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Purpose Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 µg/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 µg · h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software. The aim of this investigation was to determine the relationship between AUC and trough concentration and the influence of dosing regimen on goal achievement. Methods The relationship between trough concentration and AUC was explored through derivation of an equation based on a 1-compartment model and simulations. Results 24-hour AUC is related to dosing interval divided by half-life in a nonlinear fashion. The target trough concentration can be individualized to achieve a desired AUC range, and limiting use of large doses (>15-20 mg/kg) can protect against excessive 24-hour AUC with trough-only monitoring. Conclusion After initially determining pharmacokinetic parameters, subsequent monitoring of AUC can be accomplished using trough concentrations only. Trough concentration may be used as a surrogate for AUC, although the acceptable target trough concentration will vary depending on dosing interval and elimination rate constant. This work included development of an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.

Purpose: We aimed to assess factors associated with therapy failure in patients with community-acquired pneumonia in the intensive care unit (ICU). Methods: Electronic charts of patients with International Classification of Diseases, Ninth Revision, codes of pneumonia who were admitted to the ICU at a tertiary academic medical center in Southern Arizona were reviewed. Results: Antipseudomonal coverage and anti-methicillin-resistant Staphylococcus aureus (MRSA) coverage were often prescribed (58.4% and 54.1%, respectively). Antipseudomonal coverage was rarely necessary as pseudomonal pneumonia was found in only one case (0.9%). Antipseudomonal and anti-MRSA coverage was not associated with improved outcomes. Conclusion: Overprescription of antibiotics in this population remains a significant problem. More work is needed to further limit unnecessary antibiotic use.

Objectives Urinary tract infection (UTI) recurrence and antimicrobial resistance remain a common problem in kidney transplant recipients. Whilst the use of annual institutional antibiograms may help guide appropriate empirical antibiotic selection, these non-disease specific antibiograms do not always account for patient-specific risk factors or disease-specific resistance patterns. This study determined the frequency of UTI recurrence during the first year after kidney transplantation as well as differences in antimicrobial susceptibility between an institutional antibiogram and the disease-specific antibiogram for patients following kidney transplantation. Methods In this study, adult patients with at least one UTI during an inpatient admission within 1 year post kidney transplantation were evaluated. A disease-specific antibiogram for UTIs in kidney transplant recipients was prepared based on culture results and was compared with the annual institutional antibiograms. Results Of 299 kidney transplants performed during the study period, 66 subjects meet the study inclusion criteria, of whom 47% had two or more UTIs within the first year after kidney transplant. In comparison with the institutional antibiogram, Escherichia coli isolated from urine samples from kidney transplant recipients were significantly more resistant to trimethoprim/sulfamethoxazole, ceftriaxone, cefepime, ciprofloxacin and gentamicin (P Conclusions Multiple UTIs are common in kidney transplant recipients during the first year post-transplantation. E. coli urinary isolates were significantly more resistant to multiple antibiotic drug classes in this patient population compared with the general hospital population. Antimicrobial stewardship programmes at transplant centres should consider producing disease-specific antibiograms specifically for transplant recipients to improve empirical antibiotic selection guidance.

To assess the severity of inflammation associated with diabetic foot infection (DFI), values of inflammatory markers such as white blood count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) are often measured and tracked over time. It remains unclear if these markers can aid the clinician in the diagnosis and management of DFI, and ensure more rational use of antibiotics. Hospitalized adult patients (n = 379) with DFI were retrospectively assessed for abnormal inflammatory markers, correlation between values of inflammatory markers, and clinical diagnosis on initial admission and on last follow-up. At admission, WBC, ESR and NLR were each elevated in patients with osteomyelitis and only ESR was significantly elevated in patients with soft tissue infection only. Only WBC was significantly elevated in patients with osteomyelitis compared with uninfected diabetic feet on last follow-up. Considering the predictive performance of these inflammatory markers, they demonstrated excellent positive predictive value at admission, and excellent negative predictive value at the last follow-up visit. Moreover, the number of elevated markers was further associated with probability of infection both at admission and last follow-up.

