Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix.

Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY-078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once-weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off-label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.

Incretin Analogs for Weight Management in Adults Without Diabetes.

OBJECTIVE: This is a narrative review of incretin analogs and their effect on weight management in adult without diabetes. DATA SOURCES: Randomized controlled trials were identified by English language. PubMed/MEDLINE, Scopus, and Embase databases were searched from inception through June 2023 to identify all pertinent trials reporting outcomes on efficacy and safety search using the terms: tirzepatide, semaglutide, liraglutide, and obesity. STUDY SELECTION AND DATA EXTRACTION: Selected studies were included if the study population was composed of adults without diabetes being treated by glucagon-like peptide 1 (GLP-1) receptor agonists or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists for weight management, and weight loss was assessed as a primary outcome. DATA SYNTHESIS: Fifteen studies involving 3 pharmacotherapies (liraglutide, semaglutide, and tirzepatide) were identified. Efficacy data supporting the use of these agents for weight management were promising when compared to placebo and/or other behavioral therapies. Percent weight loss ranged from 5.7% to 11.8%, 14.9% to 17.4%, and 15% to 20.9% for liraglutide, semaglutide, and tirzepatide, respectively. Safety data were relatively similar across all trials and identified gastrointestinal adverse effects as most common. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Glucagon-like peptide 1 agonists are preferred for overweight or obese patients by the American Gastroenterological Association. Future guidelines may address tirzepatides' place in therapy as new evidence comes forth. Providers should consider patient-specific factors such as cost, adverse effects, drug interactions, and comorbidities when prescribing these agents and provide education regarding the need for concurrent diet and exercise modifications. CONCLUSIONS: All incretin analogs in this review are superior to placebo when used for weight management in adults without diabetes.

Systemic-Sclerosis-Related Interstitial Lung Disease: A Review of the Literature and Recommended Approach for Clinical Pharmacists.

OBJECTIVE: To describe the efficacy, safety, and clinical utility of pharmacologic agents in the treatment of systemic sclerosis-related interstitial lung disease (SSc-ILD). DATA SOURCES: A review of the literature was performed using the terms lung diseases, (interstitial/therapy) AND (scleroderma, systemic/therapy) OR (scleroderma, systemic) AND (lung diseases, interstitial/therapy) in PubMed, Ovid MEDLINE, CINAHL, and Web of Science. ClinicalTrials.gov was also searched to identify ongoing studies. The initial search was performed in October 2022, with follow-up searches performed in October 2023. STUDY SELECTION AND DATA ABSTRACTION: Articles reviewed were limited to those written in the English language, human studies, and adult populations. DATA SYNTHESIS: A variety of therapeutic agents, including mycophenolate, azathioprine, cyclophosphamide (CYC), rituximab (RTX), nintedanib, and tocilizumab (TCZ) have slowed the rate of decline in forced vital capacity (FVC) and disease progression. Only nintedanib and TCZ have a labeled indication for SSc-ILD. Two agents, belimumab and pirfenidone, have shown encouraging results in smaller phase II and phase III studies, but have yet to be approved by the Food and Drug Administration. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patients with pulmonary manifestations of SSc-ILD have worse outcomes and lower survival rates compared with those without. It is imperative that disease management be individualized to achieve optimal patient-centered care. Pharmacists are uniquely suited to support this individualized management. CONCLUSION: Numerous pharmacologic agents have been studied and repurposed in the treatment of SSc-ILD, with nintedanib and TCZ gaining approval to slow the rate of decline in pulmonary function in SSc-ILD. Other agents, including belimumab and pirfenidone, are on the horizon as potential treatment options; but further studies are needed to compare their efficacy and safety with the current standard of care.

Zavegepant Intranasal Spray for Migraines.

