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.

Antimicrobial stewardship education in US colleges and schools of pharmacy.

Background: Pharmacists are key members of antimicrobial stewardship (AS) teams. It is unknown if and how US colleges and schools of pharmacy incorporate AS into their Doctor of Pharmacy (PharmD) curricula. Methods: This study was a cross-sectional, multicentre, electronic survey distributed to infectious diseases faculty or department chairs of 137 accredited and candidate-status PharmD programmes. Results: One hundred and sixteen programmes participated, representing an 84.7% response rate. AS education was integrated into the required didactic, elective didactic and experiential education components of the curricula in 79 (68.1%), 43 (37.1%) and 97 (83.6%) PharmD programmes, respectively. The most common AS topics in required and elective didactic curricula were AS definitions, principles and purpose (98.7% and 86.0%) and the pharmacist's role in AS (93.7% and 83.7%). In the required and elective didactic curricula, lecture (93.7% and 86.0%) and case-based instruction (57.0% and 83.7%) were the most common instructional methods. For experiential education, the pharmacist's role in AS (96.9%), de-escalation of antimicrobials (96.9%) and antimicrobial dose optimization (95.9%) were the most common AS topics. PharmD programmes employing a faculty member who specializes in AS were more likely to offer AS experiential education than programmes without AS faculty (88.1% versus 71.9%, P = 0.049). Conclusions: Integration of AS education in US PharmD curricula is variable and there are considerable differences in the AS activities and topics delivered. PharmD programmes should attempt to expose students to AS education to prepare future pharmacists for AS practice. Efforts should be made to incorporate interprofessional collaboration into AS education.

Meropenem/Vaborbactam, the First Carbapenem/ß-Lactamase Inhibitor Combination.

OBJECTIVE: To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V). DATA SOURCES: A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical, phase I studies, and phase III studies written in the English language were evaluated. DATA SYNTHESIS: M/V is a novel carbapenem/ß-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea. CONCLUSION: M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

Impact of the use of local fidaxomicin treatment algorithms for managing Clostridium difficile infection in hospitalized patients in southeastern United States.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is a major public health threat that results in increased length of stay, hospital readmissions, deaths, and economic burden. CDAD treatment is often guided by severity of disease. Although various tools exist to determine CDAD severity, real-world data evaluating the use of such tools in treatment algorithms are sparse. METHODS: A local CDAD treatment pathway was developed independently to guide fidaxomicin prescribing at wellStar Health System (WellStar) and at Lee Health (LH) and Sarasota Memorial Hospital (SMH). Each algorithm was designed locally by the stewardship pharmacist and was utilized to identify patients at high risk for C. difficile recurrence. Patient and clinical data was retrospectively gathered to evaluate the utility and outcomes of the treatment pathway. RESULTS: There were 262 patients that received fidaxomicin at these three hospitals during the study time period. Only 30% at WellStar and 20% at LH or SMH met the study criteria and adhered to the pathway requirements. After completion of fidaxomicin, 30-day recurrence rates at WellStar was 0 and at LH and SMH 7%. Clinical cure rates were 83% in WellStar and 93% in LH and SMH. CONCLUSIONS: The results from these two pathways show positive outcomes for the use of fidaxomicin in patients at high risk for CDAD recurrence. This data supports the potential utility of fidaxomicin against CDAD.

Bezlotoxumab for the Prevention of Clostridium difficile Recurrence.

OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosing, and administration of bezlotoxumab (BEZ), as well as its place in the prevention of Clostridium difficile infection (CDI) recurrence. DATA SOURCES: A search of PubMed and Google Scholar using the terms "bezlotoxumab," "CDB1," "MDX-1388," and "MK-6072" was performed. The manufacturer's website was also reviewed to further identify relevant information. STUDY SELCTION: All English-language articles from 2006 to May 2017 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. DATA SYNTHESIS: BEZ is a human monoclonal antibody that binds to Clostridium difficile toxin B. It is approved by the Food and Drug Administration to reduce CDI recurrence in adult patients who are receiving antibiotic therapy for CDI and are at high risk for CDI recurrence. It is given as a single dose of 10 mg/kg via an intravenous infusion. It is eliminated by catabolism. Phase III clinical trials demonstrated that BEZ was associated with significantly lower rates of CDI recurrence, compared with placebo. The most common adverse events reported during clinical trials were diarrhea and nausea. There is a warning regarding the use of BEZ in patients with a history of congestive heart failure. The most common adverse reactions associated with BEZ are nausea, pyrexia, and headache. CONCLUSION: BEZ has been proven safe and effective in preventing CDI recurrence. Given its high cost, it should be reserved for patients at high risk for CDI recurrence.

