Return to School and COVID-19 Vaccination for Pediatric Solid Organ Transplant Recipients in the United States: Expert Opinion for 2021-2022.

2021

2021 Nov 03

2048-7207

<p>The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021.</p>

10.1093/jpids/piab098

J Pediatric Infect Dis Soc

34734268

Procalcitonin in Pediatric Sepsis: What Is It Good for?

2021

2021 Jul 30

2048-7207

10.1093/jpids/piab066

J Pediatric Infect Dis Soc

34329449

American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID-19 Pandemic: Version 2.

2021

2021 Jun 10

2326-5205

<p><strong>OBJECTIVE: </strong>To provide clinical guidance to rheumatology providers who treat children with pediatric rheumatic disease (PRD) in the context of the coronavirus disease 2019 (COVID-19) pandemic.</p>

<p><strong>METHODS: </strong>The task force, consisting of 7 pediatric rheumatologists, 2 pediatric infectious disease physicians, 1 adult rheumatologist, and 1 pediatric nurse practitioner, was convened on May 21, 2020. Clinical questions and subsequent guidance statements were drafted based on a review of the queries posed by the patients as well as the families and healthcare providers of children with PRD. An evidence report was generated and disseminated to task force members to assist with 3 rounds of asynchronous, anonymous voting by email using a modified Delphi approach. Voting was completed using a 9-point numeric scoring system with predefined levels of agreement (categorized as disagreement, uncertainty, or agreement, with median scores of 1-3, 4-6, and 7-9, respectively) and consensus (categorized as low, moderate, or high). To be approved as a guidance statement, median vote ratings were required to fall into the highest tertile for agreement, with either moderate or high levels of consensus.</p>

<p><strong>RESULTS: </strong>To date, 39 guidance statements have been approved by the task force. Those with similar recommendations were combined to form a total of 33 final guidance statements, all of which received median vote ratings within the highest tertile of agreement and were associated with either moderate consensus (n&nbsp;=&nbsp;5) or high consensus (n&nbsp;=&nbsp;28).</p>

<p><strong>CONCLUSION: </strong>These guidance statements have been generated based on review of the available literature, indicating that children with PRD do not appear to be at increased risk for susceptibility to SARS-CoV-2 infection. This guidance is presented as a "living document," recognizing that the literature on COVID-19 is rapidly evolving, with future updates anticipated.</p>

10.1002/art.41772

Arthritis Rheumatol

34114365

Precision dosing of vancomycin: in defence of AUC-guided therapy in children.

2021

2021 Jun 07

1460-2091

<p>In 2020, new vancomycin guidelines were released, recommending the transition from trough-based to AUC24 monitoring for adult and paediatric patients. Given the resources required to achieve this transition, there has been debate about the costs and benefits of AUC24-based monitoring. A recent narrative review of vancomycin therapeutic drug monitoring in paediatrics claims to have uncovered the methodological weaknesses of the data that informed the guidelines and advises against premature adoption of AUC24-guided monitoring. In this article, we present supporting arguments for AUC24-guided monitoring in children, which include that: (i) troughs alone are inadequate surrogates for AUC24; (ii) vancomycin-associated nephrotoxicity has significant consequences that warrant optimization of dosing; (iii) a substantial portion of children receiving vancomycin are at high risk for poor outcomes and deserve targeted monitoring; and (iv) limited efficacy data in support of AUC24 is not a justification to revert to a less supported monitoring approach.</p>

10.1093/jac/dkab194

J Antimicrob Chemother

34096598

Estimating renal function for drug dosing in critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome.

2021

2021 May 31

1970-9366

10.1007/s11739-021-02770-4

Intern Emerg Med

34057652

The case for precision dosing: medical conservatism does not justify inaction.

2021

2021 Apr 12

1460-2091

<p>The need for precision dosing has been challenged on the basis of insufficient evidence. Herein, we argue that adequate evidence exists to conduct therapeutic drug monitoring (TDM) and precisely target antibiotic exposures. While achievement of any antibiotic concentration does not guarantee efficacy sans toxicity for any single patient, stochastic control optimizes the probability of achieving favourable responses across patients. We argue that variability in targets (such as the organism's MIC) can be considered with models. That is, complexity alone does not relegate the decision-making framework to 'clinician intuition'. We acknowledge the exposure-response relationships are modified by patient-specific factors (other drugs, baseline organ functional status etc.) and describe how precision dosing can inform clinical decision making rather than protocolize it. Finally, we call for randomized, controlled trials; however, we suggest that these trials are not necessary to make TDM standard of care for multiple classes of antibiotics.</p>

10.1093/jac/dkab086

J Antimicrob Chemother

33843994

Too much of a good thing: defining antimicrobial therapeutic targets to minimize toxicity.