OBJECTIVE: The objective is to review the pharmacology, efficacy, and safety of intranasal zavegepant in the acute treatment of migraine with or without aura. DATA SOURCE: PubMed, Embase database, and ClinicalTrials.gov were searched using the following terms: Zavzpret, Zavegepant, BHV-3500, and migraine. STUDY SELECTION AND DATA EXTRACTION: Articles published in English from January 2013 to September 2023 related to pharmacology, safety, efficacy, and clinical trials were assessed. DATA SYNTHESIS: In a phase 2/3 trial, zavegepant 10 and 20 mg were more effective than placebo on primary endpoints of freedom of pain (22.5%, 23.1%, and 15.5%, respectively), and freedom from most bothersome symptoms (MBSs) (41.9%, 47.9%, and 33.7%, respectively) 2 hours after treatment. The incidence of adverse effects for both doses was similar to placebo. In a phase 3 trial, zavegepant 10 mg was compared with placebo. Two hours after treatment, more patients in the zavegepant group achieved pain freedom (24% vs 15%) and relief from MBSs (40% vs 31%) compared with placebo. Common adverse events included dysgeusia (21% zavegepant vs 5% placebo) and nasal discomfort (5% zavegepant vs 1% placebo). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Zavegepant is indicated for acute treatment of migraine with or without aura in adults. Zavegepant method of administration and prompt relief of migraine symptoms may be an attractive alternative to triptans for those in need of relief. CONCLUSION: Zavegepant may be a convenient and useful acute treatment option for migraines with and without aura.

Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections.

OBJECTIVE: To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. DATA SOURCES: PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed. DATA SYNTHESIS: A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference -13.2%; 95% CI [-30.0 to 3.5]). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections. CONCLUSIONS: SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.

Evaluation of High-dose versus Standard-dose of Dexamethasone on Mortality among the Mechanically Ventilated COVID-19 Patients.

INTRODUCTION: Anti-inflammatory agents like dexamethasone (DEX) are a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX. METHOD: This was a multi-site, retrospective, observational study on ventilated COVID-19-positive patients who received DEX for at least three days between June 1, 2020, and January 31, 2022. The primary outcome of this study was the association between mortality and SD (<6mg daily) versus HD (>10mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS), and ICU LOS. RESULTS: Of the 212 included patients, 53 (25%) received SD DEX, and 159 (75%) received HD DEX. There was no significant effect of DEX dose on mortality, number of BG readings >200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors, no difference in mortality persisted (OR 1.34 95% CI 0.62- 2.90). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019, respectively). CONCLUSION: There was no association between HD DEX and mortality among ventilated COVID-19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients.

Biomarkers in the intensive care setting: A focus on using procalcitonin and C-reactive protein to optimize antimicrobial duration of therapy.

Managing the critically ill patient with infection is complex, requiring clinicians to synthesize considerable information relating to antimicrobial efficacy and treatment duration. The use of biomarkers may play an important role in identifying variation in treatment response and providing information about treatment efficacy. Though a vast number of biomarkers for clinical application have been described, procalcitonin and C-reactive protein (CRP) are the most thoroughly investigated in the critically ill. However, the presence of heterogeneous populations, variable end points, and incongruent methodology in the literature complicates the use of such biomarkers to guide antimicrobial therapy. This review focuses on an appraisal of evidence for use of procalcitonin and CRP to optimize antimicrobial duration of therapy (DOT) in critically ill patients. Procalcitonin-guided antimicrobial therapy in mixed critically ill populations with varying degrees of sepsis appears to be safe and might assist in reducing antimicrobial DOT. Compared to procalcitonin, fewer studies exist examining the impact of CRP on antimicrobial DOT and clinical outcomes in the critically ill. Procalcitonin and CRP have been insufficiently studied in many key intensive care unit populations, including surgical patients with concomitant trauma, renally insufficient populations, the immunocompromised, and patients with septic shock. We believe the available evidence is not strong enough to warrant routine use of procalcitonin or CRP to guide antimicrobial DOT in critically ill patients with infection. So long as its limitations are recognized, procalcitonin could be considered to tailor antimicrobial DOT on a case-by-case basis in the critically ill patient.

Podcasts and videos and slides oh my!: Traditional vs. nontraditional teaching methods in remote settings.

