Statin Use and the Point Prevalence of Antibiotics in Ambulatory Patients with Diabetes in the National Health and Nutrition Examination Survey (NHANES) 2003-2012.

In patients with diabetes, the risk of infections is increased, hypothesized to be due to alterations in the immune system, among other changes. The pleotropic effects of statins have been investigated to assess their role in reducing the risk of infection and infection-related outcomes with varying results. The aim of this study is to determine if the use of statins is associated with a decrease in the point prevalence of oral antibiotic use in ambulatory patients with diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012, all adult patients diagnosed with diabetes were analyzed. Patients were grouped into those who were prescribed statins and those who were not. Oral antibiotic use between the two groups was compared. Data were standardized to national estimates. A total of 3240 patients with diabetes were identified, with 1575 statin users and 1665 non-statin users. After controlling for baseline socio-demographic and clinical variables, the overall point prevalence of oral antibiotic use in diabetes population was 3.5% with no difference between statin users and non-statin users (2.9% vs. 4%, p = 0.116). Based on the results of this study, the use of statins in patients with diabetes was not associated with a reduction in the point prevalence of antibiotic use.

Elvitegravir for the treatment of HIV.

INTRODUCTION: Current antiretrovirals (ARVs) have demonstrated the ability to prolong the life of an HIV infected individual via suppression of the virus and subsequent restoration of immune function. Despite significant advancement, there remains an opportunity for improvement. One ARV that attempts to fill global HIV therapeutic needs by balancing convenience, safety, and efficacy is elvitegravir (EVG). Areas covered: Using MEDLINE/PubMed, a literature search was conducted for published articles on the safety and efficacy of EVG in the treatment of HIV infection. Expert opinion: EVG offers clinicians a convenient choice for HIV-positive patients that is safe and effective for both treatment-naïve and experienced patients, as well as an option for regimen simplification in virologically suppressed patients. EVG is conveniently co-formulated in fixed dose combination tablets to be taken once daily with food. EVG does not require dose adjustment for patients with severe renal impairment or mild to moderate liver disease. Importantly, EVG requires co-administration with a pharmacokinetic enhancer (i.e., ritonavir or cobicistat) in order to achieve therapeutic levels and facilitate once daily dosing. As a consequence, clinicians must carefully review concomitant medications and navigate potential drug-drug interactions mediated through potent inhibition of cytochrome P450 3A enzymes by ritonavir and cobicistat.

Cobicistat: Review of a Pharmacokinetic Enhancer for HIV Infection.

PURPOSE: This article reviews the clinical pharmacology, pharmacodynamic and pharmacokinetic (PK) properties, clinical efficacy and tolerability, drug interactions, and dosing and administration of cobicistat. METHODS: Searches of MEDLINE and International Pharmaceutical Abstracts from 1964 to February 2015 were conducted using the search terms cobicistat and GS-9350. Relevant information was extracted from the identified clinical trials and review articles. Abstracts from the Conference on Retroviruses and Opportunistic Infections (2014-2015) and the Interscience Conference on Antimicrobial Agents and Chemotherapy (2013-2014) were also searched. FINDINGS: Cobicistat is a PK enhancer lacking antiviral activity that, via selective cytochrome P-450 (CYP) 3A inhibition, inhibits the metabolism of certain antiretroviral medications and is used for prolonging their effect. Cobicistat has been studied as a booster of elvitegravir, a second-generation integrase inhibitor, and of the protease inhibitors atazanavir and darunavir. Data on its clinical efficacy and tolerability have been presented in 2 Phase II trials and in 9 Phase III trials, which reported durable efficacy in terms of achievement of sustained suppression of HIV-1 RNA levels to <50 copies/mL for at least 48 weeks. Cobicistat was generally well-tolerated in these studies. Cobicistat may increase serum creatinine levels via the inhibition of proximal renal tubular cell transporters and thus reduce estimated glomerular filtration rate, although it does not appear to affect actual glomerular filtration rate. Given the potent CYP3A inhibition by cobicistat, its coadministration with drugs metabolized by CYP3A may result in increased plasma concentrations of such agents. Moreover, as cobicistat is metabolized predominantly by CYP3A, plasma concentrations may increase or decrease on coadministration with CYP3A inhibitors or inducers, respectively. IMPLICATIONS: With potent durability through 48 weeks, a tolerability profile comparable to other first- and second-line antiretroviral therapies, and a convenient dosing schedule with low daily pill burden in fixed-dose combination tablets, cobicistat is a potential addition to the management of HIV infection as a PK enhancer. However, the effects of cobicistat on serum creatinine and its considerable drug-interaction potential may warrant additional monitoring.

An Elective Course on Antimicrobial Stewardship.

OBJECTIVE: To implement an antimicrobial stewardship (AS) elective course for second-year and third-year pharmacy students and to assess its impact on students' perceptions regarding the application of AS principles. DESIGN: A 2-credit elective course focusing on principles of AS incorporated prelecture didactic recordings with primary literature and guideline-based reading assignments, in-class active-learning group work and student-led presentations, and student-generated examination items. ASSESSMENT: Perceptions were assessed by precourse and postcourse survey items. Graded course assessments included completion of preclass assignments (readings, prerecorded lecture and writing assessment items), in-class active participation and group presentations, a midpoint examination, and a final examination. CONCLUSION: An AS-themed elective course in a doctor of pharmacy curriculum incorporating preclass, self-directed learning and in-class group-based active-learning strategies positively impacted students' perceived understanding of AS strategies.

