bluuebunny/crossref_metadata_2025_split huggingface dataset:
1099. The Correlation Between Antimicrobial Utilization and Resistance in a Medical Intensive Care Unit
Authors: Ahern John W , Smith Lindsay , Alston W Kemper 
Published: October 2019

Abstract

Background
The relationship between antimicrobial utilization and the incidence of antimicrobial-resistant pathogens can be obscured by a lack of longitudinal data. We used 9 years of antimicrobial utilization data combined with a unique metric of antimicrobial resistance to examine this relationship.

Methods
The medical intensive care unit (MICU) at UVMMC has 22 beds. The unit’s size and location did not change during the study. Since 2010, defined daily doses (DDD) in the MICU for ceftazidime, ceftriaxone, cefepime, ciprofloxacin, levofloxacin, piperacillin–tazobactam, meropenem, and vancomycin were measured. Concurrently, a database of positive cultures acquired in MICU, whether colonization or infection, was built for 6 selected organisms: Clostridioides difficile, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, ceftazidime-resistant Gram-negative bacilli, fluoroquinolone-resistant Pseudomonas aeruginosa (QRPA), and Stenotrophomonas maltophilia. The occurrence of these 6 organisms/1,000 patient-days is termed “resistance index.” Data for both metrics were collected in the same way, by the same person, throughout. The relationship between these 2 measures was analyzed with simple linear regression.

Results
From 2010 to 2018, the use of 8 broad-spectrum antibiotics fell in a linear fashion from 12.11 to 4.39 DDD/100,000 patient-days. The resistance index for the 6 multidrug-resistant organisms in MICU also fell in parallel from 6.5 to 1.5/1,000 patient-days (figure, r = 0.9, P = 0.001). For the 2 quinolones specifically, use fell from 2.26 to 0.18 DDD/100,000 patient-days, while the occurrence of QRPA fell from 1.5 to 0/1,000 patient-days (figure, r = 0.84, P = 0.004).

Conclusion
These longitudinal data, collected consistently over 9 years, clearly demonstrate a significant correlation between broad-spectrum antibiotic use and the occurrence of multidrug-resistant organisms in a MICU. A steep, linear decline in antibiotic use was correlated with a parallel fall in these 6 organisms. These data demonstrate that sustained, meaningful reductions in antimicrobial utilization in a MICU can result in significant reductions in the incidence of antimicrobial-resistant pathogens.

Disclosures
All authors: No reported disclosures.
1103. Improving Perioperative Prophylactic Antimicrobial Guideline Concordance in Liver and Lung Transplant Recipients
Authors: Nguyen Cynthia T , Marrs Rachel , Pisano Jennifer , Pettit Natasha N , Potter Lisa 
Published: October 2019

Abstract

Background
Surgical site infection (SSI) is a common complication among patients undergoing solid-organ transplantation. Administration of perioperative antimicrobials is one modifiable factor that may reduce the risk of SSIs. We sought to evaluate antimicrobial stewardship efforts to improve concordance of perioperative antimicrobial selection (AS) and dose timing (DT) with the institution’s perioperative antimicrobial guidelines among liver (LVR) and lung transplant recipients (LNG).

Methods
This was a single-center, observational study of LVR and LNG between January 1, 2017 and December 31, 2018. Patients receiving antimicrobials for the treatment of infection immediately prior to transplant were excluded. Throughout the study period, several interventions were performed, including: updating AS and DT protocols (2017 Q2) and preoperative order sets (2017 Q4), improving availability of antibiotics in the operating room (2018 Q1), and most recently developing a guideline and providing education for intraoperative redosing based on renal function (2018 Q3). The primary outcome was overall guideline concordance (GC). This was a composite endpoint including preoperative and intraoperative AS and DT, based on the institution’s guideline. Secondary outcomes included SSI rates based on the CDC National Healthcare Safety Network definition and rate of new C. difficile or vancomycin-resistant Enterococci infection or colonization.

Results
Among 112 patient screened, 79 patients were included (45 LNG and 34 LVR). The median age was 60 years and BMI was 26.5 kg/m2. The median procedure length was 7.8 hours for LNG and 6.9 hours for LVR. Results are shown in Table 1, Figure 1 and Figure 2. All GC rates demonstrate improvements over time, except for intraoperative DT for LNG.

Conclusion
Limited by a small sample size, our study demonstrates that noninvasive antimicrobial stewardship strategies can yield improvements in GC.