INTRODUCTION: Nontraditional teaching methods are student-centered and motivate students to participate in class activities. Some studies have shown benefit in using various teaching activities; however, data are limited regarding students' perspective and performance after implementation of nontraditional learning strategies. The study compared student preference and performance assessment with traditional and nontraditional presentation methods. METHODS: This study included first-year pharmacy students enrolled in a course at a research-intensive, public university. Students in 2020 received traditional lectures while students in 2021 were presented three topics as nontraditional activities, including a podcast, an escape room, a video inspired by Khan Academy, and a traditional asynchronous lecture using slides with voice-over. First-year pharmacy students were surveyed in 2021 regarding their perspective on the nontraditional presentations. Students' performance was compared between 2020 and 2021. RESULTS: Ninety-eight students in 2020 and 89 students in 2021 were enrolled in the course. Sixty-seven students completed the 2021 survey. Most students (71.6%) preferred the traditional lecture; the Khan Academy and escape room activities were the least favored. Most students (86.5%) responded they learned "quite a bit" or a "tremendous amount" with the traditional lecture, and 59.7% of students felt they would perform better on assessments with the traditional lecture compared to nontraditional. Students in 2021 only performed better on all exam questions related to the nontraditional podcast activity. CONCLUSIONS: Students preferred traditional lectures and also seemed to perform better on assessment, with the exception of the nontraditional presentation podcast style. Further studies are needed to confirm these findings.

Evaluation of References Supporting Hospital Pharmacy Policies.

There is a lack of research evaluating the role of references in hospital policies. The goal of this study was to describe the type of literature used as a reference in medication policies and evaluate the agreement of the policy with evidence-based guidelines. One hundred forty-seven pharmacy owned policies met inclusion criteria; 27.2% of the policies contained references, in which tertiary literature was the most frequently cited source (90%), followed by primary (47.5%), and lastly secondary (27.5%). When references were used, all policies agreed with current guidelines. For policies without references, 3.7% disagreed with published guidelines. Disagreement with guidelines may negatively impact patient care, therefore health systems should incorporate librarians into clinical policy development and review to ensure the best available evidence is incorporated into polices.

Tezepelumab in the Treatment of Uncontrolled Severe Asthma.

OBJECTIVE: To review the pharmacology, efficacy, and safety of subcutaneous tezepelumab in the treatment of severe uncontrolled asthma. DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: tezepelumab, Tezspire, AMG157, and MEDI9929. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 2000 and March 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In a phase 2 trial, tezepelumab at low, medium, and high doses reduced the annualized asthma exacerbation rate by 62%, 71%, and 66%, respectively, when compared with placebo (P < 0.001). In addition to significant reduction of asthma exacerbation rate in the overall treatment population, a phase 3 trial showed significant reduction of asthma exacerbation across all subgroups analyzed regardless of serum eosinophil count (EOS), fractionated exhaled nitric oxide (FeNO) level, or allergic status as determined by IgE sensitivity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tezepelumab is indicated to treat nonallergic and noneosinophilic severe uncontrolled asthma phenotypes in addition to type 2 inflammatory asthma. When selecting the most appropriate biologic agent, consider the risks, benefits, and costs. There is a paucity of data on the efficacy of tezepelumab in patients with comorbid conditions. In the case of a patient presenting with uncontrolled severe asthma with such comorbid conditions, it may be prudent to consider a biologic therapy that can target both. CONCLUSION: Tezepelumab has shown clinical utility in severe uncontrolled asthma regardless of phenotype, fulfilling the need for treatment options in individuals with severe, uncontrolled, noneosinophilic, and nonallergic asthma.

Intranasal Olopatadine-Mometasone in the Treatment of Seasonal Allergic Rhinitis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR). DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older. CONCLUSION: OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

Azithromycin Versus Beta-lactams in Hospitalized Patients with Acute Exacerbations of COPD.

BACKGROUND: There is a lack of data comparing azithromycin to alternative antibiotic choices in managing COPD exacerbations, making appropriate antibiotic selection controversial. OBJECTIVE: To compare treatment failure in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) receiving azithromycin or beta-lactams. DESIGN: Retrospective, multicenter cohort study using logistic regression for multivariable analysis. Patients were included if they were at least 18 years old, admitted with AECOPD, and received at least two consecutive days of either a beta-lactam or azithromycin. Patients were excluded if they received concomitant azithromycin and beta-lactam antibiotics during the first 2 days, had a history of other severe underlying pulmonary diseases, pregnancy, COVID-19, alpha-1 antitrypsin deficiency, or received a corticosteroid for a diagnosis other than COPD. PARTICIPANTS: Five hundred ninety-five patients were included, of which 428 (72%) received azithromycin and 167 patients (28%) received a beta-lactam. MAIN MEASURES: The primary endpoint was treatment failure rate in patients receiving azithromycin versus beta-lactams, which was a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, initiation of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. KEY RESULTS: The composite primary outcome occurred in 84 patients (19.6%) in the azithromycin group and 54 (32.3%) in the beta-lactam group (p<0.01). The difference in the composite outcome was a result of higher rates of new antibiotics during admission (12.6% vs 4.2%; p<0.01) and higher readmission within 30 days (19.3% vs 12.4%; p=0.032). After controlling for potential confounders, beta-lactams continued to demonstrate a higher risk for treatment failure (OR, 2.30; 95% CI, 1.46-3.63). There was no difference in adverse effects between the groups. CONCLUSION: Azithromycin was associated with less treatment failure in AECOPD which was driven by lower readmission rates and prescription of new antimicrobials.

