bluuebunny/crossref_metadata_2025_split huggingface dataset:
2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018
Authors: Silveira Fernanda P , Hughes Kailey L , Balasubramani G K , Middleton Donald , Nowalk Mary Patricia , Martin Emily T , Gaglani Manjusha , Talbot H Keipp , Ferdinands Jill , Zimmerman Richard 
Published: October 2019

Abstract

Background
Immunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults.

Methods
We analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions.

Results
Of 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1).

Conclusion
Vaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts.

Disclosures
All authors: No reported disclosures.
2752. Peptide Vaccines Utilizing Conserved Hemagglutinin, Neuraminidase, and Matrix Ectodomain Influenza Epitopes Demonstrate Functional Activity Against Group 1 and 2 Influenza Strains
Authors: Sei Clara J , Rikhi Nimisha , Hidajat Rachmat , Schuman Richard F , Muema Kevin , Mutunga Jasmine M , Daum Luke T , Fischer Gerald W 
Published: October 2019

Abstract

Background
Globally, prevention and control of seasonal influenza has faced many challenges in the selection of a vaccine composition that antigenically matches circulating viruses. A universal influenza vaccine approach that targets small conserved influenza virus epitopes/peptides such as the extracellular domain of Matrix 2 (M2e) and induces broadly reactive antibodies may be helpful for both seasonal influenza outbreaks and pandemics. Here we report the ability of two composite peptide vaccines, individually and in combination, to induce broadly reactive antibodies that have binding and functional activity across several contemporary influenza strains in Group 1 and 2.

Methods
Mice were immunized with peptide composite vaccines against Hemagglutinin (HA), Neuraminidase (NA) and M2e, individually and in combination. Peptide composite vaccines, conjugated to CRM were administered subcutaneously with adjuvant and at least two booster doses. Serum antibody titers were analyzed using an anti-influenza ELISA for binding activity to peptides and live influenza viruses (H3N2 and H1N1) and functional activity was evaluated in vitro using Microneutralization, Hemagglutination Inhibition (HAI), and Antibody-Dependent Cellular Cytotoxicity (ADCC) assays.

Results
Mice given the peptide composite conjugate vaccines, individually and in combination, had strong humoral responses producing high serum anti-influenza titers post-booster immunization. Anti-influenza serum antibodies demonstrated functional activity against influenza A (H3N2 and H1N1) contemporary strains showing neutralization, HAI and ADCC activity.

Conclusion
Peptide conjugate vaccines were highly immunogenic in mice. Broadly reactive serum antibodies against the peptides and live influenza viruses were detected. These vaccines individually or in combination, induced antibodies that demonstrated functional activity against contemporary influenza strains in Group 1 and 2 and induced functional anti-influenza monoclonal antibodies. A vaccine that targets one or more HA, NA and M2e influenza epitopes may more closely approach the goal for a true universal influenza vaccine. In vivo protection studies are currently being designed.

Disclosures
All authors: No reported disclosures.
2801. Post-Natal Zika Virus Infection and Impact on Neurodevelopment Among a Cohort of Children in Rural Guatemala
Authors: Olson Daniel , Lamb Molly , Connery Amy , Colborn Kathryn , Natrajan Muktha S , Waggoner Jesse , Paniagua-Avila Alejandra , Bauer Desiree , Anderson Evan J , Calvimontes Mirella , Bolanos Guillermo , Watson Nora , Sahly Hana El , Munoz Flor M , Munoz Flor M , Asturias Edwin J 
Published: October 2019

Abstract

Background
The impact of early post-natal Zika virus (ZIKV) infection on neurodevelopment (ND) is unknown. A prospective study of post-natal ZIKV infection in rural Guatemala (ZIKV study) enrolled a cohort of children ages 1–5 years, including children previously enrolled in a dengue virus (DENV) study during the 2015–2016 ZIKV epidemic. We evaluated ND outcomes by age and ZIKV infection status.

Methods
Subjects enrolled in the ZIKV study June 2017–April 2018 underwent ND testing using the Mullen Scales of Early Learning (MSEL) at baseline and 12 months later. ZIKV/DENV-1/2 FRNT50 was performed on enrollment and on banked serum samples from the 2015 to 2016 subset. ZIKV serostatus and MSEL scores were correlated using multiple linear mixed models, adjusted for age and gender when appropriate, to evaluate their association. Geolocation was used to explore clustering of ZIKV serostatus and MSEL score.

