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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A Guide to Bacterial Culture Identification And Results Interpretation.

PURPOSE: To provide a guide to interpreting bacterial culture results. METHODS: Studies were identified via a PubMed literature search (from 1966 to January 2018). Search terms included microbial sensitivity tests, microbial drug resistance, and anti-infective agents/pharmacology. Articles were included if they were published in English. References within identified articles were also reviewed. RESULTS: This paper reviewed core concepts of interpreting bacterial culture results, including timing of cultures, common culture sites, potential for contamination, interpreting the Gram stain, role of rapid diagnostic tests, conventional antibiotic susceptibility testing, and automated testing. CONCLUSION: This guide can assist pharmacists in their role as integral members of the antimicrobial stewardship team in an effort to improve patient care.

Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-α Antagonists.

OBJECTIVE: To review the mechanism and association of infectious risk among the tumor-necrosis factor α (TNF-α) antagonists used in inflammatory bowel disease. DATA SOURCES: A PubMed literature search was performed using the following search terms: infliximab, adalimumab, certolizumab, golimumab, inflammatory bowel disease, crohn's, ulcerative colitis, adverse effects, adverse events, safety, and infection. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses and cohort studies with outcomes pertaining to quantitative infectious risk were reviewed. Case reports and case series describing association between TNF-α inhibitors and infection were also reviewed. DATA SYNTHESIS: A total of 7 recent meta-analyses of randomized trials demonstrate inconclusive association of infection with TNF-α antagonists. Registry data suggest that medications carry an independent risk of opportunistic infections. Risk factors for infection include older age, malnutrition, diabetes, and possibly combination therapy. Reported infections vary widely but include intracellular and granulomatous bacteria, viruses, and fungi. CONCLUSION: TNF-α antagonists are associated with an increased risk of opportunistic infection, although this risk has not been demonstrated conclusively in randomized controlled trials. Knowledge of concomitant risk factors, mechanism of infectious risk, and available treatment options can improve patient care in the clinical setting.

"I Never Would Have Caught That Before": Pharmacist Perceptions of Using Clinical Decision Support for Antimicrobial Stewardship in the United States.

To systematically improve the appropriateness of antibiotic prescribing, antimicrobial stewardship programs have been developed. There is a paucity of literature examining how pharmacists perform antimicrobial stewardship using a clinical decision support system in a hospital setting. The purpose of this qualitative study was to develop a model exploring how pharmacists perform antimicrobial stewardship to identify areas for programmatic improvement. Semistructured interviews were conducted across a health care system until saturation of themes was reached. Pharmacists identified that self-efficacy and time were vital for antimicrobial stewardship to be performed, while culture of the hospital and attitude facilitated the process of stewardship. Antimicrobial stewardship programs using clinical decision support tools should ensure pharmacists have adequate time to address rules, provide easy-to-use resources and training to support self-efficacy, and engage influential physicians to support a culture of collaboration.

Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report
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PURPOSE: A case of daptomycin-associated acute eosinophilic pneumonia (AEP) with positive rechallenge is reported. SUMMARY: AEP associated with daptomycin is reported in the literature, and the product labeling contains a warning and precaution statement. Criteria for diagnosing daptomycin-induced AEP varies and generally includes bronchoalveolar lavage (BAL) eosinophils ≥ 25%. We report a case of a 70-year-old woman with cough, shortness of breath, and altered mental status who presented ~ 9 days after starting therapy with daptomycin to treat methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Daptomycin was utilized because of a presumed vancomycin allergy. Aspiration pneumonia was suspected and IV ampicillin and sulbactam was initiated. Clinical status improved initially but ~ 1 week later, her respiratory status declined. During work-up, peripheral eosinophils were abnormal at 11.6%, so daptomycin therapy was discontinued. BAL revealed 5% eosinophils with negative infectious work-up. Respiratory status rapidly improved after discontinuation of daptomycin. Linezolid therapy was initiated. Due to an uncertain association with daptomycin and concerns associated with long-term linezolid therapy, the patient agreed to rechallenge with daptomycin. Within 24 hours, respiratory symptoms returned and daptomycin was permanently discontinued. The patient rapidly recovered without the need for systemic corticosteroid treatment. CONCLUSIONS: Our case supports a broadened definition of pulmonary eosinophilia associated with daptomycin administration. It is important for clinicians to consider daptomycin as an etiology of pneumonia with abnormal eosinophils when other causes have been excluded. Clinicians could also consider peripheral eosinophilia as a possible indication of AEP when BAL is not available or cannot be obtained.
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Meta-Analysis: Vancomycin Treatment Failures for MRSA Bacteremia Based on MIC Determined by E-test.

