bluuebunny/crossref_metadata_2025 huggingface dataset:
666. Human Granulocytic Anaplasmosis and Ehrlichiosis Presenting to an Upstate New York Emergency Department
Authors: Waxman Michael , White Jennifer , Dufort Elizabeth M , Eichelman Abigale , Stellrecht Kathleen , Kennedy Jeffrey
Published: November 2018

Background

Human granulocytic anaplasmosis (HGA) is an increasingly common tickborne infection in the North-East United States. Statewide incidence of human cases of anaplasmosis in New York (excluding New York City) increased 407% from 2010–2017, with a corresponding increase in Anaplasma phagocytophilum prevalence in ticks. While previous observational studies have described the clinical features of HGA, there has been little documentation of HGA diagnosed in the emergency department (ED) setting.

Methods

Demographic and clinical data were extracted from electronic records of cases with a positive polymerase chain reaction (PCR) for HGA or the closely related clinical entity ehrlichiosis from 2016 to 2017. HGA and ehrlichiosis PCR were performed by the Albany Medical Center laboratory on patients treated in the ED. Basic descriptive analyses were performed.

Results

During the 2-year period, there were 37 cases of PCR-positive HGA and four cases of PCR-positive ehrlichiosis treated in the ED. Electronic data were available for extraction for 40 of these cases. Mean age was 54 years old (range 7–94 years). Thirty-four (85%) patients presented with fever, and 9 (23%) reported a tick bite or tick exposure. Twenty-two (55%) patients had leukopenia; 32 (80%) thrombocytopenia; 26 (65%) hyponatremia; 24 (60%) elevated transaminases; 38 (95%) at least one of these laboratory abnormality; and 13 (33%) all four laboratory abnormalities. Twenty-four patients (60%) were given the empiric diagnosis of a tickborne illness upon disposition from the ED, with 19 (48%) patients admitted to the hospital.

Conclusion

To our knowledge, this study represents the first description of patients diagnosed with HGA (and ehrlichiosis) in the ED setting. Because of the inherent testing bias, further study is needed to establish the true ED prevalence of HGA in highly endemic regions. Notably, only 23% reported either a tick bite or tick exposure, highlighting the need to consider this for diagnosis in patients presenting to the ED with consistent symptoms and laboratory findings in endemic areas. Further study might explore whether there exists a collection of laboratory findings that could accurately identify HGA in ED patients.

Disclosures

All authors: No reported disclosures.
667. An Emerging Tick-Borne Disease in Long Island, New York: Relapsing Fever Caused by Borrelia miyamotoi
Authors: Marcos Luis , Smith Kalie , Weinbaum Fredric , Spitzer Eric
Published: November 2018

Background

Suffolk County (Long Island, New York) reports annually the highest absolute number of tick-borne diseases in New York. A new Borrelia species, Borrelia miyamotoi which causes a relapsing fever, has been reported in New York recently. The aim of this study was to identify the number of cases of B. miyamotoi diagnosed in Suffolk county.

Methods

A retrospective chart review was performed in Stony Brook (SB) Medicine hospitals, SB University Hospital (the only tertiary medical center in Suffolk County) and Southampton Hospital (a major hospital in the east end of Suffolk County). Laboratory records were queried for a positive B. miyamotoi PCR test from blood or a positive IgG antibody with a B. miyamotoi-specific EIA that utilizes a recombinant GlpQ antigen (both tests performed in a commercial laboratory).

Results

Twenty-eight cases were positive for serology (IgG EIA; n = 19) or PCR (n = 9). None of the IgG-positive cases had a positive PCR result indicating that individuals were likely exposed to B. miyamotoi in the past. Of the nine PCR-positive cases (median age:67 years), eight were men, three were diagnosed in the outpatient clinic (33.3%) and six were diagnosed through the emergency department and required hospitalization (66.6%). Thrombocytopenia and transaminitis were common findings. Two-thirds of these nine cases were diagnosed in the period of 2016–2017 and one-third in the period, 2013–2015 (P = 0.17).

Conclusion

An increasing number of cases of B. miyamotoi were observed in Suffolk County during 2013–2017 and two-thirds required hospitalization. The real burden of this tick borne disease in Suffolk County and the rest of the state is unknown.