Background Fluconazole (fluc) is a common antifungal used at hospitals and is an important target for antimicrobial stewardship (AS). Fluc is also used for management of coccidioidomycosis (C). The objective of our study was to describe fluc prescribing patterns at two academic centers in Arizona. Methods We conducted a retrospective analysis of fluc usage in adult patients. One month from each quarter in a one-year period (November 2017-November 2018) was selected (4 months in total). All adult patients that received fluc at Hospital A and Hospital B in the selected months were identified. Patient demographic information and Charlson comorbidity index (CCI) to quantify the degree of comorbidity were collected. We then analyzed patients in the study by defining the fluc usage as directed towards C management or non-C management (e.g., candidiasis). In the C management group, we characterized the initial fluc dose during the patient’s course as directed for empiric, targeted, or prophylaxis treatment. Finally, we performed further analysis of the empiric C group. The study received IRB approval from our institution. Results During our study period, 1239 patients were included in the analysis. Patient information is shown in Table 1. Overall, most of the fluc usage was directed towards C management (63.5%, 787/1239). A significant amount of that usage was directed towards C prophylaxis at both Hospital A and B (67.4% (234/347) and 75% (330/440), respectively). In addition, fluc usage directed towards empiric C management was higher at Hospital A versus Hospital B (18.4% (64/347) versus 9.5% (42/440), respectively). Further patient data for the empiric C group is shown in Table 2. Conclusion We report the results of a descriptive study that demonstrate that 63.5% of fluc usage in adults at two academic medical centers in Arizona was directed for C management. In addition to traditional fluc targets for AS, our study highlights C prophylaxis in solid organ transplant recipients and empiric C management as AS targets in endemic regions. These targets are especially important due to the risk for selection of azole-resistant Candida species and invasive molds with increased antifungal exposure. Disclosures All Authors: No reported disclosures

We surveyed urgent care centers (UCCs) in the state of Arizona to determine whether they offered the influenza vaccine during the 2016-2017 influenza season. Overall vaccine availability was 80.3% at these facilities. During this season, one-third of the UCCs offered influenza vaccination to children 6 months or older; approximately two-thirds offered influenza vaccination to children and young adults 16 years or older. This is the first study of influenza vaccine availability at UCCs.

Skin and soft-tissue infections (SSTIs) are commonly encountered by medical students, residents, and trainees. The Infectious Diseases Society of America (IDSA) has updated its recommendations regarding SSTI diagnosis and management in June 2014. We assessed knowledge, attitude, and practices toward diagnosis and management of SSTIs using an online survey. We disseminated the survey to medical students, residents, and attending physicians practicing in family and internal medicine department at a university-based hospital. A total of 103 surveys were completed out of 121 sent (85.1%) between July 2015 and March 2016. There were nine medical questions in the survey. The mean of correct answers was 4.5/9 ± 2.0. Medical knowledge correlated with the level of education (P < 0.001) but not with subspecialty (P = 0.97). Around 35% were familiar with the updated IDSA guidelines pertaining to SSTIs. The majority (85%) responded that the hospital staff would benefit from additional training and 75% agreed that more antibiotic stewardship education is needed. Our study shows that there are significant opportunities for development among students and physicians who encounter SSTIs.

The significance of bacteriuria in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is unclear. It is not known whether treatment of asymptomatic bacteriuria is associated with lower rates of urinary tract infection or readmission. Adult patients with ESRD on HD were retrospectively evaluated to assess factors associated with the recurrence of bacteriuria and readmission. We included 68 patients in the analysis. There were 20 patients (29.4%) with urinary symptoms. All symptomatic patients received antibiotic therapy, whereas half of the asymptomatic patients received antibiotics. Antibiotic use was not associated with lower rates of readmission or the recurrence of bacteriuria.

We developed an interactive online module to improve the knowledge of students and physicians regarding respiratory infections. Our study showed that the completion of this module was associated with substantial improvement in knowledge, with modest retention after 2 months.

