Use of Cumulative Assessments in U.S. Schools and Colleges of Pharmacy.

The Accreditation Council of Pharmacy Education (ACPE) has taken a strong stance on assessment in pharmacy education. One available assessment tool is cumulative assessments, which may be administered at various points in the curriculum. This article presents the results of a survey of U.S. schools of pharmacy regarding the use of cumulative assessments within their curriculum. A 20-question survey tool was emailed to 125 schools of pharmacy. A total of 105 out of 125 schools participated (response rate 84%). Of these, 52 schools currently have a cumulative assessment program; 18 have one cumulative exam prior to advanced pharmacy practice experiences (APPEs); 19 have a cumulative exam every didactic year; and seven have accumulative exams every semester, except during APPEs (n = 44). Increased faculty workload emerged as the top challenge faced by schools that have implemented a cumulative assessment program. Eighteen schools indicated that no outcomes are measured to determine the utility of the cumulative assessment. From these results, it appears that almost half of participating U.S. schools have implemented a cumulative assessment plan. However, it is apparent that more research needs to be done to determine which outcomes are expected to improve with the implementation of such an assessment plan.

Antibiotic dosing in cirrhosis.

PURPOSE: Published evidence regarding the influence of cirrhosis on the clinical pharmacokinetics of antibacterial agents is reviewed; dosing recommendations and a decision algorithm are provided. SUMMARY: A systematic PubMed search (1960-2013) was conducted to identify literature pertaining to the use of antibacterials with hepatobiliary clearance in adult patients with cirrhosis. Clinical drug databases, conference abstracts, and package inserts were also reviewed for pertinent information. Twenty-two antibiotics that undergo hepatic or mixed renal-hepatobiliary clearance were identified. Overall, published pharmacokinetic data to guide antibiotic dosing in adults with cirrhosis are sparse, and many relevant studies were conducted before wide adoption of the Child-Pugh method for classifying the severity of cirrhosis. Dose adjustments should be considered in the setting of decompensated liver disease, particularly with antibiotics that undergo phase I metabolism, have high protein binding, or are associated with a high frequency of hepatotoxicity or other concentration-dependent toxicities. Individualization of dosing regimens should take into account a number of variables: the intent of therapy (treatment versus prophylaxis); the duration of therapy; the site and severity of infection; the degree of organ dysfunction, as indicated by Child-Pugh class; the patient's immune status, weight, and fluid status; and the pharmacokinetic and pharmacodynamic properties of the antibacterial agents under consideration. CONCLUSION: Cirrhosis has multiple effects on the disposition of a wide range of antibacterial agents. Appropriate antibiotic therapy selection and individualized dosing can contribute to optimal clinical outcomes while decreasing the risk of hepatotoxicity.

Managing an outpatient parenteral antibiotic therapy team: challenges and solutions.

Outpatient parenteral antimicrobial therapy (OPAT) programs should strive to deliver safe, cost effective, and high quality care. One of the keys to developing and sustaining a high quality OPAT program is to understand the common challenges or barriers to OPAT delivery. We review the most common challenges to starting and managing an OPAT program and give practical advice on addressing these issues.

Evaluation of the treatment of vancomycin-resistant enterococcal urinary tract infections in a large academic medical center.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are a common cause of nosocomial urinary tract infections (UTIs) among hospitalized patients. Clinicians need to differentiate between VRE-associated urinary colonization, asymptomatic bacteriuria, and UTIs to determine the need for treatment and length of therapy. OBJECTIVE: To characterize the diagnosis and management of VRE from urinary sources, including compliance with institutional treatment guidelines, and identify risk factors associated with clinical failure. METHODS: We performed a retrospective, single-center, cohort study among patients with VRE-positive cultures from urinary sources over a 3-year study period (July 2008-September 2011). Descriptive statistics were used to evaluate demographics, diagnostics, guideline compliance, pharmacotherapy, and outcomes. Risk factors associated with clinical failure were identified by multivariate logistic regression analysis. RESULTS: Two hundred sixty-nine distinct episodes of VRE met inclusion criteria among 252 patients. Forty-seven percent and 77% of episodes occurred in patients admitted to an intensive care unit and hospitalized for 7 or more days, respectively. Fifty-eight percent of the episodes were classified as asymptomatic bacteriuria or colonization. Compliance with institutional treatment guidelines for the appropriate drug, dose, and duration occurred in approximately 70% of the cases. Among noncompliant cases (n = 83), 48 (58%) were overtreated, and 35 (42%) were undertreated. Clinical failure among all cases was common, including mortality (17.1%). Factors independently associated with clinical failure determined on multivariate analysis included weight 100 kg or more (OR 5.30; 95% CI 1.42-12.21; p = 0.014), renal disease (OR 2.57; 95% CI 1.02-6.47; p = 0.048), indwelling catheter (OR 4.62; 95% CI 1.05-18.24; p = 0.046), and VRE bloodstream infection (OR 15.71; 95% CI 2.9-128.7; p < 0 .001). CONCLUSIONS: Improved education is needed to minimize cases of overtreatment and undertreatment of VRE-associated UTIs and decrease inappropriate drug-related costs and clinical failure rates. Risk factors for clinical failure can be used to risk stratify VRE-associated UTIs and further guide treatment decisions.

