Comparison of Cefazolin and Ceftriaxone Enterobacterales Susceptibilities for Inpatient Treatment of Urinary Tract Infections and Risk of Hospital-Onset Clostridioides difficile Infection.

PURPOSE: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost, and perceived safety. However, third-generation cephalosporins increase the risk of health care facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States is limited. This analysis assessed the comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empirical agent to manage inpatient UTI and limit ceftriaxone collateral damage. METHODS: This was a retrospective single-center observational study. Microbiologic susceptibility data were analyzed for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis urinary specimens taken from adult inpatients admitted from January 1, 2022, to December 31, 2022. Primary outcome was incidence of E coli, K pneumoniae, and P mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC <16 µg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. FINDINGS: A total of 1150 urine samples were identified as E coli, K pneumoniae, and P mirabilis in 2022. Susceptibility to cefazolin was observed in 1064 (92.5%) of 1150 isolates using the MIC breakpoint for uncomplicated UTI and to ceftriaxone in 1115 (97.0%) of 1150 isolates (P < 0.001). From 2016 to 2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions, with HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure, and 11 cases (0.15%) developed in cefazolin-exposed admissions (adjusted odds ratio, 2.44; 95% CI, 1.25-4.76; P < 0.001). IMPLICATIONS: Cefazolin exhibits high susceptibility for uropathogens commonly implicated in cases of uncomplicated UTI, the most common UTI diagnosis among inpatients. Although ceftriaxone shows a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared with cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage such as HOCDI, use of cefazolin for uncomplicated UTI may be evaluated by using local susceptibility data.

Evidence-Based Medicine and Pharmacotherapy Content Alignment.

OBJECTIVE: When effectively executed, content alignment can aid student performance in associated courses. Limited research exists for content alignment of evidence-based medicine (EBM) and pharmacotherapy courses. This study assesses the impact of EBM and pharmacotherapy course alignment on student performance. METHODS: Content alignment included assignment of 6 landmark trials in EBM coursework. The articles were identified by pharmacotherapy instructors as "landmark" to management of associated diseases in the aligned pharmacotherapy semester. Articles were the basis for quizzes over skills taught in the EBM course and were referenced during pharmacotherapy lectures. RESULTS: During the alignment semester, students were more likely to cite specific guidelines and/or primary literature to rationalize pharmacotherapeutic plans on examinations compared with the prealignment period (54% vs 34%). Overall, pharmacotherapy case performance and plan rationale scores were significantly higher in the alignment semester compared with prealignment. Student performance on the Assessing Competency in Evidence-Based Medicine tool improved from the start of the semester (8.64, SD 1.66) to the end (9.5, SD 1.49; mean score +0.86). Comfort in applying EBM analysis to primary literature increased significantly between the first and final assignments, with 6.7% and 71.7% of students self-reporting a high degree of confidence, respectively. Students (73%) reported an enhanced understanding of pharmacotherapy due to alignment compared with a previous semester of pharmacotherapy without alignment. CONCLUSION: The use of landmark trial assignments to align EBM and pharmacotherapy coursework demonstrated a positive impact on student rationale for clinical decision-making and student confidence in evaluating primary literature.

Saccharomyces boulardii prophylaxis for targeted antibiotics and infectious indications to reduce healthcare facility-onset Clostridioides difficile infection.

BACKGROUND: Probiotic prophylaxis for Clostridioides difficile infection (CDI) is controversial stemming from deficits in strain and disease specificity considerations and concern for adverse effects. Here risk for healthcare facility-onset CDI (HO-CDI) dependent on concomitant antibiotic and infectious indication is assessed to identify opportunities for targeted prophylaxis. METHODS: Retrospective matched-cohort study from January 2016 through March 2019. Patient-admissions administered high risk antibiotics were categorized by Saccharomyces boulardii administration and matched 1:1 to non-recipients. Unadjusted and adjusted HO-CDI risk estimated using Cox proportional hazards regression. RESULTS: S. boulardii administration was associated with 48% risk reduction for HO-CDI compared to non-recipients (aHR 0.52, 95% CI: 0.31-0.87). Patient-admissions administered antibiotics and S. boulardii for a pneumonia indication exhibited a 57% reduction in risk for HO-CDI (aHR 0.43, 95% CI: 0.19-0.95). Administration of S. boulardii with ceftriaxone was associated with a 76% reduced risk of HO-CDI (aHR 0.24, 95% CI: 0.11-0.53) compared to ceftriaxone without S. boulardii, number needed to treat of 100. CONCLUSIONS: S. boulardii administration is associated with a significant HO-CDI risk reduction for inpatients receiving antibiotics associated with CDI. Institutions interested in targeted use of S. boulardii to limit potential adverse effects may consider prophylaxis for inpatients with pneumonia or receiving ceftriaxone.

Incidence of Saccharomyces cerevisiae fungemia in hospitalised patients administered Saccharomyces boulardii probiotic.