Disclosures

All authors: No reported disclosures.
671. Increased Disease Severity and Larger Household Size Among Hispanic Infants With Pertussis: Chicago, IL, 2010–2016
Authors: Ramirez Enrique , Arwady Allison , Ruestow Peter , Fricchione Marielle
Published: November 2018

Background

Infants experience higher pertussis incidence and mortality compared with other age groups and 85% of infant cases are acquired from a household member. The Chicago Department of Public Health (CDPH) noted increased pertussis incidence among Hispanics from 2014 (5.3 cases per 100,000 population) to 2016 (12.3 cases per 100,000 population) while other ethnicities remained stable.

Methods

All pertussis cases reported to CDPH through the Illinois National Electronic Disease Surveillance System with onsets from January 1, 2010 to December 31, 2016 were included in the analyses. Variables of interest were age, race/ethnicity, household size, disease severity, healthcare location of diagnosis, and hospitalization. To assess differences in demographic and care-related indicators between Hispanic and non-Hispanic White (NHW) infants, chi-square tests were performed; risk ratios and 95% confidence intervals were estimated.

Results

From 2010–2016, 1,036 pertussis cases were reported to CDPH including 276 infants aged <1 year. Among infant cases, 187(68%) were <4 months of age, 143(52%) male, 151(55%) were Hispanic and 54(20%) were NHW. Median household size for infants of all ethnicities was four members (range: 0–15). Of all infants with household member size of ≥4 persons (157), 64% were Hispanic. 185 (67%) of infants had ≥1 severe symptom (apnea, cyanosis, pneumonia, seizure, encephalopathy) and 133 (48%) were hospitalized. Diagnosis occurred in the emergency room (ER) for 199 (72%) infants. Hispanics were more likely than NHW to have household member size ≥4 (RR 1.9, P < 0.05), severe symptoms (RR 1.6, P < 0.05), hospitalization (RR 2.3, P < 0.05), and diagnosis in the ER (RR 2.8, P < 0.05) (Table 1).

Conclusion

Among Chicago infant pertussis cases, Hispanic infants have larger household sizes and more severe disease at time of diagnosis compared with NHW.

Disclosures

All authors: No reported disclosures.
679. Mass-Scale Post-Hurricane Sheltering of Evacuees From Hurricane Harvey: Infectious Disease Surveillance and Prevention: Dallas County, Texas, 2017
Authors: Chung Wendy , Shim Kyoo , Blackwell James , Henderson Joel , Stocks Meredith , Richardson Folasuyi , Hughes Sonya , Ward Michelle
Published: November 2018

Background

The record rainfall following Hurricane Harvey’s landfall along the Texas coast on August 25, 2017 caused prolonged, widespread flooding, which devastated Houston and areas along the southern Gulf Coast. With shelters in Houston at capacity, residents from adjacent affected regions were evacuated elsewhere, and Dallas received over 3,800 evacuees at a single convention center shelter. Approaches to infectious disease surveillance and prevention in this mega-shelter setting were assessed and refined during the response.

Methods

Teams of epidemiologists and medical students reviewed all clinical records daily from the on-site, 24/7 walk-in medical clinic, which was staffed by local volunteer physicians. Demographic data, chief complaints, and diagnosis for each patient visit were reviewed, and daily aggregate summaries of visits for potential communicable disease symptoms were compiled. An additional infection control team consisting of health department staff and volunteer hospital infection preventionists implemented aggressive infection prevention measures in the shelter and clinic.

Results

Of the evacuees registered at this mass-scale shelter, 92% were from counties outside of Houston and 36% were 18 years of age or younger. During the shelter’s 23 days of operation, the shelter medical clinic received a cumulative volume of 2,654 clinic visits from 1,560 evacuees. The most common reasons for clinic visits included: need for medication refills (27.2%); respiratory symptoms (18.8%); and skin-related complaints (8.6%). Isolated cases of scabies, lice, norovirus, and influenza were confirmed, with no outbreak transmission of communicable diseases reported in the shelter.

Conclusion

The need for acute-care medical services and resources at a central shelter location was highlighted by the high proportion (40%) of evacuees seeking care at least once at the shelter medical clinic. The 24/7 accessibility of this on-site medical clinic to evacuees additionally provided a reliable mechanism for daily syndromic surveillance for potential outbreaks of infectious disease in a large shelter. Given the challenges of mass-sheltering and provision of clinical care in non-residential structures, dedicated staffing with infection control expertise was critical in this shelter setting.

