bluuebunny/crossref_metadata_2025 huggingface dataset:
2704. Molecular Technology to Detect Pneumococcal Colonization in Young Children Reveals Increased Prevalence of Vaccine Serotypes as Compared with Enhanced Culture Methods
Authors: Pelton Stephen I , Shea Kim , Shaik-Dasthagirisaheb Yazden , Little Brent
Published: October 2019

Background

Human challenge studies demonstrate enhanced sensitivity of molecular technology for identification of vaccine serotype pneumococcal (SP) carriage in PCV13 immunized adults. We hypothesized that PCV13 immunized children would similarly harbor vaccine serotypes in their nasopharynx (NP) that could only be identified by molecular technology.

Methods

We compared use of enhanced microbiologic culture vs. molecular technology to characterize SP colonization among NP swabs collected from 995 healthy or sick children <5 years old at Boston Medical Center from November 2015 to May 2017. NP specimens were broth enriched for 4 hours and cultured on selective blood agar. Specimens were evaluated for presence of SP using both routine microbiologic methods and RT–PCR. RT–PCR assays targeted the lytA, and piaB (SP membrane permease) genes, and 26 SP serotypes: all serotypes included in 13-valent pneumococcal conjugate vaccine and 13 prevalent non-vaccine serotypes

Results

A total of 162 (16.3%) NP specimens were positive for SP via enhanced culture, and an additional 163 (16.3%) were SP positive via lytA+ RT–PCR molecular technology. Prevalence of SP carriage was equivalent in children aged 0<2 years and 2≤5 years, but greater in children with respiratory tract infections (RTI) compared with children without RTI (26.5% vs. 9.6% among culture+ specimens only; and 43.2% vs. 25.8% among combined culture+ and molecular+ specimens). Using enhanced culture only, vaccine serotypes (VST) were identified in 4 (1%) of 450 children <2 years and 14 (2.6%) of 545 children 2 ≤5 years; adding molecular positive specimens increased the prevalence of VST to 2.9% in children <2 years and 4.6% in children 2 ≤5 years (table). Serotypes 3 and 19A were the two most commonly identified VST.

Conclusion

Combining molecular technology with enhanced culture reveals an increased prevalence of vaccine serotype colonization in young children. The ability of sensitive molecular methods to detect vaccine serotypes in culture-negative specimens suggests low-density vaccine serotype carriage persists in a highly immunized pediatric population. The importance of culture negative but RTPCR positive carriage for transmission requires further evaluation.

Disclosures

All authors: No reported disclosures.
2705. Serotype Replacement Following Childhood Pneumococcal Conjugate Vaccination Programs in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah
Published: October 2019

Background

Pneumococcal conjugate vaccines have substantially reduced the incidence of invasive pneumococcal disease (IPD); however, the impact of the vaccine on non-vaccine serotypes (NVT) remains unclear. We evaluated the effect of PCV13 use in British Columbia, Canada.

Methods

The annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) was calculated using provincial laboratory surveillance data. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–10) and pre-PCV7 (2002–03) baselines using Poisson regression for non-conjugate vaccine type IPD.

Results

A total of 4,490 cases were reported over the 14 year period. The overall annual incidence increased from 5.73 cases per 100,000 population in 2002 to 7.90 cases per 100,000 population in 2015. Compared with baseline, PCV7 reduced VT-IPD (IRR: 0.49; 95% CI: 0.42–0.56), but the additional 6 serotypes in the PCV13 vaccine caused 214% increase in IPD (IRR: 2.65; 95% CI: 2.12–3.39). The majority of this increase is related to an increase in NVT disease (IRR: 3.17; 95% CI: 2.62–3.87) such as 23B, 23A, 9N, 20, 33F, 15C, 17F and 6C. IPD from PCV13 vaccine serotypes 19A and 7F which emerged after PCV7 continue to be high.

Conclusion

The introduction of PCV13 has a modest impact on IPD rates, due to inadequate control of serotypes 19A and 7F, and, of concern, IPD rates continue to escalate due to serotype replacement by non-vaccine serotypes.

Disclosures

All authors: No reported disclosures.
2709. Immune Response After Diphtheria and Tetanus Toxoid Booster in Patients with Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibody
Authors: Tovikkai Dissaruj , Vanichanan Jakapat , Jutivorakool Kamonwan
Published: October 2019

Background

Immunization were the key of prevention in tetanus and diphtherial disease. Nevertheless, in previous observational study, low seroprotection rate of both diphtheria and tetanus were observed in Thai healthy population. Reduced-dose diphtheria and tetanus toxoid vaccine (dT) was recommended to all adult patients regardless of immunologic status. However, data on vaccine efficacy in interferon gamma (IFN-γ) autoantibody were limited. We therefore conducted clinical study to evaluate efficacy and safety of one dose of dT in IFN-γ autoantibody patient compared with healthy individuals at 4 weeks after vaccination.

Methods

Study was conducted from February to April 2019. Total 18 patients with confirmed IFN-γ autoantibody were enrolled. Baseline tetanus and diphtheria serologic study and 4 weeks after vaccination were examined. Antibody levels were measured with a solid-phase IgG-specific ELISAs (EUROIMMUN, Germany). Geometric mean titers (GMTs) were calculated using the log transformation of serological titers and from taking the antilog mean of the transformed values.