Cost Reduction of Inhaled Tobramycin by Use of Preservative-Free Intravenous Tobramycin Given via Inhalation.

This study evaluates drug cost outcomes related to automatic therapeutic substitution of branded tobramycin solution for inhalation (TOBI(®)) with inhaled generic preservative-free intravenous tobramycin (PFIT). A retrospective single-center evaluation of inhaled tobramycin use from 2008 through 2012 was performed. Number of doses dispensed and acquisition costs were obtained. Hourly wage data was acquired, pharmacy production costs were estimated and total cost-savings calculated. Days of therapy (DOTs) were determined for each year. Quality assurance and safety data was collected. In 2008, TOBI(®) drug costs and doses dispensed were $118,665 and 1769, respectively. Following implementation of the interchange in May 2009, TOBI(®) utilization ceased. PFIT costs in 2010 through 2012 averaged $34,775 annually and TOBI(®) cost-avoidance exceeded $94,000 annually when accounting for pharmacy production costs, which were determined to be at most $5.28 per dose. The maximum estimated pharmacy production cost ranged from $8812 to $11,299 annually. PFIT doses dispensed exceeded 1650 each year and annual DOTs ranged from 815 to 1069. The 40-month savings were calculated to be $374,706. Quality assurance and safety data identified one patient who refused PFIT due to odor complaints and one patient who was inappropriately administered a dose orally. Therapeutic substitution of TOBI(®) with PFIT can produce immediate and sustained savings with an acceptable safety profile.

Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline.

Effectiveness of pre-operative cefazolin in obese patients.

BACKGROUND: Cefazolin remains the preferred preoperative antibiotic for the majority of surgical procedures. However, outcome evidence supporting current dosing recommendations for pre-operative prophylaxis is scarce, particularly for obese patients. With more than 33% of adults in the United States classified as obese, it is crucial that we determine the correct dosing regimen in order to maximize the potential to prevent surgical site infections (SSIs). The purpose of this study was to evaluate whether surgical prophylaxis with cefazolin 2 g, as recommended by practice guidelines, is as effective in preventing SSIs in obese as compared to non-obese patients. METHODS: In retrospective fashion, data were collected from the electronic medical records of patients who received 2 g of cefazolin preoperatively during a 13-mo period. Patients who met the inclusion criteria were allocated to an obese (n=99) and non-obese (n=96) group according to body mass index (BMI). Charts were reviewed for identification of SSIs as defined by the U.S. Centers for Disease Control and Prevention. For the primary outcome, the numbers of SSIs in the two groups were compared using the Pearson χ(2) test. RESULTS: Patient characteristics were similar in the two groups with the expected exception of weight (mean 90 vs. 110 kg; p<0.001) and BMI (27 vs. 35 kg/m(2); p<0.001). The highest patient weight was 182 kg with a BMI of 55 kg/m(2). The most common surgical service was orthopedics/hand, accounting for 35% of patients. No significant difference was found in the number of SSIs in the two groups (7 vs. 5; p=0.56). No differences between weight and BMI were seen in patients with or without a SSI. CONCLUSIONS: Obese patients may continue to receive 2 g of cefazolin preoperatively until large-scale controlled trials show differently.

Tedizolid: a new oxazolidinone antimicrobial.

PURPOSE: The mechanism of action, pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of an investigational second-generation oxazolidinone are reviewed. SUMMARY: Tedizolid is a protein synthesis inhibitor in clinical development for the treatment of gram-positive infections. Similar to linezolid, tedizolid works by binding to the 23S ribosomal RNA of the 50S subunit, thereby preventing the formation of the 70S initiation complex and inhibiting protein synthesis. Tedizolid has demonstrated potent in vitro activity against multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and vancomycin-resistant enterococci (VRE), including some linezolid-resistant strains. Tedizolid has a favorable pharmacokinetic profile that allows for once-daily dosing and easy i.v.-to-oral conversion. Unlike linezolid, tedizolid has not been shown to interact with serotonergic agents in clinical studies. Two Phase III studies in patients with acute bacterial skin and skin structure infections have demonstrated the noninferiority of 6 days of tedizolid therapy (200 mg i.v. or orally once daily) relative to 10 days of linezolid therapy. In clinical trials to date, overall rates of treatment-related adverse effects with linezolid and tedizolid were comparable (40.8% versus 43.3%), with nausea being the most commonly reported adverse effect associated with tedizolid use (16% of patients). Planned studies will investigate tedizolid's potential role in the treatment of community-acquired bacterial pneumonia, hospital-acquired/ventilator-associated bacterial pneumonia, and bacteremia. CONCLUSION: Tedizolid is an investigational oxazolidinone antibiotic for the treatment of multidrug-resistant gram-positive pathogens such as MRSA, Streptococcus pneumoniae, and VRE, including some linezolid-resistant strains.

Penicillin skin testing: potential implications for antimicrobial stewardship.

As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred ß-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a ß-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test.