bluuebunny/crossref_metadata_2025_split huggingface dataset:
702. Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria
Authors: Crane John , Sutton Mark , Cheema Muhammad , Olyer Michael 
Published: November 2018

Abstract

Background
The SOS response is a conserved response to DNA damage that is found in Gram negative and Gram-positive bacteria. When DNA damage is sustained and severe, activation of error-prone DNA polymerases can induce a higher mutation rate then normally observed, which is called the mutator phenotype or hypermutation. We previously showed that zinc blocked the hypermutation response induced by quinolone antibiotics and mitomycin C in E. coli and Klebsiella pneumoniae (Bunnell BE, Escobar JF, Bair KL, Sutton MD, Crane JK (2017). Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli. PLoS ONE 12(5): e0178303. https://doi.org/10.1371/journal.pone.0178303.) In addition to causing copying errors in DNA replication, Beaber et al. showed that induction of the SOS response increased the frequency of horizontal gene transfer into Vibrio cholerae, an organism naturally competent at uptake of extracellular DNA. (Beaber JW, Hochhut B, Waldor MK. 2003. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427:72–74.) Methods. In this study, we tested whether induction of the SOS response could induce transfer of antibiotic resistance from Enterobacter cloacae into E. coli, and whether zinc could inhibit that inter-species transfer of antibiotic resistance. Results. Ciprofloxacin, an inducer of the SOS response, increased the rate of transfer of an extended spectrum β-lactamase (ESBL) gene from Enterobacter into a susceptible E. coli strain. Zinc blocked SOS-induced horizontal transfer of §-lactamase into E. coli. Other divalent metals, such as iron and manganese, failed to inhibit these responses. Conclusion. In vitro assays showed that zinc blocked the ability of RecA to bind to ssDNA, an early step in the SOS response, suggesting the mechanism by which zinc blocks the SOS response.

Disclosures
All authors: No reported disclosures.
709. Activity of Key β-Lactam Agents Against Gram-Negative Bacilli From ICU Patients with Lower Respiratory Tract Infections, SMART United States 2015–2017
Authors: Lob Sibylle , Kazmierczak Krystyna , Hoban Daryl , Hackel Meredith , Young Katherine , Motyl Mary , Sahm Dan 
Published: November 2018

Abstract

Background
Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in clinical development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against Gram-negative bacilli and resistant phenotypes collected in the United States as part of the SMART surveillance program from patients with lower respiratory tract infections (RTI) in ICUs, where antimicrobial resistance is typically higher than in non-ICU wards.

Methods
In 2015–2017, 26 hospitals in the United States each collected up to 100 consecutive Gram-negative pathogens from RTI per year. Antimicrobial susceptibility was determined for 1,298 non-Proteeae Enterobacteriaceae (NPE) and 638 P. aeruginosaisolates collected in ICUs, using CLSI broth microdilution and breakpoints; for comparison purposes, the IMI susceptible breakpoint was applied to IMI/REL. Proteeae were excluded due to intrinsic nonsusceptibility to IMI. Susceptibility was calculated for the 4 United States census regions and overall.

Results
Susceptibility of NPE was lowest in the Midwest to ceftazidime (81%) and cefepime (87%) and highest in the Northeast (88% and 94%, respectively); susceptibility to imipenem (89–93%) and piperacillin–tazobactam (86–90%) showed less variability across regions. Susceptibility of P. aeruginosa to the four agents was lowest in the West region (57–65%) and highest in the Northeast (68–76%). Susceptibilities to IMI/REL of NPE and P. aeruginosa as well as of phenotypes nonsusceptible (NS) to β-lactams are shown below.

Conclusion
The studied β-lactams showed some variability in activity against pathogens from RTI patients in ICUs across census regions, whereas IMI/REL maintained activity in all regions against NPE (&gt;96%) and P. aeruginosa (90–95%). IMI/REL remained active against ≥98% of resistant phenotypes of NPE, except the imipenem-NS subset (67.5% susceptible), which was composed mainly of Serratia spp., and remained active against 77–82% of resistant phenotypes of P. aeruginosa, including 77.2% of imipenem-NS isolates. IMI/REL may provide a valuable therapeutic option for the treatment of ICU patients with respiratory tract infections caused by organisms resistant to commonly used β-lactams.