Results

Seroprevalence of tetanus was 94.5% in healthy population compared with 60.1% in IFN-γ autoantibody patients. While, seroprevalence of diphtheria was 27.8% and 77.8%, respectively. After vaccination, all healthy adults had reached seroprotection level in both diphtheria and tetanus. For patients with IFN-γ autoantibody, 88.9% and 94.4% had anti-tetanus toxin IgG and anti-diphtheria toxin IgG level above 0.1 IU/mL, respectively. These results indicated seroconversion rate of 71% for tetanus and 75% for diphtheria after dT vaccination. (Table 2). In the subgroup analysis, unboosted IFN-γ autoantibody patient had lower tetanus seroconversion rate compared with previously boosted patient (50% vs 100%). Active infection was also associated with lower immune response after tetanus vaccination. There was no severe adverse event in both group.

Conclusion

This is the first study on immune response after dT vaccination in IFN-γ autoantibody patient. Seroconversion rate of dT vaccine in IFN-γ autoantibody patient were slightly lower than healthy adults. Active infection and previously unboosted patient provided lower immune response of tetanus.

Disclosures

All authors: No reported disclosures.
2716. Persistence of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Serotypes in Invasive Pneumococcal Disease in Adults in Southern Ontario Canada Despite Routine Pediatric Vaccination
Authors: McGeer Allison , Plevneshi Agron , Green Karen , Coleman Brenda , Nayani Sarah , Rudnick Wallis , Simor Andrew , Gold Wayne , Katz Kevin , Kitai Ian , Johnstone Jennie , Martin Irene , Muller Matthew P , Richardson David , Sarabia Alicia
Published: October 2019

Background

In Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population.

Methods

TIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada.

Results

Since 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P = .03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3.

Conclusion

A significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults.

Disclosures

All authors: No reported disclosures.
2726. Meningococcal Vaccination Among Patients Newly Diagnosed at High-Risk for Meningococcal Disease in the United States
Authors: Bengtson Lindsay , Marshall Gary S , Buikema Ami R , Koep Eleena , Novy Patricia , Hogea Cosmina
Published: October 2019

Background

Quadrivalent conjugate and polysaccharide meningococcal vaccines (MenACWY) have been recommended in the United States for patients at high-risk due to functional or anatomic asplenia, complement component deficiency (CD) and human immunodeficiency virus (HIV) infection. Serogroup B vaccines (MenB) are recommended for patients ≥10 years of age with asplenia or CD. Little is currently known about meningococcal vaccine uptake and time to vaccination among patients with incident high-risk diagnoses.

Methods

Patients newly diagnosed (1 inpatient or ≥2 outpatient medical claims with evidence of the condition ≥30 days apart) with functional or anatomic asplenia (excluding sickle cell disease), CD or HIV infection were identified in the Optum Research Database. Continuous enrollment for ≥12 months before and ≥6 months after the diagnosis date (index date) was required. Patients with evidence of pre-existing conditions were excluded. MenACWY uptake was assessed among patients ≥2 years of age at index date from January 1, 2010 for asplenia and CD, and January 1, 2016 for HIV infection, through March 31, 2018; and MenB uptake among patients ≥10 years of age at index date from January 1, 2015 through March 31, 2018. Current Procedural Terminology and National Drug Codes on medical claims were used to capture vaccinations. For each condition, Kaplan–Meier analysis was used to estimate uptake and time to receipt of ≥1 dose of each vaccine for up to 5 years post-index date; vaccinations within 90 days before the index date were also included in calculations.

Results

Among asplenia patients, the percentage with receipt of ≥1 dose of MenACWY at 1, 2.5, and 5 years post-index date was 6.6%, 9.4%, and 13.3%, respectively; for CD patients the corresponding percentages were 2.2%, 4.8%, and 8.3%; and for HIV patients at 1 and 2.5 years post-index date the percentages were 10.8% and 19.8% (Figure 1). Receipt of ≥1 dose of MenB at 1 and 2.5 years post-index date was 1.7% and 3.1%, respectively, for asplenia patients and 1.1% and 2.5%, respectively, for CD patients (Figure 2).

Conclusion

Uptake of meningococcal vaccines in patients newly diagnosed with high-risk conditions is very low and the time to vaccination is long, leaving patients vulnerable to invasive meningococcal disease for extended periods of time.

Disclosures

All authors: No reported disclosures.
2728. Proportion of Invasive Pneumococcal Disease Potentially Covered by Current and Next-Generation of Higher-Valency Pneumococcal Conjugate Vaccines in Canada, 2010–2016
Authors: Dion Stephane B , Vojicic Jelena , Major Maria , Nepal Rajeev M , Gessner Bradford D , Cane Alejandro , Suaya Jose A
Published: October 2019

Background

In Canada, routine pediatric immunization with 7-valent pneumococcal conjugate vaccine (PCV7) was introduced between 2002 and 2006. Two of ten provinces transitioned to PCV10 in 2009; by mid-2011, following a national preferential recommendation, PCV13 replaced PCV7/PCV10 across Canada. PCV13 also has been recommended for immunocompromised adults since 2013, and immunocompetent adults aged ≥65 years on an individual basis since 2016. Immunization with 23-valent polysaccharide vaccine (PPV23) is recommended in adults with certain comorbidities, and routinely in those aged ≥65 years. Two higher-valency PCVs, PCV15, and PCV20 are currently under development.

