Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later.

BACKGROUND: Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. METHODS: We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. RESULTS: Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859-923) in the pre-implementation phase to 655 (95% CI 637-694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686-722) to 544 (95% CI 525 -562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49-54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. CONCLUSIONS: The handshake method is an effective and sustainable approach to stewardship.

Hospital-wide Description of Clinical Indications for Pediatric Anti-infective Use.

PURPOSE: This study is the first description of hospital-wide anti-infective use according to clinical indication for a pediatric hospital. Children's Hospital Colorado (CHCO) is uniquely poised to examine its anti-infective use after the implementation of provider-selected order indications (PSOIs), which are distinct from Diagnosis Related Group classifications in that they are used for clinical treatment as opposed to final diagnosis codes for billing and thus are more granular. METHODS: This study used our institution's mandatory PSOIs to describe overall clinical indications for anti-infective use. For 2016, all anti-infective orders were extracted from the electronic medical record (Epic), including drug name, route, prescribing unit, and PSOI. We calculated the number of times each drug was associated with each indication and the number of times an indication was attributed to each drug, and then analyzed these data in Excel. FINDINGS: There were 29,258 orders at CHCO in 2016 with at least 1 indication. The most common clinical indication was "prophylaxis-medical/surgical," accounting for 23% of all orders and commonly associated with cefazolin (42% of prophylaxis-medical/surgical orders). This was followed by the indications of "sepsis/bacteremia" and "pneumonia/sinusitis." The most commonly prescribed anti-infectives for nonprophylactic clinical indications were IV vancomycin (14%), ceftriaxone (11%), and ampicillin (6%). IMPLICATIONS: Knowledge of the clinical reasons for hospital-wide anti-infective use enables hospitals to identify targets for improved use through education and guideline and policy development. This description provides better details than billing codes about the clinical reasons anti-infectives are used and offers a useful template for implementation at other hospitals.

Oral Fluoroquinolone Administration and Interacting Substances: The Pediatric Diet Dilemma.

Concomitant administration of enteral fluoroquinolones (FQs) with divalent or trivalent cation-containing compounds results in a reduction in FQ bioavailability. A review of enteral FQ administration with regards to the timing of divalent or trivalent cation-containing compounds in pediatric patients revealed a high number of inappropriately administered FQs. Suggestions for reducing the number of inappropriately timed FQ administrations are presented here.

Experience with Continuous Infusion Vancomycin Dosing in a Large Pediatric Hospital.

BACKGROUND: There is a paucity of data on dosing of continuous infusion of vancomycin (CIV) in pediatric patients, despite it being an attractive treatment option for limiting escalating doses of intermittent infusion of vancomycin. The purpose of this study was to determine the total daily dose of CIV required to attain therapeutic serum vancomycin concentrations (SVCs) in pediatric patients according to age (≥31 days to <2 years, 2 to <8 years, and 8 to <18 years). METHODS: We retrospectively evaluated patients who were transitioned from intermittent infusion of vancomycin to CIV between January 2013 and December 2016. Demographic data, vancomycin data (indication, dosing, steady-state SVCs, and time to reach goal SVC), and adverse-effect data (infusion reactions and serum creatinine level) were collected. RESULTS: Of the 240 patients included, 76 had a goal SVC of 10 to 15 µg/mL and 164 had a goal of 15 to 20 µg/mL. The dose of CIV required to reach an SVC of 10 to 15 µg/mL in the youngest age group was 48.4 mg/kg per day versus 45.6 and 39.4 mg/kg per day in the older age groups (P < .005). The 2 younger age groups of patients with a goal SVC of 15 to 20 µg/mL required 50.2 and 50.6 mg/kg per day, respectively, whereas patients aged ≥8 years required 44.7 mg/kg per day (P = .008). One patient experienced renal injury, and 1 experienced renal failure. CONCLUSIONS: CIV is an effective method for attaining a therapeutic SVC in pediatric patients. Patients <8 years of age require higher dosing than older pediatric patients to reach the goal SVCs of 10 to 15 and 15 to 20 µg/mL.

Intervention and Acceptance Rates Support Handshake-Stewardship Strategy.

We instituted a new antimicrobial stewardship approach that involves review of all antimicrobial agents and communication of interventions in person by a pharmacist-physician team termed handshake stewardship. The acceptance rate in this study was 86%, intervention rates were higher with a physician, and interventions on antibiotics not reviewed by other strategies were made frequently.

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis.

OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.

Effect of provider-selected order indications on appropriateness of antimicrobial orders in a pediatric hospital.

