bluuebunny/crossref_metadata_2025 huggingface dataset:
1056. Evaluation of Clinical Outcomes Following Implementation of Real-Time Stewardship Team Interventions for Multi-Drug-Resistant Organisms
Authors: Xhemali Xhilda , Patel Twisha S , Eschenauer Gregory , Lew Alison , Kaye Keith S , Albin Owen , Nagel Jerod
Published: October 2019

Background

Infections due to multidrug-resistant organisms (MDRO) are associated with an increased risk of mortality. Accurate assessment of culture results and prompt initiation of effective antibiotic therapy have the potential to improve patient outcomes. The purpose of this study was to assess the time to effective therapy and associated clinical outcomes following the implementation of real-time stewardship alerts for infections due to MDRO.

Methods

This pre–post quasi-experimental study identified patients admitted to Michigan Medicine with a positive culture for one of 14 pre-defined MDRO. An alerting system was implemented within the institution’s electronic health record (EHR) in October 2018, which notifies the antimicrobial stewardship (ASP) pharmacist upon detection of an MDRO, regardless of source. The ASP pager is monitored 24/7 by a clinical pharmacy specialist who reviews the patient’s chart and recommends antibiotic modifications if necessary. In the pre-intervention period, no structured alerting or assessment was performed. Inclusion: ≥18 years old and trigger of an alert. Exclusions: pediatric service, cystic fibrosis, discharged or deceased prior to alert sensitivities, outside hospital (OSH) transfer growing identical organism upon admission, culture contamination or colonization. The primary outcome of time to effective therapy is determined from time of alert for MDRO to the order time of the effective antimicrobial agent. Secondary outcome measures include: length of stay, 30-day all-cause mortality, and 30-day readmission.

Results

152 alerts were included in the study (post, n = 75 and pre, n = 77). Outcomes were assessed in patients not on effective therapy at the time of alert (68.0% vs. 70.1%). Time to effective therapy was significantly improved in the intervention group (2.08hours vs. 3.72hours, P = 0.0010). Length of stay (18 days vs. 15.5 days, P = 0.1662) and 30-day all-cause mortality (17.6% vs. 18.5%, P = 0.9088) were not different between groups. However, 30-day readmission rates were significantly reduced with the intervention (21.4% vs. 43.2%, P = 0.0316).

Conclusion

Real-time stewardship team interventions for infections due to MDRO improve time to effective therapy and are associated with a decrease in hospital readmissions.

Disclosures

All authors: No reported disclosures.
1060. Impact of Laboratory Cessation of Extended-Spectrum β-Lactamase (ESBL) Reporting on Minimum Inhibitory Concentration (MIC) Distribution Trends and Associated Clinical Outcomes
Authors: Chiang Anthony , Beganovic Maya , Dela-Pena Jennifer , Gandhi Kelvin , Miller Jessica , LaChance Erik , Anderson Morgan , Wieczorkiewicz Sarah
Published: October 2019

Background

The Clinical and Laboratory Standards Institute (CLSI) lowered the minimum inhibitory concentration (MIC) breakpoints of various β-lactam antimicrobials eliminating the need for confirmatory testing of extended-spectrum β-lactamase (ESBL) organisms. Our institution adopted the new CLSI breakpoints in June 2015. This multi-site study assessed the impact of laboratory cessation of ESBL reporting on the MIC distribution of commonly used antimicrobials and clinical outcomes.

Methods

This retrospective study included adult inpatients with positive blood cultures for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis from June 2012 to June 2018. Patients were included in the pre-implementation group if they had an ESBL-positive blood culture from June 2012 to May 2015 and in the post-implementation group if they had a ceftriaxone-resistant organism from June 2015 to June 2018. Patients who died or transitioned to hospice within 48 hours of blood culture identification or before final susceptibilities were excluded. The primary outcome was MIC distribution of ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, fluoroquinolones, and carbapenems. Secondary outcomes were antimicrobial prescribing patterns, 30-day all-cause mortality, 30-day re-infection rate, and time to microbiological clearance.