BACKGROUND: Bloodstream infection is an untoward effect of probiotic administration described by case reports and a cited reason to avoid using in the critically ill. The incidence rate of bloodstream infection in a population administered probiotics remains unknown. METHODS: A retrospective observational analysis of incident Saccharomyces cerevisiae fungemia in a population of hospitalised patients administered Saccharomyces boulardii for primary prevention of hospital-onset Clostridioides difficile infection. Adult patients admitted to an inpatient medical unit for 48-h or more between January 1, 2016 and December 31, 2019 are included. Facility medication administration records and microbiology records were evaluated for S boulardii probiotic administration and incidence of S cerevisiae positive blood cultures. Microbiologic identification methods were unable to distinguish S cerevisiae from S boulardii. RESULTS: Administration of S boulardii probiotic occurred in 16,404 of 46,729 patients analysed. S cerevisiae fungemia was identified in 18 probiotic recipients (0.11%). The observed incidence of fungemia attributable to S boulardii administration is 1.70 cases per 10,000 patient-days. Central-line days numbered 52,949 yielding an incidence of 0.26 cases of S cerevisiae per 1,000 central-line days. Intensive care unit admission was significantly associated with an increase in the risk of S cerevisiae (OR 6.55, CI 2.28-18.87), incidence rate of 0.47 cases per 1,000 patient-days. CONCLUSION: The risk of bloodstream infection as a result of S boulardii probiotic use appears restricted to S boulardii recipients. The risk for probiotic-related bloodstream infection does not appear greater than the risk of any hospital-acquired bloodstream infection both inside and outside of the intensive care unit.

The Effect of Saccharomyces boulardii Primary Prevention on Risk of Hospital-onset Clostridioides difficile Infection in Hospitalized Patients Administered Antibiotics Frequently Associated With C. difficile Infection.

BACKGROUND: Hospital-onset Clostridioides difficile infection (HO-CDI) is a costly problem leading to readmissions, morbidity, and mortality. We evaluated the effect of a single probiotic strain, Saccharomyces boulardii, at a standardized dose on the risk of HO-CDI within hospitalized patients administered antibiotics frequently associated with HO-CDI. METHODS: This retrospective cohort study merged hospital prescribing data with HO-CDI case data. The study assessed patients hospitalized from January 2016 through March 2017 who were administered at least 1 dose of an antibiotic frequently associated with HO-CDI during hospitalization. Associations between S. boulardii administration, including timing, and HO-CDI incidence were evaluated by multivariable logistic regression. RESULTS: The study included 8763 patients. HO-CDI incidence was 0.66% in the overall cohort. HO-CDI incidence was 0.56% and 0.82% among patients coadministered S. boulardii with antibiotics and not coadministered S. boulardii, respectively. In adjusted analysis, patients coadministered S. boulardii had a reduced risk of HO-CDI (odds ratio [OR], 0.57 [95% confidence interval {CI}, .33-.96]; P = .04) compared to patients not coadministered S. boulardii. Patients coadministered S. boulardii within 24 hours of antibiotic start demonstrated a reduced risk of HO-CDI (OR, 0.47 [95% CI, .23-.97]; P = .04) compared to those coadministered S. boulardii after 24 hours of antibiotic start. CONCLUSIONS: Saccharomyces boulardii administered to hospitalized patients prescribed antibiotics frequently linked with HO-CDI was associated with a reduced risk of HO-CDI.

Inpatient Proton Pump Inhibitor Administration and Hospital-Acquired Clostridium difficile Infection: Evidence and Possible Mechanism.

The incidence of Clostridium difficile infection continues to increase globally. Particularly concerning are hospital-acquired cases that attribute significant morbidity, mortality, and expenditures to the health care system. Proton pump inhibitors, which are widely prescribed and generally considered to have minimal adverse effects, have recently come under scrutiny for positive associations with C. difficile infection development. This article will specifically review the current state of evidence demonstrating a positive association between nosocomial proton pump inhibitor administration and the incidence of hospital-acquired C. difficile infection. In addition, the article delivers state-of-the-art knowledge relative to mechanisms by which proton pump inhibitor exposure may propagate the manifestation of C. difficile infection.

The role of aldosterone antagonism agents in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease is a common consequence of the development of diabetes. In the United Kingdom 18-30% of chronic kidney disease cases and 44% of end-stage renal disease cases in the United States have been attributed to complications of diabetic kidney disease. Angiotensin blockade using angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the standard for slowing the progression of diabetic kidney disease. Evidence suggests that aldosterone antagonism added to standard therapy may be beneficial. AIM OF REVIEW: This paper aims to explore the pathophysiological contribution of aldosterone in diabetic kidney disease and review available literature for aldosterone antagonism through mineralocorticoid receptor blockade. METHODS: A comprehensive literature search was conducted. Results were analysed and summarised. RESULTS: Nine trials evaluating a total of 535 patients with diabetic kidney disease were identified that evaluated the use of aldosterone antagonists for reducing the signs of diabetic kidney disease. All trials demonstrated a marked decrease in urinary protein excretion when compared to, or added to angiotensin converting enzyme inhibition or angiotensin receptor blockade. The most commonly reported side effect in all of the trials was hyperkalaemia, which occurred in 6.1% of all patients evaluated. Aldosterone antagonists were generally well tolerated in the evaluated patient populations. CONCLUSION: Aldosterone antagonism may represent a safe and effective complimentary therapy to the use of angiotensin converting enzyme inhibition, or angiotensin receptor blockade, for slowing the progression of diabetic kidney disease.

