bluuebunny/crossref_metadata_2025 huggingface dataset:
745. Surveillance for Oseltamivir-Resistant Influenza A(H1N1)pdm09 Virus Infections During 2016–2017 and 2017–2018, United States
Authors: Spencer Sarah , Nguyen Ha , Elal Anwar Abd , Laplante Jennifer , George Kirsten St , Fry Alicia M , Gubareva Larisa , Campbell Angela P
Published: November 2018

Background

Three neuraminidase inhibitors (NAIs) are approved and recommended for treatment of influenza in the United States; however, antiviral resistance can emerge during or after treatment, and sporadic resistant viruses unrelated to NAI exposure may occur, especially in influenza A(H1N1)pdm09 viruses. Limited transmission of oseltamivir-resistant A(H1N1)pdm09 viruses between persons has also occurred. Oseltamivir resistance is most commonly caused by an H275Y substitution in the neuraminidase (NA). We describe findings from surveillance for oseltamivir-resistant A(H1N1)pdm09 viruses.

Methods

The CDC requested state public health laboratories to submit up to eight viruses (two of each subtype/lineage) every 2 weeks for virus sequencing and NA inhibition assay testing; up to five additional A(H1N1)pdm09 clinical specimens were requested for H275Y pyrosequencing. NA sequencing and functional phenotypic NA inhibition assays were performed on drug-resistant virus isolates. A standard case form was collected on persons infected with oseltamivir-resistant viruses.

Results

From October 1, 16 to April 18, 18, 1,368 A(H1N1)pdm09 viruses were tested (median 89 specimens, range 20–328, tested/month during the influenza season). Overall, 12 (~0.9%) oseltamivir-resistant A(H1N1)pdm09 viruses were detected from nine states; all contained H275Y in the NA. All viruses were also resistant to peramivir, but none to zanamivir. The 12 patients had a median age of 34 years (range, 2 months–69 years). Eight (67%) had an immunosuppressive condition. Six (50%) reported no exposure to NAIs before specimen collection, two were taking oseltamivir (for 1 and 20 days) at the time of specimen collection, and antiviral receipt was unknown for 4. Three (23%) patients were hospitalized; there were no deaths.

Conclusion

During the 2016–2017 and 2017–2018 influenza seasons, influenza A(H1N1)pdm09 viruses resistant to both oseltamivir and peramivir were infrequently detected; all retained susceptibility to zanamivir. Among those with available information, half had no exposure to oseltamivir. Viruses harboring H275Y continue to circulate at low levels in the community. Ongoing surveillance for trends in oseltamivir- and peramivir-resistant A(H1N1)pdm09 is critical to inform clinical care and public health policies.

Disclosures

All authors: No reported disclosures.
749. Healthcare Utilization After Hospitalization for Respiratory Syncytial Virus or Unspecified Bronchiolitis in the First Year of Life
Authors: Ledbetter Joel , Brannman Lance , Wade Sally , Diakun David , Gonzales Tara , Kong Amanda
Published: November 2018

Background

Respiratory syncytial virus (RSV) is the leading cause of infant hospitalizations and risk varies by gestational age (GA). Healthcare utilization following early hospitalizations caused by RSV (RSVH) or unspecified bronchiolitis (UBH) is not well understood. This study examined healthcare resource utilization (HRU) across GA categories within 12 months after an initial RSVH or UBH occurring in the first year of life.

Methods

Infants born July 1, 2009 to June 30, 2015 were identified in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases and assigned to GA categories using DRG and ICD codes and to an initial hospitalization cohort using inpatient claim diagnosis codes (RSVH, UBH without RSVH, or COMP [a comparator without RSVH or UBH]). Index dates (first admission dates for hospitalized infants) were assigned to COMP infants using times from birth to index dates among RSVH infants. HRU (hospitalizations, outpatient pharmacy fills, and visits for emergency department [ED], urgent care, wellness, other office or outpatient) excluded index hospitalizations and was assessed from 14 days post-index (or discharge if later) through 12 months post-index. Results were propensity score weighted to balance pre-index characteristics (age, sex, region, GA, birth hospitalization characteristics) across cohorts. Proportions were compared with chi-squared tests.

Results

Among all infants (all GA categories combined), the proportions of RSVH and UBH cohorts with follow-up hospitalizations or ED visits were greater (P < 0.05) than COMP (hospitalizations: COM +5.8%, +9.3%; MED +9.1%, +12.0%; ED visits: COM +15.8%, +16.2%; MED +14.4%, +17.1%). Follow-up hospitalizations in COM and MED and ED visits in COM declined with greater GA (Figures 1 and 2). HRU in other categories (fills, visits) was significantly (P < 0.05) greater among RSVH or UBH infants relative to COMP for nearly all GA categories in both COM and MED.

Conclusion

Infants hospitalized for RSV or UB in their first year of life had greater use of inpatient and outpatient resources in the 12 months following their initial hospitalizations compared with nonhospitalized infants. Inpatient care during follow-up was greatest among infants born at earlier GA.

