bluuebunny/crossref_metadata_2025 huggingface dataset:
1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients
Authors: Khawaja Fareed , Shigle Terri Lynn , Ghantoji Shashank S , Batista Marjorie , Ariza-Heredia Ella , Chemaly Roy F
Published: November 2018

Background

Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections.

Methods

All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison.

Results

A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%.

Conclusion

HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials.

Disclosures

All authors: No reported disclosures.
662. Tick Borne-Associated Thrombocytopenia Among United States Veterans in Long Island New York
Authors: Kaplun Olga , Lemaitre Beth , Lobo Zeena , Psevdos George
Published: November 2018

Background

Long Island, New York, is highly endemic for tick borne illnesses (TBI) with rising numbers of cases in the past years. Thrombocytopenia is a known complication of babesiosis caused by Babesia microti, anaplasmosis caused by Anaplasma phagocytophilum, and ehrlichiosis caused by Ehrlichia chaffeensis. We identified cases of thrombocytopenia attributed to TBI in our institution.

Methods

Retrospective chart review of patients diagnosed with babesiosis, anaplasmosis, and ehrlichiosis from 2000 to 2017 at Northport Veterans Affairs Medical Center. Demographics, method of diagnosis (PCR/serologies), CBC/chemistries, treatment choices, and outcomes were analyzed.

Results

Thirty-two veterans (VETS) were identified with the following TBI: Babesiosis 22, Ehrlichiosis 6, Anaplasmosis 4. The majority of cases (19) were from Suffolk County, Long Island. The median (MED) age of this group was 62 years (range 31–89). Ninety-one percent were Caucasian, 9% Black. 37.5% had history of tick bite. The MED temperature on presentation was 101.9°F (range 97.6–105.2°F). 56% had HTN, 6% DM, 37% HLD, 9% hepatitis C, 3% HIV. Laboratory studies: MED platelet count 88,000/µL (36,000–161,000); MED hemoglobin 12 gm/dL (5.6–15.6); MED ALT 41 IU/L (6–330); MED LDH 335 IU/L (193–1,322). Twelve VETS had positive C6 peptide. The peak MED B. microti parasitemia was 1.4% (0.1–3%). PCR tests were available in the later years of the study period: three were positive for E. chaffeensis, two for A. phagocytophilum, and 14 for B. microti. The majority of the cases (19) were observed after year 2010. Morulae were seen in only one case. Haptoglobin in eight VETS was undetectable. One veteran with history of splenectomy and babesiosis with 3% parasitemia required exchange transfusion with 12 units of PRBCs. Two other babesiosis cases required regular transfusion of PRBCs. 20 babesiosis cases were treated with azithromycin-atovaquone and two with clindamycin-primaquine. Doxycycline was used in the other cases. One patient developed NSTEMI and required coronary stent placement. Platelet counts returned to baseline levels with treatment. No deaths occurred.

Conclusion

The incidence of TBI in Long Island, New York is rising. PCR testing for TBI can be utilized in our VETS presenting with febrile illness and thrombocytopenia to help identify the possible tick borne pathogen during the months of high tick activity.

Disclosures

All authors: No reported disclosures.
663. Characteristics, Treatment Patterns, and Outcomes of Outpatients With Rickettsial Diseases in a Large, Commercially Insured Population: United States, 2005–2016
Authors: Binder Alison , Peterson Amy E , Armstrong Paige
Published: November 2018

Background

Rickettsial diseases (RD) include Spotted Fever Group (SFG) Rickettsiosis, Ehrlichiosis, Anaplasmosis, Typhus Group (TG) and Rickettsialpox, among others. Doxycycline is the treatment of choice in all age groups; early treatment based on clinical diagnosis is important to prevent severe and fatal outcomes. SFG, Ehrlichiosis, and Anaplasmosis are nationally notifiable in the United States, but data on treatment patterns are not collected.

Methods

We conducted a retrospective analysis using Truven Health MarketScan® Commercial Claims and Encounters databases. We included any individual with an outpatient claim using an ICD-9/10-CM code for RD, who had one-year continuous pre- and 3 months post-diagnosis enrollment and pharmaceutical claim data. The first outpatient record with RD was considered the incident diagnosis, and those with an RD hospitalization in the prior 1 year were excluded. Epidemiologic characteristics, treatment patterns, and outcomes were summarized.