National Survey Regarding the Importance of Leadership in PGY1 Pharmacy Practice Residency Training.

BACKGROUND: Leadership is considered a professional obligation for all pharmacists. It is important to integrate leadership training in residency programs to meet the leadership needs and requirements of the profession. OBJECTIVE: To evaluate the importance of leadership development during postgraduate year 1 (PGY1) pharmacy practice residency training as perceived by new practitioners. METHODS: A 15-question online survey was distributed to residency-trained new practitioners to assess (1) amount of time dedicated to leadership training during residency training, (2) different leadership tools utilized, (3) residents' participation in various committees or councils, (4) perceived benefit of increased leadership training, (5) importance of having a mentor, (6) understanding of the residency organization's strategic objectives, (7) discussion of Pharmacy Practice Model Initiative (PPMI) during residency training, and (8) adequacy of leadership training in preparation to become a pharmacy practice leader. RESULTS: Although the majority of resident respondents had less than 20% of their residency devoted to leadership, nearly all survey participants acknowledged that leadership is an important component of PGY1 residency training. Residents agreed that their residency experience would have benefited from increased leadership opportunities. Most residents were knowledgeable about their organization's strategic objectives but did not have a full understanding of pharmacy initiatives such as the PPMI. CONCLUSION: Feedback from residents indicates that an optimal dedication to leadership training would range between 20% and 30% of the residency year. Increased focus on PPMI, mentorship, and expanded use of leadership tools can serve as a way to help meet the future leadership needs of the pharmacy profession and help to better prepare residents to become pharmacy practice leaders.

Tebipenem pivoxil hydrobromide-No PICC, no problem!

Tebipenem pivoxil hydrobromide is a novel orally bioavailable prodrug of tebipenem, a carbapenem antimicrobial, that binds to penicillin-binding proteins, inhibiting the synthesis of the bacterial cell wall. This results in weakening of peptidoglycan, leading to lysis of bacterial cells. Tebipenem displays a broad spectrum of activity against anaerobic, gram-positive, and gram-negative pathogens, including extended-spectrum ß-lactamase producing Enterobacterales. In a large phase 3 clinical trial (ADAPT-PO), oral tebipenem pivoxil hydrobromide 600 mg every 8 h was shown to be non-inferior to intravenous ertapenem 1 g every 24 h. Overall response at test of cure was 58.8% [264/449] in the tebipenem pivoxil hydrobromide group compared to 61.6% [258/419] in the ertapenem group for the treatment of complicated urinary tract infections, including acute pyelonephritis. At the test of cure, clinical cure rates were 93.1% and 93.6% and microbiological eradication was 59.5% and 63.5% with tebipenem pivoxil hydrobromide and ertapenem, respectively. The most common adverse reactions associated with tebipenem pivoxil hydrobromide are diarrhea, headache, and nausea. As with other carbapenems, tebipenem pivoxil hydrobromide is expected to have the potential to decrease the seizure threshold and will likely require renal dosage adjustment for patients with altered renal function due to high renal clearance. If approved in the United States, tebipenem pivoxil hydrobromide can serve as a potential oral antimicrobial option to decrease hospital length of stay and prevent hospital admissions due to resistant pathogens.

Preparing pharmacy students for postgraduate training through a residency preparedness elective course.

