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Background: Vancomycin is commonly used to treat acute pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus. Optimizing vancomycin exposure during therapy is essential and area under-the-curve (AUC)-guided dosing is now recommended. Model-informed precision dosing (MIPD) utilizing Bayesian forecasting is a powerful approach that can support AUC-guided dose individualization. The objective of the current study was to examine the impact of implementing an AUC-guided dose individualization approach supported via a MIPD clinical decision support (CDS) tool on vancomycin exposure, target attainment rate, and safety in pediatric patients with CF treated with vancomycin during clinical care., Methods: A retrospective chart review was performed in patients with CF at a single children's hospital comparing pre- and post-implementation of a MIPD approach for vancomycin supported by a cloud-based, CDS tool integrated into the electronic health record (EHR). In the pre-MIPD period, vancomycin starting doses of 60 mg/kg/day (<13 years) or 45 mg/kg/day (≥13 years) were used. Dose adjustment was guided by therapeutic drug monitoring (TDM) with a target trough 10-20 mg/L. In the post-MIPD period, starting dose and dose adjustment were based on the MIPD CDS tool predictions with a target 24 h AUC (AUC 24 ) 400-600 mg*h/L. Exposure and target achievement rates were retrospectively calculated and compared. Rates of acute kidney injury (AKI) were also compared., Results: Overall, 23 patient courses were included in the pre-MIPD period and 21 patient courses in the post-MIPD period. In the post-MIPD period, an individualized MIPD starting dose resulted in 71% of patients achieving target AUC 24 compared to 39% in the pre-MIPD period (p < 0.05). After the first TDM and dose adjustment, target AUC 24 achievement was also higher post-MIPD versus pre-MIPD (86% vs. 57%; p < 0.05). AKI rates were low and similar between periods (pre-MIPD 8.7% vs. post-MIPD 9.5%; p = 0.9)., Conclusion: An MIPD approach implemented within a cloud-based, EHR-integrated CDS tool safely supported vancomycin AUC-guided dosing and resulted in high rates of target achievement., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children., Methods: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion., Results: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children., Conclusions: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics., Methods: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion., Results: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available., Conclusions: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Model-informed precision dosing (MIPD) can serve as a powerful tool during therapeutic drug monitoring (TDM) to help individualize dosing in populations with large pharmacokinetic variation. Yet, adoption of MIPD in the clinical setting has been limited. Overcoming technologic hurdles that allow access to MIPD at the point-of-care and placing it in the hands of clinical specialists focused on medication dosing may encourage adoption., Objective: To describe the hospital implementation and usage of a MIPD clinical decision support (CDS) tool for vancomycin in a pediatric population., Methods: Within an academic children's hospital, MIPD for vancomycin was implemented via a commercial cloud-based CDS tool that utilized Bayesian forecasting. Clinical pharmacists were recognized as local champions to facilitate adoption of the tool and operated as end-users. Integration within the electronic health record (EHR) and automatic transmission of patient data to the tool were identified as important requirements. A web-link icon was developed within the EHR which when clicked sends users and needed patient-level clinical data to the CDS platform. Individualized pharmacokinetic predictions and exposure metrics for vancomycin are then presented in the form of a web-based dashboard. Use of the CDS tool as part of TDM was tracked and users were surveyed on their experience., Results: After a successful pilot phase in the neonatal intensive care unit, implementation of MIPD was expanded to the pediatric intensive care unit, followed by availability to the entire hospital. During the first 2+ years since implementation, a total of 853 patient-courses (n = 96 neonates, n = 757 children) and 2,148 TDM levels were evaluated using the CDS tool. For the most recent 6 months, the CDS tool was utilized to support 79% (181/230) of patient-courses in which TDM was performed. Of 26 users surveyed, > 96% agreed or strongly agreed that automatic transmission of patient data to the tool was a feature that helped them complete tasks more efficiently; 81% agreed or strongly agreed that they were satisfied with the CDS tool., Conclusions: Integration of a vancomycin CDS tool within the EHR, along with leveraging the expertise of clinical pharmacists, allowed for successful adoption of MIPD in clinical care., (Copyright © 2020 Frymoyer, Schwenk, Zorn, Bio, Moss, Chasmawala, Faulkenberry, Goswami, Keizer and Ghaskari.)

Objective: To determine the presence of pregnancy warnings on over-the-counter (OTC) dermatologic products with hydroquinone, a potentially harmful ingredient., Study Design: Data were obtained from the Food and Drug Administration National Drug Code Directory and Label Repository to identify OTC dermatologic products containing hydroquinone. Products were stratified based on pregnancy or general warning presence (WP) or absence (WA). Product characteristics were compared between groups: hydroquinone concentration, presence of external packaging, indication and warning statements., Results: Of the 112 products studied, 21 had a pregnancy warning and 3 included a general warning against use: WP (n=24) and WA (n=88) group. External packaging was more prevalent in the WP group compared to WA (62.5% vs 29.5%, P=0.004)., Conclusions: Majority of OTC dermatologic products containing hydroquinone did not have a pregnancy warning. This highlights the need for improved labeling and informs providers caring for pregnant women of OTC labeling limitations.

Although a statement on Neonatal Drug Withdrawal was published in 1998 by the American Academy of Pediatrics, pharmacologic management of neonatal abstinence syndrome (NAS) remains a challenge. Published clinical trials are limited, restricting treatment decision making to practitioner's experience and preference rather than evidence-based medicine. To optimize withdrawal symptom prevention, drug selection is often based on the offending agent (opioids versus polysubstance exposure), clinical presentation, mechanism of action (agonist versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters and available drug formulations. This review addresses risk factors and pathophysiology of NAS, summarizes parameters of common drugs used for the management of NAS, and reviews published literature of standard therapies as well as newer agents. Based on the current literature, paregoric is no longer recommended and oral morphine solutions remain the mainstay of therapy for opiate withdrawal. Other potential therapies include methadone, buprenorphine, phenobarbital and clonidine with the latter two agents as adjunctive therapies.