Disclosures
All authors: No reported disclosures.
1108. Impact of Implementing a Urine Culture Order Set on Antibiotic Utilization and Rates of Catheter-Associated Urinary Tract Infections in an Urban Academic Medical Center
Authors: Alnafoosi Zainab , Doan Huynh Chi , Al-Sadawi Mohammed , Moy Stanley , Otto Caitlin , Augenbraun Michael , Nakeshbandi Mohamed 
Published: October 2019

Abstract

Background
Overutilization of urine cultures may lead to inappropriate use of antibiotics. We implemented a computerized urine culture order set where urine specimens are not processed for culture unless there is evidence of pyuria (≥10 WBC per high power field) on urinalysis (UA), or if a patient is pregnant, neutropenic, neonate, renal transplant recipient, planned for or had a recent urologic procedure. Here we evaluated the impact of this order set on antibiotic utilization, urine culture volumes and rates of catheter-associated urinary tract infections (CAUTI).

Methods
We performed a retrospective chart review before and after the order set implementation (August–December 2017 and 2018, respectively). The analysis had two distinct components: first was at institution-level, where data for all adult and pediatric inpatients were compared for urine culture volumes and antibiotic use regardless of indication. The second component was done at patient-level, where we compared clinical data and days of therapy (DOT) for all adult inpatients who had urine cultures without pyuria in the specified pre-intervention period, and those with canceled urine cultures due to absence of pyuria post-intervention.

Results
At the institution-level analysis, a statistically significant reduction was observed in rates of urine cultures performed (P = 0.02), as well as use of penicillins, carbapenems and Trimethoprim-Sulfamethoxazole (TMP-SMX) (P < 0.05). However, the use of cephalosporins has increased post-intervention (P < 0.001). No significant change was noted for aminoglycosides or fluoroquinolones.
At the patient-level analysis, DOT means in patients with negative pyuria did not change significantly (5.16 pre-intervention, 6.54 post-intervention, P = 0.202). Prevalence of treatment for bacteriuria despite absence of pyuria was 5.3% (20/380) pre-intervention, vs. 1.9% (1/53) post-intervention (P = 0.494). In the pre-intervention period, three cases met the criteria for CAUTI despite negative pyuria. This misdiagnosis could have been avoided by implementation of the urine culture order set.

Conclusion
Implementation of a urine culture order set in our institution led to a statistically significant reduction in rates of urine cultures performed, as well as use of penicillins, carbapenems and TMP-SMX.

Disclosures
All authors: No reported disclosures.
1109. Use of Prospective Audit with Intervention and Feedback (PAIF) for Urine Culture (UCx) Interpretation at a Veteran Affairs Medical Center
Authors: Nowalk Nathan , Wu Eric , Zhang Hal , Hunter Andrew , Kulkarni Prathit , Rodriguez-Barradas Maria C 
Published: October 2019

Abstract

Background
Diagnosis of urinary tract infections (UTI) vs. asymptomatic bacteriuria (ASB) is challenging and inappropriate treatment of ASB is common. PAIF to prescribers decreases inappropriate antimicrobial use.We postulated that a quality improvement strategy using PAIF aimed at interpretation of UCx would reduce antimicrobials for ASB.

Methods
Single-center QI project to evaluate PAIF for positive UCx on Veterans admitted from December 11/2018 - 3/27/2019 to medicine teaching services at a VA Medical Center. Residents and hospitalists received an educational conference on UTI diagnosis one month prior to PAIF initiation. Using available software (Theradoc®), an electronic alert was created to notify 3 project physicians of every positive UCx ( >10K CFU). Chart review was performed against a diagnostic algorithm for UTI based on the 2011 IDSA guidelines. Feedback was provided by a phone call to residents caring for these patients.

Results
Charts of all 211 patients with positive UCx (mean age 74 y, 98% male) were audited within 72 hours of culture positivity. Of this group, 38% (80/211) were diagnosed as UTI by auditors vs. 45% (94/211) diagnosed as UTI by providers (P = 0.24). Between auditor diagnosis at 72 hours and provider diagnosis at discharge, an absolute inter-rater agreement of 94% (Cohen’s kappa 0.86) was observed. In 7% (14/211) of cases, the auditor diagnosed ASB, but the patient later received treatment for UTI. Auditors recommended discontinuation of antimicrobials for 8 of these 14 patients. For these 8 patients who received feedback, antimicrobials were discontinued in 4 cases. In the other 6 inappropriately treated ASB, providers had not started antimicrobials at the time of the audit, but later treated for UTI. No recommendation for starting antimicrobials was made by auditors.

Conclusion
Providers who had been exposed to academic detail on ASB, appropriately diagnosed UTI in the majority of their patients. Auditor and provider disagreements were rare, thus need for intervention was low. However, a small portion of patients still received antimicrobials for ASB. We are now exploring PAIF for urinalysis interpretation—an earlier upstream clinical decision point—and reviewing outcomes on those assessed as ASB.