Results
We enrolled 183 children (43% female, mean age 3.2 years). Of these, 38 (21%) were classified as ZIKV-positive (+), 111 (61%) ZIKV-negative (-), 31 (17%) ZIKV-possible, and 3 (2%) ZIKV-indeterminate. ZIKV(+) cases and higher composite MSEL scores clustered in more densely populated areas (Figure 1). ZIKV(+) serostatus was associated with higher MSEL composite (increase in log score 0.09, P = 0.003) and subdomain scores: fine motor (0.13, P = 0.011), visual reception (0.15, P = 0.002), receptive language (0.09, P = 0.041), gross motor (0.14, P = 0.09), and expressive language (0.09, P = 0.058) (Figure 2). Of the 78 children (43%) with 2015–2016 samples, 46 (59%) remained ZIKV(−), 16 (21%) seroconverted from ZIKV(−) or possible/indeterminate to ZIKV(+), and 16 (21%) were indeterminate when enrolled in the ZIKV study. ZIKV seroconversion was associated with higher composite (0.13, P = 0.02) MSEL scores compared with ZIKV(−).

Conclusion
In this exploratory analysis, post-natal ZIKV infection was not associated with adverse ND outcomes in children age 1–5 years. Overall, ZIKV(+) status was associated with higher average ND scores than ZIKV(−), and scores decreased with age for most children, independent of ZIKV status. The correlation of ZIKV(+) status and higher MSEL scores may be confounded by geographic-related factors or other confounders. NIAID Contract HHSN272201300015I Task Order HHSN27200013 (Co-PIs: FMM & EJA).

Disclosures
Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.
174. Temporizing Surgical Measures for Deep Mechanical Circulatory Support Device Infections: Case Series Report
Authors: Kabirpour Armita , Tang Daniel G , De laCruz Oveimar 
Published: October 2019

Abstract

Background
Durable mechanical circulatory support device (MCSD) use continues to grow. MCSD deep-seated infections are a serious complication. Removal of the infected hardware is not always possible.

Methods
Single institution retrospective review of all culture-proven deep MCSD infection (pump and/or driveline) from 2009–2019. Patients were managed with intravenous (IV) and oral (PO) antibiotics; definitive surgical interventions included incision and drainage (I&D), device replacement, and heart transplant; and temporizing surgical measures were chronic chest tube (CCT) drainage for pump pocket and mediastinum and antibiotic impregnated bead implantation for driveline infection. Outcomes were analyzed.

Results
Total of 29 patients identified, 23 (79%) were male. Median age at device implantation was 44 years (20–68). MCSD were 18 (62%) destination therapy and 11 (38%) bridge to transplant. MCSD included 1 Heartmate I, 17 Heartmate II, 1 Heartmate III, 4 Heartware HVAD, and 6 Syncardia TAH. The median time to infection of 258 days (43–1551), affecting pump in 8 (28%), pump + driveline in 13 (44%), and driveline in 8 (28%). Microorganisms were S. aureus in 17 (60%, MRSA 11 and MSSA 6); coag-negative staphylococci in 3 (10%); Viridans streptococci in 1; Serratia marcescens in 3; P. aeruginosa in 2; Klebsiella oxytoca in 1; Mycobacterium abscessus in 1 and C. albicans in 1. Antibiotics are given to 28 patients, 23 (80%) with initial IV for a median of 6 weeks (1–14) and 5 (17%) with initial PO, for a median of 7 weeks (2–20). Nineteen patients (83%) on IV received PO antibiotics after. 17 patients (61%) remained on chronic suppression antibiotics (13 PO, 2 IV, 2 PO and IV). Twenty-six (90%) patients had I&D, 6 (21%) had device replacement and 11 (38%) had transplant. Of 21 patients with pump infection 16 (76%) had CCT drainage of pump pocket site or mediastinum for a median of 116 days (range 10–887 days). Of 21 patients with driveline infections, 6 (29%) had antibiotic impregnated bead implants. Overall survival at 90 days was 28/29 (95%) and 24/29 (83%) at 1 year. Infection-related mortality in Table 1.

Conclusion
Deep MCSD infection remains a challenging clinical problem. CCT drainage (for pump) and antibiotic-impregnated bead implant (for driveline) may be temporizing options for patients unable to undergo timely device replacement or heart transplant.

Disclosures
All authors: No reported disclosures.
488. Epidemiology and Outcomes for Stenotrophomonas maltophilia Infections at a Tertiary Care Center in Detroit, MI
Authors: Oring Justin , Awali Reda , Chopra Teena 
Published: October 2019

Abstract

Background
Stenotrophomonas maltophilia is a gram-negative, biofilm-forming bacterium. The increasing use of antibiotics has allowed this bacterium to become a predominant nosocomial pathogen with inherent resistance to several antibiotics. In this study, we describe the epidemiology and outcomes for patients treated for S. maltophilia infections who were admitted to Detroit Medical Center from January 1, 2010 to August 31, 2018.

