Economic models for sustainable interprofessional education.

Limited information exists on funding models for interprofessional education (IPE) course delivery, even though potential savings from IPE could be gained in healthcare delivery efficiencies and patient safety. Unanticipated economic barriers to implementing an IPE curriculum across programs and schools in University settings can stymie or even end movement toward collaboration and sustainable culture change. Clarity among stakeholders, including institutional leadership, faculty, and students, is necessary to avoid confusion about IPE tuition costs and funds flow, given that IPE involves multiple schools and programs sharing space, time, faculty, and tuition dollars. In this paper, we consider three funding models for IPE: (a) Centralized (b) Blended, and (c) Decentralized. The strengths and challenges associated with each of these models are discussed. Beginning such a discussion will move us toward understanding the return on investment of IPE.

Professional and interprofessional differences in electronic health records use and recognition of safety issues in critically ill patients.

During interprofessional intensive care unit (ICU) rounds each member of the interprofessional team is responsible for gathering and interpreting information from the electronic health records (EHR) to facilitate effective team decision-making. This study was conducted to determine how each professional group reviews EHR data in preparation for rounds and their ability to identify patient safety issues. Twenty-five physicians, 29 nurses, and 20 pharmacists participated. Individual participants were given verbal and written sign-out and then asked to review a simulated record in our institution's EHR, which contained 14 patient safety items. After reviewing the chart, subjects presented the patient and the number of safety items recognised was recorded. About 40%, 30%, and 26% of safety issues were recognised by physicians, nurses, and pharmacists, respectively (p = 0.0006) and no item recognised 100% of the time. There was little overlap between the three groups with only 50% of items predicted to be recognised 100% of the time by the team. Differential recognition was associated with marked differences in EHR use, with only 3/152 EHR screens utilised by all three groups and the majority of screens used exclusively only by one group. There were significant and non-overlapping differences in individual profession recognition of patient safety issues in the EHR. Preferential identification of safety issues by certain professional groups may be attributed to differences in EHR use. Future studies will be needed to determine if shared decision-making during rounds can improve recognition of safety issues.

Frequency of outpatient antibiotic prescription on discharge to hospice care.

The use of antibiotics is common in hospice care despite limited evidence that it improves symptoms or quality of life. Patients receiving antibiotics upon discharge from a hospital may be more likely to continue use following transition to hospice care despite a shift in the goals of care. We quantified the frequency and characteristics for receiving a prescription for antibiotics on discharge from acute care to hospice care. This was a cross-sectional study among adult inpatients (≥18 years old) discharged to hospice care from Oregon Health & Science University (OHSU) from 1 January 2010 to 31 December 2012. Data were collected from an electronic data repository and from the Department of Care Management. Among 62,792 discharges, 845 (1.3%) patients were discharged directly to hospice care (60.0% home and 40.0% inpatient). Most patients discharged to hospice were >65 years old (50.9%) and male (54.6%) and had stayed in the hospital for ≤7 days (56.6%). The prevalence of antibiotic prescription upon discharge to hospice was 21.1%. Among patients discharged with an antibiotic prescription, 70.8% had a documented infection during their index admission. Among documented infections, 40.3% were bloodstream infections, septicemia, or endocarditis, and 38.9% were pneumonia. Independent risk factors for receiving an antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR]=7.00; 95% confidence interval [95% CI]=4.68 to 10.46), discharge to home hospice care (AOR=2.86; 95% CI=1.92 to 4.28), and having a cancer diagnosis (AOR=2.19; 95% CI=1.48 to 3.23). These data suggest that a high proportion of patients discharged from acute care to hospice care receive an antibiotic prescription upon discharge.

Variation in antibiotic susceptibility of uropathogens by age among ambulatory pediatric patients.

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001), while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.

Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study.

