Drug-Induced Hepatitis in an Adolescent During Concomitant Use of Azithromycin and Lisdexamfetamine Dimesylate.

This case report describes a 14-year-old male with signs and symptoms of drug-induced hepatotoxicity after receiving azithromycin and lisdexamfetamine dimesylate. The patient was admitted to the hospital and a liver biopsy revealed findings suggestive of drug-induced hepatitis. In this patient, it is unclear whether 1 agent individually or a combination of azithromycin and lisdexamfetamine was the cause of hepatitis. Although hepatotoxicity has been reported with azithromycin and other macrolide antibiotics in adults, such a condition has yet to be reported in pediatrics. In light of this report, providers should be aware of a potentially rare reaction of acute hepatitis when combining azithromycin and lisdexamfetamine in pediatric patients.

Evaluation of Academic and Nonacademic Factors of First-Generation Students Transitioning to a Pharmacy Program.

OBJECTIVE: To evaluate the academic transition of first-generation (FG) students to a Doctor of Pharmacy program and the impact of early intervention/outreach. METHODS: The retrospective study evaluated the first semester performance in three classes of student pharmacists (beginning fall 2020, 2021, 2022) at a public university in the mid-South. Student demographics (age, sex, race, relationship status), nonacademic factors (Grit, impostor syndrome, testing anxiety, perceived stress), and academic factors (grade point average, academic probation, early intervention) were assessed. In fall 2022, a required academic meeting was added to the early intervention process after exam one for high-risk students. The data between FG and non-FG students were compared; Mann-Whitney tests for continuous variables and Chi-square tests with risk estimates for categorical variables. RESULTS: There were 152 FG and 274 non-FG students identified over the three classes. A total of 88 (57.9%) FG students represented racial minority groups. More FG students and non-White students were identified for early intervention. First-generation students were more likely to receive two or more grades less than C- and less likely to progress to the spring. No significance was noted with generational status and undergraduate grade point average, academic performance, or nonacademic factors. The required meeting after exam one in fall 2022 resulted in less disparity between FG and non-FG students identified for early intervention for exam two. CONCLUSION: First-generation and non-White students were more likely to struggle when transitioning to the Doctor of Pharmacy curriculum. A proactive, individualized approach incorporated into early intervention procedures is needed to promote academic success and belonging.

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.

Impact of a stroke interprofessional simulation on health professional students.

INTRODUCTION: The objective was to describe the interprofessional stroke simulation delivered across three campuses with seven types of health professions students and the impact the activity had on the students. METHODS: An interprofessional stroke simulation event was completed with pharmacy, medical, nursing, physician assistant, occupational therapy, physical therapy, and speech pathology students across a multi-site campus. Pre-activity, demographic information was requested including age, gender, discipline, year in respective program, number of experiences in prior interprofessional events, and comfort working with other health care professionals. The survey was repeated after the session and gathered free-text responses on whether learners gained information on working together, if they learned about the roles of other health care workers, and if they found the session useful. RESULTS: A total of 1820 health care professional students completed the simulation activity over four years. Of those students, 1035 (57%) completed the pre-survey, and 884 (49%) completed the post-survey. From the post-survey results, 91.5% of participants felt that they learned how health care disciplines can work together. Also, 87% of participants felt more comfortable working with learners from other professions. Most participants agreed the session was useful (77.1%) and rated it as moderately to extremely effective (81.8%). CONCLUSIONS: Interprofessional sessions with health care professional students are beneficial for learning new information about other professions and enhancing comfort levels in working with interprofessional groups. The interprofessional simulation improved the comfort level of students working with other health care professional students and should be considered in professional student curricula.

Comparison of student performance in therapeutics and communications courses to outcomes of objective structured clinical examinations: A retrospective analysis.

INTRODUCTION: The objective was to examine the association between course grades and objective structured clinical examination (OSCE) performances in a pharmacy student cohort. METHODS: A retrospective analysis of demographics, final grades in the Therapeutics I through IV and Communications courses, and multiple OSCE scores (therapeutic knowledge and general communication skills [GCS]) was performed for two cohorts. RESULTS: Female students scored higher than male students on the warfarin OSCE therapeutic knowledge (P = .008) and GCS scores (P = .02). Age was inversely correlated with warfarin OSCE therapeutic knowledge score (P = .001). The warfarin OSCE therapeutic knowledge score was positively related to Therapeutics II final grades (P < .001). The Communications course final grade was positively correlated to the warfarin OSCE faculty-rated GCS score (P = .005). Therapeutics final grades were not significantly related to station scores of a multi-station OSCE (P > .05). The final regression model included gender and Therapeutics II final grade and explained 6% of the variance in warfarin OSCE therapeutic knowledge scores. CONCLUSIONS: A number of significant associations were found between demographics, final course grades, and specific OSCE scores. A regression model was significant, but only explained a low percentage of the warfarin OSCE therapeutic knowledge score variance, suggesting other factors not evaluated had a greater effect on scores. This research suggests that OSCEs play an important role in demonstrating student competency in educational domains other than knowledge and brings forth new data suggesting that age and/or gender may influence OSCE performance.

