Overview of Antibiotic Prophylaxis in Orthopaedic and Cardiac Procedures.

Antibiotic prophylaxis (AP) in surgical procedures is commonly used to prevent infections that may occur after operations. There are multiple factors that can contribute to increased risk of postsurgical complications that include prolonged hospitalization, reoperation, and readmissions. One of the strategies of decreasing the risk of bacterial contamination and developing infections is preprocedural antibiotic administration. When selecting an appropriate antibiotic, it is important to take into account surgery type and patient's characteristics which would also impact timing of administration and prophylaxis duration. Although surgical AP is significant for avoiding bacterial complications, it is also associated with some drawbacks such as increased antibiotic resistance and development of adverse reactions. Therefore, it is important to assess risks and benefits and select the most appropriate antibiotic regimen before initiating AP.

Osteoporosis: A Review of Novel Agents.

Osteoporosis is a bone disease characterized by decreased new bone formation, increased bone resorption, or both processes occurring simultaneously. This disease affects more than 10 million individuals older than 50 years in the United States. If this disease is left untreated, it can result in fragility fractures, which are currently seen in more than 1 million people in the United States. New agents have been developed to add to the list of treatment options that can be used to treat this disease. This article summarizes two specific agents that were approved by the Food and Drug Administration within the last few years: abaloparatide (Tymlos) and romosozumab (Evenity). This article also highlights the crucial role that nursing staff may play in the management of osteoporosis.

Newly Approved Antimicrobials.

In recent years, government-backed policies have promoted the development of new antimicrobials to combat increases in antibiotic-resistant organisms. This article summarizes the 10 new antibacterial agents to be approved in the last 5 years.

Treatment of Hepatitis C Virus: An Update on Medications and Patient Education.

The treatment of hepatitis C virus (HCV) has evolved significantly, marked by the approval of combination, direct-acting antiviral medications, which have improved the tolerability and efficacy of therapy. As the number of patients engaged in HCV treatment increases, it is important that all members of the healthcare team remain current on treatment options and equipped with the knowledge to educate patients. Nursing staff play a critical role in understanding the role of new medications in treatment, significant drug interactions, and patient counseling points on administration, potential adverse reactions, and the importance of adherence.

Time Requirements for Acquisition of Hepatitis C Virus Therapy in HIV/HCV Coinfected Patients.

Background: The process of obtaining approval for hepatitis C virus (HCV) treatment may be time consuming and complicated due to prior authorizations and the need to appeal denials. Pharmacists are poised to play a critical role in the acquisition and management of oral direct acting antivirals (DAAs) for the treatment of HCV infection; however, the time expended in this activity requires assessment. Objective: The objective of this study was to assess time expenditures by pharmacists to acquire DAAs for HCV therapy. Methods: Patients were enrolled in the Northwestern University Viral Hepatitis Registry, a prospective, observational cohort of ambulatory, adult patients living with human immunodeficiency virus (HIV) coinfected with chronic hepatitis B and/or C virus, and recruited since 2013 from the Infectious Disease Center at Northwestern Memorial Hospital, Chicago, IL. Patients were included in the current study if they were referred to the pharmacist for HCV DAA acquisition, drug-drug interaction management, and adherence counseling between February 1, 2014, and April 30, 2015. Patient demographics, virus-specific characteristics, and time required to secure HCV DAA treatment, counsel patients, and follow-up therapy were collected. Results: Among 54 HIV/HCV coinfected patients referred for treatment, all eventually received approval for DAA therapy. However, 87% (n = 47) required prior authorization. Pharmacists dedicated 2.1 hours/patient (interquartile range 1.5-2.8 hours; range 0.75-6.5 hours) to manage DAA therapy. Conclusion: Successful acquisition of HCV DAA therapy relied heavily on pharmacist effort, reflecting the vital role that pharmacists play in this process. Dedicated resources for medication access should be considered to ensure timely DAA acquisition.

Analysis of an Infectious Diseases Pharmacist on Call Pager Program to Inform Educational Efforts.

Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent-related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians.

A Review of Antiviral and Antifungal Use and Safety during Pregnancy.

Antiviral and antifungal use in pregnancy presents challenges because of the paucity of clinical and safety data for many agents in these classes. If untreated, viral and fungal infections can have deleterious effects on both maternal and fetal health. Understanding the use and risks of these medications in pregnancy is vital to provide appropriate care. This article reviews the current literature for the use of antiviral and antifungals, the pharmacokinetics of these agents, and their safety in pregnancy.

Impact of hyperglycemia on outcomes of patients with Pseudomonas aeruginosa bacteremia.

