bluuebunny/crossref_metadata_2025 huggingface dataset:
2736. Insurance Disparity in United States Cancer Survivors’ Influenza Vaccination Rates: A Trend Study from NHIS 2005–2017
Authors: Zheng Xin , Jiang Changchuan
Published: October 2019

Background

Patients with underlying cancer often have suppressed immunity from disease process and cancer therapy, making this population particularly vulnerable to influenza. Few studies have investigated the overall flu vaccination rates; however, little is known regarding the trend of vaccination rates in US cancer survivors and how it varied by individuals’ insurance coverage.

Methods

We conducted a retrospective cross-sectional study to evaluate the temporal trend of flu vaccination rates using the National Health Interview Survey from 2005 through 2017. Adult cancer survivors (n = 24,381) were included in the analysis. The outcomes were self-reported flu vaccination during the past 12 months with either inactivated or live attenuated nasal vaccine. Insurance coverage was categorized into private (age ≤65), other coverage (age ≤65), uninsured (age ≤65), Medicare and private (age > 65), and other coverage (age > 65). We combined every 2 years data to improve statistical power in the subgroup analysis. Weighted analyses were performed with SAS 9.4 to account for the complex design and NCI-Joinpoint 4.7 was used for joinpoint regression in the trend analysis.

Results

The overall cancer survivors’ flu vaccination rates improved from 45% in 2005 to 63% in 2017, whereas the cancer-free group improved from 18% in 2005 to 41% in 2017. With cancer survivors, influenza vaccination rates varied remarkably by insurance status (P < 0.001). Elderly survivors (age 65+) with any type of insurance consistently had higher flu vaccination rates than survivors younger than 65 (averaging 70% vs. 40%). For cancer patients age 65 or younger, whether insured or not, the overall flu vaccination rates had improved since 2005. However, for the subgroup who had coverage but not with private insurance, the vaccination rates had been declining since 2012 (50% in 2012/2013 to 45% in 2016/2017).

Conclusion

Despite the overall increase of flu vaccination rates in both cancer survivors and cancer-free participants since 2005, the growth rate has plateaued since 2015. This is likely related to shifts in healthcare law on the national level. Such impact is particularly significant in cancer patients who are younger and do not have private insurance coverage. Such vulnerable and underserved population will need more resources to help improve their influenza vaccination rate.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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.
206. Variations in the frequency and impact of polymicrobial cultures in adults with invasive Group B Streptococcal (GBS) infection at the US Veterans Health Administration
Authors: Briggs Janet , Wilson Brigid , Zappernick Taissa , Banks Richard , Baechle2; Sunah Song Daniel , Jump Robin L , Perez Federico
Published: October 2019

Background

GBS, a colonizer of human skin, genitourinary and gastrointestinal tracts, is responsible for increasing rates of invasive infection among non-pregnant adults in the United States. GBS is often isolated with other bacteria; however, the clinical significance of polymicrobial cultures in patients with invasive GBS infection is unknown. Our aim was to characterize polymicrobial cultures in patients with invasive GBS infection and explore their impact on mortality at 30 days.

Methods

Within the VHA Corporate Data Warehouse, we identified veterans active in VHA between 2008–2017 with invasive GBS infection according to CDC’s surveillance definitions. Reports of cultures from blood, bone and sterile fluid with GBS were assessed for the presence of other bacteria.We used International Classification of Disease (ICD) codes to define the type of invasive GBS infection. We compared 30-day all-cause mortality between patients with cultures that identified only GBS (monomicrobial cases) and patients with cultures that identified GBS and other bacteria (polymicrobial cases).

Results

Of 4780 incident cases of invasive GBS infection identified between 2008–2017, 1204 (25%) were polymicrobial. The proportion of polymicrobial cases varied by type of invasive GBS infection, ranging from 58% in osteomyelitis to 10–15%in meningitis, endocarditis, skin and soft-tissue infections, and septic arthritis (table). Staphylococcus aureuswas found in 516 (43%) of polymicrobial cases;there were variations in the bacteria isolated by type of infection (figure). Overall, there was no difference in 30-day mortality between polymicrobial and monomicrobial cases of invasive GBS infection (both 8%). However, when compared with monomicrobial cases, 30-day mortality was doubled in polymicrobial cases of pneumonia and bacteremia (15% vs. 31% and 11% vs. 22%, respectively).