A Comprehensive Review of Vaping Use in Pediatric Patients and Recent Changes in Regulatory Laws.

The use of electronic cigarettes (e-cigarettes), also known as vapes, by adolescents and young adults has dramatically increased over the past several years. E-cigarettes continue to be the most used form of tobacco among youth. As a result of this concerning trend, policies at both the state and federal levels have been implemented to limit availability in this population. Additionally, the coronavirus disease 2019 (COVID-19) pandemic has had some positive and negative effects on the youth vaping epidemic with adolescent consumers reporting limited access to retail sites during the stay-at-home executive orders, but easier access with online purchasing because age verification was often not required. Complications resulting from vaping have been reported and include e-cigarette or vaping product use-associated lung injury (EVALI) and thrombotic events. Data suggest that the use of vaping devices can lead to both short- and long-term respiratory morbidity in the pediatric population. This review serves to provide a comprehensive examination of vaping use in pediatric patients and recent changes in regulatory laws to equip pharmacists with the knowledge to be aware of the different devices and products available, ask their pediatric patients regularly about use, and counsel and educate on the potential harmful effects.

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.

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.

Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism.

We describe an 11-year-old female who presented with severe hypersomnolence after receiving 1 week of modest doses of clobazam (CLB). In reviewing the above case, we considered that the hypersomnolence could be related to a pharmacodynamic, pharmacokinetic, or pharmacogenomic issue associated with CLB or to a combination of these factors. Although serum concentrations of CLB and its active metabolite are sensitive to factors that affect cytochrome-dependent metabolism, drug-drug interactions were omitted as a cause of the hypersomnolence. Subsequent DNA analysis of the cytochrome P450 2C19 gene revealed the patient as *2/*2 genotype with poor metabolizer enzyme activity. Because genetic testing of all patients treated with CLB is currently not practical, CLB dose/concentration ratios and pharmacokinetic drug-drug interaction impact models may be indicated. Genetic testing should be considered when an adverse effect suggests the possibility of a polymorphism important to drug metabolism.

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).

Examining the Association of GPA and PCAT Scores on Objective Structured Clinical Examination Scores.

Objective. To examine the association between certain demographic and admission measures and Objective Structured Clinical Examination (OSCE) performance in a cohort of pharmacy students. Methods. A retrospective review of demographic characteristics, admissions data [cumulative and science admission Grade Point Average (GPA), Pharmacy College Admissions Test (PCAT) scores], and OSCE scores was performed for the Class of 2017 at the University of Tennessee College of Pharmacy. Results. Female students scored significantly higher than male students on the Warfarin OSCE - Standardized Patient (SP) rated General Communication Skills and on the Warfarin OSCE - Faculty rated Patient Interviewing Skills. Age was significantly, inversely correlated with Warfarin OSCE - Faculty rated Therapeutic Knowledge score. Warfarin OSCE - SP rated General Communication Skills score was significantly, positively related to PCAT composite score and PCAT reading comprehension score. PCAT composite score was significantly, inversely correlated to Warfarin OSCE - Faculty rated Patient Interviewing Skills score. Warfarin OSCE - Faculty rated General Communication Skills score was significantly, positively related to cumulative admission GPA and admission science GPA. Conclusion. Eight statistically significant correlations were found between demographic and admissions measures and specific OSCE scores. Regression models were significant but explained a low percentage of the variance in OSCE scores, suggesting other factors not included in the study have a greater effect on scores. Such factors may include knowledge acquired in pharmacy school courses such as the therapeutics course series.

Impact of Drug Interactions on Clobazam and N-Desmethylclobazam Concentrations in Pediatric Patients With Epilepsy.

