bluuebunny/crossref_metadata_2025_split huggingface dataset:
237. Inpatient and Discharge Antibiotic Use for Hospitalized Patients Growing Multi-Drug Resistant Bacteria in Urine Cultures
Authors: Zou James , Boly Frances , Stwalley Dustin , Olsen Margaret A , Kwon Jennie H , Burnham Jason P 
Published: January 2021

Abstract

Background
Multidrug resistant organism (MDRO) infections are a threat to public health. Urinary tract infections (UTIs) are the most common MDRO infection and are responsible for a significant proportion of antibiotic use. Studies demonstrate both duration and type of antibiotics prescribed to patients with MDRO UTI are inappropriate, and that asymptomatic MDRO bacteriuria is inappropriately treated. In addition, antibiotics prescribed at hospital discharge are inappropriate in ~70% of patients. We sought to characterize inpatient and outpatient antibiotic durations to describe burden of antibiotic use for patients with an MDRO isolated from a urine specimen during a hospitalization.

Methods
This retrospective study was conducted at Barnes-Jewish Hospital, a 1266-bed academic medical center in St. Louis, Missouri from 11/7/12-11/7/17. Patients ≥ 18 years of age were included if they had an MDRO isolated from a urine specimen and no other positive bacterial cultures during their hospitalization. Demographics, comorbidities, cultures, and antibiotics were collected via data pulls and chart review. MDROs were defined according to European and US Center for Disease Control and Prevention guidelines. Antibiotic use was described as percentages of all antibiotics used.

Results
A total of 1052 patients had MDROs in urine cultures. Of these patients, 747 (71.0%) were discharged on oral antibiotics for a mean duration of 6.7 days, while 135 (12.8%) were discharged on IV antibiotics for a mean of 10.9 days. The five most commonly administered inpatient antibiotics after urine culture results were available (% prescribed) were IV ceftriaxone (43.0%), IV vancomycin (26.0%), PO ciprofloxacin (25.6%), IV cefepime (24.5%), and PO trimethoprim-sulfamethoxazole (17.6%). The five most commonly prescribed antibiotics at discharge were PO ciprofloxacin (22.3%), PO trimethoprim-sulfamethoxazole (17.8%), PO nitrofurantoin (8.4%), PO cephalexin (6.2%), and PO doxycycline (5.0%).

Conclusion
Patients with MDROs in urine cultures receive prolonged durations of inpatient and outpatient antibiotics, longer than what is recommended by current evidence and guidelines.

Disclosures
Dustin Stwalley, MA, AbbVie Inc (Shareholder)Bristol-Myers Squibb (Shareholder) Margaret A. Olsen, PhD, MPH, Merck (Grant/Research Support)Pfizer (Consultant, Grant/Research Support)
238. Novel Way to Evaluate Antibiotic Use Appropriateness: Moving Towards the “Never Event” Classification by Electronic Algorithm
Authors: Patel Twisha S , Petty Lindsay A , Liu Jiajun , Scheetz Marc H , Mercuro Nicholas , Davis Susan L , Davis Susan L , Yarnold Paul R , Pais Gwendolyn M , Kaye Keith S 
Published: January 2021

Abstract

Background
Antibiotic use is commonly tracked electronically by antimicrobial stewardship programs (ASPs). Traditionally, evaluating the appropriateness of antibiotic use requires time- and labor-intensive manual review of each drug order. A drug-specific “appropriateness” algorithm applied electronically would improve the efficiency of ASPs. We thus created an antibiotic “never event” (NE) algorithm to evaluate vancomycin use, and sought to determine the performance characteristics of the electronic data capture strategy.

Methods
An antibiotic NE algorithm was developed to characterize vancomycin use (Figure) at a large academic institution (1/2016–8/2019). Patients were electronically classified according to the NE algorithm using data abstracted from their electronic health record. Type 1 NEs, defined as continued use of vancomycin after a vancomycin non-susceptible pathogen was identified, were the focus of this analysis. Type 1 NEs identified by automated data capture were reviewed manually for accuracy by either an infectious diseases (ID) physician or an ID pharmacist. The positive predictive value (PPV) of the electronic data capture was determined.
Antibiotic Never Event (NE) Algorithm to Characterize Vancomycin Use