PURPOSE: The effect of mandatory provider-selected order indications (PSOIs) on appropriateness of antimicrobial ordering in a tertiary pediatric hospital was evaluated. METHODS: Mandatory PSOIs for 14 antimicrobials were implemented in September 2013. Data on initial and final orders in the first 24 hours after ordering were collected from the electronic medical record. Orders from pre-PSOI and post-PSOI implementation were randomly selected and compared with documentation at the time of order to elicit the documentation-determined clinical indication (DDCI). Appropriateness of the order for the DDCI was evaluated and compared between groups using 2-sample t tests, chi-square tests, and logistic regression. RESULTS: Among the total 1,304 orders included in the review, 275 (21.1%) were inappropriate based on DDCI. The indications associated with the greatest number of inappropriate orders in both groups were suspected sepsis/bacteremia, meningitis/central nervous system infection, and pneumonia. A total of 128 (18.3%) of 700 initial orders were inappropriate compared with the DDCI in the pre-PSOI period, and 82 (17.8%) of 461 initial orders were inappropriate in the post-PSOI period (p = 0.83). A total of 78 (11.1%) of 700 final orders were inappropriate in the pre-PSOI period, and 29 (6.3%) of 461 final orders were inappropriate in the post-intervention period (p = 0.01). Overall, 84 (12%) of 700 inappropriate orders reached the patient in the pre-PSOI period versus 43 (9.3%) of 461 inappropriate orders in the post-PSOI period (p = 0.15). CONCLUSION: PSOIs were effective in reducing inappropriate antimicrobial orders in the first 24 hours after ordering if the correct indication was selected.

Use of Intravenous Posaconazole in Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Posaconazole is a broad-spectrum antifungal used for prophylaxis and treatment of invasive fungal infections. There is no published data to inform prescribers on dosing of the intravenous (IV) formulation in the pediatric population. We describe our experience including dosing, serum concentrations, and tolerability. OBSERVATIONS: Four patients (3 to 9 y) received IV posaconazole for treatment of documented/suspected invasive fungal infections. Patients achieved therapeutic concentrations on daily doses of 8.4 to 12.2 mg/kg and adverse effects were minimal. CONCLUSIONS: Higher dosing per body weight of IV posaconazole may be required in the pediatric population compared with adults to consistently achieve therapeutic concentrations.

Anti-infective Acquisition Costs for a Stewardship Program: Getting to the Bottom Line.

BACKGROUND: Though antimicrobial stewardship programs (ASPs) are in place for patient safety, financial justification is often required. In 2016, the Infectious Diseases Society of America (IDSA) recommended that anti-infective costs be measured by patient-level administration data normalized for patient census. Few publications use this methodology. Here, we aim to compare 3 methods of drug cost analysis during 3 phases of an ASP as an example of this recommendation's implementation. METHODS: At a freestanding pediatric hospital, we retrospectively assessed anti-infective cost using pharmacy purchasing data, patient-level administration data from the electronic medical record (EMR), and patient-level administration data from the Pediatric Hospital Information Systems (PHIS) database, all normalized to patient census. Costs pre-ASP, while planning the ASP, and post-ASP were then compared for each method. RESULTS: Significant differences in costs between the methods were observed. Pharmacy purchasing endorsed minimal financial benefit (decrease planning to post-ASP of $590 dollars per 1000 patient-days), while the EMR and PHIS data endorsed a decrease of $12785 and $21380 per 1000 patient-days, respectively, for a total yearly cost savings of $54656 for pharmacy purchasing data, $1184336 for EMR data, and $2117522 for PHIS data. CONCLUSIONS: Pharmacy purchasing data underestimated cost savings compared with EMR and PHIS data, while EMR and PHIS data were comparable in magnitude of savings. At Children's Hospital Colorado, savings justified the full cost of the ASP. EMR patient-level administration data, normalized to patient census, offers a readily available and standardized measure of anti-infective costs over time.

A Handshake From Antimicrobial Stewardship Opens Doors for Infectious Disease Consultations.

Implementation of a unique in-person pediatric antimicrobial stewardship program was associated with a significant increase in infectious disease consultations at a quaternary care children's hospital. This study demonstrates that antimicrobial stewardship programs support, and do not compete with, infectious disease programs.

Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results.

BACKGROUND: Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Children's Hospital Colorado. METHODS: A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. RESULTS: The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. CONCLUSIONS: Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers.

Once-Daily Ceftriaxone Plus Metronidazole Versus Ertapenem and/or Cefoxitin for Pediatric Appendicitis.

BACKGROUND: Appendicitis is a common surgical emergency in pediatric patients, and broad-spectrum antibiotic therapy is warranted in their care. A simplified once-daily regimen of ceftriaxone and metronidazole (CTX plus MTZ) is cost effective in perforated patients. The goal of this evaluation is to compare a historic regimen of cefoxitin (CFX) in nonperforated cases and ertapenem (ERT) in perforated and abscessed cases with CTX plus MTZ for all cases in terms of efficacy and cost. METHODS: A retrospective review compared outcomes of nonperforated, perforated, and abscessed cases who received the historic regimen or CTX plus MTZ. Length of stay, time to afebrile, time to full feeds, postoperative abscess, and wound infection rates, inpatient readmissions, and antibiotic costs were evaluated. RESULTS: There were a total of 841 cases reviewed (494 nonperforated, 247 perforated, and 100 abscessed). Overall, the CTX plus MTZ group had a shorter time to afebrile (P < .001). Treatment groups did not differ in length of stay. Postoperative abscess rates were similar between groups (4.1% vs 3.3%, not significant). Other postoperative complications were similar between groups. Total antibiotic cost savings were over $110 000 during the study period (from November 2010 to June 2013). CONCLUSIONS: Both CFX and/or ERT and CTX plus MTZ result in low abscess and complication rates, suggesting both are effective strategies. Treatment with CTX plus MTZ results in a shorter time to afebrile, while also providing significant antibiotic cost savings. Ceftriaxone plus MTZ is a streamlined, cost-effective regimen in the treatment of nonperforated, perforated, and abscessed appendicitis.