Conclusion

The frequency, composition and mortality of polymicrobial cases vary according to the type of invasive GBS infection. Polymicrobial infection could be an important determinant of outcome in certain invasive GBS infections. The effect of polymicrobial infection involving GBS, relative to age, severity of illness and underlying comorbidities, needs further exploration.

Disclosures

All authors: No reported disclosures.
208. Early Infectious Disease Consultation is Associated with Lower Mortality in Patients with Severe Sepsis or Septic Shock who Complete the 3-hour Sepsis Bundle
Authors: Wadskier Montagne Francis G , Mowrey Wenzhu , Eisenberg Ruth , Malik Maria , Kaur Jaskiran , Nori Priya , Pirofski Liise-anne , White Deborah , Sarwar Uzma N , Madaline Theresa
Published: October 2019

Background

Severe sepsis and septic shock bundles have been shown to reduce mortality. Infectious Diseases (ID) consultation, particularly early in a hospital course, is associated with improved patient outcomes. Antibiotic Stewardship Program (ASP) decision support in the ED has also shown clinical benefit. We aim to examine the addition of early ID consultation to existing ASP decision support in the Emergency Department (ED) in patients with sepsis with organ dysfunction and/or shock (SODS) who completed the 3-hour bundle.

Methods

This is a retrospective study of 248 adult patients with clinical SODS who met inclusion criteria per Center for Medicare and Medicaid Services SEP-1 core measure in the ED and completed the recommended 3-hour sepsis bundle using ASP decision support tools. Patients who received ID consultation in the first 12 hours after ED triage (n = 111) were compared with patients who received standard care (n = 137). Pearson’s chi-square test was used to compare groups for all-cause 30-day readmissions and in-hospital mortality. Logistic regression was used to adjust for covariates (age, race/ethnicity, Charlson score, lactate level ≥4, hypotension, recent hospital admission, recent IV antibiotics, history of MDR organisms, intra-abdominal source of infection). Time from ED triage to death and time to hospital discharge alive were analyzed using Fine and Gray models for competing risks.

Results

In-hospital mortality was lower among patients who received early ID consultation (24.3% vs. 38.0%, P = 0.0220). This association persisted after adjustment for covariates (odds ratio 0.49, 95% CI 0.26–0.91, P = 0.0236). There was no significant difference in 30-day readmissions between groups (22.6% vs. 23.5%, P = 0.8883). Early ID consultation was predictive of time to death (adjusted hazard ratio 0.58, 95% CI 0.35–0.98, P = 0.0406) and time to hospital discharge alive (adjusted hazard ratio 1.51, 95% CI 1.07–2.12, P-value 0.0174) after adjustment.

Conclusion

Early ID consultation was associated with lower mortality and time to hospital discharge among patients receiving the 3-hour severe sepsis/septic shock bundle. Further investigation is needed to explore specific interventions by ID consultants that might reduce the risk of mortality in this population.

Disclosures

All authors: No reported disclosures.
209. What’s So Complicated About Complicated Staphylococcus aureus Bacteremia: Does Day 5 Matter?
Authors: Hilsendager Cami , Strnad Luke
Published: October 2019

Background

Prolonged Staphylococcus aureus bacteremia (SAB) poses challenges in clinical practice, particularly when a source is not readily identified. While SAB greater than 3 days has been identified as a risk factor for complications, little is known about risk for specific complications with each successive day of bacteremia. We sought to determine the risk for specific complications with the duration of bacteremia.

Methods

We retrospectively reviewed all cases of SAB between 1 January 2017 and 31 December 2017 at a 500-bed academic hospital. Adult patients (≥18 years) with at least one blood culture positive for S. aureus were identified. Patients were excluded if withdrawal of care or death occurred within 48 hours of blood culture results or if the infection was associated with a ventricular assist device. Medical records were reviewed for the duration of bacteremia, complications, treatment decisions and clinical outcomes. This study was approved by the Institutional Review Board.