BACKGROUND: Clobazam (CLB) is approved as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. It is converted to an active metabolite N-desmethylclobazam (NCLB) by CYP3A4, which is then broken down to an inactive metabolite by CYP2C19. This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. METHODS: This was a retrospective chart review including patients older than 1 month, who received CLB between April 2012 and March 2017. Extracted data included patient demographics, CLB daily dose, CLB and NCLB Cp, calculated CLB and NCLB Cp/Cp and Cp/D ratios, and all concomitant drugs. RESULTS: The study included 995 CLB concentration sets from 302 patients (median age 7.6 years and range 0.2-40.1 years). Pharmacokinetic variability was extensive, as seen by widespread ranges of CLB and NCLB Cp, NCLB/CLB Cp ratio, and 3 Cp/D ratios (CLB, NCLB, and CLB + NCLB). Comedications, described as CYP3A4 inducers and/or CYP2C19 inhibitors (carbamazepine, eslicarbazepine, felbamate, (fos)phenytoin, oxcarbazepine, pentobarbital, phenobarbital, rufinamide, and topiramate), generally increased NCLB/CLB Cp ratio (267%-400%), NCLB Cp/D ratio (167%-202%), and CLB + NCLB Cp/D ratio (142%-185%) and decreased CLB Cp/D ratio (47%-76%) compared with a group of concentration sets in patients receiving only neutral comedications (P < 0.025 for all comparisons). Older age was associated with higher Cp/D ratios (mg/kg), indicative of decreased clearance. CONCLUSIONS: Pharmacokinetic variability of CLB in pediatric patients is extensive, and it is influenced by drug-drug interactions and age. Therapeutic drug monitoring of CLB and active metabolite NCLB with calculation of various Cp/Cp and Cp/D ratios can provide useful insight into CLB pharmacokinetics and help differentiate between causes of variability.

A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens.

This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.

Bumetanide continuous infusions in critically ill pediatric patients.

OBJECTIVE: Limited data exist for the use of bumetanide continuous infusions in children. The purpose of this study was to evaluate the use of bumetanide continuous infusions in critically ill pediatric patients. DESIGN: This study was an institutional review board approved, single-center, retrospective chart review of 95 patients. Dosing practices were described by rate (µg/kg/hr), duration (days), and previous diuretic use. Efficacy, determined by ability to achieve negative fluid balance and time to reach negative fluid balance, was assessed at 12, 24, and 48 hours. Safety was evaluated based on prevalence of adverse drug reactions. Adverse drug reactions were predefined as serum potassium concentration less than 3 mEq/L, serum chloride concentration less than 90 mEq/L, serum carbon dioxide concentration greater than 35 mEq/L, and serum creatinine increased greater than 1.5 times baseline and above patient-specific normal range. SETTING: Le Bonheur Children's Hospital, Memphis, TN. PATIENTS: Critically ill patients who are 18 years old or younger and received bumetanide continuous infusions. A total of 95 patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean dose of bumetanide was 5.7 ± 2.2 µg/kg/hr (1-10 µg/kg/hr) with a median duration of 3.3 days (0.3-18.5). The total percentage of patients achieving negative fluid balance by 48 hours was 76% with 54% of patients reaching negative fluid balance within 12 hours. CONCLUSIONS: This study showed that a bumetanide dose of 5.7 µg/kg/hr was effective in achieving negative fluid balance in the majority of critically ill pediatric patients. Additionally, bumetanide appears to be a safe loop diuretic for use as a continuous infusion at the doses described in critically ill pediatric patients.

Glomerular filtration rate equations do not accurately predict vancomycin trough concentrations in pediatric patients.

BACKGROUND: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. OBJECTIVE: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. METHODS: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. RESULTS: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r (2) = 0.028) and Bedside CKiD equation (r (2) = 0.028). A weak relationship between serum creatinine and troughs was observed (r (2) = 0.132). Limitations include small sample size and retrospective design. CONCLUSIONS: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications.

Limb swelling in a pediatric sickle cell patient after revaccination with pneumococcal vaccine.

CASE (DESCRIPTION): This report describes an incident of limb swelling after revaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A 5-year old female with sickle cell disease experienced severe arm swelling with edema to the extent that it was difficult to put a shirt over the arm. The day prior, she received PPSV23 concomitantly with the meningococcal vaccine. She had received the PPSV23 vaccine 2.5 years prior to the event. The patient was managed with analgesics, antiemetics, and antibiotic prophylaxis and the arm swelling resolved 24 h later. A decreased length of time between revaccination and concurrent administration with the meningococcal vaccine could have contributed. CONCLUSION: Although rare, limb swelling after revaccination could be a concern in special at-risk populations where repeated vaccination is necessary for pneumococcal protection.