Nirsevimab: Expansion of Respiratory Syncytial Virus Prevention Options in Neonates, Infants, and At-Risk Young Children.

OBJECTIVE: Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. DATA SOURCES: A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. DATA SYNTHESIS: Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING AGENTS: Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. CONCLUSIONS: Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

Impact of Intravenous Fat Emulsion Choice on Candida Biofilm, Hyphal Growth, and Catheter-Related Bloodstream Infections in Pediatric Patients.

BACKGROUND: Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. METHODS: Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. RESULTS: Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11, HGC1, and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non-albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval, .46-3.26]). CONCLUSIONS: MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6-dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed.

Delivery of carbohydrates, amino acids, and lipids via intravenous catheters is necessary for some patients to supply daily caloric needs. These nutrient-dense parenteral solutions can promote microbial biofilm growth on the catheter surface, which may seed subsequent catheter-related bloodstream infection (CR-BSI). In fact, receipt of parenteral nutrition is an established risk factor for CR-BSI caused by the polymorphic fungal pathogen Candida albicans. New intravenous fat emulsions (IFEs) have gained market share and IFEs containing capric acid (mixed-oil [MO] IFE) compared with those without (soybean-oil [SO] IFE) impair the C. albicans yeast-to-hypha switch­a trait strongly associated with pathogenicity and biofilm formation. In this study, we found that MO-IFE and capric acid reduced expression of a transcriptional regulator involved in hyphal extension (UME6) and down-regulated genes involved in cell partitioning (HGC1). Overexpression of these genes enabled hyphal growth in MO-IFE. Secondly, we sought to determine whether the type of IFE administered was associated with the clinical incidence of CR-BSIs caused by C. albicans or other common non-albicans Candida species. There was a nonsignificant numerical reduction in C. albicans infections in patients administered MO-IFE compared with SO-IFE. Collectively, this work shows that IFEs differentially affect Candida biology with potential infectious consequences for the patient.

Improvement in Pharmacy Student Responses to Medication-Related Problems with and without Clinical Decision Support Alerts.

OBJECTIVE: To assess pharmacy student responses to medication problems with and without clinical decision support (CDS) alerts during simulated order verification. METHODS: Three classes of students completed an order verification simulation. The simulation randomized students to a different series of 10 orders with varying CDS alert frequency. Two of the orders contained medication-related problems. The appropriateness of the students' interventions and responses to the CDS alerts were evaluated. In the following semester for 2 classes, 2 similar simulations were completed. All 3 simulations contained 1 problem with and 1 without an alert. RESULTS: During the first simulation, 384 students reviewed an order with a problem and an alert. Students exposed to prior inappropriate alerts within the simulation had less appropriate responses (66% vs 75%). Of 321 students who viewed a second order with a problem, those reviewing an order lacking an alert recommended an appropriate change less often (45% vs 87%). Among 351 students completing the second simulation, those who participated in the first simulation appropriately responded to the alert for a problem more often than those who only received a didactic debrief (95% vs 87%). Among those completing all 3 simulations, appropriate responses increased between simulations for problems with (n = 238, 72-95-93%) and without alerts (n = 49, 53-71-90%). CONCLUSIONS: Some pharmacy students displayed baseline alert fatigue and overreliance on CDS alerts for medication problem detection during order verification simulations. Exposure to the simulations improved CDS alert response appropriateness and detection of problems.

A Review of the Data Supporting Use of COVID-19 Vaccinations in the Pediatric Population.