Results

One hundred forty-two discrete episodes of SAB were identified with a median age of 54 years (IQR 40–63). Most cases were community-acquired (83.8%) and 33.8% were MRSA. Active injection drug use was present in 22.5% (33.3% MRSA, 17% MSSA). The median duration of bacteremia was 2.6 days (IQR 1.8–4.6) and 3.9 days (IQR 2.2–7.5) for MSSA and MRSA, respectively. The median time to first source control procedure was twice as long with bacteremia over 5 days than with a shorter duration of bacteremia (2.6 vs. 1.3 days). Complication rates increased with bacteremia duration and bacteremia longer than 5 days was associated with significantly higher rates of endocarditis (46.2%, P < 0.001), epidural abscesses (35.9%, P = 0.001), intracranial infections (12.8%, P = 0.02), and presence of at least one endovascular nidus (76.9%, P < 0.001) compared with bacteremia less than 5 days (28.4%), but 30 day mortality rates were similar (7.7% and 9.8%, respectively).

Conclusion

Complication rates increase significantly with SAB greater than 5 days duration. Early source control and investigation to identify metastatic and especially endovascular foci of infection are paramount in patients with prolonged bacteremia even if complications are not discovered on initial evaluation.

Disclosures

All authors: No reported disclosures.
211. Coxiella burnetii: 7 Years of Experience at a Tertiary-Care Center
Authors: Gurram Pooja , Shweta F N U , Castillo Almeida Natalia E , Khalil Sarwat , Cano Cevallos Edison J , Mahmood Maryam , Abu Saleh Omar
Published: October 2019

Background

Q fever is a zoonotic disease caused by Coxiella burnetii. Primary infection can progress to persistent infection irrespective of initial symptomatology. Our aim is to describe the clinical features, treatment, risk of progression, use of prophylaxis, and outcomes of Coxiella burnetii infection at our institution.

Methods

We did a retrospective review of all adult patients with positive Coxiella burnetii serology at Mayo Clinic, Rochester from 1st January 2012 to 31st December 2018. Centers for Disease Control and Prevention (CDC) case definition and classification were used to group the patients into confirmed and probable acute Q fever, and confirmed and probable chronic/persistent Q fever. Data on demographics, clinical presentation, comorbid conditions, exposure history, risk factors associated with progression, serology, treatment and outcomes were collected.

Results

We found 266 patients with positive titres of Coxiella IgG or IgM greater than 1:16, of which 49 patients met the CDC case definition for Q fever. Median age at presentation was 62 years. 45/49 (91. 8%) were men, while 4/49 (8%) were women. 20/49 (40. 8%) patients presented with acute Q fever of which 5 (25%) patients progressed to persistent infection. 29/49 (59%) patients presented with persistent Q fever of which 4 patients could recall symptoms suggestive of acute Q fever. The most common presentation of acute Q fever was acute febrile illness (65%). Endocarditis (11/29) was the most common presentation of chronic/persistent Q fever. Of the 5 patients with acute Q fever that progressed to persistent infection, 3/5(60%) progressed despite being on doxycycline and hydroxychloroquine. 8/29 patients with persistent Q fever had serological resolution at last follow-up. 2/4(50%) deaths were attributable to Q fever.

Conclusion

Minority of the patients tested met the case definition. 25% of patients with acute disease progressed to chronic Q fever out of which 60%(3/5) progressed despite prophylaxis. Endocarditis and vascular infections were the most common chronic cases. Interestingly we found 4 cases of MPGN in association with Q fever. Prosthetic valves are the most important risk factors for progression (P = 0.02). Serological cure often lags behind clinical cure (27% vs. 68% in persistent infection)(Table 4).

Disclosures

All authors: No reported disclosures.
215. Invasive Group A Streptococcus-Associated Hospitalizations and Risk Factors for In-Hospital Mortality Among Adults in California, 2000–2016
Authors: Karmarkar Ellora , Jain Seema , Sondermeyer Cooksey Gail L , Myers Jennifer , Kamali Amanda
Published: October 2019

Background

Invasive group A Streptococcus (iGAS) causes severe illness and death but is not vaccine preventable or nationally notifiable. We describe the epidemiology of adult patients hospitalized with iGAS in California and risk factors for in-hospital death.

Methods

Using 2000–2016 California hospital discharge data, we extracted records for adults (≥18 years) with ≥1 group A Streptococcus (GAS)-associated International Classification of Diseases, Ninth or Tenth Revision discharge diagnosis code (e.g., unspecified GAS; GAS-specific pharyngitis, pneumonia, and sepsis) or known GAS-associated syndromes (e.g., acute rheumatic fever, erysipelas, scarlet fever). To identify patients hospitalized with iGAS, we selected extracted records that also had codes consistent with invasive disease (e.g., sepsis, pneumonia, intubation, or central line placement). We calculated iGAS-associated hospitalization incidence rates per 100,000 population and described patient demographics and comorbidities. We calculated the odds of in-hospital death using multivariable logistic regression (P < 0.05).