BACKGROUND: Epidemiologic studies of skin and soft tissue infections (SSTIs) depend upon accurate case identification. Our objective was to evaluate the positive predictive value (PPV) of electronic medical record data for identification of SSTIs in a primary care setting. METHODS: A validation study was conducted among primary care outpatients in an academic healthcare system. Encounters during four non-consecutive months in 2010 were included if any of the following were present in the electronic health record: International Classification of Diseases, Ninth Revision (ICD-9) code for an SSTI, Current Procedural Terminology (CPT) code for incision and drainage, or a positive wound culture. Detailed chart review was performed to establish presence and type of SSTI. PPVs and 95% confidence intervals (CI) were calculated among all encounters, initial encounters, and cellulitis/abscess cases. RESULTS: Of the 731 encounters included, 514 (70.3%) were initial encounters and 448 (61.3%) were cellulitis/abscess cases. When the presence of an ICD-9 code, CPT code, or positive culture was used to identify SSTIs, 617 encounters were true positives, yielding a PPV of 84.4% [95% CI: 81.8-87.0%]. The PPV for using ICD-9 codes alone to identify SSTIs was 90.7% [95 % CI: 88.5-92.9%]. For encounters with cellulitis/abscess codes, the PPV was 91.5% [95% CI: 88.9-94.1%]. CONCLUSIONS: ICD-9 codes may be used to retrospectively identify SSTIs with a high PPV. Broadening SSTI case identification with microbiology data and CPT codes attenuates the PPV. Further work is needed to estimate the sensitivity of this method.

Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common infections treated in ambulatory care settings, however the epidemiology differs by age and sex. The incidence of UTI is far greater in females than males, and infection in pediatric patients is more often due to anatomical abnormalities. The purpose of this research was to describe age- and sex-specific trends in antibiotic susceptibility to common urinary anti-infectives among urinary isolates of Escherichia coli from ambulatory primary care patients in a regional health maintenance organization. METHODS: Clinical microbiology data were collected for all urine cultures from patients with visits to primary care clinics in a regional health maintenance organization between 2005 and 2010. The first positive culture for E. coli tested for antibiotic susceptibilities per patient per year was included in the analysis dataset. The frequency of susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole (TMP/SMX) was calculated for male and female patients. The Cochrane-Mantel-Haenzel test was used to test for differences in age-stratified susceptibility to each antibiotic between males and females. RESULTS: A total of 43,493 E. coli isolates from 34,539 unique patients were identified for study inclusion. After stratifying by age, E. coli susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, and nitrofurantoin differed significantly between males and females. However, the magnitude of the differences was less than 10% for all strata except amoxicillin-clavulanate susceptibility in E. coli isolated from males age 18-64 compared to females of the same age. CONCLUSIONS: We did not observe clinically meaningful differences in antibiotic susceptibility to common urinary anti-infectives among E. coli isolated from males versus females. These data suggest that male sex alone should not be used as an indication for empiric use of second-line broad-spectrum antibiotic agents for the treatment of UTIs.

Frequency and Characteristics of Patients Prescribed Antibiotics on Admission to Hospice Care.

Background: Little is known about antibiotic prescribing on hospice admission despite known risks and limited evidence for potential benefits. Objective: To describe the frequency and characteristics of patients prescribed antibiotics on hospice admission. Design: Cross-sectional study. Subjects: Adult (age ≥18 years) decedents of a national, for-profit hospice chain across 19 U.S. states who died between January 1, 2017 and December 31, 2019. Measures: The primary outcome was having an antibiotic prescription on hospice admission. Patient characteristics of interest were demographics, hospice referral location, hospice care location, census region, primary diagnosis, and infectious diagnoses on admission. We used multivariable logistic regression to quantify associations between study variables. Results: Among 66,006 hospice decedents, 6080 (9.2%) had an antibiotic prescription on hospice admission. Fluoroquinolones (22%) were the most frequently prescribed antibiotic class. Patients more likely to have an antibiotic prescription on hospice admission included those referred to hospice care from the hospital (adjusted odds ratio [aOR] 1.13, 95% confidence interval [CI] 1.00-1.29) compared with an assisted living facility, those receiving hospice care in a private home (aOR 3.85, 95% CI 3.50-4.24), nursing home (aOR 3.65, 95% CI 3.24-4.11), assisted living facility (aOR 4.04, 95% CI 3.51-4.64), or hospital (aOR 2.43, 95% CI 2.18-2.71) compared with inpatient hospice, and those with a primary diagnosis of liver disease (aOR 2.23, 95% CI 1.82-2.74) or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (aOR 3.89, 95% CI 2.27-6.66) compared with those without these diagnoses. Conclusions: Approximately 9% of hospice patients had an antibiotic prescription on hospice admission. Patients referred to hospice from a hospital, those receiving care in a noninpatient hospice facility, and those with liver disease or HIV/AIDS were more likely to have an antibiotic prescription. These results may inform future antimicrobial stewardship interventions among patients transitioning to hospice care.