Clinical Outcomes of Zinc Supplementation Among COVID-19 Patients.

BACKGROUND: Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed. OBJECTIVE: Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness. METHODS: We performed a multicenter, retrospective, observational chart review of patients admitted to Ascension St. John Hospital or Detroit Medical Center from January 1st, 2020 to May 31st, 2020. All included patients received concomitant hydroxychloroquine due to its zinc ionophore activity. Our primary outcome was a change in Sequential Organ Failure Assessment (SOFA) score with secondary outcomes including all-cause mortality, need for intubation, and QTc prolongation as a safety outcome. RESULTS: We identified 489 patients who received zinc and 587 patients who did not. The primary outcome showed a small difference in the change in SOFA score in patients receiving zinc in univariate analysis (1.08 vs. 1.43, p=0.02), but this difference was not significant after adjustment for confounding factors such as receipt of corticosteroids and ICU admission. Mortality was not different between those that received zinc compared to those that did not (32.7% vs. 35.9%, p=0.268). CONCLUSION: Our retrospective study, including 1064 patients hospitalized in Detroit, demonstrated no differences in mortality or disease severity with zinc combination. Furthermore, prospective studies are needed to establish the utility of zinc in the treatment of COVID-19.

Mechanisms and Potential Roles of Glucose-Lowering Agents in COVID-19: A Review.

OBJECTIVE: To explore mechanistic benefits of glucose-lowering agents that extend beyond glycemic control with the potential to mitigate coronavirus disease 2019 (COVID-19) complications. DATA SOURCES: The following PubMed literature search terms were used from July 2020 to January 2, 2021: diabetes, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), glucose-lowering agents, and pharmacology. STUDY SELECTION AND DATA EXTRACTION: English-language studies reporting on the association between diabetes, COVID-19 adverse outcomes, and the potential roles of glucose-lowering agents were reviewed. DATA SYNTHESIS: Selected glucose-lowering agents have benefits beyond glycemic control, with the potential to reduce the risks of severe complications during SARS-CoV-2 infection. Key benefits include anti-inflammatory, anticoagulant, immune modulating, and enzyme/receptor effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review summarizes the current knowledge of glucose-lowering agents and their potential roles in COVID-19 outcomes. Considering beneficial mechanisms on COVID-19 outcomes that extend beyond glycemic control as well as safety profiles, current data suggest that dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin may have the most promise and warrant further investigation. CONCLUSIONS: Certain glucose-lowering agents may offer additional benefits beyond glucose control-namely, by modulating the mechanisms contributing to adverse outcomes related to COVID-19 in patients with diabetes. DPP-IV inhibitors and metformin appear to have the most promise. However, current published literature on diabetes medications and COVID-19 should be interpreted with caution. Most published studies are retrospective and consist of convenience samples, and some lack adequate analytical approaches with confounding biases. Ongoing trials aim to evaluate the effects of glucose-lowering agents in reducing the severity of COVID-19 outcomes.