OBJECTIVE: To determine the benefit of a residency preparedness elective course and assess the ability of the course to provide students with the knowledge and experiences needed to competitively apply for residency programmes. METHODS: A pre-/postsurvey study on a 2-credit hour elective course for third-year pharmacy students. This course was designed to provide them with the knowledge and experiences needed to competitively apply for pharmacy residency programmes. KEY FINDINGS: Students' perceptions of the elective course were captured through pre- and postcourse evaluations utilizing a 15-item survey. The main reasons students participated in this course was to gain a better understanding of the residency application process (median Likert score = 5; 1 = strongly disagree and 5 = strongly agree), develop interviewing techniques (5) and enhance clinical competency (5). By the end of the course, students felt more confident with their understanding of pharmacy residency programmes (4 versus 5, P = 0.002) and of the residency application process (2 versus 5, P = 0.001). CONCLUSION: Upon completion of a pharmacy residency preparedness elective course, students felt more confident in their understanding and ability to apply for a residency programme.

Acute Care Pharmacy Practice: A Perspective for Pharmacy Students, Residents, and Other Health-Care Providers.

PURPOSE: To describe the acute care setting with a specific focus on acute care pharmacy practices. SUMMARY: Acute care is the sector of health care where time-sensitive episodes of illness are managed. Acute care pharmacy practice includes both hospital and clinical pharmacists serving, in a variety of domains, as medication experts and authority on patient-centered medication therapy. Pharmacists serving in this area can have a beneficial impact on patient care and the health-care system. CONCLUSION: The demand for acute care services is likely to grow as the population continues to grow and age. Pharmacists are key members of interdisciplinary teams in the acute care setting.

Ridinilazole: a novel antimicrobial for Clostridium difficile infection.

Clostridium difficile (C. difficile) infection remains a global healthcare threat worldwide and the limited options available for its treatment are of particular concern. Ridinilazole is one potential future agent, as it demonstrates rapid bactericidal activity against C. difficile. Current studies show that ridinilazole has a lower propensity for collateral damage to the gut microbiome and appears to diminish the production of C. difficile toxins. Results from phase II studies demonstrate that patients receiving ridinilazole had a higher sustained clinical response compared with patients receiving vancomycin (66.7% vs. 42.4%; P=0.0004). Adverse reactions were similar between ridinilazole and vancomycin (40% vs. 56%, respectively), with most being gastrointestinal-related. Nausea (20%) and abdominal pain (12%) were the most commonly reported adverse reactions associated with ridinilazole. Phase II study results are promising and future availability of phase III trial results will help further delineate the role and value of ridinilazole.

Pharmacy faculty and students' perceptions of standardized patients for objective structured clinical examinations.

BACKGROUND AND PURPOSE: Objective structured clinical examinations (OSCEs) are one method of assessing clinical competency and communication in doctor of pharmacy programs. The purpose of this study was to capture student and faculty perceptions regarding the use of standardized patients (SPs) in administering OSCEs. EDUCATIONAL ACTIVITY AND SETTING: Pharmacy students in our program initially participated in OSCEs using internal-SPs (I-SPs) that consisted of faculty and staff acting as patients. One year later, we piloted use of trained actor-based SPs and surveyed students and faculty about the experience. FINDINGS: Fifty-four (80.6%) students and 12 (92.3%) faculty members completed the survey. When asked about their interactions with SPs, 42 (77.8%) students either agreed or strongly agreed that SPs portrayed patients more realistically and 41 (75.9%) students perceived SPs created a more comfortable environment for patient communication than I-SPs. Thirty-six (66.7%) students either agreed or strongly agreed to feeling more confident when communicating with patients, and 33 (61.1%) felt more confident making recommendations. Ten (83.3%) faculty members either agreed or strongly agreed that SPs portrayed patient interactions more realistically, and 7 (58.3%) felt SPs were more consistent in their simulated patient portrayal for the duration of the OSCE. SUMMARY: Pharmacy students felt more confident in their ability to communicate and interact with the patient during their OSCEs when actor-based SPs were used. Both students and faculty members perceived this SP portrayal of patient interactions as more realistic than I-SPs and recommended the continued use of actor-based SPs for OSCEs.