OBJECTIVE: The objective of this study was to review the effectiveness and safety of COVID-19 vaccinations in the pediatric population. DATA SOURCES: PubMed/Medline (September 2020 to December 2022), the Centers for Disease Control and Prevention, and Food and Drug Administration (FDA) websites. STUDY SELECTION AND DATA EXTRACTION: Publications regarding the safety and efficacy of COVID-19 vaccinations in children were included. DATA SYNTHESIS: Vaccines authorized for use in children include two monovalent mRNA vaccines (≥6 months old) and one monovalent protein subunit adjuvant vaccine (adolescents only). Omicron-specific mRNA bivalent boosters are authorized for children ≥6 months old. Studies after monovalent vaccine authorization illustrated efficacy in children >5 to 6 years of age, specifically decreased severe COVID-19 (including mortality) and multisystem inflammatory response syndrome occurrence (including during Omicron predominance). Available data for children <5 to 6 years suggests efficacy, although data are limited. Monovalent vaccine efficacy against Omicron infections may wane as early as 2 months, but protection against severe disease complications may last longer, and bivalent Omicron boosters are anticipated to increase effectiveness. Myocarditis/pericarditis is a safety concern associated with the COVID-19 vaccinations but occurs less frequently then COVID-19 complications and thus the benefit outweighs the risks. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Caregivers seek information from health care professionals regarding vaccine safety and efficacy. Pharmacists can use the objective information in this review to educate caregivers and effectively administer COVID-19 vaccines to patients. CONCLUSIONS: There is sufficient and continually growing safety and efficacy data available to recommend COVID-19 vaccinations for children ≥6 months of age.

Comparison of catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition with soybean oil-based intravenous fat emulsion versus a mixed oil fat emulsion.

STUDY OBJECTIVE: To compare rates of catheter-related bloodstream infections (CR-BSI) in pediatric patients who received parenteral nutrition (PN) with either soybean oil-based intravenous fat emulsion (SO-IFE) or mixed oil-IFE (MO-IFE). We hypothesized that the use of MO-IFE would be independently associated with reduced infection rates compared with SO-IFE. DESIGN: Retrospective cohort study. SETTING: Tertiary referral children's hospital and its associated gastrointestinal rehabilitation clinic (01 January, 2015-31 July, 2019). PATIENTS: Days of IFE exposure were counted for patients aged <18 years on IFE initiated during the review period, who had a central venous catheter (CVC) placed for PN administration, received IFE at least three times weekly, and for at least 7 days. MEASUREMENTS: The primary outcome included total and categorical CR-BSI rates expressed as the average with standard error (SE) number of infections per 1000 fat emulsion days. The following categories were specified: Candida albicans, non-albicans Candida spp., coagulase-negative Staphylococcus (CoNS), Enterobacterales, methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and Pseudomonadales. Average infection rate comparisons were quantified as incidence rate ratios (IRR) using generalized linear mixed modeling with a Poisson distribution. MAIN RESULTS: Seven hundred and forty-three SO-IFE and 450 MO-IFE exposures were reviewed from 1131 patients, totaling 37,599 and 19,796 days of therapy, respectively. From those found significantly different, the average rate of infections with CoNS was 3.58 (SE 0.5)/1000 days of SO-IFE and 1.39 (SE 0.45)/1000 days of MO-IFE (IRR [95% confidence interval, CI]: 0.27 [0.16-0.46]; p < 0.01). Total average rates of infection were 7.33 (SE 0.76)/1000 days of SO-IFE and 4.52 (SE 0.75)/1000 days of MO-IFE (IRR [95% CI]: 0.60 [0.44-0.81]; p < 0.01). Other factors associated with higher infection rates include female gender, neonatal age, and inpatient-only IFE exposure. CONCLUSIONS: Receipt of MO-IFE was associated with lower rates of CoNS and total CR-BSIs compared with SO-IFE in pediatric patients. These findings could have major implications on IFE selection for pediatric patients receiving PN.

Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units: Updates in the Pharmacologic Prophylaxis.

Purpose of review: The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). Recent findings: Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants < 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older. Summary: Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population.

A Multicenter Analysis of Changes in Pediatric Antibiotic Susceptibilities Among Staphylococcus aureus and Pseudomonas aeruginosa Isolates: 2014-2018.