Antibiotic prescribing without documented indication in ambulatory care clinics: national cross sectional study.

OBJECTIVES: To identify the frequency with which antibiotics are prescribed in the absence of a documented indication in the ambulatory care setting, to quantify the potential effect on assessments of appropriateness of antibiotics, and to understand patient, provider, and visit level characteristics associated with antibiotic prescribing without a documented indication. DESIGN: Cross sectional study. SETTING: 2015 National Ambulatory Medical Care Survey. PARTICIPANTS: 28 332 sample visits representing 990.9 million ambulatory care visits nationwide. MAIN OUTCOME MEASURES: Overall antibiotic prescribing and whether each antibiotic prescription was accompanied by appropriate, inappropriate, or no documented indication as identified through ICD-9-CM (international classification of diseases, 9th revision, clinical modification) codes. Survey weighted multivariable logistic regression was used to evaluate potential risk factors for receipt of an antibiotic prescription without a documented indication. RESULTS: Antibiotics were prescribed during 13.2% (95% confidence interval 11.6% to 13.7%) of the estimated 990.8 million ambulatory care visits in 2015. According to the criteria, 57% (52% to 62%) of the 130.5 million prescriptions were for appropriate indications, 25% (21% to 29%) were inappropriate, and 18% (15% to 22%) had no documented indication. This corresponds to an estimated 24 million prescriptions without a documented indication. Being an adult male, spending more time with the provider, and seeing a non-primary care specialist were significantly positively associated with antibiotic prescribing without an indication. Sulfonamides and urinary anti-infective agents were the antibiotic classes most likely to be prescribed without documentation. CONCLUSIONS: This nationally representative study of ambulatory visits identified a large number of prescriptions for antibiotics without a documented indication. Antibiotic prescribing in the absence of a documented indication may severely bias national estimates of appropriate antibiotic use in this setting. This study identified a wide range of factors associated with antibiotic prescribing without a documented indication, which may be useful in directing initiatives aimed at supporting better documentation.

Healthcare-associated urinary tract infections with onset post hospital discharge.

OBJECTIVE: Current surveillance for healthcare-associated (HA) urinary tract infection (UTI) is focused on catheter-associated infection with hospital onset (HO-CAUTI), yet this surveillance does not represent the full burden of HA-UTI to patients. Our objective was to measure the incidence of potentially HA, community-onset (CO) UTI in a retrospective cohort of hospitalized patients. DESIGN: Retrospective cohort study. SETTING: Academic, quaternary care, referral center. PATIENTS: Hospitalized adults at risk for HA-UTI from May 2009 to December 2011 were included. METHODS: Patients who did not experience a UTI during the index hospitalization were followed for 30 days post discharge to identify cases of potentially HA-CO UTI. RESULTS: We identified 3,273 patients at risk for potentially HA-CO UTI. The incidence of HA-CO UTI in the 30 days post discharge was 29.8 per 1,000 patients. Independent risk factors of HA-CO UTI included paraplegia or quadriplegia (adjusted odds ratio [aOR], 4.6; 95% confidence interval [CI], 1.2-18.0), indwelling catheter during index hospitalization (aOR, 1.5; 95% CI, 1.0-2.3), prior piperacillin-tazobactam prescription (aOR, 2.3; 95% CI, 1.1-4.5), prior penicillin class prescription (aOR, 1.7; 95% CI, 1.0-2.8), and private insurance (aOR, 0.6; 95% CI, 0.4-0.9). CONCLUSIONS: HA-CO UTI may be common within 30 days following hospital discharge. These data suggest that surveillance efforts may need to be expanded to capture the full burden to patients and better inform antibiotic prescribing decisions for patients with a history of hospitalization.

