bluuebunny/crossref_metadata_2025_split huggingface dataset:
710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)
Authors: Jones Chelsea E , Kline Ellen G , Nguyen Minh-Hong , Clancy Cornelius J , Shields Ryan K 
Published: October 2019

Abstract

Background
Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods.

Methods
ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions.

Results
148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored blaKPC, which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm).

Conclusion
This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint.

Disclosures
All authors: No reported disclosures.
714. Analysis of the Effect of Urine on the In Vitro Activity of Gepotidacin and Levofloxacin Against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus
Authors: Koeth Laura M , DiFranco-Fisher Jeanna M , Scangarella-Oman Nicole 
Published: October 2019

Abstract

Background
Gepotidacin (GSK2140944) is a first in class novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study was undertaken to determine the effect of various urine parameters on the in vitro activity of gepotidacin and a comparative agent, levofloxacin, against a variety of bacteria.

Methods
Study strains were tested according to the reference CLSI broth microdilution method using cation-adjusted Mueller–Hinton broth (CAMHB) and the following method variations: CAMHB with 25%, 50%, and 100% urine (not pH adjusted) and 100% urine (pH adjusted to 7.2–7.4, and 8). Quality control strains were concurrently tested each day.

Results
MIC endpoints in the reference method and in 100% urine were easily determined (i.e., clear buttons of growth up to the first well of no growth). Gepotidacin MIC results are summarized in the table. For E. coli and S. saprophyticus, there was a trend for higher gepotidacin MIC results with the addition of increasing amounts of urine. However, the increase was minimal such that mean dilution differences were ≤ 1.54. Against S. epidermidis, gepotidacin MICs were not significantly impacted by the addition of urine as 100% of urine condition MICs were within ±1 doubling dilution of the reference method MIC. The gepotidacin results for E. coli indicate that the average 1–2 dilution MIC increase observed in the unadjusted 100% pooled urine MIC may be associated with lower pH. A similar increase in levofloxacin MIC results for E. coli were also associated with pH, but at the higher pH of 8.0. In contrast, the increase in MIC observed in both the gepotidacin and levofloxacin S. saprophyticus results in 100% pooled urine do not appear to be a function of pH.

Conclusion
Overall, the effect of urine on the gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains tested.

Disclosures
All authors: No reported disclosures.
715. Bulgecin A lowers Imipenem MICs in Clinical MDR Acinetobacter baumannii (ACB) Strains
Authors: Skalweit Marion J , Rojas Laura J , Bonomo Robert A , Dik David A , Tomoshige Shusuke , Mobashery Shahriar 
Published: October 2019

Abstract

Background
Genetic screening of ACB has revealed genes that confer increased susceptibility to β-lactams when these genes are disrupted suggesting novel drug targets. One such target is lytic transglycosylase, LT. Bulgecin A (BlgA) is a natural product of Paraburkholderia acidophila and an LT inhibitor that potentiates the activity of β-lactams.

Methods
Broth microdilution MICs were performed using carbapenem-resistant (CR)-colisitin susceptible (ColS) and CR-ColR clinical ACB strains, with a variety of resistance mechanisms, previously studied via whole-genome sequencing. A fixed concentration of pure BlgA at 100 μg/mL was combined with varying concentrations of imipenem. Sequences of the putative LTs in ACB strains were analyzed to look for amino-acid substitutions and correlated with the MIC lowering effect of BlgA. Homology models of the LTs of AB0057 ACB strain were generated.

Results
ACB MltE most resembles soluble LTs of other species with 22.39% sequence identity and 92% query coverage to Slt70 of E. coli. MIC results and amino-acid sequence variations in MltE LT of ACB are shown. There were no clear amino-acid substitution patterns to account for differences in BlgA effect. The mutations are distal to the BlgA binding site at residue E506.

Conclusion
These are the first MICs reported for BlgA in combination with a carbapenem demonstrating reduction in the MIC by four-fold for several MDR ACB clinical strains. Mutations in MltE Lt do not account for variations in the MICs observed. Changes in the MICs may be related to other factors such as drug penetration and alterations in PBP expression. Additional studies are underway to examine these factors.

Disclosures
All authors: No reported disclosures.
730. Cefiderocol for the Treatment of Achromobacter xylosoxidans Infections in Two Lung Transplant Patients with Cystic Fibrosis
Authors: Warner Nathaniel C , Bartelt Luther , Lachiewicz Anne , Lachiewicz Anne , Tompkins Kathleen Marie , Miller Melissa B , van Duin David 
Published: October 2019

Abstract

Background
Achromobacter xylosoxidansis a highly resistant Gram-negative bacterium that causes chronic infections in patients with cystic fibrosis (CF). Treatment options for A. xylosoxidans are limited. In the peri-lung transplant setting, the treatment of A. xylosoxidans infections is especially challenging. Cefiderocol is a novel siderophore cephalosporin antibiotic with broad anti-Gram-negative activity, including against A. xylosoxidans. We report here two cases of compassionate use of cefiderocol in CF lung transplant recipients with A. xylosoxidans infection.