OBJECTIVE: To describe antibiotic susceptibilities for Staphylococcus aureus and Pseudomonas aeruginosa among pediatric institutions in 2018. To assess correlations between antibiotic utilization and susceptibilities. METHODS: Institutional antibiograms from 2018 were compiled among 13 institutions via a survey. Resistant pathogens and antibiotic days of therapy/1000 patient days (PD) were collected from 6 institutions over 5 years. Correlations were assessed as pooled data among all institutions and relative changes within individual institutions. RESULTS: All 8552 S aureus isolates in 2018 were vancomycin susceptible and 40.1% were methicillin resistant (MRSA). Among MRSA, 96.3% and 78.8% were susceptible to trimethoprim/sulfamethoxazole and clindamycin, respectively. Pooled yearly MRSA/1000 PD decreased from 2014-2018 and correlated with pooled yearly decreases in vancomycin utilization (R = 0.983, p = 0.003). Institutional relative decreases in vancomycin utilization from 2014-2018 did not correlate with institutional relative decreases in MRSA susceptibility (R = -0.659, p = 0.16). Susceptibility to meropenem was 90.9% among 2315 P aeruginosa isolates in 2018. Antipseudomonal beta-lactam susceptibility ranged from 89.4% to 92.3%. Pooled yearly meropenem-resistant P aeruginosa/1000 PD and meropenem utilization did not significantly decrease over time or correlate (both p > 0.6). Institutional relative change in meropenem utilization from 2013-2017 correlated with the institutional relative change in P aeruginosa susceptibility to meropenem from 2014-2018 (Rs = -0.89, p = 0.019). CONCLUSIONS: Among included institutions, the burden of MRSA decreased over time. Institutional MRSA prevalence did not consistently correlate with institutional vancomycin utilization. Institutional changes in meropenem utilization correlated with P aeruginosa susceptibility the following year. Pooled analyses did not illustrate this correlation, likely owing to variability in utilization between institutions.

How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?

ABSTRACT: Broader spectrum Gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional Gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% vs42.3%, respectively, P  = 0.78). 1.8% and 10.3% (P = 0.125) of Gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.

Analysis of Community-Acquired Urinary Tract Infection Treatment in Pediatric Patients Requiring Hospitalization: Opportunity for Use of Narrower Spectrum Antibiotics.

Background: The most narrow-spectrum antibiotic possible should be used for empiric and definitive treatment of pediatric urinary tract infections (UTIs). Objectives: The objectives of this study were to determine an appropriate narrow-spectrum antibiotic for empiric UTI treatment, factors differentiating empiric first-generation cephalosporin (FGC) versus third-generation cephalosporin (TGC) coverage, and factors associated with unnecessarily broad-spectrum definitive antibiotic treatment. Methods: This was a retrospective chart review of children admitted from 2013 to 2015 who were diagnosed with a UTI and received treatment. Multivariable logistic regression assessed independent factors associated with our outcomes. Results: Of 568 diagnosed UTIs, 88.6% received empiric TGC treatment. Empiric coverage among cultured organisms was only 5.4% lower in FGC versus TGC. Adolescent age group (odds ratio [OR] = 8.83, 95% confidence interval [CI] = 1.47-53.11), uncircumcised males (OR = 4.52, 95% CI = 1.27-16.08), Hispanic ethnicity (OR = 4.37, 95% CI = 1.14-16.82), and hospitalization within the preceding 3 months (OR = 4.73, 95% CI = 1.38-16.23) were associated with FGC nonsusceptibility among TGC susceptible Enterobacteriaceae pathogens. De-escalation occurred in 55.8% of diagnosed UTIs eligible for de-escalation at discharge. Urine white blood cell (WBC) count >5 (OR = 2.89, 95% CI = 1.14-7.21), serum WBC count (OR = 1.04, 95% CI = 1.01-1.07), and having only one narrow-spectrum treatment option (OR = 5.1, 95% CI = 2.43-10.66) were associated with unnecessarily broad-spectrum definitive treatment. Conclusion and Relevance: FGC would be an appropriate narrow-spectrum empiric agent for UTIs at our institution. The factors associated with FGC nonsusceptibility can further stratify empiric treatment decisions. The factors associated with unnecessarily broad-spectrum definitive treatment illustrate areas for educational efforts and future research regarding UTI treatment.