Results

A total of 249 patients were included (n = 40, pre-implementation; n = 209, post-implementation). Pitt Bacteremia Scores were significantly higher in the pre-implementation group (3.59 ± 2.85 vs. 2.21 ± 2.06; P = 0.0004). The median MIC distribution for each antimicrobial stayed within one dilution throughout the study timeframe. Carbapenem use decreased in the post-implementation group [n = 35 (87%) vs. n = 131 (63%)]. No significant differences were noted for other secondary outcomes: 30-day all-cause mortality (15% vs. 10%; P = 0.40), 30-day re-infection rate (2.5% vs. 4.3%; P = 1), and time to microbiological clearance (2.28 ± 1.2 vs. 2.41 ± 1.76 days; P = 0.72).

Conclusion

Adoption of lowered CLSI breakpoints did not impact MIC distribution of select antimicrobials for Enterobacteriaceae; however, it has affected antimicrobial prescribing patterns.

Disclosures

All authors: No reported disclosures.
1061. Decreased Utilization of Piperacillin–Tazobactam for Escherichia coli and Klebsiella Bacteremia due to Selective Susceptibility Reporting
Authors: Zahlanie Yorgo , Hall Brenton , Wei Wenjing , Mang Norman , Ortwine Jessica , Anderson Shelby S , Morgan Kristi , Guzman Tamara , Prokesch Bonnie C
Published: October 2019

Background

Over 2 million people in the United States are diagnosed with antibiotic-resistant infections annually. The Infectious Diseases Society of America (IDSA) recommends cascade reporting of antibiotic susceptibility data by the clinical microbiology laboratory as an intervention to decrease resistance, though this is based on low-quality evidence.

Methods

We conducted a retrospective study to assess the effect of cascade susceptibility reporting on prescribing practices and patient outcomes. A cascaded testing algorithm was executed wherein susceptibility data for piperacillin–tazobactam (PT) was suppressed from the susceptibility report if an organism was susceptible to ceftriaxone. Patients with positive monomicrobial blood cultures with non-ESBL Escherichia coli (E. coli) or Klebsiella isolates in blood cultures and receiving empiric PT were included. Data were collected one year prior and one year after cascading protocol implementation, and included patient demographics, length of stay (LOS), duration of antibiotics, time to de-escalation, and adverse events including acute kidney injury (AKI) and Clostridioides difficile infection (CDI).

Results

212 patients (108 pre-intervention and 104 post-intervention) were included. 87% of patients were de-escalated from PT pre-intervention, while 90% were deescalated post-intervention. Mean time to deescalation decreased from 30 hours before to 17 hours after cascade implementation (P = 0.02) (Figure 1). Median LOS decreased from 15 to 10 days following the intervention (P = 0.12). While the rate of AKI increased from 14 to 19% post-intervention (P = 0.89), the rate of CDI (2 vs. 2 patients) was comparable among both cohorts (P = 0.97) (Figure 2).

Conclusion

While cascade susceptibility reporting is recommended by the IDSA as a tool for antimicrobial stewardship, this recommendation has weak support due to paucity of data. In this study, we found that selective susceptibility reporting has the potential to decrease the use of PT and to reduce LOS in patients with E. coli and Klebsiella bacteremia. Further research to better identify patient populations most impacted by a cascade algorithm and its overall effectiveness as a stewardship tool is needed.

Disclosures

All authors: No reported disclosures.
1063. A Healthcare Worker-Informed Approach to the Hospital-to-Home Transition on Oral Antibiotics
Authors: Sharara Sima L , Cosgrove Sara E , Cosgrove Sara E , Arbaje Alicia , Gurses Ayse P , Dzintars Kate , Keller Sara C
Published: October 2019

Background

Improved antibiotic decision-making during the hospital-to-home transition is an important but under-addressed target for antimicrobial stewardship. This study aims to provide a healthcare worker-informed approach to characterize prescriber antibiotic decision-making and patient medication management at discharge to identify barriers to and strategies for antibiotic stewardship during the hospital-to-home transition.

Methods

Semi-structured interviews were conducted at an academic medical center with relevant stakeholders including house staff (n = 10), nurses (n = 2), nurse practitioners (n = 5), inpatient pharmacists (n = 4), and discharge coordinators (n = 2). Interviews focused on challenges to antibiotic decision-making and patient medication management at discharge. Transcripts were independently coded and analyzed by two physicians using the constant comparative method.