Dual- Versus Mono-Bronchodilator Therapy in Moderate to Severe COPD: A Meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) guidelines recommend both long-acting and dual bronchodilator therapy. It is unclear if there are differences in efficacy and safety. OBJECTIVE: This meta-analysis evaluates the efficacy of dual therapy with long-acting ß-agonist (LABA) + long acting muscarinic antagonist (LAMA) compared with monotherapy with LAMA for COPD. METHODS: We searched PubMed, CINAHL, and Web of Science databases from inception through March 2020 to identify English-language, prospective randomized controlled trials (RCTs) that compared dual therapy with monotherapy in adult patients with COPD. Risk of bias was assessed using the Jadad score. Overall analysis was performed using Review Manager 5.3. Treatment effect was determined with the random-effects model using the Mantel-Haenszel method and was reported as mean difference (MD) with 95% CI. RESULTS: A total of 18 RCTs were included (n = 6086; median Jadad score 5/5) that compared LAMA + LABA with LAMA. There was a greater improvement in forced expiratory volume at 1 s (FEV1) with dual therapy compared with LAMA: MD = 0.08; 95% CI = [0.05, 0.11]. There was no difference in St George Respiratory Questionnaire (SGRQ) scores between groups: OR = -0.85; 95% CI = [-1.83, 0.13]. There were no differences in overall adverse events (OR = 1.00; 95% CI = 0.92, 1.09), serious adverse events (OR = 1.01; 95% CI = 0.86, 1.18), or cardiovascular events (OR = 0.88; 95% CI = 0.58, 1.34). CONCLUSION AND RELEVANCE: Dual therapy improves FEV1 and is as safe as LAMA. Dual therapy does not improve SGRQ scores more than LAMA.

Combination of Vancomycin or Daptomycin and Beta-lactam Antibiotics: A Meta-analysis.

INTRODUCTION: Observational and randomized controlled trials of the combination of vancomycin or daptomycin with a beta-lactam (BL) in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia have shown conflicting results on patient outcomes. OBJECTIVES: The primary purpose of this meta-analysis was to compare clinical failure with the combination of vancomycin or daptomycin with a BL versus vancomycin or daptomycin monotherapy in MRSA bacteremia or endocarditis. METHODS: A systematic literature search of PubMed, Embase, CINAHL, and meeting proceedings was conducted from inception through February 11, 2020, to identify relevant studies. The primary outcome was clinical failure and secondary outcomes were mortality, nephrotoxicity, and bacteremia. The meta-analysis was performed using Comprehensive Meta Analysis (version 3.0) with a random effects model. Outcomes were reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: Nine studies of 1636 patients receiving vancomycin or daptomycin monotherapy versus the combination of vancomycin or daptomycin plus BL for MRSA bacteremia were included. Results showed combination therapy was associated with significantly lower clinical failure rates (OR 0.56, 95% CI 0.39-0.79, I2  = 26.22%, p=0.001). Improvement in clinical failure was driven by lower rates of bacteremia relapse and persistence. However, no difference was seen with mortality. CONCLUSIONS: Combination therapy with vancomycin or daptomycin plus BL for MRSA bacteremia showed lower clinical failure rates, however, no significant difference was seen in mortality.

Adverse drug reactions in drug information databases: does presentation affect interpretation?

OBJECTIVE: Formatting of adverse drug reaction (ADR) information differs among drug information (DI) resources and may impact clinical decision-making. The objective of this study was to determine whether ADR formatting impacts adverse event interpretation by pharmacy practitioners and students. METHODS: Participants were randomized to receive ADR information in a comparative quantitative (CQUANT), noncomparative quantitative (NQUANT), or noncomparative qualitative (NQUAL) format to interpret 3 clinical vignettes. Vignettes involved patients presenting with adverse events that varied in the extent to which they were associated with a medication. The primary outcome was interpretation of the likelihood of medication-induced adverse events on a 10-point Likert scale. Lower scoring on likelihood (i.e., ADR deemed unlikely) reflected more appropriate interpretation. Linear regression was performed to analyze the effects of ADR information format on the primary outcome. RESULTS: A total of 108 participants completed the study (39 students and 69 pharmacists). Overall, the CQUANT group had the lowest average likelihood compared to NQUAL (4.0 versus 5.4; p<0.01) and NQUANT (4.0 versus 4.9; p=0.016) groups. There was no difference between NQUAL and NQUANT groups (5.4 versus 4.9; p=0.14). In the final model, at least 2 years of postgraduate training (-1.1; 95% CI: -1.8 to -0.3; p<0.01) and CQUANT formatting (-1.3; 95% CI: -0.9 to -1.7; p<0.01) were associated with reduced likelihood. CONCLUSIONS: Formatting impacts pharmacists' and pharmacy students' interpretation of ADR information. CQUANT formatting and at least two years of postgraduate training improved interpretation of adverse events.

