower odds of 30-day mortality (OR 0.18; 95% CI: 0.03-0.99) than antibiotic durations of <10 days. In the sensitivity analysis (N = 667), antibiotic duration was not predictive of any outcomes.

Conclusions: A 10-day course of antibiotics for E coli bacteremia with normal CSF results is likely sufficient for term and preterm infants.