bluuebunny/crossref_metadata_2025_split huggingface dataset:
1613. Global 2018 Surveillance of Eravacycline Against Gram-negative Pathogens, Including Multi-drug Resistant Isolates
Authors: Lijfrock Virgil , Morgan Steven , Hwang Sara , Efimova Ekaterina , Lawrence Kenneth , Hawser Stephen , Morrissey Ian 
Published: January 2021

Abstract

Background
Eravacycline (ERV) is a fully-synthetic, fluorocycline antibacterial approved by the FDA and EMA for treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age. The purpose of this study was to describe the in vitro activity of ERV against Gram-negative pathogens, including multi-drug resistant (MDR) isolates, collected in 2018.

Methods
Isolates were collected during 2018 from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using the most updated CLSI breakpoints, except for ERV and tigecycline (TGC) where FDA breakpoints established in 2018 and 2005 respectively, were used. MDR was defined as resistance to ≥3 antibiotics from aztreonam, a carbapenem (meropenem or ertapenem [ETP]), cefepime/cefotaxime/ceftazidime/ceftriaxone (any one), gentamicin, levofloxacin, piperacillin-tazobactam TZP, tetracycline or TGC.

Results
Summary MIC data for ERV and select comparators are shown in the Table. ERV MIC90 for all-Enterobacteriaceae was 0.5 μg/ml and for MDR-Enterobacteriaceae was 1μg/ml. The susceptibilities for all-Enterobacteriaceae were 93%, 95%, 93% and 82% for ERV, TGC, ETP and TZP, respectively. ERV further demonstrated higher rates of susceptibility than ETP and TZP against MDR-Enterobateriaceae, 81% vs 71% vs 38%. ERV MIC50/90 for carbapenem-resistant Acinetobacter baumannii (CRAB) were 4-fold lower than TGC.
Table

Conclusion
ERV in vitro activity was demonstrated and comparable susceptibility rates were observed for clinically important Gram-negative pathogens, including resistant isolates. Overall, ERV MIC90 values were 2- to 8- fold lower than TGC. this study further highlights the in vitro activity of ERV against Gram-negative pathogens identified in patients with cIAI.

Disclosures
Virgil Lijfrock, PharMD, Tetraphase (Employee) Steven Morgan, PharMD, Tetraphase Pharmaceuticals (Employee) Sara Hwang, PharMD, Tetraphase Pharmaceuticals (Employee) Ekaterina Efimova, PharMD, Tetraphase Pharmaceuticals (Employee) Kenneth Lawrence, PharmD, Tetraphase Pharmaceuticals (Employee) Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Ian Morrissey, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator)
1615. Isolation of Lytic Bacteriophages with Broad Host Range Activity Against Pseudomonas aeruginosa Strains Isolated from Respiratory Samples from Cystic Fibrosis Patients Intended for Therapeutic Application
Authors: Alexander Jose , Navas Daniel , Flowers Marly , Charles Angela , Carr Amy 
Published: January 2021

Abstract

Background
With the rise of the antimicrobial resistance between different genera and species of bacteria, Phage Therapy is becoming a more realistic and accessible option for patients with limited or no antimicrobial options. Being able to have rapid access to a collection of clinical active phages is key for rapid implementation of phage therapy. The Microbiology Department at AdventHealth Orlando is performing routine screening of environmental and patient samples for isolation of phages against non-fermenting Gram negative bacteria to develop a Phage Bank.

Methods
Protocols for phage isolation from environmental sources such as lakes, rivers and sewers and clinical samples were developed. A series of respiratory, throat, stool and urine samples were processed following an internal protocol that includes centrifugation, filtration and enrichment. Clinical samples were centrifugated for 10 minutes, filtered using 0.45µm centrifugation filters, seeded with targeted host bacteria (clinical isolates) and incubated at 35°C for 24 hours. The enriched samples were centrifugated and filtered for a final phage enriched solution. Screening and isolation were performed using the Gracia method over trypticase soybean agar (TSA) for plaque morphology and quantification. Host range screening of other clinical isolates of P. aeruginosa was performed using the new isolated and purified phages.

Results
4 lytic phages against clinical strains of P. aeruginosa from patient with diagnosis of cystic fibrosis (CF), were isolated and purified from 4 different respiratory samples, including sputum and bronchial alveolar lavage. All phages showed phenotypical characteristics of lytic activity. 1 phage was active against 4 strains of P. aeruginosa, 1 phage was active against 2 strains of P. aeruginosa and the remaining 2 phages were active only against the initial host target strain.