Results

13,353 individuals were included; median age was 45 years (IQR: 28–55 years), 2,045 (15%) were under 18 years of age, and 51% were male. The most common diagnosis was SFG (7,133; 50%), followed by Ehrlichiosis (3,920; 30%), and Typhus (1,281; 10%); 36 individuals had >1 diagnosis. Over half (7,075; 53%) received doxycycline within 30 of the index date; of these, 3,634 (51%) received it within 14 days. The majority (5,369; 86%) were treated for at least 10 days at the recommended dose. The proportion with a pharmaceutical claim for doxycycline varied considerably across diagnoses and ranged from 24% for TG to 60% for SFG Rickettsiosis. Among the 6,278 (47%) without a claim for doxycycline, 2,185 (35%) were prescribed another antibiotic; 4,093 (28%) were not prescribed any antibiotic. Hospitalization within 30 days of the incident diagnosis was infrequent (149, 1.1%), and the majority were due to either SFR (40%) or ehrlichiosis (37%). No in-hospital deaths were recorded.

Conclusion

RD continues to be an important cause of disease in the outpatient population, but providers are still only prescribing the recommended treatment to about half of those in whom they suspect the disease. Continued education and increased awareness is critical to prevent severe outcomes from RD.

Disclosures

All authors: No reported disclosures.
669. Changing Epidemiology of Murine Typhus in Texas
Authors: Shuford Jennifer , Hunt Patrick , Mayes Bonny
Published: November 2018

Background

Murine (also known as flea-borne) typhus is uncommon in the United States, but it is considered endemic in certain parts of Texas, especially the southernmost region. It is caused by Rickettsia typhi, which is transmitted to humans by rat and cat fleas. Murine typhus is often a mild illness with nonspecific clinical findings, though delayed treatment may result in severe disease and increased risk of complications. Diagnostic tests have low sensitivity in early disease. Therefore, correctly diagnosing patients with murine typhus is challenging unless clinical suspicion is high. In endemic regions, physicians are aware of the disease and diagnose it readily. However, in areas that have not historically been affected, physicians may be less familiar with the presentation of this rickettsial infection, impacting their ability to diagnose and treat it effectively.

Methods

Probable and confirmed murine typhus cases reported in Texas were collected for 1944–2017. Cases were mapped by county for each of the last 5 years. Cases reported over the last 5 years were also geocoded by residence for spatial cluster analysis by year.

Results

There has been an overall rise in the number of murine typhus cases reported per year over the last 13 years (Figure 1). The distribution of reported cases throughout Texas has changed over the last 5 years. There continues to be a high number of reported cases in South Texas and Central Texas, while reported cases are increasing in the Harris County/Houston area, Tarrant County/Ft. Worth area, and Dallas County/Dallas area. Spatial cluster (hot spot) analysis of typhus cases in Texas over the last 5 years shows areas of increased risk of murine typhus in South Texas that have persisted over time, while other areas of increased risk have appeared more recently in North Texas and Central Texas (Figures 2 and 3).

Conclusion

Murine typhus can be a difficult diagnosis to make based on clinical presentation, and physician awareness of its epidemiology is important. The gradual increase in case counts and the changing distribution of cases within Texas may put patients at risk of missed diagnoses. Recognizing the changing epidemiology of typhus in Texas may help inform public health education and control efforts.

Disclosures

All authors: No reported disclosures.
672. The Impact on Humans of Treating Dogs with Amoxicillin/Clavulanate
Authors: Beaulac Kirthana R , Doron Shira , Fellman Claire , Wayne Annie , McDermott Laura A , Snydman David
Published: November 2018

Background

It has been shown that the use of antibiotics promotes resistance to that antibiotic, and that colonization with resistant pathogens can be transmitted from companion animals to their human owners. There is an evolving concern that use of medically important antibiotics in pets can confer colonization by resistant organisms in their human owners.

Methods

In dogs receiving amoxicillin/clavulanate for 14 days for a diagnosed infection, we screened stool both at the time of antibiotic initiation and at the end of the course for the dog taking antibiotics and their human owner. Owners had to meet a closeness score of 3 or 4, meaning living in same household with frequent contact, with or without oral contact, and have no recent antibiotic exposure. Stool samples were quantitatively cultured for enteric flora and incubated on selective media for ampicillin/sulbactam resistance (A/S-r), ciprofloxacin resistance (CIP-r), ESBL, MRSA, and VRE.