Bacteremia caused by Pseudomonas aeruginosa is associated with significant morbidity and mortality. In other bacterial infections, hyperglycemia has been identified as a risk factor for mortality in nondiabetic patients. The objective of this study was to determine the impact of early hyperglycemia on outcomes in diabetic and nondiabetic patients with P. aeruginosa bacteremia. A retrospective cohort study was performed in adult patients (≥18 years old) with P. aeruginosa bacteremia. Patients received at least 1 drug empirically to which the isolate was susceptible in vitro. Classification and regression tree analysis was used to determine the threshold breakpoint for average blood glucose concentration within 48 hours of positive blood culture (BG48). Logistic regression was used to explore independent risk factors for 30-day mortality. A total of 176 bacteremia episodes were identified; patients in 66 episodes were diabetic. Diabetic patients had higher BG48 (165.2±64.8 mg/dL versus 123.7±31.5 mg/dL, P<0.001) and lower 30-day mortality (10.7% versus 22.7%, P=0.046) than nondiabetic patients. Multivariate regression revealed 30-day mortality in nondiabetic patients was associated with Acute Physiology and Chronic Health Evaluation II score (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.0-1.2) and BG48 >168 mg/dL (OR 6.3; 95% CI 1.7-23.3). However, blood glucose concentration was not identified as an independent risk factor for mortality in diabetic patients by multivariate regression analysis. Hyperglycemia did not appear to affect outcomes in diabetic patients, whereas nondiabetic patients had a higher risk of mortality from P. aeruginosa bacteremia. Prospective studies evaluating the impact of glycemic control in these patients are needed.

Outcomes and Risk Factors for Mortality among Patients Treated with Carbapenems for Klebsiella spp. Bacteremia.

BACKGROUND: Extensive dissemination of carbapenemase-producing Enterobacteriaceae has led to increased resistance among Klebsiella species. Carbapenems are used as a last resort against resistant pathogens, but carbapenemase production can lead to therapy failure. Identification of risk factors for mortality and assessment of current susceptibility breakpoints are valuable for improving patient outcomes. AIM: The objective of this study was to evaluate outcomes and risk factors for mortality among patients treated with carbapenems for Klebsiella spp. bacteremia. METHODS: Patients hospitalized between 2006 and 2012 with blood cultures positive for Klebsiella spp. who received ≥ 48 hours of carbapenem treatment within 72 hours of positive culture were included in this retrospective study. Patient data were retrieved from electronic medical records. Multivariate logistic regression was used to identify risk factors for 30-day hospital mortality. RESULTS: One hundred seven patients were included. The mean patient age was 61.5 years and the median APACHE II score was 13 ± 6.2. Overall, 30-day hospital mortality was 9.3%. After adjusting for confounding variables, 30-day mortality was associated with baseline APACHE II score (OR, 1.17; 95% CI, 1.01-1.35; P = 0.03), length of stay prior to index culture (OR, 1.03; 95% CI, 1.00-1.06; P = 0.04), and carbapenem non-susceptible (imipenem or meropenem MIC > 1 mg/L) infection (OR, 9.08; 95% CI, 1.17-70.51; P = 0.04). CONCLUSIONS: Baseline severity of illness and length of stay prior to culture were associated with 30-day mortality and should be considered when treating patients with Klebsiella bacteremia. These data support the change in carbapenem breakpoints for Klebsiella species.

In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy.

Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P = 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P = 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P = 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P = 0.04). In a matched analysis based on the risk factors identified (n = 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P = 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.

Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS.

Diarrhea is a common comorbidity present in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) who are treated with highly active antiretroviral therapy. With a multifactorial etiology, this diarrhea often becomes difficult to manage. In addition, some antiretrovirals are associated with chronic diarrhea, which potentially creates an adherence barrier to antiretrovirals and may ultimately affect treatment outcomes and future therapeutic options for HIV. A predominant type of diarrhea that develops in HIV patients has secretory characteristics, including increased secretion of chloride ions and water into the intestinal lumen. One proposed mechanism that may lead to this type of secretory diarrhea is explained by the activation of the cystic fibrosis transmembrane conductance regulator and calcium-activated chloride channels. Crofelemer is a novel antidiarrheal agent that works by inhibiting both of these channels. The efficacy and safety of crofelemer has been evaluated in clinical trials for various types of secretory diarrhea, including cholera-related and acute infectious diarrhea. More recently, crofelemer was approved by the US Food and Drug Administration for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Results from the ADVENT trial showed that crofelemer reduced symptoms of secretory diarrhea in HIV/AIDS patients. Because crofelemer is not systemically absorbed, this agent is well tolerated by patients, and in clinical trials it has been associated with minimal adverse events. Crofelemer has a unique mechanism of action, which may offer a more reliable treatment option for HIV patients who experience chronic secretory diarrhea from antiretroviral therapy.

Significant publications on infectious diseases pharmacotherapy in 2011.