Results

During 2000–2016 in California, 37,532 adults were hospitalized with iGAS; 1,045 (3%) died in-hospital. Mean annual hospitalization incidence was 9.4/100,000 population, and was highest (16.3/100,000) in 2016 (Figure 1). Most patients were male (56%), aged 40–65 (45%) or ≥65 (28%) years, and white (60%); 18% were immunocompromised. The percent of patients who died in-hospital increased with age and was highest among those with comorbidities such as malnutrition, cardiovascular disease (CVD), and chronic kidney disease (CKD) (Figure 2). In a multivariable model including age as a continuous variable, sex, and race-ethnicity, the odds of in-hospital death was significantly increased for patients with diagnosis codes for malnutrition, liver disease, CVD, immunosuppression, and CKD (Figure 2); within the race/ethnicity variable Asian/Pacific Islander patients had a higher odds of death compared with white patients.

Conclusion

Hospitalization and subsequent in-hospital death due to iGAS is substantial in California. Adults with iGAS who have specific comorbidities are at greater risk for death when hospitalized with iGAS.

Disclosures

All authors: No reported disclosures.
217. Combination Salvage Therapy with Cefazolin Plus Ertapenem for Refractory Methicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Rose Ulloa Erlinda , Singh Kavindra V , Geriak Matthew , Haddad Fadi , Murray Barbara E , Nizet Victor , Sakoulas George
Published: October 2019

Background

Suboptimal therapy against methicillin-sensitive Staphylococcus aureus (MSSA) may have catastrophic consequences in severe infections such as endocarditis or epidural abscess. High MSSA inocula have been associated with clinical failure in patients receiving cefazolin (CZ), particularly when used at low doses, associated with a CZ inoculum effect. We previously described that adding ertapenem (ETP) to CZ led to synergism against MSSA and sensitized the pathogen to host innate immune factors. Here we expand our experience with CZ plus ETP as salvage therapy for 11 cases of refractory MSSA bacteremia (lacking source control problems) and explore CZ+ETP combination in vitro and in vivo.

Methods

Six available MSSA strains from patients treated with CZ+ETP for refractory bacteremia were tested in Mueller–Hinton Broth or RPMI media at standard (105 CFU/mL) or high (107 CFU/mL) inocula by MIC, checkerboard, and time-kill assays using ETP, CZ or nafcillin (NAF) alone vs. ETP+NAF or ETP+CZ. Disk diffusion synergy assays between CZ and ETP were also performed. CZ, ETP and CZ+ETP were tested in a rat endocarditis model using well described MSSA, TX0117 and TX0117c.

Results

11 consecutive patients with MSSA bacteremia (6 confirmed endocarditis) refractory to standard CZ or NAF rapidly cleared with CZ+ETP. 9 patients had daily positive blood cultures, and 8 cleared in ≤24 hr, including those with ≥2 cm vegetations. All 11 survived hospitalization. In MHB, 3/6 MSSA exhibited a CZ inoculum effect (CZ MIC >3 log2 in 107 vs. 105 CFU/mL), but only 1 showed a significant CZ inoculum effect in RPMI. CZ+ETP was significantly more efficacious than CZ in a rat model of MSSA endocarditis utilizing a strain displaying a CZ inoculum effect, despite only modest benefit observed in vitro for 6 MSSA isolates.

Conclusion

CZ+ETP combination therapy yielded profound clinical success in severe MSSA infections with high bacterial densities, as demonstrated by rapid bacteremia clearance. Enhanced efficacy was also observed in a rat endocarditis model. The anti-staphylococcal activity of CZ+ETP in vivo exceeded that observed in vitro, consistent with our prior observations of host innate immune cooperativity with the regimen. CZ+ETP warrants further study for the treatment of refractory MSSA bacteremia and endocarditis.