Disclosures
S. Lob, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Kazmierczak, Merck: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. D. Hoban, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. M. Hackel, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Young, Merck: Employee and Shareholder, Dividends and Salary. M. Motyl, Merck: Employee and Shareholder, Dividends and Salary. D. Sahm, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee.
717. Cumulative Incidence of Asthma/Wheezing Among Neonates/Infants/Toddlers Clinically Diagnosed with Respiratory Syncytial Virus Infection in the United States: A Retrospective Database Analysis
Authors: Wyffels Veronique , Smulders Maartje , Gavart Sandra , Mazumder Debasish , Tyagi Rohit , Gupta Nikhil , Fleischhackl Roman 
Published: November 2018

Abstract

Background
The role of respiratory syncytial virus (RSV) in the development of asthma/wheezing (AW) has been evaluated in several studies, mostly among pre-term infants or among infants after developing severe RSV-related disease. We describe the cumulative incidence (CI) of AW among hospitalized/ambulatory neonates/infants/toddlers after RSV/bronchiolitis infection diagnosis, in a large clinical database.

Methods
Using deidentified Optum Integrated commercial claims and electronic medical records, we identified patients (0–&lt;3 years old) with a first clinical diagnosis of RSV/bronchiolitis infection from 01 January 2008–31 March 2016. Patients with a diagnosis of asthma/wheezing ≤30 days after first RSV/bronchiolitis diagnosis were excluded. Three cohorts were created with 1/3/5 years of follow-up time required, respectively. Patients were grouped by specific high-risk factors (HRF+/−), including pre-term births and predefined pre-existing disease. Descriptive statistics are reported, with comparisons made by logistic regression analyses.

Results
9,811/4,524/1,788 patients with RSV/bronchiolitis infection and HRF− were included in the 1/3/5-years follow-up cohorts. 14.9%/28.2%/36.3% had AW events by the end of follow-up in the three cohorts. 6.5%/6.9%/5.8% were hospitalized for RSV/bronchiolitis. 3,030/1,378/552 patients with RSV/bronchiolitis infection and HRF+ were included in the 1/3/5-years follow-up cohorts. 18.1%/32.9%/37.9% had AW events by the end of follow-up in the three cohorts. 11.4%/11.1%/11.6% were hospitalized for RSV/bronchiolitis. The CI rates of AW in the 1/3/5-year HRF+/− cohorts, stratified by hospitalized for RSV/bronchiolitis Y/N, are shown in Figure 1.

Logistic regression confirmed that hospitalization for RSV/bronchiolitis was associated with an increased (P &lt; 0.05) likelihood of AW, for HRF+ and HRF− patients at each follow-up year.

Conclusion
Thirty-eight percent of RSV/bronchiolitis infants/neonates/toddlers HRF+, and 36% among infants/neonates/toddlers HRF−, developed AW in the 5 years after first RSV/bronchiolitis diagnosis. RSV/bronchiolitis hospitalization was associated with a significantly increased risk of AW development in 1/3/5 years of follow-up; confirming previous observational study results.

Disclosures
V. Wyffels, Janssen: Employee, Salary. M. Smulders, SmaertAnalyst: Consultant, Consulting fee. S. Gavart, Janssen: Employee, Salary. D. Mazumder, SmartAnalyst: Consultant, Consulting fee. R. Tyagi, SmartAnalyst: Consultant, Consulting fee. N. Gupta, SmartAnalyst: Consultant, Consulting fee. R. Fleischhackl, Janssen: Employee, Salary.
719. The Respiratory Pathogen Panel and Antibiotic Utilization in the Emergency Department
Authors: Taupin Daniel , Stachel Anna , Ding Dan , Hochman Sarah , Phillips Michael 
Published: November 2018

Abstract

Background
The multiplex polymerase chain reaction respiratory pathogen panel (RPP) is used frequently in emergency departments (EDs) for the rapid identification of viruses and atypical bacteria of the respiratory tract. Its clinical value is unclear, as numerous studies have demonstrated that its use has a limited impact on antibiotic prescribing. We aimed to describe the relationship between RPP results and antibiotic prescribing rates for ED patients in our large academic medical center.

Methods
We retrospectively analyzed the charts of 1,061 patients aged 18–90 who were treated and released from two EDs from January 1, 2015 to January 31, 2018 and underwent RPP testing. Patients with evidence of bacterial infection were excluded based on RPP detection of atypical bacteria and microbiological analysis of blood, urine, wound, and sputum specimens. The results of the RPP and the rates of subsequent respiratory pathogen-directed antibiotic prescribing (including ED and outpatient pharmacy orders) were compared.

