Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation.

Objectives: The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. Methods: This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxic medications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. Results: One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST ( P < 0.001), ALT ( P < 0.001), alkaline phosphatase (ALK) ( P < 0.001), total bilirubin (TBILI) ( P < 0.001) and QTc ( P = 0.05) from baseline. Posaconazole levels were not associated with increases in AST [ß (SE) = -0.33 (2.2), P = 0.88], log ALT [ß (SE) = -0.02 (0.03), P = 0.63], ALK [ß (SE) = 2.2 (2.9), P = 0.46] and TBILI [ß (SE) = -0.01 (0.04), P = 0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL ( P = 0.02) and ALK of 7.1 U/L ( P = 0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. Conclusions: We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

Feasibility, Benefits, and Limitations of a Penicillin Allergy Skin Testing Service.

OBJECTIVE: To critically examine the feasibility, benefits, and limitations of an inpatient penicillin skin testing service and how pharmacists can be utilized. DATA SOURCES: A PubMed search was performed from July 2016 through September 2016 using the following search terms: penicillin skin testing, penicillin allergy, ß-lactam allergy. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language studies assessing the use of penicillin skin testing as well as management and clinical outcomes of patients with a ß-lactam allergy were evaluated. DATA SYNTHESIS: The prevalence of people self-identifying as penicillin allergic ranges from 10% to 20% in the United States. Being improperly labeled as penicillin allergic is associated with higher health care costs, worse clinical outcomes, and an increased prevalence of multidrug-resistant infections. Penicillin skin testing can be a tool used to clarify penicillin allergies and has been demonstrated to be a successful addition to antimicrobial stewardship programs in multiple health care settings. Prior to implementing a penicillin skin testing service, institutions will need to perform a feasibility analysis of who will supply labor and accept the financial burden as well as identify if the positive benefits of a penicillin skin testing service overcome the limitations of this diagnostic test. CONCLUSION: We conclude that institutions with high percentages of patients receiving non-ß-lactams because of penicillin allergy labels would likely benefit the most from a penicillin skin testing service.

Consequences of avoiding ß-lactams in patients with ß-lactam allergies.

BACKGROUND: The choice of empiric antibiotics for the treatment of gram-negative bacilli (GNB) bloodstream infections (BSIs) in patients presenting with a ß-lactam (BL) allergy is often a difficult decision given that these agents are first-line treatment in many guidelines. OBJECTIVE: We sought to compare rates of clinical failure between patients with a history of BL allergy who received either a BL or a non-ß-lactam (NBL). METHODS: Adult patients with a past medical history of BL allergy and receipt of antibiotics for treatment of a GNB BSI were included from 3 academic medical centers. Treatment groups were classified as BL or NBL groups based on the empiric antibiotics received. Clinical failure was assessed 72 to 96 hours after initiation of empiric antibiotics. Hypersensitivity reactions during receipt of antibiotic therapy for the index BSI were recorded. RESULTS: A total of 552 patients were included for analysis: 433 patients in the BL group and 119 patients in the NBL group. Clinical failure was higher in the NBL group compared with the BL group (38.7% vs 27.4%, P = .030). The most common cause of clinical failure was a temperature of greater than 38.0°C 72 to 96 hours after receipt of empiric antibiotics (NBL group: 22.7% vs BL group: 13.9%, P = .016). Hypersensitivity occurred in 16 (2.9%) of 552 patients. Thirteen (2.5%) of 552 patients experiencing hypersensitivity reactions were exposed to a BL during treatment for GNB BSI. CONCLUSION: Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

Impact of Cefepime Susceptible-Dose-Dependent MIC for Enterobacteriaceae on Reporting and Prescribing.

The CLSI cefepime breakpoints were revised to include a susceptible-dose-dependent (SDD) category for Enterobacteriaceae, with the intention that higher cefepime doses be used for these isolates. In this study, 1.6% of Enterobacteriaceae isolates were reported as SDD, with Escherichia coli the most common SDD organism. Cefepime was prescribed in three cases (4.8%); the majority of SDD isolates were treated with a carbapenem. Enterobacteriaceae with cefepime SDD MICs were not commonly treated with cefepime at our institution.

Assessing Naltrexone Prescribing and Barriers to Initiation for Alcohol Use Disorder: A Multidisciplinary, Multisite Survey.