Methods

Case counts of invasive pneumococcal disease (IPD) by serotype and age group were obtained from published annual reports of passive laboratory-based national IPD surveillance conducted by the National Microbiology Laboratory (NML) since April 2010.

Results

In all ages, the proportion of IPD due to PCV13 serotypes declined from 55% in 2010 to 31% in 2016 (Figure 1); in children age < 5 years, from 66% to 19%; in adults age 50–64 years, from 52% to 34%, and in adults age > 65 years from 51% to 25%. While most age groups have experienced declines in the proportion of PCV13-type IPD, this proportion has plateaued since 2014 in all age groups except 2–4 years old. During 2016, among all ages, the proportions of IPD due to PCV13, PCV15, and PCV20 types were 31%, 43%, and 58%, respectively; among children age < 5 years 19%, 35%, and 50%, respectively, among adults 50–64 years, 34%, 47%, and 61%, respectively, and among adults age ≥65 years, 25%, 38%, and 53%, respectively.

Conclusion

The proportion of PCV13-type IPD has declined across all ages since the introduction of PCV13 in children. The plateau in this proportion observed across most age groups since 2014 suggests that herd effect may have been maximized, and additional reductions could be expected primarily from direct PCV13 adult immunization. PCV20 could potentially protect against a large proportion of the remaining IPD burden in Canada.

Disclosures

All authors: No reported disclosures.
2732. Estimate of the Effectiveness of Influenza Vaccine among Children for the 2017–2018 Season
Authors: Powell Lauren , Bégué Rodolfo
Published: October 2019

Background

The 2017–2018 influenza season was one of the deadliest in decades, with 180 pediatric deaths, 80% among children who did not receive the vaccine. Circulating influenza strains change periodically, making it important to determine vaccine efficacy on an annual basis specifically in susceptible populations. The primary aim of our study was to estimate the effectiveness of the influenza vaccine for the 2017–2018 season. Secondary aims were to determine effect of weaning immunity and of previous season vaccination.

Methods

Children 6 months to 17 years tested for influenza during the 2017–2018 season at Children’s Hospital of New Orleans were included. Clinical charts were reviewed, and immunization status confirmed via the Louisiana Immunization Registry. Using a multivariable logistic regression model vaccine effectiveness (VE) was estimated by comparing vaccination status of influenza-positive vs. influenza-negative cases with the formula VE = (1 − OR) × 100%.

Results

4,825 children were included; 22% of them tested positive for influenza, mostly influenza A (61.9%); 21% had received an influenza vaccine prior to illness: 14% among the influenza-positive and 23% among influenza-negative (P < 0.0001). Overall, VE for the 2017–2018 influenza season was 43% (95% CI 30, 53); 44% for influenza A and 38% for influenza B. While receiving current year (2017–2018) vaccine had the most effect, receiving the previous year (2016–2017) vaccine had additional benefit. We found no waning immunity of the vaccine for the 2017–2018 season.

Conclusion

Influenza VE was modest for children in the local area of New Orleans and similar to the CDC’s findings for the nation as a whole. Previous year vaccination had a small, but significant benefit and there was no evidence of waning immunity in our cohort. Ongoing national and local surveillance is important to understand the benefit of influenza vaccination.

Disclosures

All authors: No reported disclosures.
2747. Relative Vaccine Efficacy of High-Dose vs. Standard Dose Influenza Vaccines in Preventing Probable Influenza in a US Medicare Fee-for-Service Population
Authors: Paudel Misti , Mahmud Salah , Buikema Ami R , Korrer Stephanie , Damon Van Voorhis , Brekke Lee , Chit Ayman
Published: October 2019

Background

High dose (HD) influenza vaccine has been shown to be more efficacious than standard dose (SD) vaccine in multiple randomized trials. HD is currently the most commonly used vaccine in US seniors (≥65 years of age). In this study, we evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over 3 influenza seasons.

Methods

This study includes a cohort of Medicare fee-for-service enrollees during influenza seasons 2011–2012 to 2013–2014 who received either HD or SD at a pharmacy or an outpatient clinic. HD recipients were matched 1:1 to SD recipients based on location, date of vaccination, age, and gender. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. The study outcome of probable influenza was defined as any inpatient stay with an influenza diagnosis on the claim, or an outpatient medical encounter with a rapid influenza test/culture followed by an antiviral prescription. Analyses were stratified based on vaccination location (clinic vs pharmacy) as it is expected that physicians carrying both vaccines may prioritize HD to frailer patients, while pharmacists may not exercise clinical judgment.

Results

Over the influenza seasons 2011–2012, 2012/–2013, and 2013–2014, 1.6–2.2 million seniors were immunized at a pharmacy; and 3.3–3.5 million at a clinic. After matching, there were 535,598; 1,017,552; and 1,548,164 in the pharmacy cohort, and 821,662; 1,151,080; and 1,559,488 in the clinic cohort, across study years. The rVE over 2011/12, 2012/13, and 2013/14 during peak influenza circulation was 21.8% (95% CI: −5.9%, 42.3%), 14.8% (9.3%,19.9%), and 16.9% (9.2%, 23.9%), respectively, in the pharmacy cohort; and 16.5% (−5.9%, 34.2%), 15.1% (10.9%, 19.1%), 10.0% (2.9%, 16.6%), respectively, in the clinic cohort.

Conclusion

HD was consistently associated with better protection against probable influenza events requiring outpatient or inpatient care. The slightly lower treatment effects observed in the outpatient clinic cohort could be a result of confounding by indication due to physicians triaging HD to frailer patients.