Results
Antibiotic prescription rates were 21.5% in patients who tested negative for any respiratory virus, compared with 14.5% in patients who tested positive (OR 0.70, P &lt; 0.01). When positive RPPs were subdivided based on virus type (influenza and non-influenza) and compared with negative RPPs, only influenza-detection was associated with a significant reduction in antibiotic prescriptions (Table 1).

Conclusion
In our study population, the presence of a respiratory virus detected by the RPP was correlated with a significant decrease in antibiotic prescribing. This effect was largely driven by influenza detection. This demonstrates that at our institution, the RPP may have a role in reducing unnecessary antibiotic utilization, but providers need further guidance in the interpretation of non-influenza respiratory virus positivity.

Disclosures
All authors: No reported disclosures.
725. Clinical Outcomes of Elderly Individuals Presenting with Acute Respiratory Infections
Authors: Bloom Allison , Suchindran Sunil , Mcclain Micah T 
Published: November 2018

Abstract

Background
Elderly individuals experience increased morbidity and mortality from acute respiratory infections (ARI), which are complicated by difficulties defining etiologies of ARI and risk-stratifying patients in order to guide care. A number of scoring tools have been developed to predict illness severity and patient outcome for proven pneumonia, however less is known about the use of such metrics for all causes of ARIs.

Methods
We analyzed risk factors, clinical course and major outcomes of individuals ≥60 years of age presenting to the emergency department with a clinical diagnosis of ARI over a 5-year period.

Results
Of the enrolled individuals 40 had proven viral infection and 52 proven bacterial infections, but 184 patients with clinically adjudicated ARI (67%) remained without a proven microbial etiology despite extensive workup. Age (71.5 vs. 65.9 years, P &lt; 0.001) and presence of cancer and heart failure were strongly predictive of illness severe enough to require hospital admission as compared with treatment in the outpatient setting. Of those with proven etiology, individuals with bacterial infection were more likely to require hospital and ICU admission (P &lt; 0.001). When applied to this study, a modified PORT score was found to correlate more closely with clinical outcome measures than a modified CURB-65 (r, 0.54 vs. 0.39). Jackson symptom scores, historically used for viral illness, were found to inversely correlate with outcomes (r, −0.34) and show potential for differentiating viral and bacterial etiologies (P = 0.02). Interestingly, a multivariate analysis showed that a novel scoring tool utilizing sex, heart rate, respiratory rate, blood pressure, BUN, glucose and presence of chronic lung disease and cancer was highly predictive of poor outcome in elderly subjects with all-cause ARI.

Conclusion
Elderly subjects are at increased risk for poor clinical outcomes from ARI and their clinical management remains challenging. However, modified PORT, CURB-65, Jackson symptom score, and a novel scoring tool presented herein all offer some predictive ability for all-cause ARI in elderly subjects. Such broadly applicable scoring metrics have the potential to assist in treatment and triage decisions at the point of care.

Disclosures
All authors: No reported disclosures.
727. Evaluation of Antibiotic Prescribing Practices for Upper Respiratory Infections in the Adult and Pediatric Emergency Departments
Authors: Lim Megan , Petty Lindsay , Dillman Nicholas , Walker Pamela , Nagel Jerod 
Published: November 2018

Abstract

Background
Emergency medicine physicians are among the top five specialties prescribing antibiotics. New accreditation standards for outpatient antimicrobial stewardship are now in effect, thus evaluation of antibiotic prescribing practices in the emergency department (ED) is needed. Upper respiratory infections (URIs) have been shown to be a common culprit for inappropriate antibiotic use and are among the leading primary diagnoses seen at ED visits. We aimed to assess the management of URIs in the adult and pediatric EDs by diagnosis and provider type, in order to target interventions to improve use.

Methods
In this retrospective, single-center cohort study, we included adult and pediatric patients seen in the ED and discharged home from September 2015 through August 2017. Patients with one of eight ICD-10 primary diagnosis codes associated with URIs were included (Figure 1). The primary outcome was to evaluate prescriber compliance with guidelines for the treatment of URIs among our adult and pediatric ED departments. Secondary outcomes included assessment of patient outcomes (14-day hospital and clinic revisit rates) between the compliant and noncompliant cohorts, and a comparison of prescribing practices among prescriber types.