Disclosures

All authors: No reported disclosures.
218. Evaluation of Clinical Outcomes with Shorter Vs. Longer Duration of Treatment for Common Inpatient Bacterial Infections Associated with Bacteremia
Authors: Hojat Leila , Bessesen Mary T , Reid Margaret , Knepper Bryan C , Miller Matthew A , Huang Misha , Fugit Randolph V , Shihadeh Katherine C , Jenkins Timothy C
Published: October 2019

Background

Pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) are the most common infections treated in the inpatient setting and often are associated with bacteremia. Though short courses of treatment are advocated for these infections in general, no established guidelines exist for cases involving bacteremia. We evaluated the clinical outcomes of patients receiving short (5–9 days) vs. long (10–15 days) duration of antibiotic treatment.

Methods

A retrospective study was conducted at 3 area hospitals comprising a university-based tertiary center, a public safety net hospital, and a Veterans’ Affairs hospital. We included hospitalized adult patients with transient bacteremia associated with uncomplicated cases of PNA, UTI, or ABSSSI. The primary outcome consisted of a composite of rehospitalization or resumption of antibiotic treatment attributed to the original infection or death due to any cause within 30 days of the antibiotic start date. Secondary outcomes included the individual composite components, Clostridioides difficile infection, and antibiotic-related adverse effects leading to change in antibiotic therapy. A propensity score weighted logistic regression model was used to mitigate factors which could bias a patient toward receiving a shorter or longer treatment duration.

Results

Of 411 patients included in the study, 123 (29.9%) received a short duration of therapy and 288 (70.1%) received a long duration of therapy. The median duration of treatment was 8 days in the short group and 13 days in the long group. In the propensity-weighted analysis, the probability of meeting the composite primary outcome was not statistically different between the short and long groups (Table 1). However, receiving a short course was associated with a higher probability of restarting antibiotics and Clostridioides difficile infection.

Conclusion

Shorter vs. longer courses of antibiotic treatment for bacteremia associated with PNA, UTI, and ABSSSI were not significantly different in a composite of readmission, restart of antibiotics, and mortality; however, further study is needed to evaluate the safety and effectiveness of short-course therapy.

Disclosures

All authors: No reported disclosures.
220. Characteristics and Outcomes of Veterans with Invasive Group B Streptococcal Infection Vary with the Type of Syndrome
Authors: Zappernick Taissa , Wilson Brigid , Banks Richard , Baechle Daniel , Song Sunah , Briggs Janet , Jump Robin L , Perez Federico
Published: October 2019

Background

Surveillance from the US Center for Disease Control and Prevention (CDC) has detected an increase in the prevalence of invasive Group B streptococcus (GBS) infections between 2008 and 2016 among non-pregnant adults. Here, we use data from the US Veterans Health Administration (VHA) to assess the underlying clinical characteristics and outcomes associated with specific types of invasive GBS infection among veterans.

Methods

We used the VA Corporate Data Warehouse to identify patients with invasive GBS infection diagnosed between 2008–2017 using CDC’s surveillance definitions. Data on the microbiological source of infection (e.g., GBS in cultures from blood, bone or sterile fluids) and associated International Classification of Disease (ICD) codes were used to classify the type of invasive infection. We determined associated co-morbid conditions and 30-day all-cause mortality for incident cases.

Results

Between 2008 and 2017, there were 4780 incident cases of invasive GBS infection in veterans with a mean age of 66.6 years (±11.7) and30-day all-cause mortality of 8%. The most common syndrome was osteomyelitis (23%, N = 1078) with 30-day mortality of 1%. Other common infections, such as bacteremia (20%; N = 972), skin and soft-tissue infections (18%, 853), and pneumonia (14%, N = 664), had higher mortality (13%, 4% and 17%, respectively; Figure). In patients with GBS peritonitis, present in 3% (N = 138) incidence cases, 46% had chronic liver disease with a 30-day mortality of 28%. Diabetes mellitus (DM) occurred in 66% of patients with any invasive GBS infection and in 86% of patients with GBS osteomyelitis. Chronic heart, kidney, or lung disease affected >25% of patients (table).

Conclusion

Invasive GBS infection is a burden for veterans with DM and other high-risk conditions, with some types of infections associated with substantial mortality. Osteomyelitis, the most common type of infection, was associated with lower mortality compared with other invasive GBS infections. DM and chronic lung, kidney and heart disease are common among veterans with invasive GBS infection.

Disclosures

All authors: No reported disclosures.