PURPOSE: Important articles on topics pertinent to infectious diseases (ID) pharmacotherapy published in prominent peer-reviewed journals in 2011 are summarized. SUMMARY: Pharmacists, physicians, and researchers from the Houston Infectious Diseases Network were asked to nominate articles published in 2011 that they perceived as having a significant impact on the field of ID pharmacotherapy. The resulting list, comprising 10 articles related to human immunodeficiency virus (HIV) disease or acquired immune deficiency syndrome (AIDS) and 38 articles on a broad range of other ID-related topics, was sent to members of the Society of Infectious Diseases Pharmacists (SIDP) for evaluation via an Internet survey. The survey participants were asked to select 10 articles from the list of general ID articles and 1 article from the HIV- or AIDS-related articles that they viewed as having the most impact on the field. Of the 328 SIDP members surveyed, 120 (37%) ranked the non-HIV-related papers and 55 (17%) ranked the HIV-related papers. The 12 highest-ranked items-including 3 guidelines-are summarized here. CONCLUSION: Due to the increasing number of articles published each year, it is difficult to maintain a current knowledge of significant publications in the field of ID pharmacotherapy. This review of the key articles in 2011 may be helpful to the nonspecialist clinician by lessening this burden.

Evaluation of a daptomycin dose-optimization protocol.

PURPOSE: The impact of an institutional protocol intended to improve daptomycin dosing for vancomycin-resistant enterococci (VRE) infections was investigated. SUMMARY: Daptomycin has been reported to have optimal activity against VRE at weight-based doses of ≥8 mg/kg. As part of an initiative to optimize daptomycin dosing for all indications and regimens, a large medical center implemented a protocol restricting daptomycin prescribing to infectious-diseases specialists and a nomogram recommending elevated daptomycin dosing for all VRE infections, with baseline and weekly creatinine phosphokinase (CPK) determinations during daptomycin therapy. Protocol implementation was preceded by educational efforts targeting medical and pharmacy staff. A retrospective study was conducted to compare prescribing behavior and safety monitoring rates during the 12 months before and 16 months after protocol implementation; the baseline characteristics of the preimplementation cohort (n = 95) and postimplementation cohort (n = 72) were similar. The mean daptomycin doses before and after the protocol was implemented were 453 mg (6.1 mg/kg) and 576 mg (7.6 mg/kg), respectively. After protocol implementation, there were significant increases in the proportion of patients who received doses of ≥8 mg/kg (52% in the postimplementation period versus 4% in the preimplementation period, p < 0.05) and in the rate of baseline CPK assessment (64% versus 43%, p < 0.05). CONCLUSION: Implementation of a daptomycin dosing protocol by a multidisciplinary antimicrobial stewardship team optimized treatment by increasing the mean dose of daptomycin administered to hospitalized adults with non-urinary VRE infections and improved the rate of safety monitoring.

A model to predict mortality following Pseudomonas aeruginosa bacteremia.

Infections caused by Pseudomonas aeruginosa are associated with significant mortality. Existing mathematical models identifying mortality risk factors lack validation. We developed and validated a model to predict mortality in patients with P. aeruginosa bacteremia. Risk factors for 30-day mortality were examined through multivariate logistic regression in 114 patients. Independent predictors of mortality included isolation of a multidrug-resistant strain, APACHE II ≥ 23, and age ≥ 65 years. Clonality was assessed for multidrug-resistant isolates. Predicted probability of 30-day mortality was validated in 49 patients, after conditioning the model by the identified risk factors. The patients were split into 'high-risk' and 'low-risk' groups based on model-predicted mortality; the observed/expected ratios were 1.21 and 1.92, respectively. Our model was reasonable in predicting 30-day mortality in patients with P. aeruginosa bacteremia. Our results may be useful for developing strategies to reduce mortality attributed to P. aeruginosa.

Crofelemer for the treatment of secretory diarrhea.

Secretory diarrhea is a leading cause of morbidity and mortality worldwide. Crofelemer is a first-in-class antidiarrheal agent that simultaneously targets two distinct channels, the cystic fibrosis conductance regulator and calcium-activated chloride channel, responsible for chloride and fluid secretion in the GI tract. Crofelemer is a novel compound extracted from the stem bark latex of the Croton lechleri tree found in the western Amazonian region of South America. There is little to no systemic absorption of crofelemer when given orally and studies have shown minimal toxicity beyond mild gastrointestinal effects. In studies in diarrheal illness associated with primarily a secretory component, such as cholera, travelers' diarrhea and acute infectious diarrhea, crofelemer has shown improvements in stool consistency and duration of symptoms. Less clear, but interesting, results have been observed in other diarrheal diseases associated with a mixed pathology, including diarrhea in patients with HIV and diarrhea-predominant irritable bowel syndrome.