Disclosures

All authors: No reported disclosures.
684. Risk Stacking for Pneumococcal Disease in Costa Rica
Authors: Chaverri-Murillo Jorge , Ramírez-Cardoce Manuel , Castro-Cordero José
Published: November 2018

Background

The value of nontraditional high-risk factor stacking is not known in the Costa Rican population. We aim to describe risk factor stacking for pneumococcal disease (PD) in patients seeking care at Social Security Hospitals in Costa Rica

Methods

Descriptive study of adult patients with microbiological culture-positive Streptococcus pneumoniae disease seeking care at two tertiary hospitals in Costa Rica between years 2014 and 2016. Information on underlying comorbidities (nontraditional) and other risk factors for PD was analyzed and stalked for each age group (G1: <50, G2: 50–64, and G3: ≥65 y/o).

Results

We included 181 culture-positive patients. We found that patients in G1 predominantly stacked ≥2 risk factors (63%), the proportion of patients with ≥2 risk factor was similar to high-risk patients in G2 (33% vs. 38%). In G3, 18% didn’t stacked any other risk factor and 46% was on high-risk. Most frequent risk factors in G1/G2 were smoking and alcoholism, and in G3 chronic pulmonary and heart diseases.

Conclusion

We conclude that risk factor stacking is more relevant than high-risk conditions and PD also occurs in persons <50 y/o. We recommend that risk factor stacking should be considered in prevention strategies for PD.

Disclosures

All authors: No reported disclosures.
685. Correlation Between Hospitalized Influenza and Group A Streptococcus Infections in Minnesota, 2010–2016
Authors: Arogbokun Olufunmilayo , Bell Austin , Abidoye Babatunde , Como-Sabetti Kathryn , McMahon Melissa , Lynfield Ruth
Published: November 2018

Background

Outbreaks of influenza can result in significant morbidity, including secondary bacterial infections. Invasive group A streptococcal (iGAS) infections are associated with a 12% case fatality rate. We used surveillance data to examine if there was a correlation between hospitalized influenza and GAS cases.

Methods

Minnesota Department of Health conducts population-based surveillance for hospitalized lab-confirmed influenza and iGAS (sterile site isolation) cases in the Minneapolis–St. Paul area as part of the CDC Emerging Infections Program. Cases were categorized by week during October–April of each year for 2010–2016, based on specimen collection date. Using STATA (v15), the correlation between the number of influenza (N = 11,768), and overall iGAS (N = 687), iGAS septic shock (n = 104), and iGAS pneumonia cases (n = 59) was assessed in weekly time periods using the Granger causality test.

Results

The number of hospitalized influenza cases was associated with an increase in the overall number of iGAS cases (Wald χ2 = 10.22, P = 0.04). Hospitalized influenza cases were associated with an increase in iGAS septic shock cases; every 1,000 increase in case counts were associated with one case of iGAS septic shock 1 week later (P = 0.02). Similarly, every 1,000 increase in hospitalized influenza cases were associated with one case of iGAS pneumonia 1 week later (P < 0.01). While the effect of Granger causality is cumulative when describing the causal relationship between hospitalized influenza and total iGAS, the correlation between influenza and the iGAS subgroups is best described with a 1-week lag.

Conclusion

Granger causality tests are commonly used in economic modeling but have not been routinely applied to infectious diseases. Using this test, we found a strong correlation between weekly cases of hospitalized influenza and iGAS cases, with a 1-week lag between influenza and iGAS septic shock or pneumonia. This approach can provide insight into the potential impact of developing prevention interventions for infections with strong correlation. Further exploration of Granger tests in infectious disease modeling should be considered.

Disclosures

All authors: No reported disclosures.
687. Modeling the Impact of Introduction of Influenza Vaccination on ILI Cumulative Case Count in Cameroon
Authors: Tamoufe Ubald , Ortiz Nancy , Saylors Karen , LeBreton Matt , Meguia Viviane , Djoko Cyrille , Njouom Richard
Published: November 2018

Background

Influenza illness can range from mild to severe, with serious outcomes occurring in children and the elderly. Flu has been studied extensively in geographies where vaccine is often plentiful. The burden of influenza is not well known in tropical regions where vaccine coverage is scant. Our study examines the impact of introducing flu vaccination on cumulative incidence in a Cameroonian population with <0.2% influenza vaccine utilization

Methods

The data consists of 1 year of flu surveillance from patients presenting with influenza-like-illness at clinics in Cameroon. Samples underwent RT-PCR influenza screening. Analysis was performed in Berkeley Madonna. We developed ordinary differential equations (ODE)s under the SEIR compartmental model and calculated R0. We estimated the proportion of cases the clinics observed to make inferences to the catchment population of these health facilities. We developed another set of ODEs to introduce vaccination using a pulse function with a 50% efficacy and 45% vaccination coverage.