Disclosures
All authors: No reported disclosures.
1116. Impact of Antimicrobial Stewardship Incentive Goals for Pharmacists on Overall Antibiotic Use and Appropriate Duration of Therapy in Urinary Tract Infections
Authors: Miller Matthew A , Huffman Mattie , Neville Nichole , Huang Misha , Barber Gerard 
Published: October 2019

Abstract

Background
Urinary tract (UTI), skin and soft tissue, and respiratory infections are among the most frequently reported indications for antibiotics, such that focusing stewardship efforts here would expectedly have dramatic effects. Antimicrobial stewardship (AMS) programs vary in structure and available resources. At the University of Colorado Hospital, a 740-bed academic medical center, dedicated resources for AMS are limited to a pharmacist, pharmacy resident, and physician; however, there is a large clinical pharmacist group. For the past 2 years, pharmacy management incorporated AMS targets as group goals tied to performance bonuses.

Methods
This is a descriptive report utilizing incentives to achieve AMS goals. The first goal (July 1, 2016 to June 30, 2017) set out to reduce inpatient antibiotic use by 10%. The second goal (July 1, 2018 to June 30, 2018) was a 10% reduction in median antibiotic duration for UTIs. The AMS team provided guidelines, education, and oversight throughout target periods. Antibiotic use was calculated as days of therapy (DOT) per 1000 patient-days. Data related to UTI treatment was collected retrospectively on a quarterly basis. This was compared with baseline data previously collected during a statewide hospital stewardship collaborative project.

Results
During the first period, overall antibiotic use declined from 497 to 403 DOT per 1000 patient-days (18.9%), and broad-spectrum antibiotic use declined 22%. During the second period, 30 patient charts were reviewed quarterly, and the median UTI duration declined from 10 to 7 days (P = 0.002). The most common UTI diagnoses were similar between periods with complicated cystitis and pyelonephritis comprising 60–70% of cases. The 30-day readmission rate was not different between the baseline and goal period, 11% vs. 6% respectively (P = 0.18).

Conclusion
The use of group pharmacist goals tied to annual performance bonuses was effective in achieving AMS goals at our institution. In larger facilities with fewer dedicated AMS personnel, clinical pharmacists covering ward and intensive care units are an essential resource to achieving AMS goals. Group performance incentives may be a feasible strategy to generate interest and motivation to achieve AMS program goals.

Disclosures
All authors: No reported disclosures.
1134. Antibiotic Indications and Appropriateness in the Pediatric Intensive Care Unit: A 10 Center Point Prevalence Study
Authors: Chiotos Kathleen , Blumenthal Jennifer , Boguniewicz Juri , Palazzi Debra , Berkman Emily , Crandall Hillary , Stalets Erika , Rubens Jessica , Desilva Stephanie , Kavanagh Robert , Stinson Hannah , Liston Kellie , Gerber Jeffrey 
Published: October 2019

Abstract

Background
Antibiotics are prescribed in up to 80% of pediatric intensive care unit (PICU) patients, but multicenter studies systematically evaluating antibiotic indications and appropriateness in this high-utilizing population are lacking.

Methods
A multicenter point prevalence study was conducted at 10 geographically diverse tertiary care US children’s hospitals. All PICU patients < 21 years of age who were receiving systemic antibiotics at 8:00 AM on each study day were included. Study days occurred in February and March 2019. Data were abstracted by critical care and/or infectious diseases trained clinicians using standardized data collection forms and definitions of antibiotic appropriateness.

Results
408 of 732 PICU patients (56%) received 618 antibiotics on the two study days. Empiric therapy for suspected bacterial infections without sepsis was the most common indication for antibiotics (22%), followed by treatment of community-acquired pneumonia and empiric therapy for septic shock (12% each, Figure 1). Overall, 194 antibiotic orders (32%) were classified as inappropriate and 158 patients (39%) received at least one inappropriate antibiotic. Vancomycin, cefepime, and ceftriaxone were the antibiotics most often inappropriately prescribed (Figure 2). Antibiotics prescribed inappropriately for the top 5 indications shown in Figure 1 accounted for 77% of all inappropriate antibiotic use. Prolonged ( >4 days) empiric therapy and prolonged ( >24 hours) post-operative prophylaxis were the most common reasons antibiotics prescribed for these indications were classified as inappropriate. Pneumonia and ventilator-associated infections were the most common infections for which antibiotics were prescribed inappropriately (46%). Reasons for inappropriate antibiotic use included lack of evidence supporting a bacterial infection (no radiographic infiltrate or significant increase in respiratory support) and use of unnecessarily broad antibiotics (Table 1).