Disclosures

All authors: No reported disclosures.
2756. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED), Influenza-Like-Illnesses (ILIs) Sub-Study at the Marine Corps Recruit Depot-San Diego, CA (MCRD-SD) During the 2018–2019 Influenza Season
Authors: Maves Ryan , Utz Gregory , Richard Stephanie , Smith Melissa , Collins Limone , Myers Christopher , Graf Paul , Colombo Rhonda , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Mende Katrin , Schofield Christina , Seshadri Srihari , Spooner Christina , Warkentien Tyler , Coles Christian L , Burgess Timothy
Published: October 2019

Background

Military recruits suffer high rates of influenza and influenza-like illness (ILI) during training. ILIs may lead to morbidity, lost training time, and hospitalization. We evaluated the incidence and clinical outcomes of ILI among recruits at Marine Corps Recruit Depot San Diego (MCRD-SD) in a prospective trial of influenza vaccine efficacy.

Methods

Recruits at MCRD-SD were enrolled to compare the effectiveness of 3 types of FDA approved influenza vaccine: Afluria®, an egg-based vaccine; Flucelvax®, a cell-culture-derived vaccine; and Flublok®, a recombinant vaccine. Four companies of recruits were enrolled sequentially from 28 November 2018 to 19 December 2018, then randomized in a 1:1:1 ratio. Participants were followed for 18 weeks at MCRD-SD and Camp Pendleton. All participants who presented with ILI symptoms at medical care sites underwent viral diagnostic testing in addition to immunologic studies. Recruits were excluded from participation if <18 years of age, if previously vaccinated in the 2018–2019 season, or if reporting allergy to the vaccines.

Results

Of 1338 recruits approached, 771 (57.6%) participants consented for enrollment. All recruits were men between 18 and 28 years. There were 182 ILIs amongst 177 recruits (23% of 771 recruits). Nasal swabs were obtained in 180/182 cases (99%). Mean duration of ILI symptoms was 7 days. Mean days of fever was 4. Subjects reported a total 168 days of reduced training (range 0–14 days; mean 0.9 days). There were 47 total days of missed training for all subjects (range of 0–4 days; mean 0.3 days/subject). There were no hospitalizations related to ILIs. Approximately 82% (148/182) of ILIs presented within the first 3 weeks of training; 44% (80/182) of ILIs occurred during the second week of training. PCR- nasal swabs results; race/ethnicity data, and frequency of ILI mapped to week of training are illustrated below.

Conclusion

ILIs can negatively impact training effectiveness. Days lost to training from ILIs and hospitalizations can prevent successful completion of training with impact on military readiness. PAIVED may inform the DoD on future strategies to minimize influenza and other respiratory threats in recruit military populations. Influenza vaccine effectiveness will be reported separately.

Disclosures

All authors: No reported disclosures.
2757. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Immunogenicity Sub-Study
Authors: Colombo Rhonda , Richard Stephanie , Schofield Christina , Collins Limone , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Maves Ryan , Mende Katrin , Seshadri Srihari , Spooner Christina , Utz Gregory , Warkentien Tyler , Coles Christian L , Burgess Timothy
Published: October 2019

Background

Despite greater than 90% of US active duty (AD) military personnel receiving influenza vaccination annually, vaccine effectiveness (VE) among AD members has been substantially lower than in groups with less vaccine uptake. The substrate used in vaccine production may impact immunogenicity and thus VE. The PAIVED study is investigating VE of 3 different influenza vaccine formulations; a sub-study assesses immunogenicity. This analysis compares demographic characteristics and influenza-like illness (ILI) experience among main and sub-study participants for the first year of PAIVED.

Methods

During the 2018–2019 influenza season, PAIVED enrolled participants at 5 military medical centers, recruiting sub-study subjects from the main cohort excluding marine recruits. All participants were randomized (1:1:1) to receive either egg-based, cell-culture based or recombinant influenza vaccine. At enrollment, participants provided key demographic and behavioral data. Weekly surveillance for ILI symptoms was performed electronically. Sub-study volunteers underwent an additional blood draw prior to and at 21–35 days post vaccination ± an optional buccal swab.

Results

200 (23.5%) of 852 non-recruit PAIVED participants enrolled in the immunogenicity sub-study. Similar to the main cohort, 46% of sub-study volunteers were female, 85% were physically active, and 6% smoked tobacco. Sub-study participants were younger (47 ± 16 years vs. 51 ± 17 years, P = 0.004) and more likely to be AD (34% vs. 22%, P = 0.001). Although 70% of both groups identified as White, the percent African American (20% sub-study; 13% main), Asian (3%; 7%), multi-racial (2%; 5%), and unknown (6%; 4%) differed (P = 0.02). More sub-study participants developed an ILI (19% vs. 12%, P = 0.02).

Conclusion

The convenience sampling method used for recruitment into the sub-study was effective. The younger age and higher AD status in the sub-study group may be informative for evaluation of military readiness issues. The greater incidence of ILI in the sub-study increases the chance differences in immune response by vaccine type may be interpretable in the context of circulating influenza strains. Targeted efforts to enhance recruitment of a racially diverse sub-study cohort may be warranted.