Results

We identified four main barriers to antibiotic decision-making at hospital discharge: (1) uncertainty over antibiotic choice (due to lack of microbiology data), (2) pressure to discharge, (3) lack of control over antibiotic decision-making (attending-led decision with little room for input), and (4) lack of awareness of cost and insurance coverage. We also identified challenges to patient medication management specific to patient education: (1) role ambiguity around who provides education and (2) lack of education to patients around side effects. To improve antibiotic decision-making, prescribers relied heavily on institutional guidelines and interaction with experts in informing antibiotic choices, and used multidisciplinary approaches to verify antibiotic cost and availability. Five strategies to improve medication management were proposed: (1) assessing patient health literacy when providing instructions, (2) an in-hospital trial of the oral antibiotic to ensure tolerance, (3) ensuring the patient leaves the hospital with the antibiotic in hand, (4) care coordination after discharge, and (5) close follow-up with prescribers after discharge.

Conclusion

Our findings identify barriers to discharge antibiotic decision-making and medication management that allow for targeted interventions to improve antibiotic decision-making during the hospital-to-home transition.

Disclosures

Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
1069. Implementation and Results of a Health-System Antimicrobial Stewardship (AMS) Program
Authors: Boldt Dayla , Anthone Jennifer , Alexander Bryan , Ased Sumaya J , Carroll Cassara , Schmidt David , Destache Christopher J , Vivekanandan Renuga
Published: October 2019

Background

AMS expansion initiative was implemented in fiscal year 18 (FY18) across a 14-member health system (~1,000 average daily census combined) consisting of 8 community hospitals, 5 rural critical access hospitals and 1 academic medical center.

Methods

The expansion initiative included a 0.5 full-time equivalent (FTE) infectious diseases (ID) physician and 2.5 FTE ID-trained clinical pharmacists to support daily AMS activities. Clinical decision support software (Theradoc) had previously been implemented across the health system. Here we report our continuation results for the first 9 months of year 2 (FYTD19) of the expansion initiative.

Results

AMS personnel documented an average of 319.8 and 313.2 interventions per month in FY18 vs. FYTD19, respectively. Mean acceptance rate of AMS interventions by providers was 87.9% and 89.4% in FY18 vs. FYTD19. Provider groups with the highest acceptance rate were Hospital Medicine, Pulmonary/Critical Care and Infectious Disease. Highest interventions in FYTD19 included recommending other diagnostic testing (17%) followed by de-escalating/targeting therapy based on culture results and recommending alternative therapy (both at 11%). Most common ID disease states AMS intervened included bacteremias (29%), pneumonias (ventilator-associated or community-acquired) 13% each, and UTIs 13%. AMS interventions generated 168 ID consults in FYTD19. The financial impact of AMS across the health system was a cumulative saving in antimicrobial expenditures of $1.29 million and $1.27 million in FY18 and FYTD19, respectively.

Conclusion

The ability to review offsite electronic medical records daily for antimicrobial optimization with ID pharmacist and physician support, identify facility-specific needs and opportunities, and collect available data endpoints to determine program effectiveness has helped to ensure program success.

Disclosures

All authors: No reported disclosures.
1082. Hold the Phone: Antibiotic Prescribing Practices Associated with Nonvisit Encounters for Urinary Tract Infections (UTIs) in Urology Clinics
Authors: Akbar Nina , Dobson Erica L , Keefer Michael , Munsiff Sonal , Dumyati Ghinwa
Published: October 2019

Background

Surveillance data uncovers a high proportion of multidrug-resistant Gram-negative organisms found in the outpatient setting, often in patients with recurrent urinary tract infections (UTIs), underlying urologic abnormalities, and prior treatment for UTIs. We assessed prescribing practices at urology clinics to identify potential stewardship strategies for UTI management.

Methods

Antibiotic prescription encounters for adult patients from nine urology clinics were obtained from July to September 2018 using the EHR. We collected encounter types (visit or nonvisit), ordering medical provider types, antibiotic classes and patient demographics. A subset of 50 randomized, unique patient telephone encounters (TEs) was reviewed for documentation of a UTI diagnosis, symptoms, urinalysis and culture results, antibiotic prescriptions and duration.