Results

We observed 82.9% reduction in flu cases by introducing vaccination at 45% coverage (US average). Cameroon would likely achieve reduced coverage. Therefore, we examined introducing vaccination with 10% coverage, and observed that flu cases were cut by over one third.

Conclusion

This analysis demonstrates that introducing vaccination in Cameroon clinics would reduce influenza cases substantially even with only a small proportion of the population vaccinated. Flu vaccination campaigns should be strongly considered as they can reduce case count which may reduce the likelihood of transmitting flu to those who are at risk the most severe outcomes.

Disclosures

All authors: No reported disclosures.
690. Bacterial Coinfections Among Adults Hospitalized with Community-Associated Influenza, 2016–2017
Authors: Kraushaar Vit , Kirley Pam Daily , Coates Ashley , Reingold Arthur
Published: November 2018

Background

Influenza and bacterial coinfection are associated with increased symptom severity and worse health outcomes. We used data from the population based Influenza Hospitalization Surveillance Network (FluSurv-Net) California site to describe adult influenza hospitalizations with and without bacterial coinfections and evaluate the risk of severe disease.

Methods

We included data from adults hospitalized with laboratory confirmed influenza during the 2016/2017 influenza season who resided in San Francisco, Alameda or Contra Costa counties and had a bacterial culture performed ≤ 3 days after admission. We excluded records for healthcare facility-associated influenza. Univariate analyses were used to describe demographics, clinical characteristics and outcomes. Multivariate logistic regression was used to evaluate the effect of bacterial coinfection as a risk factor for severe outcome, defined as admission to an intensive care unit (ICU) or death during hospitalization.

Results

Among 2,029 adult influenza hospitalizations, 102 had ≥1 positive bacterial cultures. There were 119 bacterial isolates from blood (58), respiratory sites (60), and joint fluid (1). The most frequent blood isolates were Streptococcus pneumoniae (11), and Staphylococcus aureus (10). The most frequent respiratory isolates were S. aureus (30) and S. pneumoniae (7). Coinfected persons were younger (median age 71 vs. 78), and more likely to have past or current alcohol abuse or immunosuppression. Coinfected patients were more likely to be admitted to an ICU (45% vs. 15%) or die (16.0% vs. 3.6%). The median length of hospital stay was twice as long for coinfected patients (6 days vs. 3). In multivariate analyses, bacterial coinfection (aOR, 4.49; 95% CI, 2.99–6.72), chronic lung disease (aOR, 1.52; 95% CI, 1.18–1.95) and cardiovascular disease (aOR, 1.48; 95% CI, 1.15–1.90) were associated with a severe outcome.

Conclusion

Bacterial coinfection was associated with a four-fold higher risk of ICU admission and death during hospitalization. This study highlights the need for clinicians to maintain a high index of suspicion for the presence of bacterial coinfection among patients with influenza requiring hospitalization.

Disclosures

All authors: No reported disclosures.
691. Real-Time Local Influenza Forecasting Using Smartphone-Connected Thermometer Readings
Authors: Miller Aaron , Singh Inder , Pilewski Sarah , Petrovic Vladimir , Polgreen Philip M
Published: November 2018

Background

Information regarding influenza activity can inform clinical and public health activities. However, current surveillance approaches induce a delay in influenza activity reports (typically 1–2 weeks). Recently, we used data from smartphone connected thermometers to accurately forecast real-time influenza activity at a national level. Because thermometer readings can be geo-located, we used state-level thermometer data to determine whether these data can improve state-level surveillance estimates.

Methods

We used temperature readings collected by the Kinsa smart-thermometer and mobile device app to develop state-level forecasting models to predict real-time influenza activity (1–2 weeks in advance of surveillance reports). We used state-reported influenza-like illness (ILI) to represent state influenza activity for 48 US states with sufficient surveillance data. Counts of temperature readings, fever episodes and reported symptoms were computed by week. We developed autoregressive time-series models and evaluated model performance in an adaptive out-of-sample manner. We compared baseline time-series models containing lagged state-reported ILI activity to models incorporating exogenous thermometer readings.

Results

A total of 10,262,212 temperature readings were recorded from October 30, 2015 to March 29, 2018. In nearly all of the 48 states considered, weekly forecasts of ILI activity improved considerably when thermometer readings were incorporated. On average, state-level forecasting accuracy improved by 23.9% compared with baseline time-series models. In many states, such as PA, New Mexico, MA, Virginia, New York and SC, out-of-sample forecast error was reduced by more than 50% when thermometer data were incorporated. In general, forecasts were most accurate in states with the greatest number of device readings. During the 2017–2018 influenza season, the average improvement in forecast accuracy was 24.4%, and thermometer readings improved forecasting accuracy in 41, out of 48, states.