Disclosures

All authors: No reported disclosures.
2760. Accounting for Vaccination History in Estimates of Current Season Vaccine Effectiveness in the US Flu VE Network, 2012–2013 Through 2017–2018
Authors: Kim Sara S , Foppa Ivo , Chung Jessie R , Belongia Edward , McLean Huong , Monto Arnold , Petrie, Joshua G , Zimmerman Richard , Nowalk Mary Patricia , Gaglani Manjusha , Murthy Kempapura , Jackson Michael L , Flannery Brendan , Patel Manish
Published: October 2019

Background

Current season vaccine effectiveness (VE) and influenza risk may vary in persons based on vaccination history. United States Influenza Vaccine Effectiveness (US Flu VE) Network studies have explored prior vaccination effects using a single referent group of patients unvaccinated in both the prior and current seasons. We investigated vaccine benefit among those with and without prior season vaccination.

Methods

Our analysis included data from the US Flu VE Network among patients aged ≥9 years old with acute respiratory illness during 6 influenza seasons, 2012–2013 through 2017–2018. We determined current and prior season vaccination status from documented immunizations. Current season VE against laboratory confirmed influenza was estimated using multivariate logistic regression with an interaction term for prior and current season vaccination. Models were adjusted for age, calendar time, high-risk status, and site.

Results

Of 31,819 patients included in the analysis over 6 seasons, 9188 were influenza positive by RT–PCR. Percent flu positivity was greatest among those unvaccinated (34%), followed by those vaccinated in the prior season only (29%), those vaccinated in both seasons (25%), and those vaccinated in the current season only (23%). Among patients with prior season vaccination, current season VE against any influenza was 14% (95% CL: 5, 22) and against A(H3N2), A(H1N1)pdm09, and B was 10% (95% CL: 3, 17), 36% (95%CL: 25, 46), and 40% (95% CL: 33, 46), respectively. Among patients unvaccinated in the prior season, VE was 42% (95% CL: 37, 46) against any influenza in the current season and was 31% (95%CL: 22, 39), 57% (95% CL: 47, 65), and 55% (95% CL: 48, 61) against A(H3N2), A(H1N1)pdm09, and B, respectively. We observed significant interaction of prior season vaccination on current season VE in 4 of 6 seasons (P < 0.20).

Conclusion

Current season vaccination was overall protective regardless of vaccination history. Among those vaccinated in the prior season, current season vaccination may provide some benefit in addition to residual protection from previous vaccination.

Disclosures

All authors: No reported disclosures.
2766. Identification and Description of Mumps Cases in a Non-Outbreak Setting and Evaluation of the Effectiveness of Mumps Containing Vaccines Over Time
Authors: Zerbo Ousseny , Glanternik Julia , Modaressi Sharareh , Goddard Kristin , Ross Pat , Lewis Ned , Klein Nicola
Published: October 2019

Background

Despite high coverage for 2 doses of MMR/MMRV vaccine, the United States and other countries have seen increases in outbreaks of mumps, mainly on college campuses and other close communities, which has been attributed to waning immunity to mumps. The objective of this study was to identify mumps cases within Kaiser Permanente Northern California, a large healthcare organization, and to assess waning of vaccine immunity against mumps in a non-outbreak setting.

Methods

Potential cases were identified by international classification of disease (ICD) 9 code 072, ICD 10 code B26 or by laboratory orders for mumps. We conducted medical chart reviews to confirm diagnoses, timing relative to vaccination and clinical characteristics. We selected cases and controls among KPNC born after 1988 who were members for ≥9 months before diagnosis or anchor date and who received their second dose at ages 4 to 6 years, matching cases with controls on geographical area. To assess for risk of mumps in relation to time since a second MMR/MMRV dose, we compared cases and controls using multivariable logistic regression adjusted for age, sex and calendar time of mumps diagnosis.

Results

Among 397 potential cases identified, chart review confirmed 178 (44.8%) as mumps. About half (87/178) were confirmed by both positive laboratory test and clinical diagnosis, with the remainder by clinical diagnosis alone. Median age at diagnosis for the 187 cases was 30 years (range 1 year–91 years). Most cases had parotitis (93%) and there were 7 cases of orchitis. The 34 cases with complete vaccination information were matched to 539,301 controls. The mean time since the second vaccine dose was shorter for cases compared with controls (6.5 years vs. 9.0 years, P = 0.008). After adjustment, there was no significantly increased risk of mumps associated with time since second MMR/MMRV dose (adjusted odds ratio = 1.08, 95% CI 0.57–2.05).

Conclusion

In the setting of a large healthcare organization, our results do not provide evidence of waning immunity following 2 doses of MMR/MMRV; however, identifying and confirming mumps cases were challenging and analyses were limited by small number of cases. Large future studies will be needed to confirm whether risk of mumps increases over time in non-outbreak settings.

Disclosures

All authors: No reported disclosures.
2775. Safety and Immunogenicity of a Seasonal Influenza Vaccine and Ad26.RSV.preF Vaccine With and Without Co-Administration: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study in Adults Aged ≥ 60 Years
Authors: Comeaux Christy , Bastian Arangassery Rosemary , Paepe Els De , Omoruyi Edmund , Haazen Wouter , Schuitemaker Hanneke , Strout Cynthia , Callendret Benoit , Sadoff Jerald
Published: October 2019

Background

Influenza and RSV can cause respiratory tract infections leading to severe illness, hospitalization and mortality in at-risk populations, particularly the elderly. The seasonality of influenza and RSV present the potential to co-administer vaccines. This study aimed to demonstrate the non-inferiority of co-administration of the experimental RSV vaccine Ad26.RSV.preF with an influenza vaccine (Fluarix) vs. Fluarix alone in terms of immunogenicity against influenza.