Results

We enrolled eight dog–human pairs. All had enteric flora present at the time of antibiotic initiation (Day 1), whereas two of the seven dog samples that could be analyzed had no detectable enteric flora by the end of antibiotics (Day 14). No humans or dogs acquired MRSA or VRE. One human lost colonization with CIP-r flora, whereas two dogs acquired CIP-r during antibiotic treatment that did not transmit to their owners. One dog and one unrelated human acquired ESBL colonization by day 14 that was not present at Day 1. There were three humans colonized with A/S-r on Day 1 which persisted through the treatment period. Of their three dogs, one had no A/S-r at either time point, one newly acquired high counts of A/S-r flora, and one did not provide enough stool at Day 14 for A/S-r testing. There was one other dog that acquired A/S-r flora and one dog that had increasing counts of A/S-r, both of which had human owners with no A/S-r on Day 1 or 14.

Conclusion

In this pilot study, we identified that use of amoxicillin-clavulanate, a common antibiotic prescribed to both humans and dogs, can lead to resistant colonization in the dog taking antibiotics, and may have some impact on their close human owners who may share or transmit colonization. Further study is under way to better understand this relationship.

Disclosures

L. A. McDermott, CutisPharma Inc.: Research Contractor, Contractual agreement with Tufts Medical Center.
673. Syphilis Outbreak in Women Who Have Sex with Men in Japan: A Case–Control Study in Tokyo, 2017–2018
Authors: Nishiki Shingo , Arima Yuzo , Yamagishi Takuya , Hamada Takashi , Takahashi Takuri , Sunagawa Tomimasa , Matsui Tamano , Oishi Kazunori , Ohnishi Makoto
Published: November 2018

Background

In Japan, syphilis notifications have increased sharply, with Tokyo accounting for a third of all cases. Importantly, the increase in women has been remarkable, with the majority being women who have sex with men. We therefore conducted a prospective case–control study to evaluate correlates of recent syphilis infection among women in Tokyo.

Methods

We employed a test-negative design case–control study among women who sought a syphilis test at a women’s health clinic in Tokyo, comparing socioeconomic status, medical history, and recent sexual behaviors/partnerships, between those who were diagnosed with recent syphilis infection based on clinical signs and serological test results (cases) vs. those who were nonreactive for the nontreponemal test (controls). Participants aged ≥20 years and sexually active in the past 6 months were recruited from June 2017 to March 2018 and completed a self-administered questionnaire. We described cases and assessed for correlates of recent syphilis infection based on odds ratios (ORs) and 95% confidence intervals (CIs).

Results

A total of 524 women, composed of 60 cases and 464 controls, were enrolled. The median age was 23 years (range = 20–54) among cases and 26 years (range = 20–59) among controls. Of the 60 cases, 10 (17%) were current students and three (5%) had a history of syphilis; in the past 6 months, while 35 (58%) had engaged in commercial exchange of sexual practices, 14 (23%) had only one sex partner. Having lower educational attainment (OR = 4.1; 95% CI = 2.1–8.1), not being employed full-time (OR = 3.1; 95% CI = 1.8–5.5), and commercial exchange of sexual practices (OR = 3.4; 95% CI = 2.0–5.9) were associated with case status in univariate analysis. The association between case status and inconsistent condom use (relative to consistent condom use) during vaginal/anal sex in the past 6 months (OR = 2.0; 95% CI = 0.9–4.3) became stronger when restricted to women engaged in commercial exchange of sexual practices (OR = 4.0; 95% CI = 1.4–10.9).

Conclusion

This was the first study to evaluate potential risk factors for recent syphilis infection among women in Japan. In light of these findings, we may need a multi-pronged approach to prevent and control syphilis, for both those engaged in commercial exchange of sexual practices and the general population.