Antibiotic prescribing upon discharge from the hospital to long-term care facilities: Implications for antimicrobial stewardship requirements in post-acute settings.

OBJECTIVE: To quantify the frequency and outcomes of receiving an antibiotic prescription upon discharge from the hospital to long-term care facilities (LTCFs). DESIGN: Retrospective cohort study. SETTING: A 576-bed, academic hospital in Portland, Oregon.PatientsAdult inpatients (≥18 years of age) discharged to an LTCF between January 1, 2012, and June 30, 2016. METHODS: Our primary outcome was receiving a systemic antibiotic prescription upon discharge to an LTCF. We also quantified the association between receiving an antibiotic prescription and 30-day hospital readmission, 30-day emergency department (ED) visit, and Clostridium difficile infection (CDI) on a readmission or ED visit at the index facility within 60 days of discharge. RESULTS: Among 6,701 discharges to an LTCF, 22.9% were prescribed antibiotics upon discharge. The most prevalent antibiotic classes prescribed were cephalosporins (20.4%), fluoroquinolones (19.1%), and penicillins (16.7%). The medical records of ~82% of patients included a diagnosis code for a bacterial infection on the index admission. Among patients prescribed an antibiotic upon discharge, the incidence of 30-day hospital readmission to the index facility was 15.9%, the incidence of 30-day ED visit at the index facility was 11.0%, and the incidence of CDI on a readmission or ED visit within 60 days of discharge was 1.6%. Receiving an antibiotic prescription upon discharge was significantly associated with 30-day ED visits (adjusted odds ratio [aOR], 1.2; 95% confidence interval [CI], 1.02-1.5) and with CDI within 60 days (aOR, 1.7; 95% CI, 1.02-2.8) but not with 30-day readmissions (aOR, 1.01; 95% CI, 0.9-1.2). CONCLUSIONS: Antibiotics were frequently prescribed upon discharge to LTCFs, which may be associated with increased risk of poor outcomes post discharge.

Comparative in vitro activities of topical wound care products against community-associated methicillin-resistant Staphylococcus aureus.

OBJECTIVES: Community-associated methicillin-resistant Staphylococcus aureus is responsible for an increasing number of skin infections. Over-the-counter topical wound care products may play a role in the prevention of these infections, but limited data are available regarding their activity. The current study utilized a modified time-kill design to evaluate the activity of three over-the-counter topical wound care products (benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin) against four unique isolates (three USA 300 and one USA 400). METHODS: All experiments were performed using commercially available formulations. Bactericidal activity was defined as a sustained 3 log(10) reduction in cfu/mL from the initial inoculum. Reductions in bacterial counts between agents were determined using analysis of variance. RESULTS: At 10 min, the reduction (mean +/- SD) in log(10) cfu/mL for all strains was 2.87 +/- 1.22, 1.86 +/- 0.76 and 0.143 +/- 0.82 for benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin, respectively. By 24 h, bactericidal activity was observed against two strains each for neomycin/polymyxin B and polymyxin B/gramicidin. Benzethonium chloride/essential oils was bactericidal against all strains by 6 h. At 24 h, all three agents were superior to controls (P < 0.05). Benzethonium chloride/essential oils was more active at 24 h than polymyxin B/gramicidin versus all four strains (P < 0.05) and more active than neomycin/polymyxin B versus three of four strains (P < 0.05). CONCLUSIONS: These topical agents demonstrated variable activity against the four strains tested. Benzethonium chloride/essential oils was more rapidly and completely active than the other agents tested.

Research publication by pharmacist authors in major medical journals: changes over a 10-year interval.