Methods
Cefiderocol was obtained through compassionate use from its manufacturer, with approval from the local Institutional Review Board. In the first case, it was used as salvage treatment, and in the second case as a planned part of the peri-transplant regimen.

Results
A male in his 20s with CF and a trimethoprim-sulfamethoxazole (TMP-SMX) allergy was chronically colonized by A. xylosoxidans, which was sensitive only to piperacillin–tazobactam (PIP-TAZ), and TMP-SMX. After lung transplant, he developed A. xylosoxidansbacteremia, and extended-infusion PIP-TAZ was started. Repeat bronchoscopy grew A. xylosoxidans. Due to lack of improvement, cefiderocol was added to PIP-TAZ with rapid clinical improvement. However, after completing his course, he was readmitted with A. xylosoxidans pneumonia. He was treated with 6 weeks of cefiderocol and imipenem and has been well since with an 8-month follow-up. In the second case, cefiderocol was used as part of the planned peri-transplant regimen for a female with CF in her late teens, with chronic A. xylosoxidans colonization, which was intermediate to PIP-TAZ, and resistant to all other drugs tested. Her native lungs grew 4+ A. xylosoxidans at the time of explant. Post-transplant, she was treated with 5 weeks of meropenem and 6 weeks of cefiderocol. At four-month follow-up, she is doing well. However, she is asymptomatically colonized with A. xylosoxidanspost-transplant. Isolates from both cases were susceptible to cefiderocol (case #1 MIC = 0.12; case #2 pretreatment MIC = 1, post-treatment MIC.

Conclusion
Cefiderocol may be a useful option for lung transplant recipients with A. xylosoxidans infections.

Disclosures
Anne Lachiewicz, MD, MPH, MicroGenDx: Consultant; Shionogi: Consultant.
734. Modeling the Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Omadacycline with and without a Loading Dose
Authors: Friedrich Lawrence , Curran Marla , Chitra Surya , Manley Amy , Bai Stephen , Noble Bob , Steenbergen Judith N , Garrity-Ryan Lynne , Tzanis Evan 
Published: October 2019

Abstract

Background
Omadacycline (OMC) is an intravenous (IV) and oral aminomethylcycline antibiotic in the tetracycline class approved in the United States to treat acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. The approved dosing regimens of OMC include a loading dose designed to achieve steady-state exposures early in the course of therapy. We assessed the impact on OMC exposure and subsequent pharmacodynamics (PD) on Day 2 and at steady state (Day 5) in the situation where a loading dose may not be given.

Methods
Phase 1 pharmacokinetic (PK) data were used to determine OMC exposure on Day 2 and at steady state (Day 5) for the following: IV regimens 100 mg IV q12h on Day 1 then 100 mg IV QD (load), 100 mg IV QD (no load); and oral regimens 450 mg oral QD on Days 1 and 2 then 300 mg QD (load) and 300 mg oral QD (no load). AUCs on Day 2 and Day 5 for no-load regimens were compared with the regimens with loading doses. Additionally, AUC:MIC ratios were calculated using OMC MIC90 for two main pathogens of interest in ABSSSI and CABP, respectively, Staphylococcus aureus (0.25 mg/L) and Streptococcus pneumoniae (0.12 mg/L). In vivo AUC:MIC targets for stasis and 1-log kill used were 21.9 and 57.7 (S. aureus) and 31.2 and 65.8 (S. pneumoniae).

Results
Day 2 and 5 AUCs are shown in the Figure. AUCs on Day 2 were lower for the two regimens without loading doses and were 72% (IV) and 73% (oral) of those with a loading dose. However, at steady state on Day 5, no-load regimen AUCs were essentially the same at 98% for both the IV and oral regimens. Despite lower AUCs on Day 2 for the no-load regimens, the AUC:MIC ratio would still be expected to exceed the stasis threshold for both pathogens and the 1-log kill threshold for S. pneumoniae (figure). This same pattern was also noted on Day 5.

Conclusion
Exposure as assessed using AUC was lower early on in therapy on Day 2 for both IV and oral regimens. However, exposures were not different on Day 5 at steady state. Despite lower exposure on Day 2, OMC would still be expected to meet or exceed PK/PD thresholds associated with stasis for S. aureus and S. pneumoniae. The 1-log kill threshold was exceeded for S. pneumoniae. Further studies are needed to confirm any clinical impact of the omission of OMC loading doses.

