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.

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.

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.

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.

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.

"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.

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.

Adherence to GOLD Guidelines in the Inpatient COPD Population.

PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease guidelines provide recommendations to manage chronic obstructive lung disease (COPD) exacerbations. This study assessed the management of inpatient COPD exacerbations at an urban teaching hospital. METHODS: A retrospective cohort analysis of adults admitted between December 2010 and August 2012 with a COPD exacerbation was conducted. Patient demographics, length of stay (LOS), Charlson comorbidity score, inpatient pulmonary medications, and 30-day readmission were collected. Descriptive statistics characterized guideline adherence and readmission. RESULTS: 94 patients were included with median LOS of 3 days (interquartile range [IQR]: 1-5 days) and median Charlson comorbidity score of 6 (IQR: 5-8). All patients received an inhaled short-acting beta agonist, and 52 (55.3%) also received an inhaled short-acting anticholinergic. Seventy-eight (83%) received systemic corticosteroids, of which 3 received guideline-recommended doses. Sixty-four (68.1%) received antibiotics for a pulmonary indication, of which 71.9% received appropriate antibiotics per indication. Of the 94 patients, 2 were managed in complete adherence with GOLD recommendations. A total of 24 (25.5%) patients were readmitted within 30 days of discharge, 9 of these for COPD. CONCLUSION: COPD exacerbation treatment deviated from GOLD recommendations. This provides opportunities for further optimization of treatment of COPD exacerbations.

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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Biosimilars in Inflammatory Bowel Disease - Accumulating Clinical Evidence.

INTRODUCTION: Biologic antagonists to tumor necrosis factor alpha (TNF- α) are effective medications and have become well established in the treatment of both Crohn's disease and ulcerative colitis. Biosimilar medications, which are medications deemed to be equivalent to reference biologic products in terms of clinical effectiveness, safety, pharmacokinetic analysis, and immunogenicity, have now been approved in inflammatory bowel diseases (IBD) based on indication exploration from clinical data in alternate disease states. Clinicians use these products with caution secondary to lack of clinical experience. Areas Covered: The authors performed a literature search using the following keywords: CT-P13, biosimilar, adalimumab, infliximab, ABP 501, and inflammatory bowel disease. Bibliographies were also reviewed for pertinent articles. Articles pertaining to the clinical efficacy of biosimilars in IBD were included. Expert commentary: The phase 3 trials, which provided the clinical justification to bring TNF- α biosimilars to market, were in rheumatoid arthritis and ankylosing spondylitis; however, new clinical data suggests that biosimilar products have equivalent safety and efficacy to reference products in IBD. This has led to an increased acceptance amongst practicing gastroenterologists and a potential reduction in healthcare costs.

Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis.

STUDY OBJECTIVE: To evaluate the association of the development of acute kidney injury (AKI) when piperacillin-tazobactam is used in combination with vancomycin compared with vancomycin with or without a ß-lactam. DESIGN: Meta-analysis of 15 observational cohort studies. PATIENTS: A total of 3258 adult inpatients who received vancomycin + piperacillin-tazobactam versus vancomycin alone (10 studies); vancomycin + piperacillin-tazobactam versus vancomycin + ß-lactam (four studies); or vancomycin + piperacillin-tazobactam versus vancomycin alone or vancomycin + other antibiotics (one study). MEASUREMENTS AND MAIN RESULTS: The PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases, as well as meeting proceedings, were searched (1966-June 1, 2016). Quality of studies was assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOQAS). The primary outcome of this meta-analysis was to evaluate the association of development of AKI with the combined use of piperacillin-tazobactam and vancomycin. A subgroup analysis was also performed that examined the outcome by comparison groups (vancomycin alone or vancomycin + ß-lactam). Sensitivity analysis was performed to explore if the results differed based on removal of abstracts and removal of low-quality studies (NOQAS scores of 6 or lower). All analyses were performed using the random effects model. NOQAS scores for the 15 studies ranged from 3-7 points (of a total of 9). Overall, there was an association with the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin ± ß-lactam (odds ratio [OR] 3.649, 95% confidence interval [CI] 2.157-6.174; I2 = 83.5%, p<0.001). The association remained significant when abstracts were removed (OR 3.498, 95% CI 1.747-7.003, I2 = 82.3%, p<0.001) and when low-quality studies were removed (OR 4.596, 95% CI 2.929-7.212, I2 = 0%, p<0.001). The association for the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin alone was significant (OR 3.980, 95% CI 2.749-5.763, I2 = 31.4%, p<0.001), although the association did not remain significant for the vancomycin + ß-lactam subgroup (OR 3.029, 95% CI 0.942-9.738, I2 = 82.3%, p=0.063). CONCLUSION: Vancomycin + piperacillin-tazobactam was associated with an increased risk of AKI compared with vancomycin ± ß-lactam. Practitioners need to be vigilant about this association when prescribing this combination of antibiotics.

New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir.

Hepatitis C is a chronic infection associated with considerable morbidity and mortality. In recent years, there has been a shift in treatment paradigm with the discovery and approval of agents that target specific proteins vital for hepatitis C replication. The NS3/4A inhibitors simeprevir and paritaprevir, the NS5A inhibitors ombitasvir, ledipasvir, and daclatasvir, and the NS5B inhibitors sofosbuvir and dasabuvir have been newly FDA approved and incorporated as first-line agents into the latest IDSA-AASLD guidelines for Hepatitis C treatment. Used in combination, these agents produce higher rates of sustained virologic response and less adverse effects than historical options, along with limited rates of resistance. Pertinent clinical data, pharmacology, and pharmacokinetics are reviewed for these new direct acting antiviral agents.