All aboard!: Involvement of medical and pharmacy trainees in antimicrobial stewardship.

Antimicrobial stewardship (AS) involves the appropriate selection of antimicrobials. Antimicrobial stewardship programs are mandated in hospitals and are expanding to involve outpatient arenas. Multiple articles have been published describing the need for AS education for medical and pharmacy students, beginning early in the students' career to develop into competent AS practitioners. Additionally, publications have described the role and impact of medical and pharmacy trainees on AS programs. Here, we review the published evidence describing medical and pharmacy trainees' involvement in AS and call for future research in this area.

Aminoglycoside Allergic Reactions.

Aminoglycosides are antimicrobial agents that are primarily used for infections caused by Gram-negative pathogens. The purpose of this article is to review the allergic reactions reported in the published literature to aminoglycoside antibiotics. A thorough PubMed search was conducted and excluded non-allergic adverse reactions to aminoglycosides. Allergic reactions to aminoglycosides occur infrequently, but can include cutaneous reactions as well as systemic reactions, including anaphylaxis. Of the evaluated aminoglycosides, gentamicin had the most reported allergic reactions, including the most reports of anaphylaxis, followed by tobramycin, and then amikacin. Most reports of allergic reactions occurred in patients who had a prior exposure to some dosage form of an aminoglycoside. Cross-reactivity among aminoglycosides is common and occurs due to the similarities in their chemical structures. Desensitization protocols to tobramycin have been described in the literature.

Macrolide Allergic Reactions.

Macrolides are antimicrobial agents that can be used to treat a variety of infections. Allergic reactions to macrolides occur infrequently but can include minor to severe cutaneous reactions as well as systemic life-threatening reactions such as anaphylaxis. Most reports of allergic reactions occurred in patients without prior exposure to a macrolide. Cross-reactivity among macrolides may occur due to the similarities in their chemical structures; however, some published literature indicates that some patients can tolerate a different macrolide. Most published reports detailed an allergic reaction to erythromycin. Desensitization protocols to clarithromycin and azithromycin have been described in the literature. The purpose of this article is to summarize macrolide-associated allergic reactions reported in published literature. An extensive literature search was conducted to identify publications linking macrolides to hypersensitivity reactions.

Plazomicin: A Next-Generation Aminoglycoside.

Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis in a concentration-dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram-negative bacteria including extended-spectrum ß-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and organisms with aminoglycoside-modifying enzymes. In a large phase III clinical trial, plazomicin was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections (cUTIs) with respect to the coprimary efficacy end points of the microbiologically modified intent-to-treat composite cure rate at day 5 (plazomicin 88% [168/191 subjects] vs meropenem 91.4% [180/197]) and at the test-of-cure visit (plazomicin 81.7% [156/191] vs meropenem 70.1% [138/197]). In a small phase III clinical trial, plazomicin was shown to be effective in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. It was associated with a lower all-cause mortality or significant disease-related complication rate (23.5% [4/17]) compared with colistin (50% [10/20]). The most common adverse reactions associated with plazomicin are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension. As with other aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women. Due to limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4-7 days. Dosage reductions and therapeutic drug monitoring are warranted in patients with moderate or severe renal impairment. Plazomicin is not recommended in patients with severe renal impairment including those receiving renal replacement therapy. With the approval of plazomicin, clinicians now have an additional option for the treatment of adults with cUTIs, particularly those caused by multidrug-resistant gram-negative rods.

A Comprehensive Survey of Infectious Diseases Curriculum Among US Pharmacy Schools.