Introduction Solid organ transplant (SOT) recipients are at high risk of Clostridium difficile infection (CDI) and CDI recurrence due to their suppressed immune systems and antibiotic exposure. A combination of metronidazole and oral vancomycin is often prescribed for SOT recipients with uncomplicated CDI despite any clinical practice guidelines supporting the need for combination therapy. This study aims to compare the CDI recurrence rates of metronidazole/vancomycin combination therapy to oral vancomycin monotherapy in SOT recipients after a first episode of uncomplicated CDI. Methods A single-center retrospective cohort study evaluated SOT recipients diagnosed with uncomplicated CDI who were treated with vancomycin monotherapy or vancomycin/metronidazole combination therapy. The primary endpoint was CDI recurrence defined as a second CDI episode within 8 weeks of completing index CDI therapy. The secondary endpoints were time between the end of CDI therapy and recurrence, length of total hospitalization after the index CDI, and length of hospitalization after index CDI diagnosis. Results Fifteen patients (25%) of 61 subjects experienced CDI recurrence. There was no statistically significant difference in CDI recurrence rate between the vancomycin monotherapy group and combination therapy group (23% versus 27%, respectively; P = .715). The median total length of hospitalization between the vancomycin monotherapy and combination therapy groups was statistically significant (9 versus 14 days, respectively; P = .047). Discussion There was no difference found in recurrence rate between oral vancomycin monotherapy versus combination therapy. The study result weakens the practice of prescribing combination therapy for uncomplicated CDI in SOT recipients.

OBJECTIVES To identify opportunities to perform point-of-care (POC) testing and/or screening for infectious diseases in community pharmacies, provide an overview of such tests and how they are used in current practice, discuss how the Clinical Laboratory Improvement Amendments of 1988 (CLIA) affect pharmacists performing POC testing, and identify and discuss barriers and provide recommendations for those wanting to establish POC testing for infectious diseases services in community pharmacies. DATA SOURCES PubMed and Google Scholar were searched from November 2012 through May 2013 and encompassed the years 2000 and beyond for the narrative review section of this article using the search terms rapid diagnostic tests, POC testing and infectious diseases, pharmacy services, CLIA waiver, and collaborative drug therapy management. All state boards of pharmacy in the United States were contacted and their regulatory and legislative websites accessed in 2012 and January 2013 to review relevant pharmacy practice laws. DATA SYNTHESIS POC testing for infectious diseases represents a significant opportunity to expand services in community pharmacies. Pharmacist education and training are addressing knowledge deficits in good laboratory practices and test performance and interpretation. Federal regulations do not define the qualifications for those who perform CLIA-waived tests, yet few pharmacists perform such services. Fewer than 20% of states address POC testing in their statutes and regulations governing pharmacy. CONCLUSION POC testing for infectious diseases could benefit patients and society and represents an opportunity to expand pharmacy services in community pharmacies. Existing barriers to the implementation of such services in community pharmacies, including deficits in pharmacist training and education along with state regulatory and legislative variance and vagueness in statutes governing pharmacy, are not insurmountable.

Voichita Ianas1, Kathryn R Matthias2, Stephen A Klotz11Section of Infectious Diseases and Department of Medicine, 2School of Pharmacy, University of Arizona, Tucson, Arizona, USAAbstract: Posaconazole is the newest azole antifungal approved by the US Food and Drug Administration, and possesses a broad spectrum of activity against numerous yeasts and filamentous fungi. It is available as an oral suspension and is generally well tolerated by patients, but gastrointestinal absorption is sometimes inadequate and remains a clinical concern in treating deep-seated infections. It is used routinely and effectively for the prophylaxis of invasive fungal infections in immunosuppressed hosts and is an effective treatment of oropharyngeal candidiasis, including azole-resistant disease.Keywords: posaconazole, azole, yeasts, filamentous fungi