Conclusion
Inappropriate antibiotic use is common in the PICU, particularly for pneumonia. Studies focused on defining optimal treatment strategies, as well as improved diagnostic approaches to curtail prolonged courses of empiric therapy, should be prioritized.

Disclosures
All authors: No reported disclosures.
LB7. A Randomized, Blinded, Placebo- and Vancomycin-Controlled, First-In-Human (FIH) Study of the Safety, Pharmacokinetics (PK), and Fecal Microbiome Effects of ACX-362E, a Novel Anti-Clostridial DNA Polymerase IIIC (polIIIC) Inhibitor
Authors: Garey Kevin W , Garey Kevin W , Kankam Martin , Mercier Julie , Seng Yue Corinne , Ducharme Murray , Gonzales-Luna Anne J , Gonzales-Luna Anne J , Jahangir Alam M , Begum Khurshida , Begum Khurshida , Silverman Michael 
Published: October 2019

Abstract

Background
ACX-362E, a novel DNA polIIIC inhibitor, is a narrow-spectrum antibacterial selectively active against certain Gram-positive bacteria, including Clostridioides difficile (MIC90 = 4 µg/mL). The objectives of this phase I study was to assess the safety, pharmacokinetics, and fecal microbiome effects of ACX-362E

Methods
This three-part FIH phase 1, double-blind, randomized healthy volunteer trial determined the safety profile, food effect, and systemic/stool pharmacokinetics of escalating single (150, 300, 600, and 900 mg) and multiple (300 and 450 mg) doses of oral ACX-362E vs. placebo (PBO). Fecal microbiome effects (metagenomic sequencing and qPCR) of multiple-dose ACX-362E were compared with 6 subjects receiving concomitant open-label vancomycin 125 mg four times daily. Dose escalation to each new cohort occurred following review of safety and PK data by a safety oversight committee.

Results
Forty-four subjects received ACX-362E (single dose = 24, multiple doses = 12, food effect = 8) and 12 PBO. Overall, ACX-362E was well tolerated at all dose levels. Adverse events were generally mild and transitory, and no moderate, severe, cumulative, or dose-limiting drug-related adverse events leading to discontinuation were observed. Mean plasma half-life was approximately 2 hours and no accumulation occurred with repeated dosing (Figure 1). Systemic exposure was less than 1 μg/mL and decreased with food. Fecal concentrations during multiple dosing exceeded the C. difficile MIC by multiples of up to ~2,500. ACX-362E had minimal effect on Bacteroidetes phylum and caused significantly less dysbiosis than vancomycin (Figure 2).

Conclusion
This FIH clinical trial with ACX-362E demonstrated a favorable safety profile, low systemic and high fecal concentrations, and favorable gut microbiome changes compared with vancomycin. These results shows promise for further clinical development to treat C. difficile infections.

Disclosures
Kevin W. Garey, MS, PharmD, Acurx (Grant/Research Support), Martin Kankam, MD, PhD, MPH, Acurx Pharmaceuticals, LLC (Research Grant or Support), Julie Mercier, BS, Acurx Pharmaceuticals, LLC (Research Grant or Support), Corinne Seng Yue, BPharm, MSc, PhD, Acurx Pharmaceuticals, LLC (Grant/Research Support), Murray Ducharme, PharmD, Acurx Pharmaceuticals, LLC (Grant/Research Support), Anne J. Gonzales-Luna, PharmD, no financial relationships or conflicts of interest, M Jahangir Alam, PhD, No financial relationships or conflicts of interest, Khurshida Begum, PhD, No financial relationships or conflicts of interest, Michael Silverman, MD, Acurx Pharmaceuticals, LLC (Consultant, Employee, Shareholder).
Effects of various ractopamine hydrochloride withdrawal periods on performance, health, and carcass characteristics in yearling steers
Authors: Bryant Tony C , Szasz Josh I , Pringle Lois F G , Crispe Eddie , Shawn Blood K , Bernhard Bryan C , Hughes Heather D 
Published: October 2019