Funded by AstraZeneca

Disclosures

J. Ledbetter, AstraZeneca: Speaker’s Bureau, Speaker honorarium. L. Brannman, AstraZeneca: Employee, Salary and Stocks. S. Wade, Wade Outcomes Research and Consulting: Employee, Salary. D. Diakun, Truven Health Analytics, an IBM Company: Employee, Salary. T. Gonzales, AstraZeneca: Employee, Salary and Stocks. A. Kong, Truven Health Analytics, an IBM Company: Employee, Salary.
756. Targeting the Birth-Cohort of the Pre-antibiotic Era: A Proposal to Screen for Tuberculosis in Seniors in Arkansas
Authors: Gu Mofan , Fischbach Lori , Patil Naveen , Bates Joseph , Mukasa Leonard
Published: November 2018

Background

Approximately 13 million (4.7%) people in the United States have latent TB infection (LTBI). Persons born prior to 1951 have disproportionately higher LTBI prevalence, and frequently experience delays in TB diagnosis and TB deaths. Nevertheless, this birth-cohort was overlooked in the 2016 US Preventive Service Task Force (USPSTF) recommendation for LTBI screening. The aims of this project are to (1) determine the LTBI prevalence in this birth-cohort, (2) assess TB complications prevented by LTBI screening in this birth-cohort, and (3) raise TB awareness among providers and the community.

Methods

We propose to: (1) Develop educational pamphlets for the physicians and community. (2) Screen 10,000 members of the target birth-cohort during their routine clinical visits for 1 year, using T-SPOT.TB. County health officers, the partners of Arkansas Department of Health, will enroll physicians in their jurisdictions to participate in TB screening. LTBI prevalence in the birth cohort will be determined, and TB complications will be compared among cohort TB cases that were screened to those not previously screened. (3) Incorporate LTBI and birth-cohort status in patient medical forms.

Results

In our preliminary study, for the period 2009–2014, 142 of 326 TB cases (43.6% of all US-born TB cases) were reported from the target birth-cohort; 72.6% of the cases had unique genotype strains.

Conclusion

If the LTBI prevalence in this birth cohort exceeds 8–10%, we recommend a nation-wide screening program for this birth-cohort. Even without treatment, we believe that screening and noting diagnosis of LTBI in the patient record will impact delayed diagnosis and mortality.

Disclosures

All authors: No reported disclosures.
761. Age-Related Incidence of TB Infection Supporting Efficacy of BCG Vaccination
Authors: Sweeney Eileen , Dahly Darren , Seddiq Nahed , Horgan Mary , Corcoran Dan , Sadlier Corinna
Published: November 2018

Background

Mycobacterium tuberculosis (MTB) is a major, and potentially preventable, cause of morbidity and mortality worldwide. Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine for TB, and while efficacy has been demonstrated in some populations, many uncertainties remain. Three BCG vaccination policies were implemented across bordering geographical regions in the South West of Ireland from 1972; neonatal vaccination (vaccinated region-a), vaccination of children aged 10–12 years (vaccinated region-b) and no vaccination (unvaccinated region-c). The aim of this study was to investigate the impact of BCG vaccination on incidence of MTB during the study period.

Methods

Surveillance data were used to identify all M. tuberculosis complex (MTC) isolates from 2003 to 2016. Residential addresses for each case were geocoded using the Google Maps API. Case locations were spatially linked to 2011 census population data and to Local Health Offices (LHO) BCG coverage data for study regions a–c. The 13-year incidence of TB was calculated assuming a steady-state population. Using SatScan (v9.4.4), spatial clusters were identified at the small area level with the spatial scan statistic based on the discrete Poisson probability distribution.

Results

Of 638 MTC infections identified (621 MTB, 16 M. bovis, 1 M. africanum), 510 occurred in study regions a–c (median age 42 years (4 months–94 years), 65% male and 66% Irish born). The incidence of MTB was higher in the unvaccinated population, region-c 132/100,000 (95% CI 116–150) vs. vaccinated region-a 56/100,000 (95% CI 45–69) and region-b 44/100,000 (95% CI 29–63). A single high-risk cluster of 138 cases within a population of 46,000 was identified in unvaccinated region-c (relative risk 4.94 (95% CI 4–6). The year-on-year incidence rates in the 20- to 35-year-old age range suggested a decreasing risk consistent with a beneficial impact of vaccination policies.

Conclusion

Prevention and treatment of TB remains a significant challenge worldwide. Our study demonstrates significant differences in incidence of MTC infection in demographically similar populations based on BCG immunization policy and thus further supports efficacy of BCG for prevention of tuberculosis infection.

Disclosures

All authors: No reported disclosures.
763. Risk Factors for Homeless Status and Mortality Among Homeless TB Cases in Texas, 2010–2017
Authors: Agarwal Saroochi , Nguyen Duc T , Graviss Edward A
Published: November 2018

Background

A disproportionate amount of tuberculosis (TB) cases and mortality occur among people experiencing homelessness in the United States. Our objective was to identify risk factors for mortality among reported homeless TB cases in Texas, a state with an increased TB prevalence in the United States.

Methods

Using data from the Centers for Disease Control and Prevention TB Genotyping Information Management System (TB GIMS), we evaluated the demographic, laboratory and clinical characteristics of people identified as being homeless in the year preceding TB diagnosis in Texas from January 1, 2010 to December 31, 2017. TB cases with missing or unknown homeless status were removed from the analysis. Multivariate logistic regression was used to analyze and evaluate risk factors associated with homeless status and mortality among homeless TB cases.

Results

Of the 10,103 newly diagnosed TB cases over the 8-year period, 543 (5.4%) were reported as being homeless in the year preceding TB diagnosis. In 412 homeless TB patients with a reported outcome as “died” or “completed,” 57 (13.8%) died during treatment and 355 (86.2%) completed therapy. Age >45, male, black ethnicity, foreign-born, urban living, excessive alcohol consumption, IDU, long-term care facility resident, diabetes, previous TB, and pulmonary TB were associated with homeless TB cases. Being homeless and having TB increased the risk of mortality compared with having TB alone (OR 2.26, P < 0.01). Age >45 years, positive HIV status, cavitary and miliary radiographic findings, no or unknown culture conversion and TB case confirmation by a positive culture/NAA/smear compared with clinical case definition/provider diagnosis were independent risk factors for mortality among homeless TB cases in Texas.