Improving patient care through implementation of an antimicrobial stewardship program.

PURPOSE: The implementation of an antimicrobial stewardship program at a health system is described. SUMMARY: In 2008, the Center for Antimicrobial Stewardship and Epidemiology (CASE) was formed at St. Luke's Episcopal Hospital (SLEH) to improve the quality of care for patients as it related to antimicrobial therapy. The charter of CASE contained specific aims for improving patient care, furthering clinical research, and training the next generation of clinical infectious diseases pharmacists. The CASE team consists of at least two infectious diseases pharmacists and one physician (the medical director) who provide direct oversight for antimicrobial utilization within the hospital. The CASE medical director, an infectious diseases physician, is responsible for overseeing the activities of the center. With the oversight of the CASE advisory board, the medical director develops and implements the antimicrobial stewardship and management policies for SLEH. Another key innovative feature of CASE is its extensive involvement in training new infectious diseases pharmacists and conducting research. CASE uses a model in which a clinical scenario or problem is identified, a research project is undertaken to further elucidate the problem, and policy changes are made to improve patient outcomes. The CASE team is supported by a CASE advisory board, a CASE research collaborative including university faculty, and a dedicated training program for pharmacy fellows, residents, and students. CONCLUSION: Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists.

Significant publications on infectious diseases pharmacotherapy in 2010.

PURPOSE: Important articles on topics pertinent to infectious diseases (ID) pharmacotherapy published in prominent peer-reviewed journals in 2010 are summarized. SUMMARY: At the end of 2010, pharmacists, physicians, and researchers in the Houston Infectious Diseases Network were asked to nominate articles published from January through December 2010 that they perceived as having a significant impact in the field of ID pharmacotherapy. The resulting list, comprising 27 articles relating to human immunodeficiency virus (HIV) disease or acquired immune deficiency syndrome (AIDS) and 52 articles on a broad range of other ID-related topics, was sent to members of the Society of Infectious Diseases Pharmacists (SIDP) for evaluation via an Internet survey. The survey participants were asked to select from the list 10 articles unrelated to HIV or AIDS and 1 HIV- or AIDS-related article that in their view had the most significant impact in the field. Of the 380 SIDP members surveyed, 105 (27.6%) ranked the non-HIV-related papers and 45 (11.8%) ranked the HIV-related papers. The 11 highest-ranked publications-including 2 articles presenting updated practice guidelines-are summarized here. CONCLUSION: Due to the increasing number of articles published each year, it is difficult to maintain a current knowledge of significant publications in the field of ID pharmacotherapy. This review of key publications in 2010 may be helpful to the nonspecialist clinician by lessening this burden.

Significant publications on infectious diseases pharmacotherapy in 2009.

PURPOSE: Significant publications on infectious diseases (ID) pharmacotherapy in 2009 are summarized. SUMMARY: On December 31, 2009, the Houston Infectious Diseases Network amassed a list of articles identified as having a significant impact on ID pharmacotherapy. Articles selected were published between January 1, 2009, and December 31, 2009, in prominent, peer-reviewed journals. Articles were selected based on their perceived potential impact on pharmacy practice in ID, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS). A list of 45 articles not related to HIV infection and 17 articles related to HIV infection was distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) via an Internet survey. Members were asked to select the 10 publications (from the list of 45 non-HIV-related articles) that they felt contributed most to ID pharmacotherapy and to select the single most significant publication from the list of 17 articles related to HIV or AIDS. Of the 531 SIDP members surveyed, 100 responded (18.8%). The top 10 articles (9 non-HIV-related and 1 HIV-related) identified from this survey are summarized in this article. Three of the top 10 articles selected from the non-HIV category included new or updated ID guidelines. Summaries of the top articles selected (9 non-HIV-related and 1 HIV-related) from this survey are included. CONCLUSION: Due to the growing number of articles published each year, it is difficult to maintain a current knowledge of significant publications in ID. This review of significant publications in ID pharmacotherapy can be helpful by lessening this burden.

Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections.

Use of nonsystemic antimicrobials with activity against enteropathogens is a promising approach for treatment of infectious diarrhea and other nonsystemic gastrointestinal infections. Rifaximin is approved by the US FDA for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients aged 12 years and older, and for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients aged 18 years or older. Rifaximin has been available in Italy since 1987 and overall is approved in 33 countries for various conditions, such as acute and chronic infections, bacterial diarrhea, HE, and pre- and postsurgical prophylaxis. There is accumulating evidence on the benefit of rifaximin for nonsystemic gastrointestinal infections. This article will serve as an update on rifaximin. The pharmacology and pharmacodynamics of rifaximin along with an updated review on the bacterial susceptibility to rifaximin will be presented. Finally, clinical trials with rifaximin for nonsystemic gastrointestinal indications will be updated.