Conclusion
With this study we demonstrated the potential use of clinical samples as source for isolating active bacteriophages against clinically significant bacteria strains. Clinical samples from vulnerable population of patients with chronic infections are part of our routine “phage-hunting” process to stock and grow our Phage Bank project for future clinical use.

Disclosures
All Authors: No reported disclosures
1617. Mecillinam susceptibility against Enterobacterales isolated from urinary tract infections from US patients in 2018
Authors: Hawser Stephen , Morrissey Ian , Charrier Cedric , De Piano Cyntia , Alexander Morton , Henriksen Anne Santerre 
Published: January 2021

Abstract

Background
Mecillinam is a unique amidinopenicillin antibiotic, being the first and the only compound in its class. In contrast to other beta-lactams, it has a unique mechanism of action whereby it exerts its antibacterial activity through binding to penicillin binding protein 2. Pivmecillinam is the oral-prodrug of mecillinam and recommended as a first line therapy in the IDSA guidelines for uncomplicated urinary tract infections (uUTI), despite not yet being available in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of both complicated UTI and uUTI this study investigated the activity of mecillinam against Enterobacterales isolates from the USA during 2018.

Methods
A total of 1,090 isolates from urinary tract infections from patients in the USA were tested. Activity of antibiotics was tested by CLSI methodology and susceptibility interpreted according to CLSI guidelines.

Results
Susceptibility and activity of each antibiotic are shown in the Table. Mecillinam MIC50 and MIC90 were 0.25 and 4 µg/mL, respectively and 94.5% of isolates were susceptible. Fosfomycin MIC50 and MIC90 were 2 and 32 µg/mL, respectively and 95.7% of isolates were susceptible. The other four comparator antibiotics showed MIC90 values &gt;8 µg/mL and a 70.5 – 79.9% susceptible isolates. The highest MIC90 against all isolates combined was 64 µg/mL for nitrofurantoin and the highest percentage of resistance was obtained with trimethoprim-sulfamethoxazole with 29.5%. Resistance towards ceftriaxone and ciprofloxacin was 19.6% and 26.1%, respectively.
Table

Conclusion
Overall, mecillinam showed the lowest MIC90 and a comparable susceptibility profile (94.5 % susceptible and 4.0 % resistant) to fosfomycin (i.e. 95.7% and 2.0% resistant) susceptible isolates). Resistance to ceftriaxone, ciprofloxacin and trimethoprim/sulfamethoxazole around or above 20% is concerning for their clinical usage to treat urinary tract infections. These encouraging susceptibility data warrant further studies to support the clinical development of mecillinam/pivmecillinam for the treatment of UTI in the USA.

Disclosures
Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Cedric Charrier, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Cyntia De Piano, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Morton Alexander, PhD, Utility Therapeutics (Employee, Shareholder) Anne Santerre Henriksen, MS, Maxel Consulting ApS (Employee)Utility Therapeutics (Independent Contractor)
1618. Meropenem-vaborbactam vs standard of care for multidrug resistant carbapenem-resistant Enterobacteriaceae
Authors: Misikir Helina , Mulugeta Surafel , Shallal Anita , Zervos Marcus 
Published: January 2021

Abstract

Background
Antimicrobial resistance to gram negative organisms is an increasing issue worldwide, particularly with regards to extended-spectrum B-lactamase (ESBL) and carbapenem-resistant Enterobacteriaeceae (CRE) producing organisms. Meropenem/vaborbactam (M-V) is an approved antimicrobial for treatment of some CRE infections. This study compares the outcomes of patients with CRE who were treated with M-V to standard of care (SoC) therapy.
Table 1. Results

Methods
A retrospective chart analysis was performed which analyzed 25 patients in the M-V group and 25 patients in the SoC group at an 800-bed tertiary care hospital in Southeast Michigan. Patients were matched by type of infection. Variables included basic demographics, infection source, bacterial species, as well as 30-day readmission, ICU admission, and creatinine pre- and post-treatment. The primary outcome of interest was 30-day mortality and clinical outcome (cure/improved/failure). Secondary outcomes included microbiological outcome (eradication/presumed eradication/persistence/presumed persistence) and acute kidney injury (AKI) on therapy. The data was analyzed using SPSS version 14.0.