Disclosures
All authors: No reported disclosures.
748. Does Improving Discharge Documentation Improve Post-Discharge Care for Patients on Outpatient Parenteral Antimicrobial Therapy (OPAT)?
Authors: Certain Laura , Benefield Russell J , Thomas Frank O 
Published: October 2019

Abstract

Background
Patients discharged on intravenous antibiotics require regular monitoring by an infectious disease (ID) specialist or other provider familiar with outpatient parenteral antibiotic therapy (OPAT). However, the lab monitoring and outpatient follow-up plan outlined prior to discharge is not always realized. We are working to understand what steps the discharging hospital can take to improve the outpatient monitoring and follow-up for patients on OPAT, who are discharged to a wide variety of institutions. We studied whether documenting the OPAT plan in a standardized note led to increased inclusion of that plan in the discharge documentation and thus to improved lab monitoring and outpatient follow-up for our patients.

Methods
We compared the pre- and post-intervention frequency of seven key OPAT elements (antibiotic, duration, end date, indication, follow-up appointment, recommend labs, fax number for labs) in the discharge documentation. Pre-intervention, this information was documented by the inpatient ID service in the Problem List (overview) section of the electronic health record. Post-intervention, OPAT plans were documented within standardized OPAT Progress Notes. Efficiency and clinical outcomes were: proportion of OPAT treatment weeks with laboratory monitoring; number of weeks the outpatient ID team had to track down missing laboratory results; number of “No Show” ID clinic visits; number of OPAT-related telephone encounters.

Results
There were 73 patients in the pre- and 68 in the post-intervention cohort. Having a formal OPAT Progress Note was associated with a significant increase in the number of OPAT elements included in the discharge documentation (7 vs. 5, P = 0.002). In addition, the entire OPAT note was included in the discharge documentation more frequently in the post-intervention cohort (3/73 vs.. 14/68, P = 0.007). However, except for reduced telephone encounters related to OPAT (2 vs. 1 per patient, P = 0.0001), there were no significant improvements in post-discharge clinical or efficiency outcomes.

Conclusion
Creating an OPAT Progress Note improves the capture of OPAT elements into discharge documentation. Except for reducing telephone encounters, no other benefits occurred. Future interventions will focus on improving the other measured outcomes.

Disclosures
All authors: No reported disclosures.
756. Impact of Infectious Diseases Pharmacists as Part of an Interdisciplinary OPAT Team Managing Vancomycin
Authors: Adamsick Meagan L , Gandhi Ronak G , Steiger Samantha N , Bidell Monique R , Nelson Sandra B , Ard Kevin L , Elshaboury Ramy H 
Published: October 2019

Abstract

Background
Outpatient Parenteral Antimicrobial Therapy (OPAT) is a growing area of Infectious Diseases (ID) that allows for the treatment of severe infections in the ambulatory setting. Massachusetts General Hospital (MGH) incorporated inpatient ID pharmacists into the OPAT team in June 2017 to assist with vancomycin monitoring and dosing. Laboratory results were received and documented by the OPAT nurse and forwarded to the pharmacists for assessment via the electronic medical record (EMR). Pharmacists then sent clinical recommendations to the physician. This study aimed to determine the impact of pharmacists’ involvement in OPAT vancomycin management.

Methods
An EMR-generated report identified patients in the OPAT program from June 2016 through May 2017 as the control group and June 2017 through May 2018 as the intervention group. One hundred patients were randomly selected during each period. Patients were excluded from the intervention group if no pharmacist documentation was present. The primary outcome was to evaluate the proportion of vancomycin levels within the patient-specific goal range and secondary outcomes included the proportion of (1) pharmacists’ recommendations accepted by the ID physician and (2) patients who experienced adverse drug events.

Results
A total of 200 patients were evaluated. The most common indication for enrollment was osteomyelitis (46%). No differences in baseline characteristics were noted, and the median age was 67 years. The percentage of vancomycin levels within goal was significantly higher in the pharmacist-managed group compared with the control group (66.8% vs. 54.2%; P < 0.0001). The number of patients who experienced adverse drug events was similar between the two groups (39% vs. 43%; P = 0.66); however, fewer patients in the pharmacist group experienced acute kidney injury (5% vs. 13%; P = 0.08). Finally, 100% of pharmacist recommendations were accepted by ID physicians.

Conclusion
Leveraging inpatient ID pharmacists at MGH in the management of OPAT vancomycin provided improved percentage of vancomycin in therapeutic range and high acceptance rate of interventions. Further evaluation is necessary to assess the inpatient ID pharmacists’ workflow for implementation into other OPAT programs.