Conclusion

Being homeless increased the risk of TB mortality by nearly 130% compared with being housed prior to TB diagnosis. Our findings indicate that homelessness may be being diagnosed and treated in more advanced TB diseased homeless individuals who probably have poorer health due to the stresses of poverty, comorbidities, and lack of access to healthcare, leading to higher mortality. Additionally, testing and treatment for HIV among those reporting homelessness may reduce mortality among this high-risk group.

Disclosures

All authors: No reported disclosures.
765. Tuberculosis and Diabetes Mellitus Among Prison Inmates in Peru: Results of a National Survey, 2016
Authors: Rojas-Bolivar Daniel , Zhu Zheng , Hurtado Yamilee , Zavaleta Milagros , Sanchez Jorge , Jandarov Roman , Alarcon Jorge , Huaman Moises
Published: November 2018

Background

Diabetes mellitus (DM) increases the risk of tuberculosis disease (TB) and is associated with poor TB treatment outcomes in the general population. We examined the relationship between TB and DM in prison inmates in Peru.

Methods

We analyzed data from a cross-sectional, national survey of adult prison inmates in Peru conducted in 2016. The survey collected sociodemographic and medical information via standardized interview. Medical conditions were defined by self-report. We used multivariate logistic models for adjusted analyses of the relationship between TB and DM.

Results

Of 75,971 inmates, 3,104 (4.3%) reported a history of TB diagnosis. Table 1 shows the characteristics of the TB and non-TB groups. The prevalence of DM was higher in the TB group compared with the non-TB group (4.2% vs. 2.4%; P < 0.001). In multivariate analysis, DM was associated with twice the odds of having had a diagnosis of TB (adjusted OR = 2.2; 95% CI: 1.8–2.7). Male sex, Spanish language, no college/university education, reimprisonment, hypertension, and HIV infection were also associated with increased odds of prevalent TB (Figure 1).

Conclusion

There was a high prevalence of TB among prison inmates in Peru. DM was associated with an increased likelihood of prevalent TB. Our results are consistent with findings in noninstitutionalized populations and underscore the need to implement aggressive screening and treatment interventions for both TB and DM in prison settings.

Disclosures

All authors: No reported disclosures.
780. Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in US Medicare, 2008–2015
Authors: Winthrop Kevin L , Adjemian Jennifer , Mirsaeidi Mehdi , Marras Theodore , Eagle Gina , Zhang Raymond , Wang Ping , Chou Engels , Zhang Quanwu
Published: November 2018

Background

Previous research has reported nontuberculous mycobacterial lung disease (NTMLD) prevalence of 47 per 100,000 among Medicare beneficiaries ≥65 years in 2007, with an average increase of 8.2% annually between 1997 and 2007. In this study, we have evaluated NTMLD incidence and prevalence in Medicare between 2008 and 2015.

Methods

Patients diagnosed for NTMLD with an ICD9 031.0 were identified from the Medicare database (N≈30 million yearly), not including the Part C portion. Individuals who incurred at least 2 medical claims ≥30 days apart between 2007 and 2015 were considered as a positive NTMLD case, yielding 58,294 patients. All individuals fulfilling the case definition each calendar year were considered as prevalent cases. Incident cases included those meeting case criteria and who did not have a Medicare claim for NTMLD in the prior year. Poisson regression was used to estimate yearly confidence intervals. ARIMA models were used to forecast incidence and prevalence over 2016–2025.

Results

Patients with NTMLD in the Medicare database had a mean age of 74 (standard deviation: ±10) years. Sixty-nine percent were women and 89% white. Yearly NTMLD incidence increased from 20.7 (95% CI: 20.2–21.3) in 2008 to 28.1 (27.5–28.7) in 2013 per 100,000 Medicare beneficiaries and leveled to 27.6 (26.9–28.2) in 2014 and 25.9 (25.3–26.5) in 2015 per 100,000. Yearly NTMLD prevalence increased throughout the observation period from 41.6 (40.9–42.3) in 2008 to 63.1 (62.2–64.0) in 2015 per 100,000 Medicare beneficiaries. Incidence was 28.1 vs. 14.7 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those <65 years, respectively. Prevalence was 70.2 vs. 27.9 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those <65 years, respectively. In 2015, incidence and prevalence were higher in women than men (33.9 vs. 16.0/100,000 and 86.2 vs. 34.6/100,000, respectively) and among individuals of Asian origin compared with White (41.1 vs. 27.6/100,000 and 89.4 vs. 68.7/100,000, respectively). The 10-year incidence and prevalence forecasts were presented in figures.

Conclusion

In US Medicare beneficiaries, NTMLD incidence increased from 2008 through 2013 and leveled off in more recent years, while NTMLD prevalence continued to rise through 2015.