Risk factors for clinical failure in patients hospitalized with cellulitis and cutaneous abscess.

OBJECTIVE: The objective of this study was to evaluate clinical outcomes and risk factors associated with clinical failure in patients hospitalized with cellulitis with or without abscess. METHODS: We performed a retrospective cohort study among adults admitted for cellulitis/cutaneous abscess from July 1, 2009 through June 30, 2010. Binary univariate and multivariate logistic regression analyses were performed to identify risk factors for clinical failure among evaluable patients. RESULTS: A total of 210 cases met inclusion criteria. Among 106 evaluable cases, clinical failure occurred in 34 (32.1%) patients. Weight over 100 kg (Odds ratio [OR] = 5.20, P = 0.01), body mass index (BMI) ≥40 (OR 4.10, P = 0.02), inadequate empiric antibiotic therapy (OR = 9.25, P < 0.01), recent antimicrobial therapy (OR = 2.98, P = 0.03), and lower end of antibiotic dosing per treatment guidelines upon discharge (OR = 3.64, P < 0.01) were independent risk factors for clinical failure. Further subgroup analysis demonstrated that morbidly obese patients were at higher risk for clinical failure if they were discharged on a low oral dose of clindamycin or trimethoprim/sulfamethoxazole (P = 0.002). CONCLUSION: Inappropriate antimicrobial selection and dosing may adversely affect clinical outcomes among patients with cellulitis/cutaneous abscess. Obese individuals may be at particular risk for clinical failure secondary to inadequate dosing of antimicrobial therapy.

Impact of a multidisciplinary team review of potential outpatient parenteral antimicrobial therapy prior to discharge from an academic medical center.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is frequently prescribed at hospital discharge, often without infectious diseases (ID) clinician oversight. We developed a multidisciplinary team, including an ID pharmacist, to review OPAT care plans at hospital discharge to improve safety, clinical efficacy, practicality, and appropriateness of the proposed antimicrobial regimen. OBJECTIVE: To evaluate the impact of the OPAT team on regimen safety, efficacy, and complexity; calculate the economic benefits of the service by avoiding hospital discharge delay, central venous catheter placement, or need for OPAT; and evaluate the discharge environment among OPAT referrals. METHODS: In an observational design, we analyzed the impact of an OPAT team from July 2009 through June 2010 at a large academic tertiary care hospital. All patients with plans for continued parenteral therapy after discharge referred to the OPAT team were included in the analysis. Patients were excluded if OPAT was cancelled prior to processing of the referral. RESULTS: During the 1-year study period, 569 of 644 consecutive referrals to the OPAT team met inclusion criteria, resulting in 494 OPAT courses. Interventions by an ID pharmacist were made for safety (56%), regimen complexity (41%), and efficacy (29%). Lack of formal ID physician consultation resulted in more interventions for safety (64% vs 48%, p < 0.001) and efficacy (36% vs 21%, p < 0.001). Discharge delays were avoided for 35 referrals, resulting in 228 hospital days avoided and approximately $366,000 in hospital bed cost savings. Use of OPAT was avoided in 75 referrals (13.2%), preventing central venous catheter placement in 48 patients (8.4%), resulting in an additional $58,080 in cost savings. CONCLUSIONS: The OPAT team optimized safety, efficacy, and convenience of OPAT while providing substantial cost savings. Further studies are needed to confirm the program's cost-effectiveness.