Disclosures
All authors: No reported disclosures.
765. Pyomyositis in the United States: Trends and Associations From the Healthcare Utilization Project Nationwide Inpatient Sample Database
Authors: Maravelas Rheanne K , Melgar Thomas , Sadarangani Sapna , Lima Neiberg , Rich Zachary , Vos Duncan 
Published: October 2019

Abstract

Background
Pyomyositis is a spontaneous infection of skeletal muscle that can lead to abscess formation and sepsis. The purpose of our study was to better describe the characteristics, risk factors, and trends of primary pyomyositis in the United States.

Methods
This study is a retrospective review of data from the Healthcare Utilization Project Nationwide Inpatient Sample Database from 2002 to 2014. We systematically searched ICD-9 codes and included diagnoses of infective myositis and/or tropical pyomyositis and excluded progressive myositis ossificans and/or traumatic myositis ossificans. We compiled lists of codes for co-occurring infections, candidate risk factors, and microbiological data. Each group of related ICD-9 codes was combined into a single composite indicator. SAS studio was utilized for analysis.

Results
The database included a total of 100,790,900 discharges accounting for 482,872,274 weighted discharges with 13,011 pyomyositis cases accounting for 62,657 weighted cases. The patients with pyomyositis were significantly more likely to be younger, male, and have a longer duration of hospitalization. The proportion of discharges with pyomyositis has steadily risen more than 3-fold from 0.0054% to 0.0209%. Of the cases of pyomyositis, a minority had co-occurring deep tissue infections: 16.9% had osteomyelitis and 8.8% had septic arthritis. We found significantly higher rates of co-occurrence with HIV, diabetes mellitus, organ transplant, alcohol abuse, and chronic kidney disease compared with the general hospitalized population, suggesting these as relevant risk factors. When microorganisms were diagnosed, Staphylococus aureus was most common, followed by Streptococcus spp.

Conclusion
Our study identified a rapid increase in pyomyositis cases in the United States over our 12-year study period. Our results substantiate risk factors for pyomyositis related to immunosuppression and suggest that diabetes mellitus may be an important risk factor in the United States. Identifying causative organisms is helpful for empiric treatment. It is important that clinicians be aware of this emerging diagnosis relevant in both temperate and tropical areas of the globe.

Disclosures
All authors: No reported disclosures.
766. Telehealth Practices, Barriers, and Future Interest among Pediatric Infectious Disease Clinicians in the United States: Results from the 2019 Pediatric Infectious Diseases Society (PIDS) Telehealth Working Group Survey
Authors: Olson Daniel , Hakim Amin , Gaviria-Agudelo Claudia , Sabella Camille , Fanella Sergio , Arun Aparna , Russo Michael E , Kronman Matthew , Adler-Shohet Felice , Holzmann-Pazgal Galit , Sanderson Susan , Phillips Terri Christene , Edwards Kathryn , Siddiqui Javeed , Bryant Kristina 
Published: October 2019

Abstract

Background
There is a paucity of access to pediatric infectious diseases (PID) physicians in the United States. To improve access, PID clinicians spend significant time providing nonreimbursed curbside consultations (CCs) to community providers. While there is increasing utilization of telehealth technologies to increase access to PID physicians, there is limited knowledge regarding adoption of these technologies and how they may be used to improve care and reimbursement.

Methods
The PIDS Telehealth Working Group developed a 33-question online survey to collect individual- and practice-level data on the burden of CCs, current telehealth practices and barriers, and interest in providing future telehealth services. It was emailed to the PIDS Listserv (n = 1,213) in April 2019.

Results
A total of 161 (13%) providers completed the survey (100% MD/DO), representing 37 states; most are university- (n = 100, 62%) and/or hospital- (n = 74, 46%) employed. Respondents’ practices provide a mean of 1–10 CCs/week to outside institutions (median 3–5 hours/week), with a median of 6–10% resulting in referrals. Outside nonreimbursed CCs are performed by phone/paging systems (n = 156, 98%), secure email (n = 66, 42%), text messaging (n = 46, 29%), and EMR-messaging (n = 38, 24%); they include a variety of services (Figure 1). Only 46 (29%) of individual respondents provide any type of reimbursed telehealth at their practices (Figure 2). Reimbursement mechanisms include fee-for-service (31%), Medicaid/Medicare (25%), private insurance (24%), and internal institutional (i.e., internal RVU) payments (16%). The majority of respondents were unaware of credentialing (n = 90, 64%) and liability coverage needs for telehealth (n = 68, 47%). Though most respondents (n = 81, 57%) were not satisfied with their current telehealth program and barriers were significant (Figure 3), the majority (n = 144, 95%) were interested in implementing a variety of reimbursable telehealth services and modalities (Figure 4).

Conclusion
PID survey respondents indicated a lack of knowledge on key aspects of telehealth and perceive significant barriers to implementing telehealth at their institutions. Nonetheless, there is a strong interest in participating in a variety of telehealth services to increase access to care, with appropriate institutional support.

Disclosures
All authors: No reported disclosures.