Disclosures

K. L. Winthrop, Insmed Incorporated: Scientific Advisor, Consulting fee and Research grant. T. Marras, Insmed Incorporated: Investigator, Consulting fee and Research grant, Horizon Pharmaceuticals: Consultant, Consulting fee, Red Hill: Consultant, Consulting fee, AstraZeneca: CME, Speaker honorarium. G. Eagle, Insmed Incorporated: Employee, Salary. R. Zhang, Insmed Incorporated: Consultant, Consulting fee. P. Wang, Insmed Incorporated: Employee, Salary. E. Chou, Insmed Incorporated: Employee, Salary. Q. Zhang, Insmed Incorporated: Employee, Salary.
792. Number and Volume of Cavitary Lesions on Chest Computed Tomography Associated With Prolonged Time to Culture Conversion in Drug-Susceptible Pulmonary Tuberculosis
Authors: Hernandez Alfonso
Published: November 2018

Background

Cavitary lesions (CLs) may be a marker of poor treatment response in pulmonary tuberculosis (PTB). Identification of CLs by chest roentgenogram (CXR) has important limitations. Chest computed tomography (CT) is more sensitive than CXR to detect CLs but the clinical relevance of CLs identified by CT remains understudied. We compared detection of CLs between CT and CXR and assessed their association with time to sputum culture conversion (tSCC). We hypothesized that increasing number and volume of CLs on CT would be associated with prolonged tSCC.

Methods

Retrospective cohort study of 141 culture confirmed PTB patients who underwent chest CT. We used multivariate Cox proportional hazards models to evaluate the association between chest radiological features and tSCC.

Results

Seventy-five (53%) patients had one or more CLs on CT. CT identified cavities in 31% of patients without a CL on CXR. Detection of cavity on CT was associated with an increased median [IQR] time to culture conversion (15 [7–35] days among noncavitary CT vs. 39 [25–55] days among cavitary CT; P < 0.0001). Among patients without CL on CXR, detection of CL on CT was associated with prolonged tSCC (median difference (CI): 16 (7–25) days, P = 0.0008). Similar results were observed among patients with 3–4+ sputum smear (median difference: 19.5 (8–31) days, P = 0.001). Adjusted Kaplan–Meier curves of number and volume of CLs and tSCC are shown in Figure 1. After confounder adjustment patients with single and multiple CL had a prolonged tSCC relative to patients without CLs on CT (adjusted Hazard Ratio [aHR] 0.56 (0.32–0.97) and 0.31 (0.16–0.60), respectively). Similarly, patients with CL volume 25 mL or more had a prolonged tSCC (aHR 0.39 (0.21–0.72)). CXR CL was not associated with prolonged tSCC.

Conclusion

We observed a dose–response relationship between increasing number and volume of CLs on CT and delayed tSCC independent of sputum bacillary load. Our findings highlight a role for CT in a clinical research setting to predict shorter time to culture conversion.

Disclosures

All authors: No reported disclosures.
795. Review of Treatment of Latent Tuberculosis Infection at VA Portland Healthcare System
Authors: Xu Teena , Forrest Graeme N
Published: November 2018

Background

Treatment of latent tuberculosis infection (LTBI) is important for tuberculosis elimination in low-incidence countries. Currently, the VA Portland Health Care System (VAPORHCS) offers both 3HP (12-dose rifapentine plus isoniazid directly observed therapy (DOT)) and 9H (9-month daily isoniazid) for treatment of LTBI. Majority of veterans are treated with 9H despite increasing evidence showing higher rates of completion with 3HP. We reviewed the rates of completion and adverse events (AE) between veterans treated with 3HP and 9H.

Methods

We performed a retrospective chart review on all patients within the VAPORHCS who initiated LTBI treatment with 9H or 3HP between January 2011 and December 2016. LTBI was diagnosed through tuberculin skin testing or interferon-γ release assay. 9H treatment was self administered while 3HP was under DOT. Collected data included demographics, co-morbid conditions, immunosuppression, treatment completion, and AE. Treatment completion was determined through chart documentation.

Results

A total of 93 patients were treated for LTBI. Most patients were white (71%) and male (86%). The median age was 57 years old. Seventy-two patients (77%) were treated with 9H, and 21 (23%) were treated with 3HP. The overall completion rate was 86%. Completion rates between 9H (91%) and 3HP (86%) were not significantly different (P = 0.46). Twenty-three patients (31.9%) on 9H and six patients (28.6%) on 3HP were on chronic immunosuppression with TNF inhibitors and/or corticosteroids (P = 0.78) with an overall completion rate of 86%. Nine patients (13%) on 9H and two patients (10%) on 3HP had HIV (P = 0.95). Overall rates of AEs were similar between the groups (4%, 14%, P = 0.11), including hepatotoxicity (2%, 0%, P = 0.57) and neurotoxicity (4%, 5%, P = 0.94).

Conclusion

The overall treatment completion rates were high and statistically similar between 9H and 3HP groups, even with immunosuppressive therapy. There were no significant differences in rates of adverse events. While the majority of patients were treated with 9H, these results suggest an opportunity for more use of the 3HP, possibly without the need for DOT regimen going forward.

Disclosures

All authors: No reported disclosures.
804. Impact of Azithromycin Prophylaxis in Lung Transplant Recipients on the Risk of Nontuberculous Mycobacterial Infections
Authors: Workman Adrienne , Kaza Vaidehi , Bennett Scott , Chong Pearlie
Published: November 2018

Background

Azithromycin has been shown to improve FEV1 in lung transplant recipients (LTR) with bronchiolitis obliterans syndrome (BOS). The impact of azithromycin use on the incidence of infections due to Mycobacterium avium complex (MAC) and M. abscessus in LTR is currently unknown.

Methods

We conducted a nested case–control study of a retrospective cohort of adult LTR transplanted between 2007 and 2017. Cases were defined as LTR with nontuberculous mycobacterial (NTM) infections due to MAC and/or M. abscessus. Controls were defined as LTR without NTM infections. NTM infection was defined by presence of pulmonary symptoms and radiographic changes (clinical criteria) in addition to positive cultures from ≥2 sputa or ≥1 bronchial specimens (microbiological criteria) according to the IDSA/ATS criteria. LTR who meet microbiological, but not clinical criteria were considered colonized and not included for analysis. Azithromycin use was defined as ≥90 days for BOS treatment.