Vancomycin-resistant enterococcal urinary tract infections.

Enterococci are a common cause of urinary tract infections (UTIs) among hospitalized patients. The rising prevalence of vancomycin-resistant enterococci (VRE) is of particular concern within many institutions because of its association with increased mortality and health care costs, as well as limited treatment options. Clinicians need to differentiate between VRE-associated urinary colonization, asymptomatic bacteriuria, and UTIs in order to determine the need for treatment, optimal therapeutic options, and length of therapy. Unnecessary use of antibiotics in patients simply colonized and not infected with VRE in the urine has become a large problem in both hospitals and long-term care facilities. A PubMed-MEDLINE search was conducted to identify all English-language literature published between January 1975 and March 2010 in order to summarize diagnostic criteria and treatment options for VRE UTIs. Several antimicrobials are discussed, with the specific focus on those with the potential to treat VRE UTIs and susceptibility patterns of VRE from urinary sources: ampicillin, amoxicillin, daptomycin, doxycycline, fosfomycin, imipenem-cilastatin, linezolid, nitrofurantoin, penicillin, piperacillin, quinupristin-dalfopristin, tetracycline, and tigecycline. Recommendations for empiric treatment of enterococcal UTIs and definitive treatment of VRE UTIs, including an evidence-based treatment algorithm, are proposed. Ampicillin generally is considered the drug of choice for ampicillin-susceptible enterococcal UTIs, including VRE. Nitrofurantoin, fosfomycin, and doxycycline have intrinsic activity against enterococci, including VRE, and are possible oral options for VRE cystitis. Linezolid and daptomycin should be reserved for confirmed or suspected upper and/or bacteremic VRE UTIs among ampicillin-resistant strains. Use of other antimicrobials, such as quinupristin-dalfopristin and tigecycline, should be evaluated on a case-by-case basis due to concerns of toxicity, resistance, and insufficient supportive data. Additional clinical data are needed to determine the optimal management and duration of therapy for VRE UTIs.

Golimumab: Review of the efficacy and tolerability of a recently approved tumor necrosis factor-α inhibitor.

BACKGROUND: Golimumab (GLM) is a tumor necrosis factor-α (TNF-α) inhibitor that was approved in the United States in 2009 for use with methotrexate (MTX) in adults with moderate to severe active rheumatoid arthritis (RA), and with or without MTX or other non-biologic disease-modifying antirheumatic drugs in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS). GLM is administered as a 50-mg subcutaneous injection once a month. OBJECTIVES: The goals of this article were to review the current literature on GLM and to provide recommendations for the use of GLM based on the published information. METHODS: The PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, International Pharmaceutical Abstracts, and other databases, as well as the Web sites for the American College of Rheumatology (ACR) and the European Union League Against Rheumatism, were searched for relevant articles published in English between the inception of the databases through April 2010. Search terms included golimumab and CNTO 148. Pharmacologic, pharmacokinetic, clinical, outcomes, and economic studies as well as meta-analyses, case reports, and select abstracts were eligible for inclusion. Review articles on GLM were not used except to identify other primary papers. RESULTS: Seven clinical studies were identified and used to evaluate the efficacy and tolerability of GLM: 5 in patients with RA (4 subcutaneous administration and 1 intravenous administration), 1 in patients with PsA (subcutaneous), and 1 in patients with AS (subcutaneous). In MTX-naive patients with RA, the number of patients satisfying the ACR20 response criteria (>20% improvement in ACR response rate) at 24 weeks was significantly higher for the GLM + MTX groups than for the MTX-only groups (62% vs 49%, respectively; P < 0.05). In patients with active RA despite MTX therapy, ACR20 responses at 14 to 16 weeks were significantly higher for the combined GLM + MTX groups than for the MTX groups (50%-79% vs 33%-37%, respectively; P < 0.001). GLM was more effective than placebo, both with and without MTX, in patients with RA and a history of treatment with 1 or 2 TNF-α inhibitors (ACR20 at 14 weeks, 35%-37% vs 18%, respectively; P < 0.001). Studies of other TNF-α inhibitors reported ACR20 responses in 53% to 59% of patients with active RA at 24 weeks. GLM was also more effective than placebo at 24 weeks in patients with PsA (ACR20, 52%-61% vs 12%, respectively; P < 0.001) (ASAS40 [40% improvement based on Assessment in Ankylosing Spondylitis International Working Group criteria], 44%-54% vs 15%, respectively; P < 0.001). Studies of other TNF-α inhibitors reported ACR20 responses at 24 weeks in 55% to 57% of patients with PsA and ASAS40 responses in 46% to 47% of patients with AS. The incidence of any adverse effect appeared to be comparable in the GLM (61.2%-93.9%) and placebo groups (59.3%-85.3%), but withdrawals because of adverse effects were higher in the GLM groups (0%-12.1%) than in the placebo groups (0%-5.9%). The incidence of serious infections was comparable for GLM (0%-4.4%) and placebo (0.8%-3.5%). The most frequently reported adverse effects in the GLM groups were injection-site reactions (2.7%-37.1%), nausea (2.7%-22.9%), headache (3.8%-21.2%), nasopharyngitis (1.9%-15.0%), and upper respiratory tract infections (5.7%-13.8%). CONCLUSIONS: Based on the results of the studies included in this review, GLM appeared to be more effective than placebo in patients with RA, PsA, or AS. Clinical studies have not directly compared GLM with other TNF-α inhibitors. However, according to the available efficacy and tolerability data, GLM should be considered as the first or second TNF-α inhibitor for the treatment of PsA or AS and as the second or possibly first TNF-α inhibitor in combination with MTX for the treatment of RA.