Handshake Stewardship: A Highly Effective Rounding-based Antimicrobial Optimization Service.

BACKGROUND: Implementation of an antimicrobial stewardship program is recommended as one solution to combat increasing antimicrobial resistance. Most antimicrobial stewardship programs use preauthorization or restrictive strategies recommended in national guidelines. We describe a unique, rounding-based strategy, handshake stewardship. Handshake stewardship is distinguished by: (1) lack of restriction and preauthorization, (2) review of all prescribed antimicrobials and (3) a rounding-based, in-person approach to feedback by a pharmacist-physician team. METHODS: We retrospectively measured antimicrobial use hospital-wide and by unit during preimplementation, planning, and postimplementation phases of the handshake stewardship approach to determine the efficacy of this strategy in decreasing use in a freestanding children's hospital. All antimicrobials prescribed on the inpatient services between October 2010 and September 2014 were included in the review. Monthly antimicrobial use (hospital-wide and by unit) was measured in days of therapy per 1000 patient days (DOT/1000 PD). RESULTS: Overall antimicrobial use decreased by 10.9% during the 4 years of the analysis (942 to 839 DOT/1000 PD, P < 0.01), with an impact of 10.3% on antibacterials (750 to 673 DOT/1000 PD, P < 0.01). Vancomycin use decreased by 25.7% (105 to 78 DOT/1000 PD, P < 0.01). Meropenem use decreased by 22.2% (45 to 35 DOT/1000 PD, P = 0.04) without a compensatory increase of other antipseudomonal agents. Decreased usage was observed both hospital-wide and on individual units for most agents. CONCLUSIONS: The handshake stewardship approach is an effective strategy for an antimicrobial stewardship program, as demonstrated by the widespread and significant decrease in antimicrobial use after implementation.

Pediatric appendicitis and need for antibiotics at time of discharge: Does route of administration matter?

INTRODUCTION: Following complicated appendicitis, there are limited data available to guide the surgeon regarding antibiotic selection, specifically in regards to route of administration. We hypothesized that among children with appendicitis who are discharged home with antibiotic therapy, the post-discharge readmission and complication rates do not differ between those children who receive IV antibiotics and those who receive PO antibiotics. METHODS: We performed a retrospective review of all children discharged home on antibiotics following appendectomy at a single institution between 11/10-10/14. We compared outcomes including ED and hospital readmission rates, and development of postoperative complications, between those children who were discharged on IV antibiotics and those discharged on PO antibiotics. RESULTS: 325 children were discharged with antibiotics following appendectomy (n=291 PO antibiotics group; n=34 IV group). On both univariate and multivariate analysis, rate of each complication did not differ between the two groups including inpatient readmission (5% PO vs. 6% IV; p=0.8), ED readmission (10% vs. 11%; p=0.8), postdischarge complications related to the operation (10% vs. 15%; p=0.4), or abscess development post-discharge (4% vs. 3%; p=1). CONCLUSIONS: Among children with complicated appendicitis who are discharged home with ongoing antibiotic therapy, our data demonstrate no differences in outcomes between those children who receive IV and PO antibiotics. Further data, collected in a prospective fashion, are needed to clarify the role of IV and PO antibiotics among children with perforated appendicitis.

Supra-therapeutic tacrolimus concentrations associated with concomitant nicardipine in pediatric liver transplant recipients.

Tacrolimus is prescribed to prevent allograft rejection in pediatric liver transplant recipients; however, its metabolism through the cytochrome P-450 enzyme system presents a multitude of challenges in regard to drug interactions. Here, we describe four children (ages 1.4-8.7 yr) who acutely developed supra-therapeutic serum tacrolimus trough concentrations, despite standard dosing, while on concomitant nicardipine therapy following liver transplantation. Even though tacrolimus regimens were altered (dosage reductions and held doses), serum tacrolimus concentrations remained elevated. Resolution of high tacrolimus concentrations was achieved only after the discontinuation of nicardipine. Following the termination of nicardipine, all children eventually required dosage increases in their tacrolimus regimens to re-achieve target serum concentrations. We conclude that concomitant use of tacrolimus and nicardipine can result in high tacrolimus concentrations due to the inhibition of cytochrome p450 enzymes responsible for the metabolism of tacrolimus. We encourage clinicians to consider alternative antihypertensive options in children on tacrolimus therapy. If nicardipine therapy is necessary, we recommend a 50% reduction in tacrolimus dose and daily serum concentration monitoring.