Results
The most commonly used antibiotics in the SoC group were ceftazidime-avibactam (64%) and cefepime (32%). In both groups, the most common infection source was intra-abdominal (56%). The most commonly isolated pathogen in each group was Klebsiella pneumoniae (52% in M-V and 48% in SoC). Mortality and re-admission at 30 days did not differ statistically between the two groups. However, patients who received M-V were found to be more likely to achieve clinical cure, although this did not achieve statistical significance. Patients who were treated with SoC were significantly more likely to achieve an improved clinical outcome and presumed microbiological eradication (p=0.001 and 0.01 respectively). Of the 50 patients, only 26 patients (52%) met criteria to analyze for AKI. Patients who received M-V were more likely to have AKI (16% compared to 8%) but this did not reach statistical significance.

Conclusion
M-V is an important option for care of patients with infections due to MDR gram-negative bacteria. However, further studies are warranted to determine whether its use is associated with reduced mortality and improved clinical outcomes.

Disclosures
Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support)
135. Designing And Evaluating A Pharmacist-Driven Approach to Outpatient Azithromycin Stewardship
Authors: Tran Christina , Lata Paul , Tindall Kristin , Barnett Susanne , Balasubramanian Prakash 
Published: January 2021

Abstract

Background
After collecting data on diminishing S. pneumoniae susceptibility rates, the Madison VA aimed to optimize azithromycin prescribing practices by enhancing the involvement of outpatient pharmacists. This study aimed to develop effective pharmacy-led stewardship teams in the outpatient setting and assess their collective impact on promoting judicious azithromycin prescribing.

Methods
Madison VA outpatient pharmacists initiated an azithromycin stewardship protocol in 4/2019 to intervene on prescriptions suspected to be discordant with expert guidelines for COPD, pneumonia, sinusitis, or bronchitis. After pharmacist follow-up with providers to discuss potentially inappropriate prescriptions, recommendations and outcomes were subsequently documented in the electronic health record. Given the longitudinal nature of outpatient pharmacist interventions, a post-hoc survey was provided to assess pharmacists’ perceptions of this protocol, barriers to intervention, and areas for improvement.

Results
Between 10/2018 and 4/2020, 18 pharmacists intervened on 42 outpatient azithromycin prescriptions to recommend alternative antibiotics with improved streptococcal coverage or supportive care alone. Indications warranting the most intervention included COPD exacerbations, upper respiratory infections, and bronchitis. Factors most often cited by pharmacists as barriers to intervention included negative impact on workload, provider reluctance, and insufficient time for follow-up. All surveyed pharmacists believed that prescribers, most commonly primary care providers, were fairly or very receptive to their recommendations. Data evaluated from 10/2018 to 12/2019 revealed a 45% decrease in azithromycin prescribing.

Conclusion
Azithromycin prescribing has steadily declined at the Madison VA, reinforced by the implementation of an outpatient pharmacist stewardship team. To more seamlessly integrate recommendation-making into pharmacist workflow, determining solutions to identified barriers is currently underway. It is hoped that continued pharmacist involvement in outpatient antibiotic stewardship can be a sustainable practice and transferrable strategy to other antimicrobial agents in the future.

Disclosures
All Authors: No reported disclosures
1622. Outcomes of Colistin Weight-Based Dosing Versus The Non-Weight-Based Dosing
Authors: Anouassi Zohour , El Lababidi Rania M , Salem Nouran , El Nekidy Wasim S , Mooty Mohamad 
Published: January 2021

Abstract

Background
The use of colistin is currently the mainstay antimicrobial for several multi-drug resistant organisms (MDROs). New guidelines were recently published recommending non-weight-based (NWB) dosing of colistin. There is limited data on outcomes with this new dosing strategy. The purpose of this study was to investigate the outcomes of the new NWB dosing strategy in comparison to the previously used weight-based (WB) dosing strategy.

Methods
A retrospective study was conducted at our quaternary care hospital between January 2016 and April 2020. Adults (≥ 18 years), who received intravenous (IV) colistin for ≥ 72 hours were included. Documented clinical cure was the primary endpoint, which was defined as having at least two of the following: normalization of white blood cell count or ≥ 25% reduction, defervescence, hemodynamic stability, normalization of inflammatory markers (C-reactive protein and procalcitonin values) or ≥ 25% reduction, or the resolution of signs and symptoms of infection by the end of the therapy. Secondary outcomes were microbiological cure, incidence of acute kidney injury (AKI), time to AKI, outcomes of AKI, time to AKI recovery, new infection while on IV colistin, recurrence of infection, and all-cause mortality.