Results

Among 538 LTR, 60% (321/538) were male and 81% (434/538) received double LTs. Indication for LT was idiopathic pulmonary fibrosis (28% [152/538]), chronic obstructive pulmonary disease (23% [121/538]), cystic fibrosis [CF] (13% [68/538]), and other (37% [197/538]). The overall incidence of NTM infections was 4.3% (23/538); of which 65.2% (15/23), 17.4% (4/23), and 17.4% (4/23) were due to MAC, M. abscessus and polymicrobial infections, respectively. Thirty-one percent (165/538) of LTR received azithromycin. LTR who received azithromycin prophylaxis had 0.21 times the odds of developing NTM infections compared with LTR who did not receive azithromycin prophylaxis (OR: 0.21, 95% CI: 0.02 – 0.86, P = 0.02). Age (P = 0.88), type of LT (P = 0.81), pretransplant NTM colonization (P = 0.46), and CF (P = 0.22) were evaluated as possible risk factors, but were not associated with increased risk of developing NTM infections in bivariable analyses. In a multivariable logistic regression model, azithromycin prophylaxis was independently associated with decreased risk of NTM infections after adjusting for CF and pretransplant NTM colonization (aOR: 0.20, 95% CI: 0.05–0.88, P = 0.01).

Conclusion

Azithromycin use was associated with lower risk of NTM infections due to M. abscessus and MAC in our LTR.

Disclosures

All authors: No reported disclosures.
809. Osteitis Caused by Bacillus Calmette-Guerin Tokyo 172 Strain in Immunocompetent Patients
Authors: González Saldaña Napoleón , Parra Mercedes Macías , De Colsa Ranero Agustín , Garza Eduardo Arias De La , Trujillo Diego Galvis , Bejarano José Iván Castillo
Published: November 2018

Background

Immunization with BCG vaccine has been associated with local and systemic complications. Osteitis secondary to Mycobacterium bovis-BCG is a rare complication with frequency of 0.1/100,000 doses. Below we report a series of a third level pediatric hospital in Mexico City.

Methods

This is a retrospective, descriptive, and observational study of subjects diagnosed with TB at the National Institute of Pediatrics (INP) in Mexico City during the 2010–2018 period. Subjects under 18 years with skeletal TB and positive culture for M. bovis-BCG strain were included.

Results

From 2010 to 2018, 118 cases of TB were treated, from which 3 (2.5%) were osteitis secondary to M. bovis-BCG Tokyo 172 strain, two male and one female. All three cases had BCG immunization at birth. The age at diagnosis was 1, 2, and 3 years, respectively. The most common symptoms were pain, edema, and limp. Sites of injury were right proximal tibia, epiphysis of left distal femur, and left ileopubic eminence. Lytic lesions with periosteal reaction were reported in plain radiographs of all cases. The TST and COMBE studies were negative. Diagnosis was confirmed by biopsy with identification of M. bovis-BCG Tokyo 172 strain by Genotype. All strains were sensitive to rifampicin. The treatment given was INH, RIF, E, PZA, and Clarithromycin during 2 months of intensive phase followed by 7 months of maintenance phase with INH-RIF. A surgical approach was performed with curettage and graft placement in two cases. Tetrazoil nitro blue tests and immunoglobulin levels were normal. Outcome was favorable in all three cases.

Conclusion

In Mexico the BCG vaccine is part of the national immunization program and is applied to 99% of newborns. This work is the first report in Mexico of osteitis secondary to M. bovis-BCG strain Tokyo 172. We suggest considering the diagnosis in patients with osteitis under 5 years of age with a history of BCG vaccination.

Disclosures

All authors: No reported disclosures.
810. Diagnosis of BCG Aortitis by Plasma Metagenomic Sequencing
Authors: Cooper Chris , Hong David , Blair Lily , Bercovici Sivan , Ahmed Asim
Published: November 2018

Background

The use of intra-vesicular Bacille Calmette-Guerin (BCG) for bladder cancer can result in disseminated/endovascular BCG infection. The diagnosis of BCGosis in this setting is complicated by the risks of biopsy of an endovascular focus and the long duration of acid-fast bacilli (AFB) cultures.

Methods

A 68-year-old male with a history of hypertension, aortic aneurysm (status post repair), and bladder cancer treated with intravesicular BCG complicated by BCGosis presented several years later with two weeks of fevers, chills, night sweats, and back pain. Computed tomography (CT) scan demonstrated aortitis with periaortic abscess. There was concern for BCG aortitis given the antecedent BCG exposure and prior BCGosis. Blood cultures were negative; AFB blood cultures were contaminated. A sample of plasma was sent to Karius (Redwood City, CA) for next-generation sequencing (NGS). Cell-free DNA was extracted and NGS performed. Human sequences were removed and remaining sequences were aligned to a curated pathogen database of >1,000 organisms. Organisms present above a statistical threshold were reported. The patient underwent surgical replacement of the infected endograft; endovascular samples were sent for AFB culture.

Results

Plasma-based NGS of cell free DNA detected M. tuberculosis (Mtb) complex at 48 hours (within 28 hours of sample receipt). Within the Mtb complex, the majority of sequences aligned to M. bovis with five reads aligning uniquely to M. bovis. No reads aligned to the region of deletion 1 (RD1) deleted in BCG. Surgical AFB cultures were positive for Mtb complex by PCR probe at nine days; Mtb complex was recovered in culture at 19 days.

Conclusion

Plasma metagenomic sequencing can be used to rapidly diagnose BCG-associated endovascular infection.