Lessons Learned from Surveillance of Antimicrobial Susceptibilities of Pseudomonas aeruginosa at a Large Academic Medical Center.

This research report assessed the differences in resistance rates and antimicrobial usage-versus-susceptibility relationships of Pseudomonas aeruginosa found in various hospital patient care areas. A simplified case control study was also performed to identify patient-specific risk factors associated with cefepime-resistant P. aeruginosa isolates. Last, we determined the consequence of combining mucoid and non-mucoid derived antimicrobial susceptibilities of P.aeruginosa into hospital antibiograms. Overall, susceptibility rates remained lower in the intensive care units (ICUs) compared to the non-ICU patient care areas, except for cefepime over the last time period. Cefepime utilization and antimicrobial-resistance rates among P. aeruginosa isolates had a significant relationship. Decreased meropenem exposure was associated with lower resistance rates relative to cefepime. Risk factors independently associated with cefepime-resistant P. aeruginosa were structural lung disease, ICU admission, recent third generation cephalosporin use, frequent hospital admission and non-urine isolates. Large and statistically significant differences were observed between non-mucoid and combined percent susceptibility data for aminoglycosides. To control antimicrobial resistance and optimize initial empiric antimicrobial therapy, antimicrobial susceptibility and utilization patterns in specific patient care areas should be monitored and risk factors for antimicrobial resistance should be assessed. Mucoid strains of P. aeruginosa should not be included into antimicrobial susceptibility data as this may underestimate activity of most antipseudomonal agents.

Pharmacokinetics of mycophenolic acid and metabolites in diabetic kidney transplant recipients.

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is an immunosuppressive agent commonly used after organ transplantation. Because diabetes mellitus may affect disposition of pharmacologic agents, we investigated the influence of diabetes on the pharmacokinetics of MPA, unbound MPA (fMPA) and its phenyl and acyl glucuronide metabolites (MPAG and AcMPAG respectively). The study included 13 diabetic and 11 nondiabetic, stable, kidney-transplant recipients who were receiving a triple maintenance immunosuppressive regimen. Serial plasma samples were obtained predose and at regular intervals for 12 hours. Gastric emptying was assessed using an acetaminophen absorption test and glomerular filtration rate was estimated using iohexol clearance. Treatment groups were well matched. The time to maximum concentration (Tmax) of MPA was 86.4 +/- 41.4 minutes versus 52.8 +/- 31.8 minutes in D and ND patients respectively (P = 0.04) indicating a delay in MMF absorption. Neither the maximum MPA concentration nor the 0- to 12-hour area under the concentration-time curve were different. All parameters derived for fMPA and the MPA metabolites were comparable between the 2 groups, except for the metabolite ratio of MPAG and AcMPAG, which was higher for diabetic patients (P = 0.03). Delayed gastric emptying seemed to have reduced the initial rate but not the extent of MPA absorption in diabetic patients. The profiles of fMPA were similar in both patient groups. With the exception of metabolite concentration ratio, none of the other parameters associated with MPA metabolism were different between the 2 groups.