STUDY OBJECTIVE: To determine the degree to which pharmacists were involved in major clinical research publications in 1993 and 2003, and to compare the difference in publication rates by pharmacists between these 2 years. DESIGN: Retrospective analysis. DATA SOURCE: Thirty-seven medical journals that had high readership, had a focus on original research, were clinically oriented, and were highly regarded by the research community. MEASUREMENTS AND MAIN RESULTS: Selection of the medical journals was first determined by those having the highest impact factors. Then journals with regular publication of original clinical research and listings of authors' degrees or licensure were included. All original research articles in these journals were reviewed for both 1993 and 2003. The primary outcome was the presence of a pharmacist as an author of one of their research articles in each of those 2 years. For those articles, the following data were collected: study subjects, study design, authors' affiliations, source of research funding, and position of author (first and/or corresponding). The primary outcome was analyzed by using multivariate logistic regression analysis. Other outcomes were compared between 1993 and 2003 by using a chi(2) test. The number of clinical research articles identified was 8127 in 1993 and 8793 in 2003. The median (mean, interquartile range) number of authors/article increased from 5 (5.3, 3-7) in 1993 to 6 (6.6, 4-8) in 2003 (p<0.01). There were 191 pharmacist-authored papers (2.4%) in 1993, compared with 271 (3.1%) in 2003, for a relative increase of 29.2%. Adjusting for the increase seen in the number of authors during that period, the odds ratio that a pharmacist was an author in 2003 compared with 1993 was 1.26 (95% confidence interval 1.04-1.53). Most (94.2%) pharmacist-authored papers described studies involving human subjects. The proportion of clinical pharmacists (but not the number) serving as the primary author declined over time, from 36.6% (70/191) in 1993 to 27.3% (74/271) in 2003 (p=0.041). The most frequent funding sources were industry (from 38.2% in 1993 to 39.5% in 2003) and federal (from 25.1% in 1993 to 31.4% in 2003); however, the differences were not statistically significant. CONCLUSIONS: An increase was noted in the proportion of publications involving pharmacists as an author in major medical journals in 2003 compared with 1993. Pharmacists must continue to be active in clinical research, with adequate training and funding remaining significant obstacles.

Empiric Antibiotic Prescribing Decisions Among Medical Residents: The Role of the Antibiogram.

OBJECTIVETo assess general medical residents' familiarity with antibiograms using a self-administered surveyDESIGNCross-sectional, single-center surveyPARTICIPANTSResidents in internal medicine, family medicine, and pediatrics at an academic medical centerMETHODSParticipants were administered an anonymous survey at our institution during regularly scheduled educational conferences between January and May 2012. Questions collected data regarding demographics, professional training; further open-ended questions assessed knowledge and use of antibiograms regarding possible pathogens, antibiotic regimens, and prescribing resources for 2 clinical vignettes; a series of directed, closed-ended questions followed. Bivariate analyses to compare responses between residency programs were performed.RESULTSOf 122 surveys distributed, 106 residents (87%) responded; internal medicine residents accounted for 69% of responses. More than 20% of residents could not accurately identify pathogens to target with empiric therapy or select therapy with an appropriate spectrum of activity in response to the clinical vignettes; correct identification of potential pathogens was not associated with selecting appropriate therapy. Only 12% of respondents identified antibiograms as a resource when prescribing empiric antibiotic therapy for scenarios in the vignettes, with most selecting the UpToDate online clinical decision support resource or The Sanford Guide. When directly questioned, 89% reported awareness of institutional antibiograms, but only 70% felt comfortable using them and only 44% knew how to access them.CONCLUSIONSWhen selecting empiric antibiotics, many residents are not comfortable using antibiograms as part of treatment decisions. Efforts to improve antibiotic use may benefit from residents being given additional education on both infectious diseases pharmacotherapy and antibiogram utilization.Infect Control Hosp Epidemiol 2018;39:578-583.

Economic analysis of inadequate fluconazole therapy in non-neutropenic patients with candidaemia: a multi-institutional study.