Religious barriers to measles vaccination.

In 2014, the United States has experienced an increase in measles activity, the most since the elimination of the virus in 2000. The measles infection occurs in unvaccinated individuals. Communities and individuals choose to not vaccinate for a number of reasons, primarily citing religious and philosophical motives. Objections based upon religion most often center on the use of aborted human fetus tissue used in the rubella component of the combined vaccine products, and animal derived gelatins used in vaccine production. Objections among religious communities may also not be faith based, rather in some cases concerns related to lack of safety and efficacy of the vaccination result in refusal.

The Value of Pharmacy Residency Training for Health Systems: An Annotated Bibliography.

PURPOSE: Identify and summarize articles that describe the value that pharmacy residency training offers to sponsoring health systems. SUMMARY: There is a tremendous gap between the number of resident applicants and the number of pharmacy residencies available. Informing health-system administration executives about the proven value of residency training is key to expanding the number of available positions. To address this disparity, a comprehensive and systematic literature search to identify publications highlighting the value that pharmacy residency training provides to the sponsor hospital or health system was conducted. Articles were identified through query of PubMed and SciVerse SCOPUS and through review of bibliographies from relevant articles. Twenty articles were identified and summarized in this annotated bibliography that demonstrate perceived and quantitative value of pharmacy residency training for health systems that sponsor residency training. CONCLUSION: Pharmacy residency training programs are essential for pharmacists that will primarily engage in direct patient care activities. This annotated bibliography includes key publications that provide evidence of the value that pharmacy residents provide to the sponsoring health system. This manuscript will aid prospective residency directors interested in developing new residency positions at new institutions or for residency program directors interested in expanding the total number of resident positions available at the existing sites.

Assessment of Tdap administration rates from 2009 to 2012 at a large urban nonteaching hospital.

Due to the significant rise in pertussis cases reported in 2012, these authors investigated the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine administration at our institution from 2009 to 2012 to determine if changes in prescribing practices reflected published updates from the Advisory Committee on Immunization Practices (ACIP). A single large, urban, private, non-teaching hospital. Documented Tdap vaccines administered from January 2009 through December 2012 were retrieved using an electronic data pull. The incidence of Tdap vaccine administration was reported as number of events per 1,000 patient visits. This data pull served to provide the longitudinal context to prescribing pattern changes at our facility, which were then compared to ACIP vaccination recommendation changes. Tdap administrations increased from 1,365 vaccinations in 2009 to 3,048 vaccinations in 2012. Tdap vaccine administration increased significantly each successive year from 2009 to 2012 from 23.96 ± 1.25 to 47.15 ± 1.63 vaccines per 1,000 patient visits to the facility. Confidence intervals did not overlap for consecutive years representing statistically significant differences between vaccination rates from year to year. Review of Tdap administrations demonstrates a clear and significant increase over consecutive years from 2009 to 2012. Over this time period there were no institutional initiatives aimed at increasing appropriate Tdap use at our institution. This study suggests a correlation between ACIP vaccination recommendations and provider prescribing of Tdap, although no definitive association can be made.

High-fidelity patient simulation series to supplement introductory pharmacy practice experiences.

OBJECTIVE: To introduce a high-fidelity simulation series into a 5-year doctor of pharmacy (PharmD) curriculum to demonstrate a hybrid model for introductory pharmacy practice experience (IPPE) delivery. DESIGN: Fourth-year pharmacy students at a satellite campus participated in a 6-week high-fidelity patient simulation series in which small groups of students worked with members of a patient care team to care for patients in the following scenarios: asthma exacerbation, acute decompensated heart failure, and infective endocarditis with a subsequent anaphylactic reaction to the antibiotic. Fourth-year pharmacy students at the main campus who did not participate in the simulation served as a comparator group. ASSESSMENT: Students' scores on a knowledge-based post-simulation quiz were significantly higher than scores on the presimulation quiz (p < 0.05). Knowledge retention was significantly higher among the simulation participants than students in the comparator group (p = 0.004). The majority (76%) of students felt more confident "making clinical recommendations to a healthcare provider" after completing the simulation series (p = 0.01). CONCLUSION: High-fidelity patient simulation is an effective active-learning strategy to augment IPPEs that allows students to apply clinical skills in a realistic but low-risk patient care setting.