Methods

This was a single-center, randomized, double-blind, placebo-controlled Phase 2a study (NCT03339713) in healthy adults ≥60 years old. Volunteers were randomized 1:1 to receive Fluarix + 1 × 1011 vp Ad26.RSV.preF on Day 1 and placebo on Day 29 (Group 1), or Fluarix + placebo on Day 1 and 1 × 1011 vp Ad26.RSV.preF on Day 29 (Group 2). Blood samples were taken prior to each vaccination and at Day 57. The primary endpoints were geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibody titers against Fluarix strains (A/Michigan, A/Hong Kong, B/Brisbane and B/Phuket) and the safety and tolerability of Ad26.RSV.preF administered with or without Fluarix. A key secondary endpoint was neutralizing antibody titers to RSV A2.

Results

Volunteers (N = 180) were included in Group 1 (n = 90) or Group 2 (n = 90). Most volunteers were white (89%) and female (63%), with a median age of 65 years. Both groups exhibited an increase from baseline in HI antibody response on Day 29. The 95% one-sided upper confidence limit of all GMT ratios were below the non-inferiority margin of 2. The frequency of solicited adverse events (AE) after Ad26.RSV.preF vaccination was similar with and without influenza co-administration. Solicited AEs were mainly of Grade 1 and 2 and of transient duration. Most unsolicited AEs were considered unrelated to the study vaccination and were Grade 1 or 2. There were no serious AEs related to the study vaccine and there were no discontinuations due to AEs. RSV neutralizing antibody titers 29 days post- Ad26.RSV.preF immunization were similar in both groups (1404, Group 1; 1690, Group 2).

Conclusion

Co-administration of Ad26.RSV.preF with Fluarix was non-inferior to Fluarix alone in terms of immunogenicity against influenza and had an acceptable tolerability profile.

Disclosures

All authors: No reported disclosures.
2792. Association of Body Mass Index with Rates of Hospitalization in Patients with Respiratory Viral Infections—Puerto Rico, 2012–2018
Authors: Tobolowsky Farrell A , Zambrano Laura , Sharp Tyler , Beckham John David , Alvarado Luisa , Paz-Bailey Gabriela
Published: October 2019

Background

Obesity is a serious public health problem in Puerto Rico, where 31% of the population is obese. Multiple studies have suggested that adults with influenza who are underweight, overweight, or obese have increased risk of hospitalization compared with those of normal weight. We sought to determine whether risk of hospitalization among patients infected with influenza or other respiratory viruses differs by BMI among patients in Puerto Rico.

Methods

We analyzed data from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS), a prospective study of patients with acute febrile illness (AFI), from May 2012 to September 2018. We evaluated those older than 24 months, who had height, weight, and clinical disposition recorded, and tested positive by RT–PCR for infection with influenza A (n = 1253), influenza B (n = 844), adenovirus (n = 435), respiratory syncytial virus (n = 289), parainfluenza virus (n = 361), metapneumovirus (n = 247), or coronavirus (n = 15). BMI categories were determined using standard cutoffs in adults and BMI-for-age percentiles for children and adolescents. Risk of hospitalization by BMI category was calculated using multivariate Poisson regression.

Results

Among the 3,388 patients included, 675 (20%) were overweight, 926 (27%) were obese, 405 (12%) were underweight, and 1382 (41%) were normal weight. Median age was 13.4 (range: 2–100 years), and 50% were male. Risk of hospitalization was not significantly different in children and adult patients infected with a respiratory virus who were overweight relative to those that had normal BMI; however, once hospitalized, obese individuals of any age had a mean length of hospital stay 1.7 days longer than normal weight persons (95% CI: 0.27–3.17 days). Among adult patients, underweight patients were nearly 3 times more likely to be hospitalized compared with normal weight patients (relative risk 2.8, 95% CI: 1.4–5.9). Underweight children were not at increased risk of hospitalization.

Conclusion

Among patients infected with a respiratory virus, risk of hospitalization was higher among underweight adult patients, and obese patients had a longer mean length of stay once hospitalized. Body mass index should be considered when evaluating risk and managing these patients.

Disclosures

All authors: No reported disclosures.
2793. Influenza and Bacterial Pneumonia Coinfection: Rates and Outcomes
Authors: Bartley Patricia , Deshpande Abhishek , Yu Pei-Chun , Haessler Sarah , Zilberberg Marya , Imrey Peter , Klompas Michael , Rothberg Michael
Published: October 2019

Background

Limited evidence suggests that influenza leads not only to bacterial colonization and greater risk of bacterial pneumonia, but to poor outcomes and increased mortality. We compared bacterial culture results between patients positive (FLU+) and negative (FLU-) for influenza in the setting of community-acquired pneumonia (CAP). Among FLU+ patients we compared bacterial etiology, characteristics, treatment and outcomes between patients with and without bacterial coinfection.

Methods

We included adults admitted with pneumonia 2010–2015 to 179 US hospitals participating in the Premier database. Pneumonia was identified using an ICD-9-CM algorithm. Among patients tested for FLU, we limited the microbiology results to the first 14 hospital days. We assessed inpatient mortality, ICU admission, use of vasopressors, mechanical ventilation (MV), cost, and LOS using mixed multiple logistic regression and gamma generalized linear mixed models.