Results
A total of 38,774 unique cases of vancomycin use were available for screening. Of these, 0.6% (n=225) had a vancomycin non-susceptible pathogen identified, and 12.4% (28/225) were classified as a Type 1 NE by automated data capture. All 28 cases included vancomycin-resistant Enterococcus spp (VRE). Upon manual review, 11 cases were determined to be true positives resulting in a PPV of 39.3%. Reasons for the 17 false positives are given in Table 1. Asymptomatic bacteriuria (ASB) due to VRE in scenarios where vancomycin was being appropriately used to treat a concomitant vancomycin-susceptible infection was the most common reason for false positivity, accounting for 64.7% of false positive cases. After removing urine culture source (n=15) from the algorithm, PPV improved to 53.8%.

Conclusion
An automated vancomycin NE algorithm identified 28 Type 1 NEs with a PPV of 39%. ASB was the most common cause of false positivity and removing urine culture as a source from the algorithm improved PPV. Future directions include evaluating Type 2 NEs (Figure) and prospective, real-time application of the algorithm.

Disclosures
Marc H. Scheetz, PharmD, MSc, Merck and Co. (Grant/Research Support)
242. Seasonality in antibiotic use and resistance across multiple bacterial pathogens and antibiotic classes
Authors: Sun Daphne S , Kissler Stephen M , Kanjilal Sanjat , Olesen Scott , Grad Yonatan H 
Published: January 2021

Abstract

Background
Antibiotic use is an important driver of antibiotic resistance. Previous studies have shown that this relationship is detectable on a seasonal timescale, where seasonally cycling antibiotic prescribing corresponds with cycling levels of resistance. Here, we evaluated the seasonal relationship between antibiotic use and resistance across multiple species and antibiotic classes in Boston, Massachusetts.

Methods
To conduct our study, we analyzed antibiotic claims data from the Massachusetts All Payers Claims Database for five antibiotic classes, beta-lactams, macrolides, quinolones, tetracyclines, and nitrofurans, which together account for 74% of the total outpatient antibiotic claims in this dataset. In addition, we analyzed antibiotic susceptibility data for clinical isolates collected from two tertiary care hospitals, focusing on three clinically important bacterial pathogens. Our analysis included a total of 131,815 Escherichia coli, 47,208 Staphylococcus aureus, and 27,237 Klebsiella pneumoniae isolates collected over the years 2007–2019, with susceptibility testing data for 5–6 antibiotics per species. To determine the extent of seasonality in use and resistance, we fit the antibiotic claims data for each antibiotic class and the minimum inhibitory concentration (MIC) data for each species-antibiotic combination to a sinusoidal model with either a 6 or 12-month period.

Results
We found that use of all 5 antibiotic classes and resistance in 9 out of 15 species-antibiotic combinations showed a significant amplitude of seasonality (p-value &lt; 0.05). Despite different seasonal peaks in antibiotic use across classes, resistance peaked in the winter for almost all species-antibiotic combinations and was most highly correlated with use of winter-peaking antibiotic classes, beta-lactams and macrolides.

Conclusion
Overall, these results suggest that co-resistance and “bystander” selection – selection for resistance in asymptomatically colonizing and potentially pathogenic bacteria that are not the direct target of treatment – mediate the effects of antibiotic prescribing on the landscape of resistance.

Disclosures
All Authors: No reported disclosures
254. Review of Clinical Outcomes in Patients Treated with Beta-lactam vs Non-beta-lactam Therapy for AmpC Producing Bacterial Bloodstream Infections
Authors: Staicu Mary L , Baumeister Tyler , Laguio-Vila Maryrose R 
Published: January 2021

Abstract

Background
AmpC beta-lactamase producing organisms are traditionally treated with carbapenem or fluoroquinolone antibiotics. Recent studies, however, describe similar clinical outcomes in patients that receive cefepime or piperacillin/tazobactam. We sought to assess outcomes in patients with bloodstream infections caused by AmpC-producing organisms that received beta-lactams compared non-beta-lactam therapy.

Methods
Data was obtained retrospectively from the electronic health record (EHR) from January 2012 to February 2020. The primary objective was 30-day mortality from the day of first positive blood cultures with Enterobacter spp., Citrobacter spp., or Serratia spp. in patients who received non-beta-lactam therapy (carbapenem, fluoroquinolone, trimethoprim/sulfamethoxazole) to those who received beta-lactam therapy (cefepime, piperacillin/tazobactam). Secondary objectives included 30-day recurrence of bacteremia, pathogen isolated, source of bacteremia, hospital length of stay, and duration of antimicrobial therapy.

