Considerations for implementation of vancomycin Bayesian software monitoring in a level IV NICU population within a multisite health system.

PURPOSE: The updated 2020 vancomycin therapeutic drug monitoring guideline advocates for area under the curve (AUC)-based monitoring in neonates, preferably with Bayesian estimation. This article describes the selection, planning, and implementation of vancomycin model-informed precision dosing (MIPD) software with Bayesian estimation in the neonatal intensive care unit (NICU) within an academic health system. SUMMARY: The selection, planning, and implementation of vancomycin MIPD software was completed in approximately 6 months throughout a health system with multiple NICU sites. The chosen software captures data on medications in additional to vancomycin, provides analytics support, includes specialty populations (eg, neonates), and offers the ability to integrate MIPD into the electronic health record. Pediatric pharmacy representatives served on a system-wide project team with key responsibilities including development of educational materials, drafting changes to policies and procedures, and assistance with department-wide software training. Additionally, pediatric and neonatal pharmacist super users trained other pediatric pharmacists on software functionality, were available the week of go-live for in-person support, and contributed to the identification of pediatric and NICU-specific nuances related to software implementation. Neonatal-specific considerations when implementing MIPD software include: the selection of appropriate pharmacokinetic model(s), continued evaluation of such model(s), selection of appropriate model(s) in infants as they age, input of significant covariates, determination of the site-specific serum creatinine assay, decision of the number of vancomycin serum concentrations obtained, discernment of patients excluded from AUC monitoring, and the utilization of actual versus dosing weight. CONCLUSION: This article serves to share our experience with selecting, planning, and implementing Bayesian software for vancomycin AUC monitoring in a neonatal population. Other health systems and children's hospitals can utilize our experience to evaluate a variety of MIPD software and consider neonatal nuances prior to implementation.

Implementation of a Pharmacist-Driven Penicillin and Cephalosporin Allergy Assessment Tool: A Pilot Evaluation.

OBJECTIVE: Penicillin is the most commonly reported drug allergy despite the low incidence of true immune-mediated reactions. Penicillin allergy labels have been shown to lead to significant patient, institutional, and public health care consequences. This project's purpose was to improve quality of care for patients with penicillin and cephalosporin allergies, admitted to a pediatric institution, by implementation of a pharmacist-driven allergy assessment tool. METHODS: A group of physicians, pharmacists, and a nurse collaborated for process development. The process was standardized, and a tool was created to assist with assessments. Pharmacists were educated on the importance of this quality improvement project and trained on the process and tool used. Implementation occurred on March 2, 2020. RESULTS: During the 3-month implementation period, 40 patients were admitted with a documented penicillin or cephalosporin allergy. Of these, 11 patients (27.5%) received an allergy assessment. Most were identified as having low or moderate risk of recurrent reaction with future use of a penicillin or cephalosporin agent (81.8%), and 2 patients (18.2%) were de-labeled from their documented allergy. CONCLUSIONS: Penicillin and cephalosporin allergy assessment implementation at a pediatric hospital was successfully implemented and allowed for identification and initiation of future quality improvement projects including implementation of penicillin skin testing and direct oral amoxicillin challenges.

Effects of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on the Sequestration of Mycophenolate Mofetil, Tacrolimus, Hydromorphone, and Fentanyl.

OBJECTIVES: With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. METHODS: ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO2, and PCO2 were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured. RESULTS: Hydromorphone hydrochloride was not as significantly sequestered by the ex vivo pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours. CONCLUSIONS: Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.

Continuous Antithrombin III Administration in Pediatric Veno-Arterial Extracorporeal Membrane Oxygenation.

The purpose of this retrospective case-control study is to determine the effect of continuous antithrombin III (ATIII) infusion on extracorporeal membrane oxygenation (ECMO) coagulation. All ECMO patients within the pediatric intensive care unit from January 2012 to July 2014 were included. Comparison was made between those who received continuous infusion ATIII through a standardized replacement protocol with historic controls receiving intermittent ATIII doses. Patients receiving the continuous infusion ATIII protocol spent more time in goal ACT range (71.9% vs 52.2%, p < 0.0001). Mean daily ATIII activity was also increased in study group (77.3% versus 68.6%, p = 0.04). No statistical differences in number of heparin dose changes per day (3 versus 3.22, p = 0.90) were present between the 2 groups. Only 28% of the historic controls receiving intermittent ATIII doses achieved normal ATIII activity as compared with 80% of study patients (p = 0.24). Maximum heparin dose was also lower in continuous infusion protocol group (p < 0.01). Compared with nonprotocolized intermittent dosing, the use of a continuous infusion ATIII protocol demonstrated increased time within goal ACT range at a lower heparin dose, no increase in hemostatic complications, and trends toward fewer heparin changes and lower blood product usage.

Inappropriate continuation of stress ulcer prophylactic therapy after discharge.

BACKGROUND: Medications for stress ulcer prophylaxis are appropriately started in critically ill patients with risks for developing stress ulcers. It is unknown whether these drugs are discontinued once the risk factors are removed. OBJECTIVE: To assess the duration of stress ulcer prophylactic therapy in critically ill patients. METHODS: A retrospective chart review was conducted at a multidisciplinary, 24 bed medical/surgical intensive care unit (ICU) of a university-affiliated tertiary referral medical center. Three hundred ninety-four patients fulfilled eligibility criteria during the study period of July 1, 2005, through September 30, 2005. Patients were considered to be appropriately discharged from the hospital on gastric acid suppressants if they met any of the following criteria: continued mechanical ventilation, gastroesophageal reflux disease, peptic ulcer disease, history of gastrointestinal ulceration or bleeding within the past year, prescribed medications used for stress ulcer prophylaxis prior to admission, gastrointestinal bleed during hospitalization, or prescriber indication of reason to continue therapy. RESULTS: Three hundred fifty-seven patients received stress ulcer prophylaxis during their ICU stay. Of these, 80% continued on gastric acid suppressants on transfer from the ICU, with 60% of the therapy being inappropriate. The percentage of critically ill patients discharged from the hospital with inappropriate prescription of gastric acid suppressants was 24.4%. Based on the average wholesale cost, the total cost for unnecessary gastric acid suppressant therapy within the follow-up period was $13,973. CONCLUSIONS: Gastric acid suppressant medications initially prescribed for stress ulcer prophylaxis are frequently prescribed inappropriately on discharge for patients who were initially admitted to the medical/surgical ICU.

Guideline for low-cost antimicrobial use in the outpatient setting.

In an effort to increase appropriate prescribing of low-cost antimicrobials in the outpatient setting, an evidence-based guideline was created to identify situations when low-cost medications can be used. A literature search identified relevant clinical trials describing the efficacy of antimicrobials used in the outpatient setting. These were analyzed to identify low-cost medications defined as $15 or less. The information was put into guideline format that includes the level of evidence for recommending the drug and information about cost. Sixteen common infections and their treatments were included in the guideline. The efficacy data were similar for the low-cost and higher-cost antimicrobials for all infections included. We created a low-cost antimicrobial guideline for common infections treated in the outpatient setting. The treatment options have similar efficacy to higher cost medications. This guideline will serve as an information source for providers to help them rapidly determine the low-cost treatments for common infections. In addition, it can serve as a template for the development of similar guidelines in other therapeutic classes. These guidelines should be customized before implementation at other health care organizations, with consideration of local resistance patterns, drug availability and patient factors. The effect of guideline implementation on future prescribing habits and providers' opinions about availability of cost information and subsequent conversations with patients and prescribers of medications deserves further study.