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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.

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.

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 =