Mortality significantly increases in patients with candidaemia who receive inappropriate fluconazole therapy. The goals of this study were to compare hospital length of stay and costs for non-neutropenic patients with candidaemia treated with fluconazole based on the empirical dose and time until initiation of therapy. A retrospective cohort study was conducted of patients with candidaemia who were prescribed fluconazole at the onset of candidaemia or later. Hospital-related costs were compared based on time to initiation of fluconazole therapy and empirical fluconazole dose. A total of 192 non-neutropenic patients (55% male; mean age+/-standard deviation, 56+/-17 years) were identified. Isolated Candida species included C. albicans (59%), C. glabrata (15%), C. parapsilosis (11%), C. tropicalis (6%), C. krusei (3%) or other Candida spp. (6%). Time to initiation of fluconazole was Day 0 (35.4%), Day 1 (14.1%), Day 2 (26.6%) or Day >or=3 (23.9%). Thirty-two patients (17%) received a dose of fluconazole >or=6 mg/kg on Day 0. Total costs were lowest for patients started on fluconazole on the culture day with adequate doses ($35,459+/-25,988) compared with all other patients ($52,158+/-53,492) (P=0.0088). After controlling for covariates, each 1-day delay in fluconazole therapy was associated with increased total hospital costs of $6392+/-3000 (P=0.0344), and an adequate fluconazole dose was associated with decreased total hospital costs of $18,744+/-7173 (P=0.0097). A delay or an inadequate dose or fluconazole in patients with candidaemia was associated with increased hospital costs. Improved methods to diagnose patients with candidaemia quickly are needed.

Antimicrobial dosing considerations in obese adult patients.

As obesity continues to increase in prevalence throughout the world, it becomes important to explore the effects that obesity has on antimicrobial disposition. Physiologic changes in obesity can alter both the volume of distribution and clearance of many commonly used antimicrobials. These changes often present challenges such as estimation of creatinine clearance to predict drug clearance. Although these physiologic changes are increasingly being characterized, few studies assessing alterations in tissue drug distribution and the effects of obesity on antimicrobial pharmacokinetics have been published. The available data are most plentiful for antibiotics that historically have included clinical therapeutic drug monitoring. These data suggest that dosing of vancomycin and aminoglycosides be based on total body weight and adjusted body weight, respectively. Obese patients may require larger doses of beta-lactams to achieve similar concentrations as those of patients who are not obese. Fluoroquinolone pharmacokinetics are variably altered by obesity, which prevents a uniform approach. Data on the pharmacokinetics of drugs that have activity against gram-positive organisms-quinupristin-dalfopristin, linezolid, and daptomycin-reveal that they are altered in the presence of obesity, but more data are needed to solidify dosing recommendations. Limited data are available on nonantibacterials. An understanding of the physiologic changes in obesity and the available literature on specific antibiotics is valuable in providing a framework for rational selection of dosages in this increasingly common population of obese patients.

Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

BACKGROUND: Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. METHODS: We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. RESULTS: A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). CONCLUSION: A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

Statewide impact of pharmacist-delivered adult influenza vaccinations.

BACKGROUND: Oregon law has allowed pharmacists to provide adult immunizations since 2000. Every vaccination delivered must be reported to the state health department. Previous reports indicate that pharmacists vaccinate individuals unlikely to receive vaccinations elsewhere. METHODS: Administration reports were analyzed in 2005 for the first three influenza seasons (2000 to 2003). The number of pharmacies participating, type and quantity of vaccinations, and county where provided were analyzed. RESULTS: A total of 13,116 adult patients received influenza vaccinations during 2000-2001 at 56 pharmacies. The number of pharmacies participating increased to 88 and 132, and vaccinations provided to 25,785 and 30,218 in the next two seasons, respectively. The mean number of vaccinations per pharmacy was 250 (standard deviation 236) for the 3-year period. Rural counties accounted for 28.4% of influenza vaccinations. CONCLUSIONS: Pharmacists provided a substantial number of influenza vaccinations during this 3-year period. More than one quarter of the vaccinations were provided in rural counties.

Clinical pharmacokinetics of quinupristin/dalfopristin.