Results

A total of 1,704 antibiotic orders were identified for 1,210 patients (48% female, median age 69 years, IQR 20). The majority (75%) of antibiotic encounters were from nonvisits: TEs (39%), orders only (25%), refills (9%), and patient email (2%). Major prescribers were advanced practice providers (APPs, 61%) followed by attending physicians (38%). Antibiotics prescribed were fluoroquinolones (FQs, 27%), nitrofurantoin (24%), first-generation cephalosporins (16%), and trimethoprim–sulfamethoxazole (15%). From the subset of 50 TEs, APPs wrote 76% of prescriptions and 32% of all orders were FQs. Thirty-nine patients had a clinical UTI diagnosis, yet 33% (13/39) did not have documentation of at least one urinary sign or symptom. For symptomatic patients, 15% (4/26) did not have a urine culture result within one week before or after the TE date. The distribution of antibiotics prescribed was similar to overall use and the median duration was 7 days.

Conclusion

Urology practices care for patients with the most complicated urinary tract pathology and appropriate antibiotic use in this population is a challenge. We found that urology providers often prescribe antibiotics to elderly patients without in-person visits, documentation of symptoms or microbiologic evidence of a UTI. Stewardship efforts should involve APPs, developing diagnostic and treatment guidelines for UTIs and improving documentation for antibiotic orders.

Disclosures

All authors: No reported disclosures.
1089. Implementation of a Febrile Neutropenia Management Algorithm on Antibiotic Use and Outcomes: An Interrupted Time Series Analysis
Authors: Trinh Trang D , Strnad Luke , Damon Lloyd E , Dzundza John H , Graff Larissa R , Griffith Laura M , Hilts-Horeczko Alexandra , Olin Rebecca L , Shenoy Samantha , DeVoe Catherine , Wang Lusha , Rodriguez-Monguio Rosa , Doernberg Sarah B
Published: October 2019

Background

Febrile neutropenia (FN) is a common complication of cancer therapy and often necessitates prolonged antibiotic treatment. Antibiotic de-escalation can be challenging given tenuous clinical status. Furthermore, a microbiological or clinical etiology is identified in a minority of FN patients. In 2016 we implemented several evidence-based strategies to guide antibiotic use in high-risk FN patients including specifying vancomycin use indications, minimizing carbapenem escalation in stable patients with ongoing fevers, and defining antibiotic durations regardless of neutrophil count. The study objective was to characterize and evaluate our experience implementing these strategies on antibiotic use and clinical outcomes.

Methods

Interrupted time series analysis of all admissions to the Malignant Hematology service at the University of California, San Francisco between June 2014 and December 2018. The primary outcome was monthly days of therapy (DOT) per 1,000 patient-days of broad-spectrum IV antibiotics (aztreonam, cefepime, piperacillin–tazobactam, meropenem, and vancomycin). Secondary outcomes included DOT/1,000 patient-days for each IV antibiotic, incidence rates of bloodstream infections (BSI) and C. difficile infections (CDI), and in-hospital all-cause mortality. A segmented regression analysis was conducted to evaluate the impact of the FN management algorithm implementation on antibiotic use and clinical outcomes. Summary statistics and time series scatter plots were used to visualize the trends and outliers.

Results

2319 unique patients with 6,788 encounters were included. The median (IQR) age was 59 (46–68) years and 60% were male. Regression results and time series plots are shown in Table 1 and Figures 1–3.

Conclusion

Implementation of an evidence-based FN management algorithm led to decreased vancomycin and meropenem use without a statistically significant impact on overall antibiotic use, CDI rates, or mortality.While BSI rates fluctuated in the 2 months post-implementation, rates returned to baseline thereafter. A multidisciplinary effort facilitated successful implementation of this stewardship project. This collaboration remains essential to addressing future antimicrobial management strategies in this population.

Disclosures

All authors: No reported disclosures.
1095. Prevalence and Characteristics of Self-Reported Antibiotic Allergies Across a Multi-Hospital Healthcare System
Authors: Perez Katherine K , Drake Ty C , Fuentes Amaris , Gentry Clare N
Published: October 2019

Background

Collaborations between medication safety and antimicrobial stewardship programs (ASP) have not been well described despite many overlapping best practice initiatives. In partnership with medication safety, the ASP at Houston Methodist (HM) reviews patient safety events submitted by hospital staff and identified a best practice opportunity in allergy reporting practices. Our objective was to benchmark self-reported antibiotic allergies among hospitalized patients and compare the prevalence and characteristics among hospital settings.