Results
A total of 1,646 adult ED encounters and 2,589 pediatric ED encounters were included, with overall 84.0% and 94.4% compliance, respectively. Among URIs, compliance rates were low for bronchitis in adult patients (68.3%) and tonsillitis in both the adult (44.3%) and pediatric patients (57.6%). No difference in outcomes, including 14-day hospital and clinic revisit rates, were observed between groups for both the adult (12.7% vs. 14.8%, P = 0.37) and pediatric (18.8% vs. 17.9%, P = 0.91) cohorts. Higher rates of noncompliance were seen in adult and pediatric physicians (37.5% and 10.3%) compared with corresponding advanced practice providers (14.9% and 9.6%) and residents (12.1% and 4.5%).

Conclusion
The ED provides care for a large number of patients with URIs and should be a focus for antimicrobial stewardship. To be most effective, future stewardship interventions in the ED should target physician groups, and bronchitis in adults and tonsillitis in all patients.

Disclosures
All authors: No reported disclosures.
736. Incidence and Etiology of Community-Acquired Pneumonia Requiring Hospitalization Among American Indian/Alaskan Native Adults
Authors: Kross Konrad , Essex Whitney , Gahn David , Mera Jorge 
Published: November 2018

Abstract

Background
A leading infectious cause of hospitalization among adults in the United States is community-acquired pneumonia (CAP). The etiology and incidence of CAP in American Indians/Alaskan Natives (AI/AN) has not been described.

Methods
We conducted a retrospective study by reviewing the medical records of all AI/AN patients 18 years or older admitted to W.W. Hastings Hospital in Tahlequah, Oklahoma with a diagnosis of a respiratory infection from January 1, 2016 to December 31, 2016. Only patients with a radiographically confirmed CAP were included and those with a recent hospitalization or immunosuppressed were excluded. Patient demographics, comorbidities and results of molecular tests, antigen detection, high quality sputum culture and blood culture were reviewed. Population-based incidence rates of CAP requiring hospitalization were calculated according to age.

Results
From January 2016 through December 2016, 763 patients were admitted with a diagnosis of a respiratory infection, of which 193 (25%) met the inclusion criteria. Of this group, 103 (53%) had at least one pathogen detected: one or more viruses were detected in 47 (24%), one or more bacteria were detected in 63 (33%). The most common pathogens were Streptococcus pneumoniae (12% of patients), rhinovirus/enterovirus (11% of patients), respiratory syncytial virus (5% of patients), legionella pneumophila (4% of patients), and human metapneumovirus (4% of patients). The annual incidence of CAP was 13.6 cases (95% confidence interval, 11.9, 15.7) per 10,000 adults, with the highest incidence among adults ages 65–79 (43 cases per 10,000 adults) and those 80 years of age or older (102 cases per 10,000 adults). Seventy-five percent of patients had an underlying medical condition, 47% had diabetes mellitus (DM), followed by chronic obstructive lung disease (38%) and chronic heart disease (32%).

Conclusion
In this AI/AN population, a respiratory pathogen was identified in 53% of the cases despite the use of cutting edge diagnostic tests in most patients. Bacteria were detected more often than viruses. Compared with recent publications of CAP affecting non-Hispanic whites, non-Hispanic blacks and Hispanics, the population described in this study was older and had higher prevalence of DM.

Disclosures
All authors: No reported disclosures.
746. Characteristics of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Adults, United States, 2014–2017
Authors: Kim Lindsay , Cikesh Bryanna , Kirley Pam Daily , Anderson Evan J , Eckel Seth , Como-Sabetti Kathryn , Dufort Elizabeth M , Felsen Christina B , Crawford Courtney , Talbot H Keipp , Langley Gayle E , Gerber Susan I 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) vaccines are in clinical development for older adults. We described RSV infections among adults requiring hospitalization and risk factors for severe outcomes using a population-based platform, the Influenza Hospitalization Surveillance Network (FluSurv-NET).