Methods
This was a retrospective cohort study that included S. maltophilia cultures isolated from sterile body sites from January 1, 2010 to August 31, 2018. Nonsterile body sites and tissue cultures were excluded, as well as cultures that were deemed to be colonization based upon clinical evaluation. Appropriate empiric antibiotic therapy was defined as a regimen administered three days prior to or four days following the S. maltophilia culture date. Appropriate definitive therapy was defined as antibiotic treatment administered five to fourteen days following the culture date. Patient data were extracted from the electronic medical record which included demographic information, length of stay and outcome data. Bivariate analysis was performed using SAS database.

Results
126 patients with S. maltophilia infections were analyzed: 89 had bacteremia, 22 had lung infections, and 15 had other infections. The median length of stay was 16 days (IQR 6–30 days). Sixty-one patients (48%) admitted to the ICU had a median length of stay of 10 days (Table 2). Among the patients that were followed after discharge, 21 were readmitted within 30 days. Table 1 highlights the bivariate analysis of patients who died within 30 days vs. survived. Patients who received definitive antibiotic therapy had lower 30-day mortality (Table 1; CI 95%, OR=0.37, P = 0.03). In addition, patients who were bacteremic had a lower 30-day mortality (Table 1; CI 95%, OR=0.40, P = 0.04). There was no significant difference in mortality among patients who received appropriate empiric antibiotic therapy (P = 0.67).

Conclusion
This study demonstrates that nonbacteremic patients infected with Stenotrophomonas have higher 30-day mortality than those with bacteremia. This necessitates that diseases associated with this bacterium should be taken seriously and treated with definitive appropriate antibiotics.

Disclosures
All authors: No reported disclosures.
179. Two Cases of Corynebacterium Striatum Prosthetic Valve Endocarditis Resulting in Opposing Outcomes
Authors: Fukuchi Takahiko 
Published: October 2019

Abstract

Background
The Corynebacterium species is associated with bacteremia, cellulitis, and rarely, endocarditis. Corynebacterium endocarditis used to be an extremely rare disease; however, the development of mechanical devices boosted its prevalence, rendering it unignorable. This bacteria is also described as an emerging multi-drug-resistant pathogen.

Methods
We encountered two cases of Corynebacterium striatum prosthetic valve endocarditis, one of which was successfully treated. We failed to treat the other case despite prolonged medical treatment. We describe their clinical courses and literature review.

Results
(Case 1) A 74-old man was admitted to our hospital because of C. striatum prosthetic valve endocarditis. He relapsed twice despite treatment with adequate dosage and duration (6 weeks) of vancomycin during the first episode, and following daptomycin during the second episode depending upon the result of drug susceptibility. However, both medical treatments failed. He had refused surgery upon each hospitalization. He was treated with intravenous vancomycin and oral rifampin for 24 weeks. His endocarditis did not relapse after 6 months’ treatment. (Case 2) A 71-year-old man who had a past medical history of enterococcal endocarditis was successfully treated with intravenous ampicillin and subsequent atrial valve replacement. He was admitted to our hospital because of fever and back pain. Prosthetic valve endocarditis was diagnosed because blood cultures revealed C. striatum, and evidence of metastatic lesions. While intravenous vancomycin and oral rifampin (600 mg/day) were initiated, several complications, such as pseudoaneurysm of ascending aorta, splenic artery aneurysm followed by a rupture, and cerebral hemorrhage occurred. The patient’s refusal of a re-operation rendered prolonged medical treatment necessary for 16 weeks. He died 20 weeks after the diagnosis of Corynebacterium endocarditis.

Conclusion
The same antibiotic treatment regimen resulted in opposing outcomes in our two patients. To the best of our knowledge, only 22 cases were previously described in English literature. However, there was no well-established medical treatment against this pathogen. Our experience might be beneficial for similar patients worldwide.

Disclosures
All authors: No reported disclosures.
198. Chart Validation of an Algorithm for Identifying Patients with Intravenous Drug Use-Associated Endocarditis Using Administrative Code Data
Authors: Kobayashi Takaaki , Beck Brice , Miller Aaron C , Polgreen Philip M , Ohl Michael 
Published: October 2019

Abstract

Background
Studies using administrative data have described increasing rates of intravenous drug use (IVDU)-associated infective endocarditis (IE) in the United States. These studies used International Classification of Disease (ICD) diagnosis codes to identify hospitalized patients with IE and any illicit drug use (i.e., opioid, amphetamine, cocaine or sedative), but were hindered by absence of specific ICD codes for IVDU. We reviewed charts to determine the positive predictive value (PPV) of ICD codes for identifying patients with IE and IVDU.

