Rifampin in device-related infections: Assessing the modern evidence.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Rifampin is commonly used to treat device-related infections (DRIs) due to its activity against biofilms, despite a history of limited clinical evidence to support its use. Evidence published since 2011 regarding rifampin use for DRIs is reviewed to describe the contemporary findings and ongoing considerations for rifampin use in these infections. SUMMARY: A literature review was performed by searching PubMed and Google Scholar to identify relevant studies evaluating systemic rifampin use for the treatment of DRIs published from 2011 to 2023. References of identified studies were also screened for additional pertinent studies. Sixty-eight studies were identified, and 48 met the inclusion criteria. Rifampin efficacy was evaluated as both a primary outcome for cardiac device infections (n = 3) and prosthetic joint infections (n = 21) and as a nonprimary outcome (n = 24). Overall, the studies were primarily retrospective (n = 36) and small, with sample sizes ranging from 14 to 842 patients, and varied greatly with respect to prosthesis site, surgical intervention, pathogen, infection time frame, and antibiotic combination and duration. Efficacy outcome results varied greatly, with statistically significant evidence for the efficacy of rifampin combination in DRIs limited to a single study of prosthetic vascular graft infections and 13 studies of prosthetic joint infections. CONCLUSION: The modern literature provides conflicting results regarding the benefit and lack of benefit with rifampin combination therapy in DRIs. Additional, robust research is imperative to solidify the ongoing role of rifampin in DRIs.

Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause.

INTRODUCTION: During menopause, the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms, offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns. AREAS COVERED: This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies. EXPERT OPINION: Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms. The most common adverse event is headache (5-10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for vasomotor symptoms, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

Managing the Drug-Drug Interaction With Apixaban and Primidone: A Case Report.

The management of the drug-drug interaction (DDI) between primidone, a moderate to strong cytochrome P-450 (CYP) 3A4 inducer, and apixaban, a direct oral anticoagulant (DOAC) and CYP3A4 substrate is complex and limited evidence exists to guide management. This case report describes a 65-year-old male, receiving primidone for essential tremor who developed an acute venous thromboembolism (VTE) requiring oral anticoagulation. DOACs are preferred over vitamin K antagonists for acute VTE treatment. Based on patient-specific variables, provider preference, and the avoidance of other DDIs, apixaban was selected. Apixaban's package insert recommends avoiding use with concomitant strong P-gp and CYP3A4 inducers due to the decreased exposure to apixaban; however, no recommendations are available for drugs that are moderate to strong CYP3A4 inducers and lack P-gp effects. Given that phenobarbital is an active metabolite of primidone, extrapolation of evidence from such literature is theoretical but provides insight into the management of this multi-faceted DDI. In the absence of the ability to monitor plasma apixaban levels, a management strategy of avoidance with a washout period of primidone based on pharmacokinetic parameters was used in this case. Additional evidence is needed to clearly understand the degree of impact and clinical significance of the DDI between apixaban and primidone.

Impact of a novel preceptor collaborative advanced pharmacy practice experience curriculum on student-perceived ability and confidence.

BACKGROUND AND PURPOSE: A novel teaching collaborative for acute care medicine advanced pharmacy practice experiences (APPEs) was formed by five faculty preceptors. The primary goal of the collaborative model was to ensure that acute care medicine APPEs provided students with opportunities to achieve Accreditation Council of Pharmacy Education Standards 2016, including strengthening students' ability to be practice- and team-ready. EDUCATIONAL ACTIVITY AND SETTING: The collaborative model included group discussions, video modules, patient cases, journal scans, and case presentations among student pharmacists completing an adult or pediatric acute care APPE. Anonymous, voluntary pre-/post-surveys were completed by a cohort of students who participated in the collaborative model from May 2018 to April 2019. Survey questions assessed student-perceived ability/confidence related to interprofessional (IP) relationships and decision-making skills for adult and pediatric patients, as well as value of activities. FINDINGS: From the cohort of 67 students, 54 pre-survey and 45 post-survey responses were obtained. Post-rotation, students showed an increase in confidence to practice pharmacy on an IP team (39% vs. 100%, P < .001). Significant increases were also found for therapeutic decision-making regarding antibiotics, anticoagulants, and pharmacokinetics for adult and pediatric patients. Among students completing the post-survey, video modules were the most valued component of the model. SUMMARY: A collaborative APPE model resulted in consistent increases in student-perceived ability and confidence related to care of adult and pediatric patients. This APPE model could be adapted within different care settings and pharmacy curricula.

Clinical potential of canagliflozin in cardiovascular risk reduction in patients with type 2 diabetes.

Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes mellitus, as well as the leading diabetes-associated health care cost. The prevalence and associated impact of cardiovascular disease among those with diabetes engenders the need to identify cardiovascular effects of antihyperglycemic agents. This review seeks to evaluate the impact of canagliflozin, a SGLT2 inhibitor, on cardiovascular risk factors and outcomes. The 14 published trials to-date exploring various cardiovascular risk factors and outcomes among patients receiving canagliflozin were identified and included within the review. Overall these studies demonstrate that among patients with type 2 diabetes mellitus, canagliflozin results in decreased systolic and diastolic blood pressure, lower body weight, and also exhibits renoprotective effects. These findings were similar when canagliflozin was compared to placebo or other antihyperglycemic agents and explored among subsets such as those with chronic kidney disease. In addition, findings from the three trials exploring cardiovascular outcomes of canagliflozin included reduction in cardiovascular mortality and lower incidence of heart failure-associated hospitalizations. Results from studies including other SGLT2 inhibitors suggest that cardiovascular benefits are likely a class-effect found among current SGLT2 inhibitors. Continued research specific to canagliflozin is needed to clarify risks of adverse effects and determine optimal dosing requirements for canagliflozin in regard to cardiovascular risk reduction.

Procalcitonin Monitoring as a Guide for Antimicrobial Therapy: A Review of Current Literature.

Effective antimicrobial stewardship practices are increasingly essential to best utilize the current arsenal of antimicrobials for the shortest necessary duration to minimize the development of antimicrobial resistance, secondary infections, and health care costs. Monitoring of serum procalcitonin (PCT) levels represents an effective antimicrobial stewardship strategy to differentiate bacterial infections from viral infections and noninfectious inflammatory conditions. Current literature illustrates the merits of PCT monitoring in reducing duration of antibiotic therapy without detrimental effects on mortality or infection relapses. However, the interpretation of PCT levels can be challenging, especially in light of comorbid disease states that can elevate PCT levels. This review sheds light on the utility of PCT monitoring, as well as providing insight into the practical interpretation of PCT levels. Much of the current literature surrounding PCT monitoring consists of use among patients with lower respiratory tract infections or in the critically ill. Overall, studies have demonstrated shorter antibiotic therapy durations when PCT monitoring is utilized. No studies to date have found increased rates of mortality or infection relapses, suggesting that PCT monitoring is not only effective, but also safe when used as a guide for antimicrobial therapy. Nonetheless, many conditions were shown to elevate PCT serum concentrations, even in the absence of bacterial infections, which can make interpretation of PCT concentrations challenging. Two common conditions that affect the accurate interpretation of PCT levels are renal dysfunction and congestive heart failure. Limited studies have been performed in these populations, but current available data propose the need for higher PCT thresholds in those with renal dysfunction or congestive heart failure and support utilizing PCT trends to monitor clinical improvement from bacterial infections. Evidence also suggests that PCT monitoring is cost-effective, as long as the test is ordered judiciously. In summary, PCT monitoring represents a promising antimicrobial stewardship strategy to limit exposure to unnecessary antimicrobial therapy.

Effectiveness and safety of oral anticoagulants in patients with sickle cell disease and venous thromboembolism: a retrospective cohort study.

Patients with sickle cell disease (SCD) experience initial and recurrent venous thromboembolism (VTE) more commonly and at a younger age than the general population, and it confers a higher mortality for patients with SCD. However, limited evidence is available to guide anticoagulant use for VTE treatment in this population. The primary objective of this study is to characterize the effectiveness and safety of direct oral anticoagulants (DOAC) and warfarin for VTE treatment among patients with SCD. This single-center retrospective study includes adult patients with SCD who were diagnosed with VTE. Data was obtained from review of electronic health records for the 6 months after VTE diagnosis. Among the 22 patients treated initially with a DOAC, 6 (27%) developed recurrent VTE, none experienced major bleeding, and 3 (14%) experienced clinically relevant non-major bleeding (CRNMB). Similarly, of 15 patients initially treated with warfarin, 3 (20%) developed a recurrent VTE, 1 (7%) experienced major bleeding, and 2 (13%) experienced CRNMB. Twelve patients received more than one oral anticoagulant during the study period, most commonly due to a recurrent VTE, concern for non-adherence, or subtherapeutic INR. Overall, the incidence of VTE recurrence and bleeding events were similar between groups, but occurred at a higher rate than those found in major clinical trials of anticoagulant agents. Prescribers should continue to individualize therapeutic decision-making regarding oral anticoagulant therapy for VTE treatment for individuals with SCD based on patient-specific factors and anticipated ability to adhere to the drug regimen or required monitoring.