Evaluation of Sequential Oral Versus Intravenous Antibiotic Treatment of Enterococcus faecalis Bloodstream Infections.

BACKGROUND: Intravenous (IV) antibiotics have historically been considered standard of care for treatment of bloodstream infections (BSIs). Recent literature has shown sequential oral (PO) therapy to be noninferior to IV antibiotics for certain pathogens and disease states. However, a gap exists in the literature for BSI caused by Enterococcus faecalis. OBJECTIVE: To compare outcomes of definitive sequential PO therapy to definitive IV therapy in patients with E faecalis BSI. METHODS: Multicenter, retrospective, matched cohort study of adult patients with at least one blood culture positive for E faecalis from January 2017 to November 2022. Patients with polymicrobial BSI, concomitant infections requiring prolonged IV antibiotic therapy, those who did not receive antibiotic therapy, and those who died within 72 hours of index culture were excluded. Subjects were matched based on source of infection in a 2:1 (IV:PO) ratio. The primary outcome was a composite of all-cause mortality and treatment failure. Secondary outcomes included hospital length of stay (LOS), antibiotic duration, and 30-day readmission rate. RESULTS: Of the 186 patients who met criteria for inclusion, there was no statistically significant difference in the primary composite outcome for PO compared to IV therapy (14.5% vs 21.8%; OR 0.53 [0.23-1.25]) or 30-day readmission (17.5% vs 29%; OR 0.53 [0.25-1.13]). Hospital LOS was significantly longer in patients receiving IV-only therapy (6 days vs 14 days; P < 0.001). CONCLUSION AND RELEVANCE: Sequential oral therapy for E faecalis BSI had similar outcomes compared to IV-only treatment and may be considered in eligible patients.

Glucagon-like peptide 1 agonists for type 2 diabetes, weight loss, or both?

ABSTRACT: Glucagon-like peptide 1 agonists (GLP1s) and the novel glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 agonist are effective drugs for reducing A1C and weight in patients with type 2 diabetes. However, clinicians may find it difficult to discern which drug to prescribe in specific clinical scenarios. This article discusses evidence-based clinical use of these drugs.

Rethinking residency recruitment, application, and interview processes to benefit applicants and programs long-term.

Pharmacy residency recruitment and interviews have been significantly impacted by the COVID-19 pandemic. Many traditional recruitment events and interviews were transitioned from in-person to virtual, and new approaches to recruitment, such as virtual open houses, were developed. There are limited data on how these changes impacted pharmacy residency applicants and programs, and the future of virtual events is currently unknown. We highlight recommendations for virtual recruitment and interviews and provide suggestions for residency programs and national organizations to improve virtual processes in the future.

Hidden Fluids in Plain Sight: Identifying Intravenous Medication Classes as Contributors to Intensive Care Unit Fluid Intake.

Introduction: Fluid stewardship targets optimal fluid management to improve patient outcomes. Intravenous (IV) medications, flushes, and blood products, collectively referred to as hidden fluids, contribute to fluid intake in the intensive care unit (ICU). The impact of specific IV medications on fluid intake is unknown. Objective: Characterize IV medication classes based on contribution to ICU fluid intake by frequency of administration and total volume infused to identify targets for fluid stewardship. Methods: This multi-center, retrospective nested cohort study included patients admitted to a medical or surgical ICU between January 2017 and December 2018. The primary outcome was to identify the volume contribution of specific IV medication classes administered over the first 3 ICU days. Secondary outcomes were the administration frequency of these medications and their proportion of total daily volume intake over the first 3 ICU days. Results: The study included 210 patients. The largest mean administration volumes over the course of the first 3 ICU days were attributed to antibacterials (968 ± 846 mL), vitamins/minerals/electrolytes (416 ± 935 mL), pain/agitation/delirium agents (310 ± 512 mL), and vasoactive agents (282 ± 744 mL). The highest frequencies over the course of the first 3 ICU days were attributed to antibacterials (n = 180; 86%), pain/agitation/delirium agents (n = 143; 68%), vitamins/minerals/electrolytes (n = 123; 59%), and vasoactive agents (n = 96; 46%). IV medications contributed 2601 ± 2573 mL of fluid volume per patient over the first 3 ICU days, accounting for 42% ± 29% of overall volume. Conclusion: IV medications contribute over 40% of total fluid intake within the first 3 days of ICU admission, with antibacterials as top contributors by administration volume and frequency. Future research implementing fluid stewardship to ICU fluid sources, such as concentrating IV medications, switching IV medications to oral formulations, de-escalation of antibacterials, and reduction of maintenance fluids, should be performed to minimize hidden fluids from IV medications.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature.

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on "Implementing an Antibiotic Stewardship Program" were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Comparison of Pharmacist-Directed Management of Multiplex PCR Blood Culture Results with Conventional Microbiology Methods on Effective and Optimal Therapy within a Community Hospital.