Purpose Over the past two decades, the minimum inhibitory concentrations (MICs) of ciprofloxacin have been steadily increasing for gram-negative bacteria. One major reason cited for this “MIC creep” is underdosing of ciprofloxacin due to a lack of understanding of its pharmacodynamic properties. The primary objective of this study was to evaluate the frequency of underdosing of ciprofloxacin in a tertiary acute care medical center based on a population pharmacokinetic model. Secondary objectives included evaluation of appropriateness of dosing based on renal function and approved product labeling. Methods Seventy-six patients were included in this single-center, retrospective study. Data collection included demographic, laboratory, and microbiology data along with details on antibiotic administration. Patient-specific predicted 24-hour area under the curve/MIC (AUC24/MIC) values were estimated using a population pharmacokinetic model with a goal predicted AUC24/MIC of at least 100 and a preferred target value of 250. Results Only 8% of the subjects obtained a predicted AUC24/MIC higher than 250, while 34% of the subjects achieved a predicted AUC24/MIC of 100 or less. The majority of patients (79%) received a total daily intravenous-equivalent dose of 800 mg, whereas only 8% of subjects received an initial total daily intravenous-equivalent dose of 1,200 mg, which is the recommended dose for most severe infections. Overall 26% of subjects were prescribed an appropriate initial dose for their estimated renal function based on infection type and severity. Conclusion Ciprofloxacin for acute infection treatment was frequently underdosed based on US Food and Drug Administration–approved labeling and estimated predicted AUC24/MIC at a tertiary acute care medical center.

Purpose The level of nurses' satisfaction regarding pharmacy services provided at a rural medical center was evaluated and compared to data collected in a previous study at the same institution. Information obtained was used to determine potential areas for pharmacy service improvements. Methods This project employed a survey research design that acquired demographic and descriptive data. The updated survey contained 43 items including 34 scaled, seven demographic, and two open-ended items. Aspects assessed by this instrument included accessibility of pharmacists, accuracy of medication delivery, quality of drug information services, and perceptions of pharmacists' value by nursing staff. All inpatient nurse practitioners, licensed practical nurses, and registered nurses who were employed at the Medical Center in the winter of 2004 were eligible to participate in this study. The a priori level of significance for all analyses was two-tailed at 0.05. Results A total of 199 surveys were returned for a response rate of 43.9%. The overall level of nurses' satisfaction with pharmacy services at the Medical Center had not significantly changed between the years of 2000 and 2004; however, satisfaction with several specific aspects of pharmaceutical services changed over time. Increased levels of satisfaction were related to medication accuracy and inpatient pharmacy hours; decreased levels of satisfaction were reported for medication availability in automated medication dispensing machines and pharmacy telephone services. The level of nurses' satisfaction with pharmacy services was increased in relation to the communication between pharmacists and nurses and decreased in relation to technology associated pharmacy services. Conclusion The data gleaned from the survey were evaluated in order to make recommendations to the Medical Center's Director of Pharmacy. An instrument was developed and validated to discern nurses' level of satisfaction with pharmacy services. This methodology may also be used at other institutions.

Background: Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors. Objective: To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD. Methods: Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling. Results: Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) × (actual body weight/70)0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity. Conclusions: These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.