A Culture Change: Impact of a Pediatric Antimicrobial Stewardship Program Based on Guideline Implementation and Prospective Audit with Feedback.

Reports analyzing the impact of pediatric antimicrobial stewardship programs (ASP) over long periods of time are lacking. We thus report our ASP experience in a pediatric tertiary referral center over a long-term period from 2011 to 2018. Our ASP was implemented in 2011. The program was based primarily on guideline development with key stakeholders, engaging and educating providers, followed by prospective audit with feedback (PAF). Monitored antibiotics included meropenem, piperacillin-tazobactam, and cefepime, followed by the addition of ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, levofloxacin, linezolid, and vancomycin at various time points. Specifically, the program did not implemented the core strategy of formulary restriction with prior authorization. Process- and outcome-related ASP measures were analyzed. We saw a 32% decrease in overall antibiotic utilization, a 51% decrease in the utilization of antibiotics undergoing PAF, and a 72% reduction in the use of broad-spectrum antibiotics such as meropenem. There was a concomitant increase in organism susceptibility and a reduction in yearly drug purchasing costs of over USD 560,000 from baseline without changes in sepsis-related mortality. Our study highlights that a pediatric ASP based primarily on the principles of guideline development and PAF can improve antibiotic utilization and institutional bacterial susceptibilities without a detrimental impact on patient outcomes by changing the culture of antimicrobial utilization within the institution.

Challenges of Antibiotic Stewardship in the Pediatric and Neonatal Intensive Care Units.

The goals of antimicrobial stewardship programs (ASPs) are to optimize antimicrobial prescribing habits in order to improve patient outcomes, reduce antimicrobial resistance, and reduce hospital costs. Multiple society-endorsed guidelines and government policies reinforce the importance of ASP implementation. Effective antimicrobial stewardship can impact unique patients, hospitals, and societal antibiotic-resistance burden. The role and subsequent success of these programs has largely been reported in the adult population. Pediatric and neonatal intensive care units present unique challenges for traditional antimicrobial stewardship approaches. The purpose of this review article is to explore the challenges of appropriate antibiotic use in the pediatric and neonatal intensive care units and to summarize strategies ASPs can use to overcome these challenges. These problems include non-specific disease presentations, limited evidence for definitive treatment durations in many pediatric infections, fewer pediatric-trained infectious disease physicians, and applicability of intensive laboratory obtainment, collection, and interpretation. Additionally, many ASP implementation studies evaluating the efficacy of ASPs exclude the PICU and NICU. Areas of focus for pediatric ASPs should likely include appropriate antibiotic initiation, appropriate antibiotic duration, and appropriate antibiotic de-escalation.

Changes in Metronidazole and Vancomycin Utilization for Nonsevere Clostridioides difficile Infection Among Institutions Caring for Children.

Clostridioides difficile infection guidelines were published in final format on April 1, 2018. Among 4962 and 3545 C. difficile infection cases in children the year before and after publication, oral metronidazole use decreased from 63.0% to 44.3% (P < 0.001) and oral vancomycin use increased from 27.3% to 47.7% (P < 0.001). Quarterly metronidazole utilization decreased postguidelines among 117 institutions, incidence rate ratios 0.86 (95% confidence intervals: 0.78-0.96).

Importance of Reviewing Antibiotic Courses by 48 Hours: Risk Factors for Third-Generation Cephalosporin Resistance Among AmpC Harboring Organisms in Urine and Respiratory Cultures.