Methods
We examined national Veterans Affairs (VA) administrative data from January 2010 to December 2017 to identify patients hospitalized for a first episode of potential IVDU-associated IE based on inpatient ICD 9 and 10 codes for both IE and any illicit drug use, the algorithm used to identify IVDU-IE in most prior studies. We randomly selected 100 of these patients nationally and reviewed hospital charts to confirm clinical documentation of: (1) IE, (2) any illicit drug use, and (3) current or past IVDU.

Results
We identified 340 patients with concurrent ICD codes for IE and drug use, increasing from 28 in 2010 to 51 in 2017 (82% increase). In chart review of 100 randomly selected patients, the PPV of ICD codes was 93% (95% CI 88–98%) for a documented clinical diagnosis of IE; 96% (95% CI 92–100%) for documented drug use by any route; and 63% (95% CI 53–73%) for documented IVDU. Among the 37% of patients without clinically documented IVDU, 30% (i.e.,11% of total patients) had clinical documentation stating that drug use was only by non-IV routes, 59% (22% of total) had documented drug use without mention of route of use, and 11% (4% of total) had clinical documentation that patients denied any drug use.

Conclusion
The incidence of first hospitalization for IE among patients with ICD codes for drug use increased by 82% from 2010 to 2017 in VA care. Concurrent ICD codes for illicit drug use had moderate PPV for identifying IVDU in setting of IE, largely due to identification of patients using drugs without documented intravenous use. There is a need to develop more accurate case-finding algorithms for identifying patients with IVDU-associated endocarditis, for both epidemiologic surveillance and quality improvement applications.

Disclosures
All authors: No reported disclosures.
201. Safety and Effectiveness of Daily vs. Every Other Day Dosing of Daptomycin in Patients with Renal Insufficiency
Authors: Oliver Meredith , Benefield Russell J , Smith Tonya 
Published: October 2019

Abstract

Background
Daptomycin administered at 48-hour (q48h) intervals is recommended in patients with renal impairment. Our institution utilizes daily dosing (q24h) of daptomycin in patients with renal impairment to theoretically optimize the area under the curve (AUC) in each 24-hour interval. However, the safety and effectiveness of this approach are unknown.

Methods
This retrospective descriptive analysis evaluated outcomes of comparable daptomycin dosing schemes administered q24h vs. q48h in patients with renal impairment (estimated creatinine clearance < 30 mL/minute). Inpatient adults ≥18 years old were included if they had at least one creatinine phosphokinase (CPK) obtained during admission and received either a q24h or q48h renally-adjusted daptomycin dose from May 2014 through December 2018. High-dose daptomycin therapy was defined as >3 mg/kg q24h or >6 mg/kg q48h. The primary outcome was difference in CPK elevations in the q24h vs. q48h dosing groups. Secondary outcomes included clinical and microbiological response, mortality, and hospital length of stay.

Results
Thirty-seven patients met inclusion criteria [23 (62%) q24h vs. 14 (38%) q48h]. Median treatment duration was 5 (7 vs. 4) days. Twenty-two (59%) patients had enterococcal infections [17 (73%) q24h vs. 5 (35%) q48h]. Twenty-two (59%) patients received high-dose daptomycin therapy [18 (82%) vs. 4 (18%)]. Nine patients [7 (19%) vs. 2 (5%)] received a statin during daptomycin therapy. One (3%) patient developed a CPK elevation (statin and q24h group). No daptomycin dose was discontinued due to CPK elevation, or rhabdomyolysis. Median hospital length of stay was 10 days in both dosing groups. Clinical response [9 (64%) vs. 16 (69%)] and microbiological response [9 (64%) vs. 15 (65%)] were similar between the two dosing groups. However, 30-day mortality [5 (35%) vs. 4 (17%)] and 90-day mortality [6 (42%) vs. 5 (21%)] were higher in the q48h dosing group. The difference in effectiveness outcomes was greatest in the subset of patients with enterococcal infections (Table 1).

Conclusion
A daily daptomycin dosing strategy in patients with renal insufficiency was well tolerated and may be associated with improved effectiveness outcomes, particularly for enterococcal infections. Additional investigations of this approach are warranted.

Disclosures
All authors: No reported disclosures.
204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies
Authors: Choi Sungim , Kim Taeeun , Bae Seongman , Yang Eunmi , Park Su-Jin , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Jae Kim Min , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Hee Woo Jun , Soo Kim Yang , Pil Chong Yong 
Published: October 2019

Abstract

Background
There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen.

Methods
We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment.

Results
In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2).

Conclusion
This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection.

Disclosures
All authors: No reported disclosures.