Are Blacks at Higher Risk for Vancomycin-Related Acute Kidney Injury?

BACKGROUND: Black individuals have a higher lifetime risk of acute kidney injury (AKI) and chronic kidney disease than whites. Vancomycin has a potential for nephrotoxicity. The objective of this study was to determine whether the incidence of AKI among patients being treated with vancomycin differs by race. METHODS: Retrospective study of adult (3 ≥18 years) inpatients who were on vancomycin for 348 hours between January 2012 and December 2014. Data on demographics, comorbid conditions, clinical characteristics, vancomycin dose, duration, and nephrotoxic drugs were collected. Patients with a creatinine clearance <30 mL/min or undergoing dialysis were excluded. RESULTS: We identified 1130 patients during the study period; 48.1% (544) were black. The overall incidence of AKI was 8.2% (10.1% blacks, 6.5% whites; P = .03). Independent predictors of AKI included black race (P = .011); higher Charlson score (P = .006); higher body mass index (BMI; P = .002); higher vancomycin trough level (P < .0001); and sepsis/systemic inflammatory response syndrome (<.0001), pneumonia (P = .001) or gastrointestinal/genitourinary (P = .025) as the source of infection. CONCLUSION: The incidence of vancomycin-related AKI was higher in blacks, independent of other risk factors. Based on our study, vancomycin trough levels and renal function need to be closely monitored in blacks.

Impact of Pharmacist Involvement in Heart Failure Transition of Care.

Background: Heart failure (HF) transition of care (TOC) programs may improve continuity of care and coordination and decrease hospital readmissions. Objective: This study evaluated the impact of pharmacy-led HF TOC on HF readmission rate. Methods: This was a single-center, pre-post quasi-experimental study. Pharmacy TOC comprised admission and discharge medication reconciliations and patient education. Patients were included if they had a primary HF diagnosis. Patients were excluded if they were admitted for a non-HF diagnosis, admitted for <24 hours, had a stage IV cancer or dementia diagnosis, or were transferred to hospice care. The primary outcome was HF 30-day readmission rate. Results: A total of 663 patients were included in the study: 330 in the control group and 333 in the intervention group. The average age for both groups was 67 ± 16 years; 48.1% were female; 56.9% were African American; and 51.4% of patients had an ejection fraction ≤40%. In the control group, 57 (17.3%) patients had a HF 30-day readmission compared with 35 (10.5%) patients in the intervention group. After adjusting for age, the intervention group continued to show a difference in readmission (odds ratio = 0.578; 95% CI = 0.367-0.911; P = 0.018). The most common interventions were medication addition (11%), dose titration (7.5%), medication discontinuation (6.6%), and duplication avoidance (2.7%). Conclusion and Relevance: Pharmacy-led HF TOC, as a component of a targeted hospital-based initiative, significantly decreased HF 30-day readmission rate. Results from this study warrant further research to explore which interventions in TOC are most effective.

Efficacy of Capsaicin for the Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review.

Objective: Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic vomiting, abdominal pain, and alleviation of symptoms via hot showers in chronic cannabinoid users. Capsaicin is recommended as a reasonable first-line treatment approach for CHS despite limited clinical evidence regarding its use. The objective of this study is to systematically review the efficacy data for capsaicin in CHS. Data Sources: A literature search using keywords related to cannabinoids, emesis, and capsaicin was performed in MEDLINE, CINAHL, and EMBASE from inception through March 31, 2019. Study Selection and Data Extraction: Studies and published abstracts in which capsaicin was used for CHS and clinical outcomes were reported were eligible for inclusion. Data Synthesis: A total of 241 articles were screened, of which 5 full-text articles and 6 conference abstracts were included. Full-text case reports (n = 3) and case series (n = 2) found capsaicin to be effective in a total of 18 patients. Published abstracts were in the form of case reports (n = 1), case series (n = 3), and retrospective cohort studies (n = 2). Relevance to Patient Care and Clinical Practice: Capsaicin use was described as beneficial in all case series and case reports; however, both retrospective cohort studies were unable to find a significant benefit for capsaicin on primary outcomes (emergency department length of stay). Conclusion: Current data for capsaicin efficacy in CHS is of low methodological quality. However, the limited data on alternative antiemetic therapies and capsaicin's favorable risk-benefit profile make it a reasonable adjunctive treatment option.