Disclosures

C. Cooper, Karius, Inc.: Consultant, Consulting fee. D. Hong, Karius, Inc.: Employee, Salary. L. Blair, Karius: Employee, Salary. S. Bercovici, Karius, Inc.: Employee, Salary. A. Ahmed, Karius, Inc.: Employee, Salary.
812. Case–Control Trial to Evaluate the Cytokine Response to the Use of Capsule Thalidomide in Erythema Nodosum Leprosum in Leprosy Patients
Authors: Chopra Ajay , Mitra Debdeep , Mitra Barnali
Published: November 2018

Background

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Type II lepra reaction or Erythema Nodosum Leposum is a Type III hypersentivity immune response during the chronic course of the illness. This immune response presents as systemic symptoms and neutrophilic leukocytosis, similar to sepsis. Capsule Thalidomide is considered the drug of choice, when it comes to the treatment of this acute immunological emergency. A rational study into the immunological markers involved in the pathogenesis of erythema nododsum leprosum and its successful suppression by Thalidomide should be helpful in early diagnosis and prompt successful therapy. On the basis of previous studies, our aim was to find a correlation with interferon-γ, tumour necrosis factor-α, and Cd-64 expression on activated circulating neutrophils during Type II lepra reaction and successful response to capsule Thalidomide.

Methods

This case-controlled study included one group of patients diagnosed to have leprosy and the other group was healthy controlled individuals with matched age, sex, and area of residence. All the patients with type II lepra reaction responded to Capsule Thalidomide clinically, and all the skin lesions resolved in 7–14 days. Blood samples and skin biopsy were subjected to histopathology, immunoflourescence assay, immunohistochemical staining, quantitative RT-PCR (reverse transcriptase-polymerase chain reaction), and flow cytometry.

Results

Interferon-γ and TNF-α are sensitive markers in diagnosing erythema nodosum leprosum and Cd-64 expression on activated circulating neutrophils is both a specific and sensitive marker in Type II lepra reaction. Cd-64 expression also had a positive correlation with Thalidomide treatment and clinical response. High polymorphonuclear Cd-64 expression was correlated with severity of ENL.

Conclusion

Cd-64 expression on circulating neutrophils is a potential early biophysical marker for diagnosing erythema nodosum leprosum and can be used as a tool to assess thalidomide response. It is however not a good index to diagnose leprosy infection as it was specific for Type II lepra reaction. Interferon-γ and TNF-α are sensitive markers to screen for lepra reactions and this study showed no significant correlation with Thalidomide therapy.

Disclosures

All authors: No reported disclosures.
986. Evaluation of Moderate-to-Severe Influenza Disease in Children 6 Months to 8 Years of Age in Colorado
Authors: Rao Suchitra , Lamb Molly , Moss Angela , Yanni Emad , Bekkat-Berkani Rafik , Schuind Anne , Innis Bruce , Cotter Jillian , Mistry Rakesh , Asturias Edwin J
Published: November 2018

Background

A clinical endpoint of moderate-to-severe (M/S) influenza has been proposed in children, defined as fever >39°C, otitis media, lower respiratory tract infection, or serious extrapulmonary manifestations. This definition has not been evaluated against clinically relevant outcomes like hospitalization, emergency room care, antimicrobial use, and child/parental absenteeism.

Methods

We conducted a prospective observational study of children aged 6 months–8 years with influenza at the Children’s Hospital Colorado Emergency Department (ED) and its affiliates during two influenza seasons (2016–2017 and 2017–2018). Children with influenza-like-illness (ILI) were enrolled and tested for influenza by polymerase chain reaction (PCR). Parents of influenza cases and matched influenza-negative controls were contacted 2 weeks later for follow-up. The primary outcome was hospitalization for M/S influenza vs. mild influenza. Secondary outcomes included recurrent ED visits, antimicrobial use, child/parental absenteeism. Interim analyses were conducted using SAS v9.4.

Results

Among the 1,480 enrolled children with ILI, 410 (28%) tested positive for influenza by PCR. The median age of influenza cases was 4.0 years (IQR 2.2–6.1), and 20% were considered high-risk for influenza complications. Of influenza cases, 284 (69%) met the definition for M/S influenza. Among M/S influenza subjects, 8.4% were hospitalized, compared with 1.6% with mild influenza (risk difference (RD) 6.9%; 95% CI: 3.0–10.8, P < 0.01). Subjects with M/S influenza were more likely to receive antibiotics (RD 12.0%, 95% CI: 3.4–20.6, P < 0.01) with a trend to higher antiviral use (RD 6.9%, 95% CI: −0.7–14.5, P = 0.09). There was no significant difference for recurrent ED visits nor child/parental absenteeism. After adjusting for comorbidities, age, and influenza strain, the relative risk (RR) of hospitalization or recurrent ED visits was higher among those with M/S influenza vs. mild influenza (RR 2.18, 95% CI: 1.02–4.64, P = 0.04).

Conclusion

Children with M/S influenza have a higher risk of hospitalization compared with mild disease. This proposed definition is a useful clinical endpoint to study the public health and clinical impact of influenza interventions in children.

Disclosures

S. Rao, GSK: Investigator, Research grant. E. Yanni, GSK: Employee, Salary. R. Bekkat-Berkani, GSK: Employee, Salary. A. Schuind, GSK: Employee, Salary. B. Innis, GSK: Employee, Salary. R. Mistry, GSK: Investigator, Research support. E. J. Asturias, GSK: Investigator, Research grant and Research support.
990. Impact of Influenza Vaccination Setting on Timing of Vaccination in a National Sample of Influenza-Vaccinated Adults
Authors: Luther Megan
Published: November 2018

Background

The CDC recommends annual influenza vaccination by the end of October if possible. Timing of vaccination is vital since people over 65 may be at risk for intraseason immunity waning. Traditionally, vaccinations occur in doctor’s offices, but other settings are increasing the availability and convenience of vaccines. The objective was to assess the association between timing and setting of influenza vaccination.