Methods

We evaluated the prevalence of self-reported antibiotic allergies in the electronic medical record for adult patients admitted to any HM entity including 1 flagship referral center (933-beds) and 6 community-based hospitals (1,379-beds) in January 2019. Antibiotics were grouped by class into penicillins, sulfas, cephalosporins, tetracyclines, macrolides, quinolones, and others. Point-prevalence rates were calculated using the total patient count as the denominator.

Results

There were 4,730 patients admitted to HM in January 2019 of which 85% (n = 4,029) self-reported 9,186 active drug allergies. There were 2,353 (49.7%) individuals who self-reported 3,665 antibiotic allergies, of which 987 (21%) reported an allergy to ≥2 antibiotic classes. The prevalence rate for a penicillin allergy was highest at 26.1% (n = 1,235), followed by allergy to sulfa 15.9% (n = 751) and quinolones 7.9% (n = 411). Antibiotic allergies were most prevalent in patients aged 70–79 (11%, n = 518) and 60–69 (10%, n = 495). Antibiotic allergies were higher among females (61.6%; n = 1,679/2,724) compared with males (40.7%; n = 662/1,305) (P = 0.002). There was no difference in prevalence rates between community-based hospitals and the flagship institution (P = 0.51).

Conclusion

We identified an antibiotic allergy point prevalence rate of 49.7% among hospitalized patients, including a 26.1% rate to penicillin, across our 7-hospital system. This analysis provides a road map to deploy system-wide efforts to improve antibiotic detailing in patients regardless of the hospital setting.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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 < 0.001) compared to CON cattle. Furthermore, carcass-adjusted ADG and feed efficiency did not differ (P > 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 < 0.001) for RAC treatments vs. CON, and no differences were detected (P > 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

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

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.
Mechanosensitive transcriptional coactivators MRTF‐A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape
Authors: Fearing Bailey V. , Jing Liufang , Barcellona Marcos N. , Witte Savannah Est , Buchowski Jacob M. , Zebala Lukas P. , Kelly Michael P. , Luhmann Scott , Gupta Munish C. , Pathak Amit , Setton Lori A.
Published: October 2019

Cells of the adult nucleus pulposus (NP) are critically important in maintaining overall disc health and function. NP cells reside in a soft, gelatinous matrix that dehydrates and becomes increasingly fibrotic with age. Such changes result in physical cues of matrix stiffness that may be potent regulators of NP cell phenotype and may contribute to a transition toward a senescent and fibroblastic NP cell with a limited capacity for repair. Here, we investigate the mechanosignaling cues generated from changes in matrix stiffness in directing NP cell phenotype and identify mechanisms that can potentially preserve a biosynthetically active, juvenile NP cell phenotype. Using a laminin‐functionalized polyethylene glycol hydrogel, we show that when NP cells form rounded, multicell clusters, they are able to maintain cytosolic localization of myocardin‐related transcription factor (MRTF)‐A, a coactivator of serum‐response factor (SRF), known to promote fibroblast‐like behaviors in many cells. Upon preservation of a rounded shape, human NP cells similarly showed cytosolic retention of transcriptional coactivator Yes‐associated protein (YAP) and its paralogue PDZ‐binding motif (TAZ) with associated decline in activation of its transcription factor TEA domain family member‐binding domain (TEAD). When changes in cell shape occur, leading to a more spread, fibrotic morphology associated with stronger F‐actin alignment, SRF and TEAD are up‐regulated. However, targeted deletion of either cofactor was not sufficient to overcome shape‐mediated changes observed in transcriptional activation of SRF or TEAD. Findings show that substrate stiffness‐induced promotion of F‐actin alignment occurs concomitantly with a flattened, spread morphology, decreased NP marker expression, and reduced biosynthetic activity. This work indicates cell shape is a stronger indicator of SRF and TEAD mechanosignaling pathways than coactivators MRTF‐A and YAP/TAZ, respectively, and may play a role in the degeneration‐associated loss of NP cellularity and phenotype.—Fearing, B. V., Jing, L., Barcellona, M. N., Witte, S. E., Buchowski, J. M., Zebala, L. P., Kelly, M. P., Luhmann, S., Gupta, M. C., Pathak, A., Setton, L. A. Mechanosensitive transcriptional coactivators MRTF‐A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape. FASEB J. 33, 14022‐14035 (2019). www.fasebj.org