Results

Among 166,273 patients hospitalized with CAP, 38,665 (23.3%) were tested for influenza and 4,313 (11.15%) were positive. In FLU+ patients the most common bacterial co-infection was Staphylococcus aureus (37.6%) followed by Streptococcus pneumoniae (25.9%) and Pseudomonas aeruginosa (10.9%), varying based on the day of coinfection (days 1–3 vs. days 4–14) (Figure 1). In FLU- patients, S. pneumoniae (30.5%) and S. aureus (30.3%) were similarly common, followed by P. aeruginosa (10.0%). FLU+ patients with bacterial co-infection were younger (66.3 vs. 69.1 years), with more comorbidities (3.2 vs. 2.7) than influenza patients with no bacterial co-infection (all comparisons P < 0.001). Bacterial co-infection was also associated with increased odds of in-hospital mortality (OR 1.86, 95% CI,1.31–2.65), ICU admission (OR 3.46, 2.44–4.9), use of vasopressors (OR 3.74, 2.61–5.36), and MV (OR 3.51, 2.49–5.36), increased cost (risk-adjusted ratio of geometric means, 1.6, (1.47–1.73) and LOS (risk-adjusted ratio of geometric means 1.42, (1.33–1.52).

Conclusion

In a large US inpatient sample hospitalized for CAP, 11% of patients with influenza had or acquired a bacterial co-infection. Bacterial co-infection was associated with significantly worse outcomes and higher cost.

Disclosures

All authors: No reported disclosures.
491. Working Together: A Tale of Carbapenemase-Producing Organism Investigations in Three New York City Nursing Homes
Authors: Ostrowsky Belinda , Snavely Emily , Kogut Sarah , Giardina Rosalie , Adams Eleanor , Nazarian Elizabeth , Musser Kimberlee A , Jean-Denis Ronald , Greenko Jane , Lutterloh Emily
Published: October 2019

Background

New York State Department of Health (NYSDOH) and Wadsworth Center (WC) participate in the Centers for Disease Control and Prevention’s Antibiotic Resistance Laboratory Network (AR Lab Network), including identification and characterization of specific bla genes in carbapenemase-producing organisms (CPO). Three investigations from November 2018–March 2019 illustrate the findings and challenges investigating CPO in a blaKPC endemic setting.

Methods

NYSDOH WC testing includes organism identification, drug susceptibility testing, detection of carbapenemase production, detection of carbapenemase genes, and whole-genome sequencing (WGS). NYSDOH epidemiologic (epi) investigations of novel resistance mechanisms review demographic and exposure data, conduct contact tracing with targeted rectal screening to identify colonized persons, and assess infection control (IC) and public health (PH) practices and provide recommendations.

Results

NYSDOH identified three nursing home residents infected with CPO with novel carbapenemase genes (Figure 1) with no travel history but multiple co-morbidities, including mechanical ventilation: blaOXA-48Klebsiella pneumoniae (KP) (Facility A), blaNDM KP (Facility B and C). Epi investigations identified CPO in 48 of 106 residents screened for rectal colonization; most isolates had genes other than the index gene. Facility A and Facility B each had no additional residents colonized with CPO with the index gene after screening; 14 and 10 residents, respectively from Facility A and B, had CPO with endemic blaKPC gene. WGS analysis identified 2 clusters of blaKPC KP within Facility A and no clusters of CPO were detected in Facility B. IC/PH recommendations were made after diagnosis at all 3 facilities; serial IC/PH assessments/recommendations and screening were needed to interrupt transmission at Facility C, where 24 residents were colonized with CPO, including 7 residents with CPO with the index gene (blaNDM), and a subset of the blaNDM isolates were related to the index case by both epi and WGS analysis.

Conclusion

Epi investigation and WGS were complementary to detect transmission, identify clusters within an endemic setting, and inform PH response and IC measures for these emerging CPO in NY Healthcare Facilities.

Disclosures

All authors: No reported disclosures.
178. Evaluation of Oral Antibiotic Stepdown Therapy for the Management of Gram-Negative Rod Bacteremia in a Tertiary Care Medical Center
Authors: Savage Heather , Stewart Kyana , Dermady Miranda , Foy Jessica , Bohan Jefferson , King Travis , Mohammed Alaa
Published: October 2019

Background

Treatment strategies surrounding bacteremia are constantly changing as new data emerges. Transition from intravenous (IV) to oral (PO) antibiotics in patients with Gram-negative rod bloodstream infections (GNR BSI) remains controversial. The objective of this study was to characterize clinical outcomes in patients who received early (≤72 hours) vs. late (>72 hours) stepdown therapy (ES vs. LS, respectively) for GNR BSIs.

Methods

A single-center, retrospective cohort study was conducted including adults with GNR BSIs admitted to a 610-bed tertiary care academic medical center between January 1, 2016 and December 31, 2017 who were transitioned from IV to PO antibiotics. Patients with severe renal impairment, inadequate source control, prolonged antibiotic course, HIV/AIDS, and pregnancy were excluded. The primary endpoint was clinical failure and secondary endpoints were 30- and 90-day all-cause mortality, duration of bacteremia, and adverse events.