Objective. To describe what and how infectious diseases (ID) topics are taught in US schools of pharmacy and summarize pharmacy faculty members' and students' perceived successes and challenges in teaching and learning about ID. Methods. A 23-item survey instrument was distributed electronically to ID faculty members at 137 US pharmacy schools. Data collected included curricular hours and format, topics covered, active-learning strategies, and curricular successes and concerns. Results. Surveys were collected from 106 schools (77% response rate). Infectious diseases curricula were allotted a median of 60 (IQR=40) hours of classroom time. Respondents dedicated 33% of curriculum hours to ID fundamentals and 66% to disease states. Greater than 94% of schools taught all tier one ID topics from the 2016 American College of Clinical Pharmacy Pharmacotherapy Didactic Curriculum Toolkit. Curricula were primarily delivered through traditional lectures rather than active learning (75% vs 25% of classroom time, respectively). The median number of active-learning strategies used was four (IQR=3). The most common active-learning modalities used either consistently or frequently were patient case application (98%) and audience response systems (76%). The most common successes cited by faculty members were implementation of active learning, the "real-world" applicability of the ID topics, and the breadth of topics and topic exposure covered in the curriculum. The most common concerns were a lack of time to cover material and the amount of material covered. Conclusion. Increased communication and collaboration between ID educators is warranted to increase consistency of ID education and distribution of educational innovations.

Learning Experiences Within Infectious Diseases Pharmacy Residency Programs in the United States: A Cross-Sectional Survey.

BACKGROUND: Pharmacists with residency training in infectious diseases (ID) optimize antimicrobial therapy outcomes in patients and support antimicrobial stewardship (AS) programs. Although most ID residencies are accredited and assessed by certain standards, the degree to which these programs are similar is not known. METHODS: A 19-item, cross-sectional, multicentered, electronic survey was distributed via e-mail to pharmacy residency program directors (RPDs) of all 101 second-year postgraduate (PGY-2) ID residency programs in the United States. RESULTS: Survey responses were collected from 71 RPDs (70.3%); 64.8% were associated with an academic medical center and 97.2% focused primarily in adult ID. Rotations in the microbiology laboratory, adult AS, and adult ID consult were required in 98.6% of residency programs. Only 28.2% of responding programs required pediatric AS and pediatric ID consult rotations. Programs at academic medical centers were more likely to offer immunocompromised host ID consult (P = .003), pediatric ID consult (P = .006), and hospital epidemiology (P = .047) rotations but less frequently offered outpatient AS (P = .003), viral hepatitis clinics (P = .001), and travel medicine clinics (P = .007) rotations compared to programs at nonacademic medical centers. Residents were frequently involved in AS committees (97.2%), pharmacokinetic dosing of antimicrobials (83.1%), precepting pharmacy trainees (80.3%), and performing research projects (91.5%). CONCLUSIONS: The PGY-2 ID pharmacy residency programs demonstrated consistency in required adult ID consult, antimicrobial management activities, committee service, and teaching and research opportunities. Pediatric experiences were less common. The PGY-2 ID residency programs prepare pharmacists to become antimicrobial stewards for adult patients.

What Is Old Is New Again: Delafloxacin, a Modern Fluoroquinolone.

Delafloxacin is a new fluoroquinolone antimicrobial approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults using dosage regimens of 300 mg intravenously every 12 hours, 450 mg orally every 12 hours, or switching from intravenous to oral regimens for a 5- to 14-day treatment duration. Dosage adjustments in patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] = 15-29 ml/min/1.73 m2 ) are not required for oral doses but should be decreased to 200 mg intravenously every 12 hours in patients requiring parenteral therapy. Due to insufficient data, use of delafloxacin is not recommended for patients on hemodialysis or with end-stage renal disease (eGFR < 15 ml/min/1.73 m2 ). Delafloxacin works through inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV, which are essential enzymes for bacterial DNA transcription, replication, repair, and recombination and exhibits bactericidal activity against gram-positive and gram-negative organisms through a concentration-dependent matter. Delafloxacin has a very broad spectrum of activity against atypical, anaerobic, and resistant gram-negative and gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. During phase 3 trials, the most common side effects associated with delafloxacin were gastrointestinal (nausea, diarrhea). Unlike other fluoroquinolones, there does not seem to be a risk of QTc prolongation or phototoxicity with delafloxacin. The availability of both parenteral and oral formulations for delafloxacin distinguishes it from many of the currently available agents approved for ABSSSIs. Phase 3 studies for the treatment of respiratory infections are currently under way, and future results of these studies will further help delineate the role of delafloxacin.