Quinupristin/dalfopristin is a streptogramin antibacterial with a wide spectrum of Gram-positive antibacterial activity. The drug has minimal oral absorption and is administered intravenously as a fixed 30 : 70 ratio of quinupristin to dalfopristin. A linear relationship has been observed between the dose administered and maximum plasma concentrations. Single-dose administration of 7.5 mg/kg produced a maximal plasma concentration of 2.3-2.7 mg/L for quinupristin and 6.1-8.2 mg/L for dalfopristin. The area under the concentration-time curve (AUC) obtained with the same dose was 2.7-3.3 and 6.5-7.7 mg. h/L for quinupristin and dalfopristin, respectively. Repeated administration results in 13-21% increases in maximum plasma concentrations and 21-26% increases in AUC for both quinupristin and dalfopristin. Quinupristin and dalfopristin exhibit steady-state volumes of distribution of 0.46-0.54 and 0.24-0.30 L/kg, respectively. Quinupristin exhibits higher protein binding (55-78%) than dalfopristin (11-26%), though both entities distribute well into tissues. Concentrations exceeding those in blood have been reported for the kidney, liver, spleen, salivary glands and white blood cells of primates. Extravascular penetration, as measured in blister fluid, is 40-80%. Both quinupristin and dalfopristin are extensively metabolised via nonenzymatic reactions. Quinupristin is conjugated to form two active compounds, a cysteine moiety and a glutathione moiety. Dalfopristin is hydrolysed to the active metabolite pristinamycin IIA. The metabolites exert antibacterial activity similar to that of the parent compounds. Quinupristin/dalfopristin is excreted primarily in the faeces (75-77%), with lesser renal excretion (15-19%). The elimination half-lives of quinupristin and dalfopristin are similar, and are 0.7-1.3 hours after single doses. The metabolites have slightly longer half-lives, ranging from 1.2 to 1.8 hours. With repeated doses, plasma clearance of quinupristin and dalfopristin is reduced by approximately 20% compared with single doses, resulting in clearances of 0.7-0.8 L/h/kg. Saturable protein binding has been hypothesised as a causative mechanism. Quinupristin/dalfopristin is an inhibitor of cytochrome P450 3A4, resulting in multiple drug interactions. Ciclosporin AUC increased by 5-222% when coadministered with quinupristin/dalfopristin. Careful monitoring of patients receiving drugs that are substrates of cytochrome P450 3A4 is suggested.Quinupristin/dalfopristin is administered at 7.5 mg/kg every 8-12 hours, depending upon the severity of infection. The pharmacodynamic parameter linked with antibacterial activity for quinupristin/dalfopristin appears to be the ratio of AUC to the minimal inhibitory concentration. The additional activity of a prolonged post-antibiotic effect may also be important for efficacy.

Neutropenia after single-dose clindamycin for dental prophylaxis.

A 68-year-old man with stable chronic myelogenous leukemia received a single dose of clindamycin before having a tooth extracted. He was neutropenic 6 days later, with an absolute neutrophil count of 945 cells/mm3. His neutrophil count returned to normal within 2 weeks. Clindamycin has been implicated in drug-induced neutropenia; however, a review of the literature produced only three reports of this reaction. Only one provided the duration of the neutropenia. To our knowledge, this case report is only the second that provides the duration of the clindamycin-induced neutropenia. Clinicians should be made aware of this potential adverse event.

Extended-spectrum beta-lactamases: frequency, risk factors, and outcomes.

STUDY OBJECTIVE: To determine epidemiologic factors of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae in a nonoutbreak setting. DESIGN: Retrospective analysis. SETTING: University teaching hospital. PATIENTS: Fifty-seven patients with cultures of presumed ESBL-producing (i.e., ceftazidime-resistant) E. coli or K. pneumoniae. INTERVENTIONS: To determine overall frequency, institutional antibiograms from 1991-1999 were examined for percentage of isolates with ceftazidime resistance. Medical records from January 1997-June 2000 were reviewed for patient demographics, comorbidities, culture site, antimicrobial therapy, and clinical and microbiologic outcomes. MEASUREMENTS AND MAIN RESULTS: From 1991-1999, frequency increased from undetectable to 4% for ceftazidime-resistant E. coli and from 2% to 6% for ceftazidime-resistant K. pneumoniae. Seventy-one isolates were identified in the 57 patients with presumed ESBL-producing E. coli or K. pneumonia. Fifty-one isolates (72%) were E. coli, with urine the primary site of infection (62%). Eighty-six percent of patients had known risk factors for infection due to ESBL-producing organisms, including hospitalization (37 patients) and residence in long-term care facilities (12 patients). However, in 14% (8 patients), the infection was community acquired in patients who resided at home. CONCLUSION: In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL-producing organisms.