Abstract
Ractopamine hydrochloride (RAC) is a β-adrenergic agonist approved for feeding during the last 28 to 42 d prior to cattle slaughter to improve feedlot performance and carcass characteristics. Three thousand crossbred yearling steers (527 ± 2.4 kg; AVG ± SD) were used in two periods to evaluate the effects of various RAC withdrawal times on feedlot performance, health, and carcass characteristics. In Period 1, 6 blocks of 30 pens totaling 1,500 steers were utilized, which was repeated for Period 2. In a randomized complete block design, cattle were assigned to 1 of 5 treatments consisting of 1) No RAC fed (CON), 2) 12-h RAC withdrawal (12-hRAC), 3) 2-d RAC withdrawal (2-dRAC), 4) 4-d RAC withdrawal (4-dRAC), and 5) 7-d RAC withdrawal (7-dRAC). Cattle were fed for a total of 62 d, and applicable treatments were supplemented with 30.0 ppm (dry matter basis) of RAC (average dose = 322 mg per steer per day) for 33 d at the end of the feeding period, corresponding to their respective withdrawal times. Initial body weight (BW) displayed a quadratic curve, with 2-dRAC and 4-dRAC withdrawal periods having the greatest BW. Accordingly, dry matter intake (DMI) responded quadratically (P = 0.034), with 2-dRAC and 4-dRAC treatments demonstrating the greatest DMI. No significant treatment differences (P ≥ 0.641) were observed in final live BW, average daily gain (ADG), or feed efficiency. Alternatively, when using a common dressing percentage to calculate live BW, cattle on RAC treatments exhibited 7.6 kg additional live BW (P &lt; 0.001) compared to CON cattle. Furthermore, carcass-adjusted ADG and feed efficiency did not differ (P &gt; 0.10) between RAC treatments but were improved compared to the CON treatment (P ≤ 0.002). Hot carcass weight (HCW) was on average 4.9 kg greater (P &lt; 0.001) for RAC treatments vs. CON, and no differences were detected (P &gt; 0.10) among RAC treatments. Within RAC treatments, carcass cutability responded quadratically (P ≤ 0.005) to withdrawal period, with the 2-dRAC and 4-dRAC treatments containing more Yield Grade 4 and 5 and fewer Yield Grade 1 and 2 carcasses than the other RAC treatments. On the basis of the results of this experiment, feeding RAC improves dressing percentage, HCW, and carcass-adjusted BW, ADG, and feed efficiency. Furthermore, extending the RAC withdrawal period to 7 d does not have a significant impact on cattle performance or health and has minimal effects on carcass characteristics.
Discerning the effects of phosphate status on the metabolism of hybrid poplar
Authors: Da Ros Letitia M , Soolanayakanahally Raju Y , Mansfield Shawn D 
Published: October 2019

Abstract
Accumulation of phosphate in leaves as external environmental phosphate concentrations increase has been observed across the plant kingdom. The excess storage of anions, such as phosphate, has various metabolic trade-offs, including a corresponding influx of counter-ions to maintain charge balance and/or the reduction in organic acid content to maintain internal pH. The leaves and roots of four hybrid poplar genotypes were tested for differences in metabolic response to increasing external phosphate and further effects on patterns of anion resorption among hybrid poplar and willow were explored. Organic acid concentrations increased or remained constant across treatments, suggesting that metabolic adjustments were made in response to greater influxes of inorganic cations rather than a response to increasing phosphate. During senescence, the hybrid poplar Tristis had higher sulfate and organic acid resorption, while hybrid willow, AAFC-5, had higher phosphate resorption proficiencies, suggesting differing anion remobilization mechanisms. Furthermore, phosphate accumulation was shown to continue well after bud-set in poplar hybrids, which may contribute to the low phosphorus resorption efficiency. This indicates that closely related species, with similar growth strategies, show preferential resorption toward different nutrients.
A new Southern Ocean species in the remarkable and rare amphipod family Podosiridae (Crustacea: Amphipoda) questions existing systematic hypotheses
Authors: Ashford Oliver S , Horton Tammy , Roterman Christopher N , Thurston Michael H , Griffiths Huw J , Brandt Angelika 
Published: October 2019

Abstract
The amphipod family Podosiridae is unusual in that it combines morphological elements of the disparate families Podoceridae and Eusiridae. Here, we describe a new species in the family from specimens collected from the Southern Ocean in the vicinity of the South Orkney Islands and South Shetland Islands. We present mitochondrial (COI and 16S) and nuclear (18S) nucleic acid sequences for this and a congeneric species and use these to investigate the phylogenetic placement of Podosiridae within the Amphipoda. Our results do not provide evidence for a close relationship between Podosiridae and Podoceridae or Eusiridae, suggesting that the superficial similarity between these families is the result of morphological convergence. Instead, it is likely that Podosiridae are more closely related to families within Amphilochidira, such as Stenothoidae. Definitive placement of Podosiridae in the Amphipoda awaits further specimen collection, additional nucleotide data (including sequences from the Hyperiopsidae and the Vitjazianidae) and a more directed analysis of relationships within this portion of the amphipod phylogeny.