Disclosures

All authors: No reported disclosures.
688. Impact of Expanded Influenza Post-exposure Prophylaxis on Healthcare Worker Absenteeism at a Tertiary Care Center During the 2017–2018 Season
Authors: Puig-Asensio Mireia , Douglas Margaret , Holley Stephanie , Kukla Mary Beth , Abosi Oluchi , Mascardo Lisa , Carmody Brenda , Gent Courtney , Diekema Daniel , Hartley Patrick , Edmond Michael , Salinas Jorge L
Published: November 2018

Background

A severe 2017–2018 influenza season was expected for the United States. We hypothesized that a surge in influenza cases paired with decreased vaccine effectiveness could increase healthcare worker (HCW) absenteeism. Because of a potential public health emergency during the 2017–2018 season, we offered oseltamivir post-exposure prophylaxis (PEP) to exposed HCWs regardless of vaccination status. We describe PEP uptake, cost, and impact on absenteeism at the University of Iowa Hospital and Clinics (UIHC).

Methods

UIHC serves as a referral and safety net health system for Eastern Iowa. Influenza seasons were defined as the period between Week 40 from 1 year to Week 13 of the following year. During the 2016–2017 season, PEP (75 mg/day for 7 days) was offered free of charge to unvaccinated exposed HCWs. Exposure was defined as proximity within 3 ft of a confirmed influenza-infected person for ≥10 minutes without mask protection, or direct contact with respiratory secretions. During the 2017–2018 season, PEP was expanded to all exposed HCWs regardless of vaccination status. We reviewed surveillance, employee health, pharmacy, and human resources records for the 2016–2017 and 2017–2018 seasons. We defined PEP uptake as prescriptions picked up/all referrals and absenteeism rate as sick-leave requests/scheduled hours.

Results

During the 2016–2017 and 2017–2018 seasons, we detected 373 and 427 confirmed influenza cases among patients at UIHC. HCW vaccination rates were similar: 89.7% and 90.9%. PEP was recommended in 49 exposures during 2016–2017 and 280 exposures during 2017–2018. A total of 22 (44.9%) and 133 (47.5%) HCWs picked up oseltamivir from the pharmacy during the 2016–2017 and 2017–2018 seasons. The estimated cost of oseltamivir was $1,791 and $10,828, respectively. Overall, 6,187 sick-leave requests (median = 12 hours, absenteeism rate = 3.2%), and 6,174 sick-leave requests (median = 12 hours, absenteeism rate = 3.4%) were reported during the 2016–2017 and 2017–2018 seasons.

Conclusion

Influenza case counts mildly increased from the 2016–2017 to the 2017–2018 season. Expanding PEP to all exposed HCWs, regardless of vaccination status, had moderate uptake and was costly. Absenteeism rates remained similar during both seasons.

Disclosures

All authors: No reported disclosures.
697. Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Monoclonal Antibody MEDI3902, Are Conserved Among Diverse Hospital Isolates Collected From an International Surveillance Study
Authors: Tabor David E
Published: November 2018

Background

Pseudomonas aeruginosa is a frequent cause of life-threatening infections in mechanically ventilated patients and is associated with high mortality rates. Bispecific monoclonal antibody MEDI3902 targeting Pa type-3-secretion system (PcrV) and the Psl exopolysaccharide is currently under phase 2b development for the prevention of pneumonia in mechanically ventilated subjects with Pa colonization in the lower respiratory tract. In this study, we sought to survey a vast collection of global Pa clinical isolates for presence of pcrV and psl loci and MEDI3902 epitope conservation to evaluate the magnitude of Pa strain coverage by MEDI3902.

Methods

913 Pa clinical isolates were collected from diverse patients and geographical locations in 2004–2014. Whole genome sequencing of the full collection was performed via MiSeq 2 × 250 runs (Illumina®). PcrV and Psl expression was detected by immunoblotting and ELISA, respectively. The crystal structure of anti-PcrV fab and PcrV fragment complex-crystals was solved at 2.8 Å resolution. MEDI3902 activity against representative isolates was tested in cytotoxicity and opsonophagocytosis assays and in a murine pneumonia model.

Results

Whole-genome sequencing revealed intact pcrV and psl genetic elements in 99% and 94% of isolates, respectively. We identified 46 variants of PcrV that were all bound by the anti-PcrV moiety of MEDI3902 and confirmed through crystal structure analysis that antibody-antigen contact residues were preserved in all variants. Similarly, anti-Psl binding was confirmed for selected isolates containing the complete Psl operon and strains lacking non-essential psl genes. Importantly, 99.9% of isolates contained the full complement of either genetic element. Consistent with these results, we observed potent MEDI3902 activity against diverse strain types, including strains that expressed only a single target.