Methods
Surveillance occurred October 1–April 30 (2014–2017) at sites located in seven states (California, Georgia, Michigan, Minnesota, New York, Oregon, and Tennessee) covering an annual catchment population of up to 13 million adults ≥18 years. Laboratory-confirmed RSV cases were identified using hospital and state public health laboratories, hospital infection preventionists, and/or reportable condition databases. Medical charts were reviewed for demographic and clinical data. International Classification of Diseases (ICD) discharge codes were abstracted. Odds ratios (Oregon) and 95% confidence intervals (CIs) were determined to assess risk factors for ICU hospitalization and deaths.

Results
A total of 2,326 hospitalized RSV cases were identified. Over half were ≥65 years (62%, n = 1,438/2,326), female (59%, n = 1,362/2,326), white (70%, n = 1,301/1,855), and had ≥3 underlying medical conditions (52%, n = 1,204/2,326). 20% (n = 398/2,000) were hospitalized in the ICU (median length of stay, 3 days; interquartile range, 1–6 days), and 5% (n = 96/2,001) died in the hospital. Congestive heart failure (CHF; OR: 1.4, 95% CI: 1.1–1.8) and chronic obstructive pulmonary disease (COPD; OR: 1.3, 95% CI: 1.1–1.7) were associated with ICU admission, while age ≥80 years (OR: 4.1, 95% CI: 1.8–12.1) and CHF (OR: 2.4, 95% CI: 1.6–3.6) were associated with in-hospital deaths. RSV-specific ICD codes were listed in the first 9 positions in only 44% (879/1,987) of cases.

Conclusion
To our knowledge, this is the largest US case series of RSV-infected hospitalized adults. Most cases were ≥65 years and had multiple underlying medical conditions. Older age, CHF, and COPD were associated with the most severe outcomes. Few cases had RSV-specific ICD codes, suggesting that administrative data underestimate adult RSV-related hospitalizations. Continued surveillance is needed to understand the epidemiology of RSV among adults as vaccine products move toward licensure.

Disclosures
E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.
747. Antibiotic Therapy for Community-Acquired Pneumonia: A Systematic Review and Network Meta-Analysis of Randomized Trials
Authors: Siemieniuk Reed , Lee Yung , Bogoch Isaac , Brignardello-Petersen Romina , Fei Yutong , Alexander Paul , Aves Theresa , Zeraatkar Dena , Sadeghirad Behnam , Li Xun , Evaniew Nathan , Bhatnagar Neera , Rochwerg Bram , Guyatt Gordon , Loeb Mark 
Published: November 2018

Abstract

Background
Community-acquired pneumonia (CAP) is one of the top causes of life-years lost globally. The optimal empiric antibiotic therapy regimen is uncertain. Randomized controlled trials (RCTs) provide useful information about relative antibiotic effectiveness.

Methods
We systematically searched Medline, EMBASE, and CENTRAL for RCTs comparing at least two empiric antibiotic regimens in patients with CAP, to March 17, 2017. We performed a systematic review and network meta-analysis and network meta-regression using a Bayesian framework. We used GRADE to assess certainty in the effect estimates.

Results
From 18,056 citations, we included 303 RCTs. Most studies (69.9%) were not blinded. All networks had low global heterogeneity (I2 0%). There were 26,423 participants included in the analysis of mortality and 30,559 for treatment failure. Seven hundred and twenty-six (2.9%) participants died. Patients randomized to third generation cephalosporins alone had higher mortality than those randomized to early generation fluoroquinolones (risk ratio [RR] 2.08, 95% credible interval 1.17–3.90), later generation fluoroquinolones (RR 2.32, 1.44–4.26), and cephalosporin-fluoroquinolone combinations (RR 3.21, 0.99–12.49). Participants who were randomized to a cephalosporin plus macrolide were less likely to die than those who received a third generation cephalosporin alone (RR 0.47, 0.21–0.99). The evidence was similar for treatment failure. Β-lactam plus β-lactamase inhibitors (e.g., piperacillin–tazobactam), early generation cephalosporins, and daptomycin appeared to confer a higher risk of mortality and/or treatment failure than most other antibiotic regimens including third-generation cephalosporins alone. For key comparisons, the GRADE quality of evidence was low or moderate.

Conclusion
In patients with CAP, an antibiotic regimen that includes a fluoroquinolone (and possibly a macrolide) may reduce mortality by ~1–2% compared with β-lactams (with or without a β-lactamase inhibitor) and cephalosporins alone. High quality, blinded and pragmatic randomized evidence would be helpful to increase certainty in the evidence.

Disclosures
All authors: No reported disclosures.