Results
A total of 104 primarily male (57.7%) patients with a mean age of 63 ± 20.23 years and weight of 70.24 ± 19.46 kg met the inclusion criteria. At baseline for both groups, the estimated creatinine clearance was 74.23 ± 70.86 mL/min and renal replacement therapy was observed in 34.62%. There was no statistically significant difference observed in clinical cure rate in the WB was 77.03% while 83.33% in the NWB (p-value 0.48). However, a higher rate of AKI was observed in NWB was 84.21% while 53.33% in WB (p-value 0.02). Amongst those who had AKI, NWB had better AKI recovery status with 60.00% while 17.95% in WB (p-value 0.00). A higher all-cause mortality rate was observed in the WB group with 55.41% while 20.00% in NWB (p-value 0.02).

Conclusion
The study showed no statistical difference in the primary outcome between the two groups, however, higher AKI rates, AKI recovery and all-cause mortality was observed in non-weight-based dosing when compared to the weight-based dosing. Our data needs to be validated in a larger study.

Disclosures
All Authors: No reported disclosures
1625. Real-World Outpatient Utilization of Ceftolozane/Tazobactam in Physician Office Infusion Centers (OICs)
Authors: Van Anglen Lucinda J , Nathan Ramesh V , Nathan Ramesh V , Metzger Brian S , Luu Quyen , Schroeder Claudia P 
Published: January 2021

Abstract

Background
Ceftolozane/tazobactam (C/T) is indicated for the treatment (tx) of complicated Gram-negative infections including urinary tract infection (cUTI), intra-abdominal infection (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonias caused by susceptible bacteria. Real-world data on the use of C/T are limited. We present a multicenter observational review of C/T outpatient utilization in Infectious Disease OICs.

Methods
Medical records of patients (pts) who received C/T for ≥3 doses from May 2015 to Sept 2019 were reviewed. Data included demographics, diagnosis, disease history, pathogens, C/T tx hospitalizations, emergency department (ED) visits and clinical outcomes. Clinical success was defined as complete or partial symptom resolution at completion of C/T with oral antibiotics as needed. Persistent infection and early discontinuation (D/C) of C/T were deemed non-successful. Indeterminant outcomes were deemed non-evaluable. Chi Square, Fisher’s exact, and t-tests were used to identify characteristics associated with clinical outcome.

Results
120 pts (mean age: 59±15 years, 60% male) from 33 OICs were identified. Median Charlson score was 5 (IQR, 3-7), with 43% immunocompromised, and 77% refractory/recurrent disease. Primary infections were bone and joint (25%), cUTI, (24%), respiratory tract (18%), cIAI (18%), complicated skin and skin-structure (12%), and bacteremia/endocarditis (3%). Most pts had multi-drug resistant Gram-negative pathogens (80/108; 74%), predominantly Pseudomonas aeruginosa. Polymicrobial infections were reported in 44%. Median duration of C/T therapy was 21 days (IQR, 14-34). C/T was initiated in the OIC in 59% of pts. Overall clinical success was 86% (100/117), with rates by infection type in Fig 1. Non-success was reported in 17, 10 due to persistent infection and 7 due to adverse events. The adverse events led to early D/C of C/T, all with resolution. Statistically, infection type did not impact success rate. Hospitalizations and ED visits during tx occurred in 5% of pts with successful outcomes and 35% of pts with non-successful outcomes (p &lt; 0.001).
Fig 1. Clinical success rates of C/T by infection type

Conclusion
These real-world results support the effectiveness of C/T in a wide variety of complicated Gram-negative infections treated in the outpatient setting.