Conclusion

Our results indicate PcrV and Psl are highly prevalent in recent clinical isolates from around the world, suggesting that MEDI3902 can mediate broad coverage against Pa.

Disclosures

D. E. Tabor, Astra Zeneca: employee, Salary.
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

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

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 (>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

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–<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 < 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

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 < 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

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 < 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 < 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

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

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

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

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.
754. Prevalence of Latent Tuberculosis Infection Among Healthcare Workers at a Tertiary Care University Hospital
Authors: Choo Eun Ju , Park Se Yoon
Published: November 2018

Background

We investigated the prevalence of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) and analyzed its risk factors in a tertiary care university hospital in South Korea in a population with intermediate tuberculosis (TB) burden.

Methods

A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant. QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay and chest radiography were performed to investigate the rate of LTBI.

Results

A total of 1,429 participants, 213 (14.9%) doctors and 988 (69.1%) nurses and 228 (16.0%) others were enrolled. The mean age of the subjects was 33.0 years old, and 1,175 (82.2%) were female. Of the participants, 94.5% had received BCG vaccine. QFT-GIT assays were positive for 156 subjects (10.9%). Of the 213 doctors, 28 (13.1%) were positive by QFT-GIT, and among the 988 nurses, 94 (9.5%) had positive QFT-GIT results. Experience of working in hospital was significantly associated with positive LTBI test results by QFT-GIT assay. Gender and duration of employment as an HCW were significantly associated with having a positive QFT-GIT result in univariate analyses. In multivariate analyses, duration of employment as an HCW (>15 years) (odds ratio, 1.98; 95% confidence interval, 1.14–3.43) was independently associated with increased risk of a positive QFT-GIT result.

Conclusion

A high prevalence of LTBI was found among our HCWs. Considering the association between the experience of working in hospital and high risk of LTBI. The risk for tuberculosis infection among HCWs was higher than general population, which suggests that stricter preventive strategies against nosocomial tuberculosis infection should be implemented.

Disclosures

All authors: No reported disclosures.
759. Molecular Characterization and Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) and Identification of Possible Cases of Local Transmission of MDR-TB in Kuwait
Authors: Mokaddas Eiman , Ahmad Suhail , Al-Mutairi Noura
Published: November 2018

Background

Increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is hampering efforts to control TB. Kuwait is a low (25/100,000) TB incidence country and ~1% of Mycobacterium tuberculosis strains are resistant to rifampin, RIF and isoniazid, INH (MDR-TB). Analysis of resistance conferring mutations in seven genes was combined with spoligotyping for detecting local transmission of MDR-TB in Kuwait.

Methods

MDR-TB strains (n = 131) from 88 TB patients and 50 susceptible strains were used. Susceptibility testing was done by MGIT 960 system, gMTBDRplus assay and PCR-sequencing of three regions of rpoB, katG codon 315 (katG315) + inhA regulatory region, embB (embB306/embB406/embB497 regions), rpsL + rrs-500–900 regions and pncA for RIF, INH, ethambutol (EMB), streptomycin (SM) and pyrazinamide (PZA), respectively. Sequencing data were used to construct phylogenetic tree by MEGA7 software. Spoligotypes were identified by SITVIT2 and phylogenetic tree was made by MIRU-VNTRplus software.

Results

Mutations were detected in most isolates in rpoB, katG+inhA, embB, rpsL+rrs and pncA which confer resistance to RIF, INH, EMB, SM and PZA, respectively. Phylogenetic analysis of multi-locus concatenated sequences showed unique patterns for 51 patient’s isolates while 37 patient’s isolates grouped in 14 clusters. Spoligotyping identified 35 patterns (19 unique patterns and 69 patients’s isolates in 16 patterns) including 11 orphan patterns. Sixteen isolates yielded six clusters (each containing two to five isolates) by both fingerprinting methods.

Conclusion

Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified six potential cases of local transmission of MDR-TB involving two to five subjects (including five Kuwaiti patients) which had escaped detection by routine surveillance studies. Prospective detection of resistance conferring mutations thus identifies possible cases of local transmission of MDR-TB in low TB incidence countries.

Disclosures

All authors: No reported disclosures.