Methods

The 2015 Behavioral Risk Factor Surveillance System (BRFSS) telephone survey was used to identify adults in the United States who reported a flu shot in the past year. Based on self-reported date of flu shot, the 2014–2015 flu season was included and divided into early (July–October) vs. late (November–May) vaccination. Settings of vaccination included doctor’s office, clinic/hospital, store, and work. Covariates of interest were demographics, having a checkup within previous 1 year, insurance, obesity (BMI ≥ 30), alcohol use, current smoking status, and comorbidities. Comorbidities (hypertension, high cholesterol, stroke, angina, heart attack, skin cancer, other cancer, arthritis, depression, kidney disease, diabetes, asthma, and chronic obstructive pulmonary disease) were categorized as 0, 1–2, or 3+ present. Logistic regression, stratified by age ≥65, identified predictors of early vaccination.

Results

A total of 130,615 patients were included. Patients vaccinated in doctor’s offices and stores tended to be older and have higher rates of comorbidities compared with those in clinics or at work. In age-stratified analyses, patients 18–64 had higher odds of early vaccination at clinics (odds ratio 1.11, 95% confidence interval 1.02–1.22), stores (OR 1.09, 95% CI 1.002–1.19), and work (OR 1.88, 95% CI 1.71–2.05) compared with doctor’s offices. Patients aged ≥65 had higher odds of early vaccination at stores (OR 1.17, 95% CI 1.07–1.27) and work (OR 1.67, 95% CI 1.33–2.09). Patients with certain traits (e.g., males, smokers, and those with children) have lower odds of early vaccination.

Conclusion

Vaccination setting is associated with vaccination timing: nontraditional (store, work) settings increase the odds of receiving a flu shot before the end of October. Age plays a key role in when and where patients receive flu vaccinations. Vaccination programs in nontraditional settings should consider targeting the later flu season to increase participation.

Disclosures

All authors: No reported disclosures.
1025. Microbial Epidemiology of Infectious Endocarditis in the Intravenous Drug Abuse Population: A Retrospective Study in East Tennessee
Authors: Lorson William , Das Avi , Heidel R Eric , Shorman Mahmoud
Published: November 2018

Background

Infective endocarditis (IE) is one of the most serious infections affecting intravenous drug users (IVDU). IVDU have a higher incidence of IE compared with the general population. There are a limited number of reports on the epidemiology of this infection from the South Eastern United States. We determined the prevalence, and the microbial epidemiology, of IE cases at our institution. We then compared this to data from other geographical regions. This was done to help aid physicians with choosing empiric treatment regimens, for IE, pending culture results.

Methods

A retrospective cohort of 299 cases of IE was analyzed between January 2013 and July 2017 at a university hospital in East Tennessee. Demographic, microbiologic, intravenous substance use status, radiographic, and echocardiographic data were collected.

Results

Of the 299 cases, 184 (61.5%) were IVDU and 115 cases (38.5%) were non-IVDU. IVDU and non-IVDU positive cultures rates were similar at 87% and 86%, respectively. Methicillin-resistant Staphylococcus aureus (MRSA) was more likely to occur in IVDU (OR 2.8, P < 0.001) and was the most common pathogen at 77 out of the 184 cases (42%). Twenty-three of the 115 (20%) cases grew MRSA in the non-IVDU population. Methicillin-sensitive Staphylococcus aureus was the second most common bacteria for IVDU with 36 out of 184 cases (19.6%). IVDU patients were more likely infected with Pseudomonas aeruginosa (OR 3.384, P = 0.027), which occurred in 20 of the 184 cases (10.9%). IVDUs also experienced more right heart involvement vs. left sided involvement (OR 2.19, P = 0.004).

Conclusion

S. aureus was the most common pathogen for IE in IVDU followed by P. aeruginosa. Data from this study solidify that in IVDU, or if there is suspicion of intravenous drug use, first-line broad-spectrum antibiotics with excellent MRSA and P. aeruginosa coverage is essential to empirically cover for IE. Extra attention for right-sided heart involvement should also be made on IVDU with imaging modalities.

Disclosures

All authors: No reported disclosures.
1026. Trends in Infective Endocarditis During the Substance Use Disorder Epidemic at an Academic Medical Center
Authors: Martin Craig A , Burgess Donna R , Wallace Katie L , Vanhoose Jeremy , Cotner Sarah , Burgess David S
Published: November 2018

Background

In many areas of the United States, substance use disorders (SUD) have increased dramatically over the past decade. Overdose deaths have increased as well, and Kentucky ranks among the nation’s leaders in deaths per 100,000 population. Infective endocarditis (IE) is a well-known complication of intravenous drug use, contributing to significant morbidity and mortality, but few studies have evaluated the effect of the current SUD epidemic on rates and demographics of IE. We sought to examine the trends in IE and IE with SUD at our institution.

Methods

We collected data from patients admitted to a large academic medical center in Kentucky between January 1, 2013 and December 31, 2016. Patients were classified according to the International Classification of Diseases, Tenth Revision. Patients were considered to have IE if they received codes I33 or I38. Patients were considered to have an SUD if they received codes F11.10, F15.10, F14.10, F19.10, or Z86.59. Data were collected through the TriNetX database (TriNetX, Cambridge, MA).