Background: Vancomycin is used to treat serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). It is unclear whether MRSA isolates with minimum inhibitory concentration (MIC) 1.5 to 2 µg/mL are successfully treated with vancomycin. Objective: Evaluate vancomycin failure rates in MRSA bacteremia with an MIC <1.5 versus ≥1.5 µg/mL, and MIC ≤1 versus ≥2 µg/mL. Methods: A literature search was conducted using MESH terms vancomycin, MRSA, bacteremia, MIC, treatment and vancomycin failure to identify human studies published in English. All studies of patients with MRSA bacteremia treated with vancomycin were included if they evaluated vancomycin failures, defined as mortality, and reported associated MICs determined by E-test. Study sample size, vancomycin failure rates, and corresponding MIC values were extracted and analyzed using RevMan 5.2.5. Results: Thirteen studies including 2955 patients met all criteria. Twelve studies including 2861 patients evaluated outcomes using an MIC cutoff of 1.5 µg/mL. A total of 413 of 1186 (34.8%) patients with an MIC <1.5 and 531 of 1675 (31.7%) patients with an MIC of ≥1.5 µg/mL experienced treatment failure (odds ratio = 0.72, 95% confidence interval = 0.49-1.04, P = .08). Six studies evaluated 728 patients using the cutoffs of ≤1 and ≥2 µg/mL. A total of 384 patients had isolates with MIC ≤1 µg/mL, 344 had an MIC ≥2 µg/mL. Therapeutic failure occurred in 87 and 102 patients, respectively (odds ratio = 0.61, 95% confidence interval = 0.34-1.10, P = .10). As heterogeneity between the studies was high, a random-effects model was used. Conclusion: Vancomycin MIC may not be an optimal sole indicator of vancomycin treatment failure in MRSA bacteremia.

Effect of bariatric surgery on hypertension: a meta-analysis.

PURPOSE: Obesity is a growing epidemic leading to worldwide public health concerns. Bariatric surgery is an option for patients with a body mass index (BMI) >40 kg/m(2) or BMI of >35 kg/m(2) with serious comorbid conditions. This meta-analysis examines the effect of bariatric surgery on the improvement or resolution of hypertension. METHODS: Two independent investigators conducted a literature search of PubMed (1990-2013) and Cochrane databases using the terms bariatric surgery and hypertension to identify appropriate human adult studies published in English. Studies were included if they reported the number of patients with hypertension prior to undergoing any bariatric surgery procedure and whether the hypertension improved or resolved postsurgery. The number of patients with hypertension and their response rates were extracted and analyzed using RevMan 5.2.5. RESULTS: In all, 31 prospective and 26 retrospective studies met all criteria. The types of bariatric surgery performed included Roux-en-Y, gastric banding, laparoscopic adjustable gastric banding, vertical gastric banding, sleeve gastrectomy, duodenal switch, and biliopancreatic diversion. The time to first follow-up after surgery varied from 1 week to 7 years. Of the 57 studies, 32 reported improvement of hypertension in 32 628 of 51 241 patients (odds ratio [OR] = 13.24; 95% CI = 7.73, 22.68; P < 0.00001); 46 studies reported the resolution of hypertension in 24 902 of 49 844 patients (OR = 1.70; 95% CI = 1.13, 2.58; P = 0.01). A random-effects model was used because the heterogeneity between the studies was high (I (2) = 97%). CONCLUSION: The results of this meta-analysis indicate that patients who undergo bariatric surgery experience improvement and resolution of their hypertension.

Teduglutide for the Treatment of Short Bowel Syndrome.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of the newly approved drug, teduglutide, for the treatment of short bowel syndrome (SBS). DATA SOURCES: Literature was retrieved through PubMed (1966-March 2014) using the search term teduglutide. The authors applied the filters Humans and English language, resulting in 47 publications. STUDY SELECTION AND DATA EXTRACTION: The authors reviewed the 47 citations to extract those that were published clinical trials. Bibliographies of recent review articles and editorials were evaluated for additional pertinent publications for inclusion. The methods and results from each of the trials were extracted. DATA SYNTHESIS: Teduglutide has been studied in SBS in 3 phase III trials. Teduglutide decreases parenteral nutrition (PN) volume requirements, with 1 study showing a reduction of 4.4 ± 3.8 L/wk with teduglutide 0.05 mg/kg versus 2.3 ± 2.7 L/wk with placebo; P < 0.001. In another study, teduglutide improved graded response scores, which are based on the intensity and duration of the reduction of PN use (16/35 assigned to teduglutide 0.05 mg/kg vs 1/16 assigned to placebo; P = 0.007). The dosing range studies have indicated that the optimal dose of teduglutide is 0.05 mg/kg daily subcutaneously. There are a number of adverse effects reported in the trials, including abdominal pain or distention, injection site reactions, nausea, headaches, and fluid overload among others. There is also a concern for the development of malignancy with teduglutide, and therefore, it is not recommended in patients with active gastrointestinal malignancies. CONCLUSIONS: Overall, teduglutide appears to be a promising agent for the treatment of SBS.