2021

2021 Feb 04

1532-6535

<p>Antimicrobials are a common cause of drug toxicity. Understanding the relationship between systemic antimicrobial exposure and toxicity is necessary to enable providers to take a proactive approach to prevent undesired drug effects. When an exposure threshold has been defined that predicts drug toxicity, therapeutic drug monitoring (TDM) can be performed to assure drug exposure does not exceed the defined threshold. Although some antimicrobials have well-defined dose-dependent toxicities, many other exposure-toxicity relationships have either not been well-defined or in some cases, not been evaluated at all. In this review, we examine the relationship between exposures and toxicities for antibiotic, antifungal and antiviral agents. Furthermore, we classify these relationships into four categories: known association between drug exposure and toxicity such that clinical implementation of a specific exposure threshold associated with toxicity for TDM is supported (category 1), known association between drug exposure and toxicity but the specific exposure threshold associated with toxicity is undefined (category 2), association between drug exposure and toxicity has been suggested but relationship is poorly defined (category 3), and no known association between drug exposure and toxicity (category 4). Further work to define exposure-toxicity thresholds and integrate effective TDM strategies has the potential to minimize many of the observed antimicrobials toxicities.</p>

10.1002/cpt.2190

Clin Pharmacol Ther

33539569

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of COVID-19 in Children and Adolescents.

2021

2021 Jan 03

2048-7207

<p><strong>BACKGROUND: </strong>In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate COVID-19 in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products.</p>

<p><strong>METHODS: </strong>A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion.</p>

<p><strong>RESULTS: </strong>The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis.</p>

<p><strong>CONCLUSIONS: </strong>Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence, and ensure implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.</p>

10.1093/jpids/piaa175

J Pediatric Infect Dis Soc

33388760

Microsampling Assays for Pharmacokinetic Analysis and Therapeutic Drug Monitoring of Antimicrobial Drugs in Children: A Critical Review.

2020

2020 Dec 03

1536-3694

<p><strong>PURPOSE: </strong>With the increasing prevalence of multi-drug resistant organisms, therapeutic drug monitoring (TDM) has become a common tool for assuring the safety and efficacy of antimicrobial drugs at higher doses. Microsampling techniques, including dried blood spotting (DBS) and volumetric absorptive microsampling (VAMS), are attractive tools for TDM and pediatric clinical research. For microsampling techniques to be a useful tool for TDM, it is necessary to establish the blood-plasma correlation and the therapeutic window of antimicrobial drugs in the blood.</p>

<p><strong>METHODS: </strong>DBS involves the collection of small volumes of blood (30 - 50 µL per spot) on a filter paper, while VAMS allows the accurate and precise collection of a fixed volume of blood (10-30 µL) with microsampling devices. One of the major advantages of VAMS is that it reduces or eliminates the volumetric blood hematocrit (HCT) bias associated with DBS. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a powerful tool for the accurate quantification of antimicrobial drugs from small volumes of blood specimens.</p>

<p><strong>RESULTS: </strong>This review summarizes the recent LC-MS/MS assays that have employed DBS and VAMS approaches for quantifying antimicrobial drugs. Sample collection, extraction, validation outcomes, including the inter- and intra-assay accuracy and precision, recovery, stability, and matrix effect, as well as the clinical application of these assays and their potential as tools of TDM are discussed herein.</p>

<p><strong>CONCLUSION: </strong>Microsampling techniques, such as VAMS, provide an alternative approach to traditional plasma sample collection for TDM.</p>

10.1097/FTD.0000000000000845

Ther Drug Monit

33278241

A whole blood microsampling assay for vancomycin: development, validation and application for pediatric clinical study.

2020

1295-1310

2020 Sep

1757-6199

<p>Vancomycin is a commonly used antibiotic, which requires therapeutic drug monitoring to ensure optimal treatment. Microsampling assays are attractive tools for pediatric clinical research and therapeutic drug monitoring. A LC-MS/MS&nbsp;method for the quantification of vancomycin in human whole blood employing volumetric absorptive microsampling (VAMS) devices (20&nbsp;μl) was developed and validated. Vancomycin was stable in human whole blood VAMS under assay conditions. Stability for vancomycin was established for at least 160&nbsp;days as dried microsamples at -78°C. This method is currently being utilized for the quantitation of vancomycin in whole blood VAMS for an ongoing pediatric clinical study and representative clinical data are reported.</p>

10.4155/bio-2020-0112

32945688