Multiplex PCR combined with a pharmacist-driven reporting protocol was compared to the standard of care within a community hospital to evaluate initial changes after notification of a positive blood culture. The intervention group demonstrated decreased times to changes in antimicrobial therapy (P = 0.0081), increased changes to optimal antimicrobial therapy (P = 0.013), and decreased vancomycin use for coagulase-negative staphylococcus contaminants (P < 0.01) with multiplex PCR implementation and pharmacist intervention.

Common Bacterial and Viral Infections: Review of Management in the Pregnant Patient.

OBJECTIVE: To review the treatment of common bacterial and viral infections occurring in the pregnant patient. DATA SOURCES: A literature search of MEDLINE was performed (inception to October 2018). The Centers for Disease Control and Prevention website was utilized for additional information. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies and those conducted in humans were considered. DATA SYNTHESIS: ß-Lactams alone or in combination are the preferred treatment for many common infections in pregnancy, such as urinary tract infections, pelvic inflammatory disease (PID), gonococcal infections, syphilis, chancroid, upper- and lower-respiratory-tract infections, certain gastrointestinal infections, Group B Streptococcus, listeriosis, and intrauterine inflammation or infection. Macrolides, particularly azithromycin, are also utilized for the treatment of PID, chlamydia, gonococcal infections, chancroid, community-acquired pneumonia, and certain gastrointestinal infections. Other antibiotics or antivirals such as vancomycin, aminoglycosides, metronidazole, nitrofurantoin, fosfomycin, acyclovir, valacyclovir, and oseltamivir are included in the preferred therapy for some common bacterial and viral infections in pregnant patients as well. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence of treatments of common infections in pregnancy and provides a concise summary to guide clinicians on empirical treatment during pregnancy. CONCLUSIONS: There are limited data on clinical outcomes in pregnant patients with common bacterial and viral infections. Empirical management decisions require balance of benefit and risk to both mother and infant. Although few clinical practice guidelines have quality evidence for strong recommendations in this population, clinicians should weigh antimicrobial dosing, pharmacokinetics, safety, and established effectiveness to optimize antimicrobial therapy in pregnancy.

Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae Bloodstream Infections? A Critical Review.

OBJECTIVE: To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum ß-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs) derived from a critical review of clinical data. DATA SOURCES: A systematic literature search using PubMed and MEDLINE databases (January 1, 2012, to June 30, 2017) was performed using key MESH terms: ESBL or extended-spectrum ß-lactamases and bacteremia or bloodstream infection with piperacillin/tazobactam, ciprofloxacin, levofloxacin, cefepime, cephamycins, carbapenem, doripenem, meropenem, and ertapenem. References within articles of interest were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All English language trials were considered, and results were limited to clinical efficacy trials. Articles were screened by title and abstract for inclusion. DATA SYNTHESIS: Studies comparing noncarbapenem versus carbapenem therapy for ESBL BSIs were critically analyzed to identify heterogeneity among studies. Data abstracted included empirical or definitive therapy, patient population, dosing, source of infection and severity, infectious etiology, and outcome. CONCLUSIONS: Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.

Effect of the 2014 Clinical and Laboratory Standards Institute urine-specific breakpoints on cefazolin susceptibility rates at a community teaching hospital.

BACKGROUND: Enterobacteriaceae, which include Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, are identified as the infectious etiology in the majority of urinary tract infections (UTIs) in community hospitals across the United States. The minimum inhibitory concentration (MIC) is a useful tool when choosing an appropriate antibacterial agent. Recent changes to the 2014 Clinical and Laboratory Standards Institute (CLSI) guidelines included reporting a urine-specific cefazolin breakpoint for enterobacteriaceae (susceptible ≤16 mcg/mL). The purpose of this study was to determine the clinical and financial impact of implementing the 2014 CLSI urine-specific breakpoints for cefazolin in a community-based teaching hospital in the Southern U.S.A. METHODS: A retrospective review of patients hospitalized from January 1, 2010 through October 1, 2014 was performed. Patients that met inclusion criteria had a documented initial clinical isolate of E. coli, K. pneumoniae, or P. mirabilis from urine cultures during each year. Descriptive statistics and two-proportion test of hypothesis were used in the analysis to compare susceptibility rates before and after implementation of the updated CLSI breakpoints for cefazolin. RESULTS: A total of 190 clinical isolates from patients were included in the study. E. coli was the most common organism isolated (63.7%), followed by K. pneumoniae (22.1%), and P. mirabilis (14.2%). 86% of the included isolates were susceptible to cefazolin using the 2010 breakpoints. Implementation of the 2014 breakpoints did not significantly impact susceptibility results for E. coli, K. pneumoniae, or P. mirabilis. CONCLUSION: Modification of breakpoints did not significantly impact susceptibility rates of cefazolin. Substituting cefazolin may decrease the overall drug cost by 77.5%. More data is needed to correlate in vitro findings with clinical outcomes using cefazolin for UTIs.

Identification of optimal renal dosage adjustments for high-dose extended-infusion cefepime dosing regimens in hospitalized patients.