Objective: To survey barriers in prescribing naltrexone for alcohol use disorder. Methods: A 12-question survey related to naltrexone prescribing patterns, perceptions, and knowledge was sent to 770 prescribers in the departments of internal medicine, family medicine, and psychiatry across a health system with sites in Arizona, Florida, and Minnesota. Results: Responses were obtained and included for 146/770 prescribers (19.0% response rate). Most respondents were in the department of internal medicine (n = 94, 64.4%), but the departments of psychiatry (n = 22, 15.1%) and family medicine (n = 30, 20.5%) were also represented. Only 34 (23.3%) respondents indicated they had prescribed naltrexone in the previous 3 months. The most common reasons for not prescribing naltrexone were "unfamiliarity with naltrexone for treatment of alcohol use disorder" and "patients do not have appropriate follow-up or are not in a formal treatment program." Compared with those representing internal/family medicine, psychiatry respondents were more likely to prescribe naltrexone and answer knowledge questions correctly. Conclusion: In this survey among primarily non-addiction-trained prescribers, a disparity was shown for prescribing naltrexone and in knowledge barriers between staff in internal/family medicine and psychiatry. There exist opportunities for education and quality improvement that promote the prescribing of naltrexone for alcohol use disorder by non-addiction specialists.

Comparison of intravenous and oral definitive antibiotic regimens in hospitalised patients with Gram-negative bacteraemia from a urinary tract infection.

OBJECTIVES: Transitioning patients from intravenous (IV) to oral antibiotic therapy has been shown to be a successful approach for several infections. However, minimal data exist evaluating outcomes following transition from to oral antibiotics for patients with bacteraemia secondary to a urinary tract infection (UTI). This study compared treatment failures between patients treated exclusively with IV antibiotics and those transitioned from IV to oral antibiotics for bacteraemia secondary to UTI. METHODS: This single-centre, retrospective cohort study included hospitalised, non-critically ill adult patients treated with culture-susceptible antibiotic therapy for 7-21 days. Patients were divided into two cohorts based on the route of definitive antibiotic administration. Treatment failure was a composite outcome of death and recurrence of the index micro-organism within 21 days following negative blood cultures. RESULTS AND DISCUSSION: Among the 346 patients enrolled, 82 (23.7%) were in the IV cohort and 264 (76.3%) were in the IV-to-oral cohort. A total of six treatment failures occurred; 2 (2.4%) in the IV cohort and 4 (1.5%) in the oral transition cohort (hazard ratio=0.62, 95% confidence interval 0.11-3.39; P=0.58). All failures were due to recurrence of the index organism. Secondary outcomes demonstrated a significantly higher rate of IV line-associated complications in the IV cohort (P=0.03) and a favourable hospital length of stay in the oral cohort (P<0.001). Patients transitioned from IV to oral antibiotics based on culture-susceptibility data experienced similarly low rates of treatment failure as those who received exclusive IV therapy.

Implementation of an interprofessional clinical pharmacology selective learning experience for pharmacy residents and medical students.

PURPOSE: The implementation of an interprofessional clinical pharmacology selective (CPS) learning experience for pharmacy residents and medical students is described. SUMMARY: The opportunity for pharmacy residents to provide didactic lectures at a college of pharmacy and to develop teaching and preceptor skills with experiential pharmacy students may be limited by institution-specific affiliations and geographic location. In order to overcome these barriers, the Mayo Clinic Hospital postgraduate year 1 (PGY1) pharmacy residency program implemented an interprofessional learning experience in which pharmacy residents serve the role of preceptors for first- and second-year medical students on a CPS. Medical students at the Mayo Medical School (MMS) work alongside the PGY1 resident to develop patient-specific, medication problem lists and gain an appreciation for pharmacy-focused interventions. Medical students teach pharmacy residents diagnostic, pathophysiologic, and patient-assessment considerations related to the medical school's curriculum. The clinical rounds component of the CPS allows for resident achievement of ASHP competency area R4, which focuses on the design of an effective educational activity; selection of a preceptor role; employment of instruction, modeling, coaching, and facilitation; use of effective presentation skills; generation of objective-based learner assessment questions; and identification of areas for continuous improvement. CONCLUSION: The Mayo Clinic Hospital PGY1 pharmacy residency program and MMS successfully implemented an innovative learning experience to promote interprofessional education between pharmacy residents and medical students. The program establishes collaborative relationships early in students' professional careers and allows for attainment of the ASHP-required competency area R4 through delivery of a CPS to medical students.