Background The BioFire FilmArray™ Gastrointestinal (GI) Panel is a 1 hour multiplex real-time PCR test that can detect the presence of 22 GI pathogens (viral, bacterial, and parasitic) known to cause infectious diarrhea. Our tertiary-care academic medical center implemented the GI Panel for all cases of suspected infectious diarrhea replacing the previous conventional testing once utilized to detect GI pathogens. Since its implementation we have not had any criteria for ordering this test to aid healthcare providers. Methods The aim of this IRB approved, retrospective investigation was to determine the appropriateness of ordering the GI panel at our academic institution. Cases were randomly selected, stratified by age group and result (specific pathogens or negative result) from May 2015 through April 2016 in the post-implementation period (n = 400 of 1117 total tests). We developed appropriateness criteria for ordering the GI panel which included: passage of at least 3 unformed stools in 24 hours plus one or more enteric symptom (nausea, vomiting, abdominal pain/cramps, tenesmus, fecal urgency, moderate to severe flatulence), and one of the following: grossly bloody diarrhea (dysenteric), persistent diarrhea (14 – 30 days), worsening or relapsing diarrhea, fever ≥ 101 F°, severe diarrhea > 10 bouts in 24hrs, immunosuppression, pregnancy, food handler, infant < 1 year and their care takers, age ≥ 65 years old, concern for disseminated GI infection, with no previous GI panel testing in the past 30 days. Results Overall appropriateness of GI panel testing based off our generated criteria was 36% (n = 144/400). This included all tests ordered in the outpatient clinics, emergency department, inpatient medical/surgical wards, and intensive care units. Conclusion Currently there is not a well-established standard criteria for ordering the GI panel for investigating suspected infectious diarrhea. After implementation at our academic tertiary-care medical center the GI panel was used inappropriately in most cases without a criteria for ordering in place to aid clinicians. Educating healthcare providers about appropriate testing indications is being performed. Further studies are needed to assess if our generated criteria will lead to decreased costs and unnecessary testing. Disclosures All authors: No reported disclosures.

The effect of protein binding on the antimicrobial activity of ertapenem was evaluated using the bacterial kill rate and concentration-response studies. Various proportions of human serum were utilized to determine the total and free-drug concentrations using a validated high-performance liquid chromatography assay. The MICs and kill curves were determined for test isolates of Enterobacter cloacae and Staphylococcus aureus at various percentages of human serum. The killing of bacteria was analyzed in relation to the free and total concentrations of ertapenem at various proportions of human serum. It was determined that unbound ertapenem was responsible for the antimicrobial activity against the test isolates.

Background Many patients with bacteremia due to Gram-negative organisms are not treated appropriately. This has been linked to high rates of multi-drug resistant organisms, hospital costs, length of stay, and mortality. The purpose of this study was to assess the effect of implementation of Verigene multiplex PCR on appropriate use of antibiotics, and the time to streamlining of therapy in this population. Methods This study included hospitalized patients with Gram-negative organisms isolated from blood cultures both six months before, and six months after the implementation of Verigene at a tertiary care academic medical center. An institutional review board approved this study. We excluded patients that had organisms isolated from autopsy sample and patients under the age of 18. Appropriate therapy was defined as any antibiotic therapy to which the organism was reported as being susceptible once susceptibility results were available. Streamlined therapy was defined as the narrowest antibiotic selection based off organism susceptibility. The primary outcome measure was the time to streamlining of therapy (before culture and susceptibility date were available). Data was compared by group (before and after Verigene implementation) using multiple logistic regression model in SAS. Results A total of 287 patients were included. 140 of the subjects were male (48.8%). Mean age in the pre-verigene group was 61.5 years (SD 17.1) and the mean age in the post-verigene group was 59.7 (SD 18.2). In 93 patients, cultures were collected in the ICU setting (32.4%). In nine post-verigene patients, ESBL with the CTX-M resistance marker was isolated. Six of these patients were switched from inappropriate therapy to a carbapenem. The time to appropriate antibiotics in the pre-verigene group was 0.4 days (SD 0.8) and in the post-verigene group 0.4 days (SD 1.0 P = 0.57). The time to streamlining of antibiotics following culture was improved in the post-verigene group (1.9 days, SD 1.3) compared with the pre-verigene group (2.6 days, SD 1.4 P = 0.01). Conclusion The use of Verigene multiplex PCR was associated with improved time to streamlining of antibiotic therapy in patients with Gram-negative bacteremia. Disclosures All authors: No reported disclosures.