Results
A total of 90 patients were included, 50 in the non-beta lactam group and 40 in the beta-lactam group. Demographics were similar between groups. Thirty-day mortality was significantly higher in the beta-lactam group (20% vs 2%, p=0.009). Enterobacter spp. was the most frequently identified pathogen (67%), most commonly isolated from a urinary (31%) or intra-abdominal source (22%). The average duration of antibiotic therapy was significantly higher in the non-beta lactam group (18 vs 12 days, p=0.001). In contrast, there was no significant difference found in hospital length of stay, recurrence of bacteremia, pathogen isolated or source of bacteremia between groups.

Conclusion
Beta-lactam therapy for the treatment of bloodstream infections caused by Amp-C producing organisms was associated with significantly greater 30-day mortality compared to patients that received non-beta-lactam therapy.

Disclosures
All Authors: No reported disclosures
265. Blood culture results pre- and post- antimicrobial administration in the Medicine Intensive Care Unit: a retrospective study in South Bronx
Authors: Chiu Chia-Yu , Sarwal Amara , Feinstein Addi 
Published: January 2021

Abstract

Background
It is intuitive that obtaining blood cultures prior to administering antibiotics can increase the likelihood of a positive blood culture result. Surviving Sepsis Campaign Hour-1 bundle stipulates that obtaining a blood culture and administering antibiotics within 1 hour is a critical determinant of survival. However, the diagnostic sensitivity shortly after antibiotic administration remains unknown. In clinical practice, some health care providers delay antibiotic administration in order to first obtain a blood culture.

Methods
Adult patients (&gt; 18 years of age) admitted to the Medicine Intensive Care Unit in Lincoln Medical Center, located in South Bronx, New York City, from 09/2019 to 12/2019. Patients needed to have at least one blood culture obtained within 12 hours of admission and have received intravenous antibiotics during the admission to the Medicine Intensive Care Unit.

Results
Of 327 patients screened, 196 met enrolment criteria and 253 sets of blood cultures underwent analysis. Blood cultures grew bacteria in 21.8% of pre-antimicrobial group whereas 26.9% in post-antimicrobial group (p=0.37). 25.9% of patients received antibiotics within 1 hour before blood culture sampling, while 34.0% of patients received antibiotics &gt;1 hour prior to obtaining blood culture. Blood culture results positive for coagulase-negative staphylococci were more prevalent in the pre-antimicrobial group.
Table 1. Patient Characteristics

Table 2. Number of blood cultures obtained and blood culture result

Table 3. Initial antimicrobial agent and 30-day mortality

Conclusion
In the sequence of blood culture and antibiotic administration, there is no 30-day survival difference in pre-antimicrobial group and post-antimicrobial group (p=0.15), as long as both received antibiotics within 12 hours of coming to the hospital. Coagulase-negative staphylococci were higher in the pre-antimicrobial group which may indicate that the health care provider hastily obtained the blood culture in a non-sterile manner. Antibiotic administration should not be delayed because of pending blood culture collection. In addition, given that more than 70% of patients were ultimately found to have negative blood cultures, it would be useful to develop practical tools to identify low-risk patients that can be treated without obtaining blood culture, as the blood culture would not be likely to provide diagnostic information.
Figure 1: Hours Before and After IV Antibiotic Started

Figure 2: Distribution of Blood Culture Before and After IV Antibiotics

Disclosures
All Authors: No reported disclosures
266. Ceftriaxone Versus Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Mohamed Adham , Bennett Nick , Ploetz Jeannette , Aragon Laura , Kennedy Kevin , Boyd Sarah E 
Published: January 2021

Abstract

Background
Few studies have evaluated the use of ceftriaxone (CRO) in the treatment of Methicillin-sensitive Staphylococcus aureus (MSSA) infections. Available studies include a small number of patients with MSSA bacteremia, with conflicting results and several limitations. The purpose of this study was to compare the safety and efficacy of CRO versus cefazolin (CFZ) for patients with MSSA bacteremia.