BACKGROUND: Citrobacter, Enterobacter, Morganella, and Serratia (AmpC organisms) species can exhibit third-generation cephalosporin (TGC) resistance after TGC exposure. We aimed to assess if institutional TGC utilization correlated with institutional AmpC organism susceptibility and if prior TGC exposure ≤48 hours were associated with TGC resistance in the first culture of a future infection episode caused by an AmpC organism. METHODS: A 5-year retrospective cohort study was performed, including AmpC organisms isolated from pediatric urinary and respiratory tract cultures at an institution with TGC courses reviewed by the antimicrobial stewardship program at 48 hours. Correlations were assessed by Pearson's correlation. Multivariable logistic regression identified factors independently associated with TGC resistance in a subcohort of infection episodes. RESULTS: Among 654 cultures, AmpC organism TGC susceptibility increased from 74% in 2013 to 89.3% in 2017, and this correlated with a 26.1% decrease in TGC utilization (R = -0.906; P = 0.034). Among 275 AmpC organism infections, 21.1% were resistant. Resistance occurred in 13.6%, 17.4%, and 56.5% of infections with no exposure, ≤48 hours, and >48 hours of TGC exposure in the past 30 days, respectively. TGC exposure ≤48 hours was not associated with resistance (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.32-4.94; P = 0.74), whereas, TGC exposure >48 hours was (OR, 8.7; 95% CI, 3.67-20.6; P < 0.001). Infections in 2017 were less likely to be resistant (OR, 0.25; 95% CI, 0.08-0.8; P = 0.019). CONCLUSIONS: Decreased TGC utilization, likely related to antimicrobial stewardship, correlated with increased AmpC organism susceptibility. Limiting TGC exposure to ≤48 hours when possible may reduce AmpC organism resistance in future infections.

Educational Outcomes Resulting From Restructuring a Scholarship Course for Doctor of Pharmacy Students.

Objective. To compare educational outcomes between two iterations of a scholarship and research course for Doctor of Pharmacy (PharmD) students at Virginia Commonwealth University's School of Pharmacy. Methods. The first iteration of a course intended to teach pharmacy students the knowledge and skills necessary to design and conduct research involved lectures and application exercises, including limited guided questions about different aspects of the research process. In the fall of 2015, multiple structured activities and accompanying grading rubrics, each designed around the structure and content of a section of a research proposal, were introduced to the course to supplement lectures. Both iterations of the course culminated with students submitting a research proposal. After establishing interrater reliability, faculty members graded a random sample of 20 research proposals, 10 from each version of the course, and section-specific and overall proposal scores were compared. Results. In the proposals submitted after the course revisions, significant improvements in three areas were identified: the overall score, the section-specific scores for research hypothesis/specific aims, and institutional review board (IRB) discussion/informed consent. Nominal, though not statistically significant, improvements were observed in other sections. Conclusion. Additional research is needed regarding the best instructional strategies to reinforce data analysis and statistical testing knowledge and skills in PharmD students. Overall, our findings support the hypothesis that a more formalized, guided approach for teaching research methods improves learning outcomes for PharmD students.

Disparate Candida albicans Biofilm Formation in Clinical Lipid Emulsions Due to Capric Acid-Mediated Inhibition.

Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid-a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.

Doxycycline and Tooth Discoloration in Children: Changing of Recommendations Based on Evidence of Safety.

Doxycycline use has historically been limited to children older than 8 years because of concerns regarding permanent tooth discoloration. Six studies assessed tooth discoloration in at least 338 patients exposed to doxycycline before 8 years of age. Six patients had potential discoloration, but studies consistently found no difference in tooth discoloration between exposed patients and controls. Recommendations have changed stating doxycycline, but not other tetracyclines, can be used for short courses (<21 days) regardless of age. Clinicians should be aware of these data because doxycycline use may extend to disease states apart from tick-borne illnesses in pediatric patients.

Antimicrobial stewardship impact on Pseudomonas aeruginosa susceptibility to meropenem at a tertiary pediatric institution.

An antimicrobial stewardship program was implemented throughout 2012 at a tertiary pediatric institution with guideline development preceding prospective audit and feedback starting in 2013. Meropenem use decreased over 62% during the next 5 years. Non-cystic fibrosis Pseudomonas aeruginosa isolate susceptibility to meropenem increased from 89% in 2011 to 98% in 2017 (P < .001) and correlated with meropenem use the preceding year (Rs: -0.78, P = .008).

Assessment of Different Methods for Pediatric Meningitis Dosing Clinical Decision Support.