Background The BioFire FilmArray™ Gastrointestinal (GI) Panel is a 1 hour multiplex real-time PCR test that can detect the presence of 22 GI pathogens (viral, bacterial, and parasitic) known to cause infectious diarrhea. Our tertiary-care academic medical center implemented the GI Panel for all cases of suspected infectious diarrhea replacing the previous conventional testing once utilized to detect GI pathogens. Methods The aim of this IRB approved, retrospective investigation was to determine the utility of the GI panel testing vs. the conventional testing to guide patient management. Cases were randomly selected, stratified by age group and result (specific pathogens or negative result) in the pre-implementation period (n = 119 of 1550 samples) from May 2014 through April 2015 and in the post-implementation period (n = 333 of 1117 samples) from May 2015 through April 2016. Results The rate of a positive test for any stool pathogen per patient was 34.2% (n = 342 of 999) for the GI panel and 11.6% (n = 162 of 1391) for conventional testing, P =

An isolation procedure is presented that yields 2.4–3.7% w/w pure shikimic acid from the seeds of Liquidambar styraciflua (Sweetgum). Shikimic acid, the starting material in the commercial synthesis of the antiviral agent oseltamivir and an important intermediate in the biosynthesis of aromatic amino acids in plants, was found by HPLC to be abundant in the granular, aborted seeds (6.5% w/w) while present only in small amounts in the developed, fertile seeds (0.14% w/w). This extraction technique makes L. styraciflua , which is found in 40 states of the continental US, a potential renewable source of this important natural product.

OBJECTIVE: To describe the use of high-dose posaconazole in 2 pediatric patients who received bone marrow transplant (BMT) and highlight concerns regarding posaconazole absorption. CASE SUMMARY: We present 2 pediatric BMT patients in whom prescribed high doses of posaconazole (120-300 mg/kg/day for >3 months) provided serum concentrations less than 1 μg/mL. Both patients received posaconazole with other antifungal therapy and surgical debridement for Rhizopus spp. infections after allogeneic BMTs. Various alternative dosing strategies to potentially enhance posaconazole absorption to increase serum concentrations were attempted, including higher daily doses, frequent or continuous oral administration via feeding tube, use of enteral nutrition, and limiting use of acid-blocking agents. During high-dose therapy, frequent posaconazole serum concentration measurement and other monitoring techniques, such as continuous telemetry, were used. While the fungal infections resolved in both patients and no serious adverse effects could be attributed to high-dose posaconazole administration, posaconazole therapy may have contributed to nausea and vomiting in 1 of the patients. DISCUSSION: These 2 cases describe complex circumstances, with several reasons that may have affected the patients' posaconazole serum concentrations. Both patients received significantly higher doses than those recommended in the posaconazole prescribing information, but potentially serious adverse events were not observed since serum concentration measurements were rarely more than 0.5 μg/mL. CONCLUSIONS: The safety of high-dose posaconazole therapy was not determined in these 2 patients. However, given that limited alternative therapy options are available for severely ill patients with suspected posaconazole malabsorption, research regarding dosing strategies should be considered.

Purpose. The adequacy of end-of-procedure free cefazolin concentrations after administration for the prevention of surgical-site infection (SSI) and compliance with national guidelines for antimicrobial prophylaxis for SSI were assessed. Methods. Patients undergoing elective surgery and receiving cefazolin for perioperative antimicrobial prophylaxis were prospectively enrolled. Antibiotic administration was controlled by the surgeon and usage was recorded. For each patient, a single blood sample for cefazolin serum free and total concentrations was obtained within 15 minutes of wound closure. A free serum concentration threshold of 4 μg/mL was arbitrarily chosen based on the minimum inhibitory concentration required to inhibit 90% of strains of methicillin-susceptible Staphylococcus aureus and Escherichia coli . Results. Fifty-seven subjects were enrolled, and noncompliance with published guidelines was observed for 26% of patients. Forty-six subjects had serum samples available for assay, 21.7% of whom had end-of-procedure free cefazolin concentrations of

We read with interest the recent article by Leong et al.[1][1] concerning the use of adjusted body weight (AdjBW) for determining clearance (CL) of vancomycin in overweight and obese patients. Several previous publications involving the pharmacokinetics of vancomycin in this population have