Methods
This was a multi-center, single health-system retrospective cohort study. Patients were included if they were at least 18 years old, had a primary episode of MSSA bacteremia within Saint Luke’s Health System and received CRO or CEFZ as definitive therapy for MSSA bacteremia. Patients were excluded if they had a previous MSSA bacteremia within 6 months, a polymicrobial infection, received combination antimicrobial therapy as definitive therapy, started treatment at outside hospital, treated for less than 72 hours, or deemed palliative or comfort care. The primary endpoint was clinical cure at 7, 10, 14, and 28 days, or discharge, whichever came first. Secondary endpoints included time to clinical cure or discharge, treatment failure at 90 days, time to treatment failure, readmission due to recurrent MSSA bacteremia at 30 and 90 days, duration of bacteremia, discontinuation of definitive treatment due to adverse drug events, incidence of Clostridiodes difficile infection, and hospital length of stay.

Results
A total of 248 patients met inclusion criteria. Among these, 87 (35.1%) received CRO and 161 (64.9%) received CFZ as definitive therapy. Patient baseline and treatment characteristics are shown in Table 1. The primary outcome occurred in 75 (86.2%) patients in the CRO group vs 145 (90.1%) patients in the CFZ group (P= 0.359), even after adjusting for Charlson Comorbidity Index, Pitt bacteremia score and serum creatinine, (aOR=0.74, 95% CI 0.32 – 1.72; p=0.473). There were no differences in time to clinical cure or discharge, treatment failure at 90 days, or safety events between the two groups. Primary and secondary endpoints are included in Table 2.
Table 1

Table 2

Conclusion
Our study suggests that there is no clinical difference between CRO and CFZ for the treatment of MSSA bacteremia. Further studies are needed to confirm these findings.

Disclosures
All Authors: No reported disclosures
277. Comparison of Oral Beta-Lactams and Fluoroquinolones for Step-Down in Uncomplicated Enterobacterales Blood Stream Infections
Authors: Ngo Nichol , Sielatchom-Noubissie Lionel , Molina Kyle , Johnson Tanner M , Huang Misha , Hojat Leila S , Kiser Ty , miller matthew 
Published: January 2021

Abstract

Background
Bloodstream infections (BSI) with Enterobacterales (formerly Enterobacteriaceae) group organisms are a frequently encountered complication, often stemming from urinary tract infections. Recent studies have demonstrated similar outcomes among patients transitioned to oral antibiotics compared to those managed solely with parenteral routes; however, most transitions utilize highly bioavailable agents such as fluoroquinolones (FQ). With limited comparative evidence on oral b-lactams (OBL) and mounting concerns over FQ safety and resistance, we sought to compare outcomes of FQ vs. OBL for Enterobacterales BSI step-down.

Methods
Single-center, retrospective cohort of adults at University of Colorado Hospital from 2015–2017 with uncomplicated Enterobacterales BSI who stepped down to OBL or FQ after initial parenteral therapy. Exclusions were: pregnant or incarcerated, causative organism identified as Salmonella spp., Enterobacter spp., Citrobacter freundii, Serratia spp. and/or Klebsiella aerogenes, parenteral antibiotic duration ≥ 5 days, death before day 5, total antibiotic duration &lt; 5 days or &gt; 21 days. Primary outcome was clinical failure, a composite of any of the following within 30-days of antibiotic completion: death, recurrence or antibiotic change for presumed failure, or readmission for original infection.

Results
Overall, 74 patients were included (n=36 OBL, n=38 FQ). Baseline characteristics were not different between groups, with overall mean age (SD) 60 (17) years and 62% female. E. coli was most commonly identified (65%), with 70% originating from the urinary tract. ICU admission was present in 18%, and median (IQR) Pitt Bacteremia Score was 2 (1–3). Treatment failure occurred in 25% OBL vs. 24% FQ recipients, p=0.55. No deaths were identified in either group within 30-days, and adverse events were rarely reported in either group. Multivariable analysis identified presence of nephrostomy tubes (OR 8.1; 95% CI: 1.1–61) but not OBL (OR 1.5; 95% CI: 0.3–7.2) as associated with clinical failure.

Conclusion
In a cohort of uncomplicated Enterobacterales BSIs there does not appear to be a difference in clinical failure associated with OBLs compared to FQs. Additional studies with a larger cohort, or prospective trials are needed to confirm these findings.