Disclosures
Lucinda J. Van Anglen, PharmD, Merck & Co. (Grant/Research Support) Ramesh V. Nathan, MD, FIDSA, Merck & Co. (Other Financial or Material Support, Grant Steering Committee Member) Brian S. Metzger, MD, MPH, Allergan (Speaker’s Bureau)Cumberland (Speaker’s Bureau)Melinta (Speaker’s Bureau)
1628. Treatment Heterogeneity in Pseudomonas aeruginosa Pneumonia
Authors: Caffrey Aisling , Bodo Emily C , Lopes Vrishali , Puzniak Laura A , LaPlante Kerry 
Published: January 2021

Abstract

Background
Serious bacterial infections present a unique challenge for studies of real-world evidence. Often, the causative organism is unknown during the initial period of treatment and clinical symptoms change day-to-day, which lead to multiple changes in therapy. While it is assumed approaches to treating specific infectious diseases are mostly similar, we’ve previously identified substantial treatment heterogeneity, even among organism-specific and site-specific infections.

Methods
Our retrospective cohort study included inpatients with positive P. aeruginosa from sputum and bronchoalveolar lavage cultures collected during VA medical center and community living center stays from 01/15-04/18. We included the first positive culture during the admission per patient. Daily antibiotic exposures were mapped from 3 days prior to the culture collection date until discharge or 30 days for longer stays. Heterogeneity was defined as patterns of antibiotic treatment (drug and duration) not shared by any other patient.

Results
Our study included 5,435 patients and 87.4% of patients had different patterns of antibiotic drug and duration. Among patients with changes in therapy (84.0%), 96.9% had different antibiotic treatment patterns, with a median time to first change of 1 day and median of 3 changes. When restricting the analysis to antibiotic classes (rather than drug), Gram-negative antibiotics, and anti-pseudomonal antibiotic classes, heterogeneity was 81.8%, 52.0%, and 48.7%, with median time to first change of 1, 3, and 3 days, and a median of 3, 2, and 2 changes, respectively.

Conclusion
Among inpatients with positive P. aeruginosa respiratory cultures, substantial heterogeneity was observed in the national VA Healthcare System. Even at the class level, and restricting the analysis to anti-pseudomonal antibiotic classes, approximately 50% of patients had different treatment patterns during their inpatient stay. Current methods to assess treatment do not adequately account for the extensive heterogeneity observed in infectious diseases and it remains unclear how local or national treatment guidelines affect heterogeneity.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Emily C. Bodo, Pham.D, VA Office of Academic Affiliations (OAA) (Other Financial or Material Support, Bodo is supported by the VA Office of Academic Affiliations (OAA)) Laura A. Puzniak, PhD, Merck (Employee) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)
136. Don’t Sweat the Small Stuff: Solutions for Large-Scale Stewardship Obstacles
Authors: Huang Joanne , Escobar Zahra Kassamali , Jain Rupali , Chan Jeannie D , Lynch John B , D’Angeli Marisa A , May Larissa , Bryson-Cahn Chloe 
Published: January 2021

Abstract

Background
In an effort to support stewardship endeavors, the MITIGATE (a Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection for Adult and Children in Emergency Department and Urgent Care Settings) Toolkit was published in 2018, aiming to reduce unnecessary antibiotics for viral respiratory tract infections (RTIs). At the University of Washington, we have incorporated strategies from this toolkit at our urgent care clinics. This study aims to address solutions to some of the challenges we experienced.
Challenges and Solutions

Methods
This was a retrospective observational study conducted at Valley Medical Center (Sept 2019-Mar 2020) and the University of Washington (Jan 2019-Feb 2020) urgent care clinics. Patients were identified through ICD-10 diagnosis codes included in the MITIGATE toolkit. The primary outcome was identifying challenges and solutions developed during this process.

Results
We encountered five challenges during our roll-out of MITIGATE. First, using both ICD-9 and ICD-10 codes can lead to inaccurate data collection. Second, technical support for coding a complex data set is essential and should be accounted for prior to beginning stewardship interventions of this scale. Third, unintentional incorrect diagnosis selection was common and may require reeducation of prescribers on proper selection. Fourth, focusing on singular issues rather than multiple outcomes is more feasible and can offer several opportunities for stewardship interventions. Lastly, changing prescribing behavior can cause unintended tension during implementation. Modifying benchmarks measured, allowing for bi-directional feedback, and identifying provider champions can help maintain open communication.

Conclusion
Resources such as the MITIGATE toolkit are helpful to implement standardized data driven stewardship interventions. We have experienced some challenges including a complex data build, errors with diagnostic coding, providing constructive feedback while maintaining positive stewardship relationships, and choosing feasible outcomes to measure. We present solutions to these challenges with the aim to provide guidance to those who are considering using this toolkit for outpatient stewardship interventions.

Disclosures
All Authors: No reported disclosures