BACKGROUND: Indication-specific medication dosing support is needed to improve pediatric dosing support. OBJECTIVE: To compare the sensitivity and positive predictive value (PPV) of different meningitis dosing alert triggers and dosing error rates between antimicrobials with and without meningitis order sentences. METHODS: We retrospectively analyzed 4-months of pediatric orders for antimicrobials with meningitis-specific dosing. At the time of the order, it was determined if the antimicrobial was for meningitis management, if a cerebrospinal fluid (CSF) culture was ordered, and if a natural language processing (NLP) system could detect "meningitis" in clinical notes. RESULTS: Of 1383 orders, 243 were for the management of meningitis. A CSF culture or NLP combination trigger searching the electronic health record since admission yielded the greatest sensitivity for detecting meningitis management (67.5%, P < 0.01 vs others), but dosing error detection was similar if the trigger only searched 48 hours preceding the order (68.8% vs 62.5%, P = 0.125). Using a CSF culture alone and a 48-hour time frame had a higher PPV versus a combination with a 48-hour time frame (97.1% vs 80.9%, P < 0.001), and both triggers had a higher PPV than others ( P < 0.001). Antimicrobials with meningitis order sentences had fewer dosing errors (19.8% vs 43.2%, P < 0.01). Conclusion and Relevance: A meningitis dosing alert triggered by a combination of a CSF culture or NLP system and a 48-hour triggering time frame could provide reasonable sensitivity and PPV for meningitis dosing errors. Order sentences with indication-specific recommendations may provide additional dosing support, but additional studies are needed.

Learning Activities to Build Population Health Management Skills for Pharmacy Students.

Objective. To describe the implementation and evaluation of population health management learning activities in a second-year Doctor of Pharmacy (PharmD) course. Methods. Population health learning sessions were implemented in a step-wise manner: population needs assessment activity to identify priority programs for implementation given a specific patient population; didactic materials to introduce program evaluation foundational knowledge; program evaluation design activity to evaluate implemented programs using the Centers for Disease Control and Prevention's Program Evaluation Framework; and evaluation of program outcome data. Students' self-rated abilities (grouped into Bloom's Taxonomy classifications) and perceptions before and after program evaluation activities were assessed. Qualitative analyses evaluated student feedback on learning sessions. Results. Students' self-rated abilities for all Bloom's classifications increased after the learning sessions. Student perceptions on importance of program evaluation also improved (from 71% reporting "agree" or "strongly agree" pre-activities to 79% post-activities). Students found the application to case scenarios and the opportunity to integrate each component of program evaluation into a complete process useful. Conclusion. Step-wise population health management learning sessions were implemented, culminating in skill-based program evaluation activities. The activities improved students' self-rated abilities and perceptions regarding program evaluation. Areas for improvement for the learning sessions were also identified and will inform future instructional design.

Variability in antifungal utilization among neonatal, pediatric, and adult inpatients in academic medical centers throughout the United States of America.

BACKGROUND: Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers. METHODS: For this hospital-level analysis, we analyzed antifungal use in hospitals across the United States of America, excluding centers only providing care for hematology/oncology patients. Analysis of variance was used to compare antifungal use between patient groups. Three multivariable linear regression models were used to determine independent factors associated with antifungal use in the neonatal, pediatric, and adult patient groups. RESULTS: For the neonatal, pediatric, and adult patient groups, 54, 44, and 60 hospitals were included, respectively. Total antifungal use was significantly lower in the neonatal patient group (14 days of therapy (DOT)/1000 patient days (PDs) versus 76 in pediatrics and 74 in adults, p < 0.05). There were no significant associations identified with total antifungal DOT/1000 PDs in the neonatal patient group (model R2 = 0.11). In the pediatric patient group (model R2 = 0.55), admission to immunosuppressed service lines and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 1.95 and 0.41, both p < 0.05). In the adult patient group (model R2 = 0.79), admission to immunosuppressed service lines, total invasive fungal infections, and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 5.08, 5.17, and 0.137, all p < 0.05). CONCLUSIONS: Variability in antifungal use in the neonatal group could not be explained well, whereas factors were associated with antifungal use in the adult and pediatric patient groups. These data can help guide antifungal stewardship initiatives.