Results

164 patients (ES = 61; NS = 103) were included. Population median age was 63 years, 56% were male, and 19% were immunocompromised. Genitourinary source was most common (48.7%), while the most common organism isolated was Escherichia coli (52.4%). Most infections were community-acquired (70.1%) and the most common step-down therapy choice was ciprofloxacin in 75% of patients. There were no major differences in baseline demographic and clinical characteristics between groups except for the greater presence of central venous catheters (16.4% vs. 35.9%; P = 0.006) in the LS group. Overall clinical failure was 9.8% vs. 13.6% between the ES and LS groups, respectively. The LS group had a higher rate of clinical failure defined by escalation from PO to IV antibiotics (1.6% vs. 10.7%; P = 0.03). Patients who failed therapy tended to be immunocompromised and/or have an intra-abdominal source of infection. Secondary endpoints did not differ between groups.

Conclusion

Higher clinical failure rates in the LS group indicate that these patients may have underlying clinical characteristics not amenable to stepdown therapy. Choice of step-down therapy was not driven by the source of infection or patient acuity. Further analysis and studies are needed to determine optimal time and population for stepdown.

Disclosures

All authors: No reported disclosures.
190. Clinical Presentation of Streptococcus gallolyticus Infections
Authors: Kannangara Don , Pandya Dhyanesh
Published: October 2019

Background

There are multiple publications on the association of Streptococcus gallolyticus (SG) with malignancies of the colon. SG has been also found in association with hepatocellular carcinoma, biliary tract infections, meningitis, endocarditis, urinary and other infections. In a preliminary analysis of SG and other streptococcal infections, we find that any of the GI flora may gain access to the bloodstream when there is a breach of the mucosa due to inflammation or malignant invasion. In our study, the majority of SG infections were polymicrobial and lower urinary tract infections were the most common presentation. Only 2 out of 45 had gastrointestinal malignancies both with polymicrobial blood culture results.

Methods

We evaluated 45 cases of SG seen in our health network hospitals for the past 15 months. The charts of all SG isolates were reviewed for age, sex, clinical presentation, laboratory data and susceptibilities.

Results

There were 34 female and 11 male patients.The majority were elderly with only 5 patients below age 50, Thirty patients presented with urinary infections, 28 lower and 2 upper tract. All except 4 urinary infections were in females. Sixteen urinary infections were polymicrobial and 14 monomicrobial. Two upper tract urinary infections were monomicrobial.There were 8 bloodstream infections, 4 polymicrobial and 4 monomicrobial. Three gall bladder infections were polymicrobial and one monomicrobial. Two liver abscesses yielded polymicrobial flora. Only 4 patients had cancer 1. Metastatic pancreatic cancer 2. Carcinoma of the ampulla of Vater 3. Advanced prostate cancer 4. Anal cancer. Only 1 and 2 had positive blood cultures, both polymicrobial.The other 2 had polymicrobial lower tract urinary infections. One patient had aortic prosthetic valve endocarditis. All SG isolates tested were susceptible to penicillin, ceftriaxone and vancomycin.

Conclusion

The most common presentation was urinary. There was a higher number of females due to a large number of urinary infections.The majority of infections were polymicrobial including all 4 cancer patients. Two bacteremias were associated with gastrointestinal malignancies but none with the colon. SG isolates were susceptible to penicillin, ceftriaxone and vancomycin.

Disclosures

All authors: No reported disclosures.
212. Outcomes of Adults with Uncomplicated Staphylococcus aureus Bacteremia Receiving Short-Course Vs. Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score–Matched Cohort
Authors: Thorlacius-Ussing Louise , Nissen Jette , Rasmussen Jon J , Skov Robert , Arpi Magnus , Schonheyder Henrik , Frimodt-Møller Niels , Dahl Knudsen Jenny , Ostergaard Christian , Benfield Thomas
Published: October 2019

Background

The recommended duration of antibiotic treatment for uncomplicated Staphylococcus aureus bloodstream infections is 14 days. We compared the outcomes of patients receiving short-course (6–10 days) vs. prolonged-course (11–16 days) antibiotic therapy for S. aureus bacteremia (SAB).

Methods

30-day outcome of patients with penicillin (PSSAB, n = 202)) or methicillin-susceptible SAB (MSSAB, n = 203) treated with in vitro active therapy in the range of 6–16 days was analyzed using pooled data from two previously published, observational studies. Individuals were matched 1:1 by nearest neighbor propensity score matching without replacement. Regression analysis was performed to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment. Eligible individuals had to have >1 day of follow-up after discontinuation of antimicrobials. Individuals with a diagnosis of endocarditis, bone infection, meningitis or pneumonia were excluded.

Results

There were 107 well-balanced matched pairs; 58 in the PSSAB and 39 in the MSSAB cohort. For PSSAB, the median duration of therapy was 8 (interquartile range [IQR], 7–10) in the short-course group and 12 days (IQR, 10–13) in the prolonged-course group. For the MSSAB cohort, these numbers were 9 days (IQR, 7–10) and 14 days (IQR, 13–16 days), respectively. No difference in mortality between short-course and prolonged-course treatment was observed (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], .23–2.41) and 1.14; 95% CI, 0.31–4.20), respectively for PSSAB and MSSAB.

Conclusion

Short courses of antibiotic therapy yielded similar clinical outcomes as prolonged courses of antibiotic therapy for S. aureus bacteremia. The findings warrant a randomized clinical trial to study the safety and efficacy of shortened antimicrobial therapy for the treatment of uncomplicated SAB.

Disclosures

All authors: No reported disclosures.