OBJECTIVES: The objective of this study was to identify optimal renal dose adjustments for 2 g of cefepime every 8 h as a 3 h infusion where the probability of target attainment was optimized and drug accumulation was minimal. METHODS: Embedded with a population pharmacokinetic model derived in a population of hospitalized patients with varying degrees of renal function, a series of 5000-subject Monte Carlo simulations using ADAPT 5 were performed for 3 h infusions of 2 g every 6, 8, 12 and 24 h. To assess exposure profiles across various levels of renal function, the estimated CLCR was fixed at values between 20 and 150 mL/min. For each regimen examined, the fraction of simulated subjects who achieved free drug concentrations in excess of the MIC for ≥60% of the dosing interval (60% fT > MIC) at the various CLCR levels was determined and this information was used to identify optimal renal dose adjustments without profound drug exposure. RESULTS: In the Monte Carlo simulations, modification of the parent regimen (2 g every 8 h) to 2 g every 6 h for CLCR >120 mL/min and extension of the dosing interval to every 12 and 24 h at CLCR of 60 and 20 mL/min, respectively, provided favourable probability of target attainment profiles without profound drug exposure. CONCLUSIONS: The findings from this study identified renal dose alteration regimens that yielded favourable pharmacodynamic profiles without excessive drug exposure. As these findings were based on mathematical models, they should be validated in the clinical arena.

Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors.

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P = 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P = 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P = 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.

What are the latest recommendations for managing severe sepsis and septic shock?

Severe sepsis is a continuum of physiologic stages characterized by infection, systemic inflammation, and hypoperfusion leading to tissue injury and organ failure. The primary goal of sepsis treatment is to prevent morbidity and mortality. Crystalloids are now recommended over colloids for volume resuscitation, one of the key interventions for patients with sepsis.

Translating Clinical Decision-Making Skills From a Critical Care Pharmacy Elective to the Required Curriculum.

OBJECTIVE: To examine the impact of a critical care pharmacy elective (CCPE) on student performance in other courses in the Doctor of Pharmacy curriculum that emphasize clinical reasoning and decision making. METHODS: This is a retrospective, cohort study including all students from the 2019-2021 graduating classes enrolled in required courses, Pharmacotherapy and Integrated Patient Cases (IPCs). Students were divided for comparison based on completion of the CCPE. The primary outcome was outstanding performance, defined by a final course grade ≥90%, in Pharmacotherapy and IPC. Baseline characteristics and outcomes were analyzed using descriptive statistics and the χ2 test or two-sided t test for categorical and continuous variables, respectively. Binary logistic regression models were constructed to identify variables associated with the primary outcome. RESULTS: Of 377 students included, 129 (34%) completed the CCPE. Baseline characteristics were similar between both groups, except more females completed the CCPE. Students that completed the CCPE were not more likely to demonstrate outstanding performance in Pharmacotherapy III (20% vs 30%) or Pharmacotherapy IV (27% vs 24%), but were more likely in IPC (34% vs 23%). In the adjusted analysis, CCPE students were almost twice as likely to exhibit outstanding performance in IPC. CONCLUSION: Students that completed the CCPE were more likely to demonstrate outstanding performance in IPC, but not in either of the Pharmacotherapy courses. Students may benefit from practicing clinical reasoning earlier in the curriculum to build-up to effective and efficient clinical decision-making. Implications of course structure on student performance should be further explored.

Counting the Cost of Daptomycin Versus Vancomycin in Hospitalized Patients: A Cost Minimization Analysis.

Daptomycin use for gram-positive infections has increased. This cost minimization analysis aimed to determine cost and/or time savings of daptomycin over vancomycin. The estimated hospital cost savings was US$166.41 per patient, and pharmacist time saved of almost 20 minutes per patient. Daptomycin has the potential to save both time and money.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Perceptions and knowledge of personal finance in doctor of pharmacy versus undergraduate students: More wisdom or just more debt?

BACKGROUND AND PURPOSE: Evolution of personal finance beliefs over the course of a college career are unknown. The purpose of this study is to compare perceptions and knowledge of personal finance in undergraduate and pharmacy students at baseline and after completing a personal finance course. EDUCATIONAL ACTIVITY AND SETTING: A personal finance elective course was implemented for second- and third-year doctor of pharmacy (PharmD) students and for undergraduate freshman students. On the first and last day of class, students completed an anonymous survey evaluating demographics, opinions and knowledge regarding personal finance, and current financial status. Baseline data between undergraduate and pharmacy students was compared and the impact of the personal finance course was assessed. FINDINGS: The median score on the baseline knowledge assessment was 58% for freshman (n = 19) and 50% for pharmacy students (n = 28) (P = .571). Five percent of freshman and 86% of pharmacy students reported having debt at baseline (P < .001) compared to 84% and 68%, respectively, having savings (p = .110). After completing the personal finance course, knowledge assessment scores were 54% and 73% for freshman and pharmacy students, respectively (P < .001). SUMMARY: Despite additional years of education and life experience, PharmD students had similar knowledge and perceptions of personal finance while reporting more debt than freshmen. Pharmacy students, however, exhibited improvement in knowledge after taking a personal finance course, while freshman students did not. Personal finance-focused education may help empower graduating pharmacists for financial decision-making upon entering the workforce.