Results

There were 2,100 cases of IE during the study period. The mean (SD) age was 53 years (21). Of those, 440 also had an SUD. The mean (SD) age of these patients was 41 years (11). Patients in both the IE and IE/SUD categories were primarily male (54% and 55%) and white (94% and 94%). The number of cases of IE increased from 190 in 2013 to 430 in 2016 (R2 = 0.9877). The number of IE cases diagnosed as having an SUD increased from 30 (16% of all IE cases) in 2013 to 130 (30% of all IE cases) in 2016 (R2 = 0.7352 for the trend). This increase in cases corresponds to a 333% increase in the number of cases of IE with SUD.

Conclusion

Between 2014 and 2016, opioid overdose deaths in Kentucky rose from 24.7 to 33.5 per 100,000 population, a 35.6% increase. During a similar timeframe, the number of IE cases associated with SUD at our institution rose 333%. While it is possible that increased coding of substance use disorders factored into this dramatic increase, it appears that the number of IE cases associated with SUD is rising at a disproportionately rapid rate.

Disclosures

All authors: No reported disclosures.
1029. Outcome of Candida Graft Vascular Infection: Results From a Prospective Cohort
Authors: Caulier Thomas , Robineau Olivier , Pasquet Armelle , D’Elia Pier-Vito , Lafon-Desmurs Barthelemy , Leroy Olivier , Alfandari Serge , Senneville Eric
Published: November 2018

Background

Candida graft vascular infections (CGVI) are rare events and little data are available in the literature. The aim of this study was to describe the characteristics and outcome of patients admitted for fungal graft vascular infections, in a reference center for CGVI treatment.

Methods

Patients admitted for a CGVI in our center from 1 January 2000 to 1 February 2018 were prospectively included. Clinical, biological, and outcome data were recorded.

Results

Two hundred patients were admitted with graft vascular infections (GVI) in our center, and 11 of them (6%) presented CGVI. They were mainly men (7; 64%), and median age was 74 years old [min–max: 39–83]. All patients had benefited from prosthetic bypass surgery prior to CGVI, and infection was considered as an early disease in six patients (55%). Candida albicans was found in 72% of cases. Infection was plurimicrobial in 10 patients (92%), involving Staphyloccocus aureus in only one case and Bacille gram negatif in six (55%) cases. The management consisted in a total or partial graft replacement for five patients (45%), and surgical revision was required in four of them (30%). The empirical antifungal therapy included an echinocandin (Caspofungine) for eight patients (73%), and was changed to fluconazole or voriconazole according to antifungigram. Two patients received Amphotericin B therapy, complicated by acute kidney injury. Intensive care unit admittance was required for nine patients (82%). After the curative treatment period, antifungal therapy could not be removed in two patients and was long-continued using fluconazole. Finally, six patients (55%) died, all within the year after CGVI.

Conclusion

To our knowledge, we report here the biggest CGVI cohort. CGVI resulted in very high morbidity and mortality, requiring ICU admission for a long time. Despite multidisciplinary management involving anesthesiologists, surgeons, intensive care, and infectious disease physicians, outcome of CGVI patients remains poor.

Disclosures

All authors: No reported disclosures.
1042. Stenotrophomans maltophilia Bacteremia, A 10-Year Tertiary Center Experience
Authors: Hamdi Ahmed , Fida Madiha , AbuSaleh Omar , Beam Elena
Published: November 2018

Background

Stenotrophomonas maltophilia is a hospital acquired infection that is associated with high morbidity and mortality. There has been a reported rise in S. maltophilia infections, presumed secondary to the increase in the population at risk.

Methods

We retrospectively reviewed all hospitalized adult patients in Mayo Clinic, MN with S. maltophilia bacteremia from January 2008 through January 2018. We analyzed patient population and described patients at risk, sources of infection, and changes in antimicrobial susceptibility profile.

Results

A total of 94 patients were analyzed, including 52 males, median age of 56 (46–65.75 IQR). The population included 60 infections in those with malignancies and 30 infections in transplant recipients. At presentation, 58 (61.7%) were febrile, while 54 (58.1%) presented with hemodynamic instability. Majority (70.2%) received broad-spectrum antimicrobials within 2 weeks of presentation. The most common source was catheter associated infection (n = 60), 15 cases were secondary to gastrointestinal, and 9 due to a pulmonary source. Almost half, 46 (48.9%) required ICU admission. Two patients were diagnosed with endocarditis. Most isolates, 61(64.9%), were resistant to ceftazidime, 2 (2.2%) resistant to TMP/SMX and 20 (21.5%) were resistant to levofloxacin. Exposure to a quinolone in the 30 days prior to presentation did not impact fluoroquinolone resistance. Five patients were exposed to Trimethoprim/Sulfamethoxazole (TMP/SMX) in the 30 days prior to presentation, which was associated with higher rate of TMP/SMX resistance compared with those without exposure (80% vs. 98.8%, P = 0.004). Treatment options commonly included combination therapy, and TMP/SMX was a primary agent used in the majority, 59 (62.8%). All-cause in-hospital mortality was 26.6%. All-cause mortality was lower for line associated infections (16.67%) vs. other sources (44.12%) with P = 0.0038.

Conclusion

S. maltophilia bacteremia should be considered in hospitalized patients with recent use of broad-spectrum antibiotics. Although TMP/SMX continues to have reliable activity, use of empiric ceftazidime pending susceptibility testing should be avoided as trend toward increasing resistance is noted. We noted a drop in TMP/SMX susceptibility in those with recent reported TMP/SMX use.

Disclosures

All authors: No reported disclosures.