Disclosures
matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)
285. Evaluation of the ePlex® Blood Culture Identification (BCID) Panels for Gram-positive/Gram-negative bacteria and yeasts
Authors: Chapin Kimberle , Tansarli Giannoula 
Published: January 2021

Abstract

Background
Multiple methods used for blood culture identification create inconsistent to reporting of critical results. Study aim was to evaluate performance characteristics of the ePlex BCID panels compared to current standard of care (SOC) methods used in our lab.

Methods
Identification sensitivity and specificity were assessed across all targets detected by the ePlex as well as time to final identification (from time of bottle positive Gram stain) between ePlex and SOC testing. SOC included Xpert MRSA/SA or latex agglutination for Gram-positive cocci in clusters (GPCC), Vitek MS + Accelerate Pheno for Gram-negative rods (GNRs), serotyping or optochin disk ± Vitek MS for Gram-positive cocci in chains (GPC chains), Vitek MS or Vitek-2 for Gram-positive rods (GPR), and PNA-FISH or Vitek MS for yeasts.

Results
313 unique prospective blood culture specimens were tested with ePlex BCID panels during a 3-month period (January-March 2020). The positive percent agreement was 100% for GNR (n= 98), S. aureus (n= 42), coagulase-negative staphylococci (n= 38), Group A Streptococcus (n= 3), Group B Streptococcus (n= 5), S. pneumoniae (n= 10), GPR (n= 21), and yeasts (n= 20). There was 1 false negative, (S.mutans) which should have been detected. The negative percent agreement was 100% across all targets except for 1 false positive Corynebacterium spp. In total, 6.7% of blood cultures had an off-panel organism which ePlex did not detect. The median time to final identification was 3 (2 – 4) hrs. for ePlex and calculated for all other SOC methods. Compared to SOC molecular methods, the ePlex reduced time to identification 0.5 h compared to Xpert MRSA/SA, 6.7 h compared to Accelerate Pheno for GNR (but Accelerate Pheno provides susceptibilities), and 3 h compared to PNA-FISH for yeasts (p&lt; 0.05). ePlex compared to non-molecular techniques (MALDI-TOF), SOC for Streptococcus spp. and Enteroococcus spp., the time to final identification was reduced by 24 – 30 hours (p&lt; 0.05).
Workflow chart comparison eplex to SOC

Time to results eplex vs SOC

Conclusion
The ePlex BCID system provided highly accurate identification results for GP and GN bacteria as well as for yeasts. Our evaluation showed that this system significantly reduced time to final identification compared to SOC testing methods.

Disclosures
Kimberle Chapin, MD, genmark (Scientific Research Study Investigator) Giannoula Tansarli, MD, GenMark (Grant/Research Support)
286. Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Are Daptomycin and Linezolid Favored over Vancomycin and Other Antibiotics?
Authors: Vu Michelle , Smith Kenneth , Aspinall Sherrie L , Clancy Cornelius J , Buehrle Deanna 
Published: January 2021

Abstract

Background
Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. We compared cost-effectiveness of vancomycin and other antibiotic regimens as MRSAB treatment.

Methods
We estimated cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin, dalbavancin) for Veterans Health Administration (VA) patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure and adverse drug event (ADE)-related discontinuation at 7-days.

Results
In base-case analyses, linezolid and daptomycin were less expensive and had fewer treatment failures than other regimens at 4 and 6-weeks. Compared to linezolid, daptomycin incremental cost-effectiveness ratios were ~$45,000 (4-weeks) and ~$61,000 (6-weeks) per composite failure avoided, respectively. In one-way sensitivity analyses, daptomycin (4-weeks) was favored over linezolid if linezolid microbiological failure or ADE-related discontinuation rates were &gt;14.8% (base case: 14.0%) or &gt;14.3% (base case: 14.0%), respectively, assuming a willingness to pay (WTP) threshold of $40,000/ composite treatment failure avoided. Vancomycin was favored if its microbiological failure risk was &lt; 16.4% (base case: 27.2%). In two-way sensitivity analyses, daptomycin was favored if linezolid microbiological failure and ADE-related discontinuation rates were &gt;19% and &gt; 16%, respectively. Linezolid, daptomycin and vancomycin were favored in 47%, 39%, and 11% of 4-week probabilistic iterations, respectively, at $40,000 WTP.

Conclusion
Daptomycin or linezolid are likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed to support safety of linezolid in MRSAB patients.

Disclosures
Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)