Conclusion

Data from smart thermometers accurately track real-time influenza activity at a state level. Local surveillance efforts may be improved by incorporating such information. Such data may also be useful for longer-term local forecasts.

Disclosures

I. Singh, Kinsa Inc.: Board Member, Employee and Shareholder, equity received and Salary. S. Pilewski, Kinsa Inc.: Employee and Shareholder, equity received and Salary. V. Petrovic, Kinsa Inc.: Employee and Shareholder, equity received and Salary.
694. The CAGE Study: Prevalence of Acute Gastroenteritis and Enteric Virus Infection in the Community
Authors: Schmidt Mark A , Salas S Bianca , Yamshchikov Vladimir , Groom Holly , Rosales Gabriela , Donald Judy , Marsh Zach , Burke Rachel , Mattison Claire , Naleway Allison , Hall Aron J
Published: November 2018

Background

There are currently limited data about the occurrence and characteristics of sporadic acute gastroenteritis (AGE). In this study, we sought to (1) estimate the average point prevalence of AGE over a 1-year period; (2) describe health-seeking behaviors among those with AGE; and (3) calculate the proportion of stool samples testing positive for enteric viral pathogens.

Methods

Starting in October 2016, we recruited 52 weekly, age-stratified, random samples of Kaiser Permanente Northwest members to complete an online survey and, for a subset of participants, to submit a stool specimen. The survey included questions about the occurrence of vomiting and/or diarrhea within the previous 30 days and, for those reporting AGE symptoms, related health-seeking behaviors. Collected stool samples were tested for norovirus, astrovirus, sapovirus, and rotavirus by RT-qPCR.

Results

We received a total of 3,483 surveys from eligible participants, 417 (12%) of whom reported having had AGE symptoms (Figure 1). Of these, 70 (17%) sought related medical care across a spectrum of clinical encounter types (Figure 2). We also received a total of 531 stool samples, 74 from symptomatic and 457 from asymptomatic individuals. Among them, we detected norovirus in 12% and 3% of samples (P = 0.0005), respectively; astrovirus and sapovirus in 1% of samples in each group; and rotavirus in 8% and 7% of samples, respectively.

Conclusion

Our findings of AGE within the community are consistent with previous estimates using models of medically attended AGE occurrence and reported rates of health-seeking behavior. The prevalence of enteric viral infection among people in the community without AGE was generally low. These data can be used to generate age-stratified incidence estimates of community AGE and specifically that associated with enteric viral pathogens. Such disease burden data are needed to guide the development, targeting, and anticipated impacts of interventions, such as vaccines.

Disclosures

M. A. Schmidt, Takeda Vaccines, Inc.: Investigator, Research grant. S. B. Salas, Takeda Vaccines, Inc.: Investigator, Research grant. H. Groom, Takeda Vaccines, Inc.: Investigator, Research grant. G. Rosales, Takeda Vaccines, Inc.: Investigator, Research grant. J. Donald, Takeda Vaccines, Inc.: Investigator, Research grant. A. Naleway, Takeda Vaccines, Inc.: Investigator, Research grant.
695. Regional and Longitudinal Mapping of Escherichia coli Antibiotic Susceptibility
Authors: Legenza Laurel , Barnett Susanne , Lacy Jim , Desotell Natalee , Eibergen Andrea , Rose Warren
Published: November 2018

Background

Antimicrobial resistance (AMR) is a serious threat to global health with local implications. AMR varies regionally; however, limited tools are available to aid practitioners in appropriate antibiotic selection based on statewide antimicrobial susceptibilities. The objective of this study was to map E. coli antibiotic susceptibility regionally and longitudinally in Wisconsin. Methods. Antibiograms from 2009, 2013, and 2015 were collected from health systems, hospitals, and clinics in Wisconsin, resulting in 218 antibiograms representing 201,091 Gram-negative isolates. E. coli antibiotic susceptibility percentages were weighted by number of isolates and aggregated by county per year. Results. Spatial interpolation methods (inverse distance weighted, Kriging) were tested by both county center points and facility geocode where available. Susceptibility data for clinically relevant urinary tract infection antibiotics were interpolated to create geographic visualizations of AMR in Wisconsin. Antibiotics included amoxicillin, trimethoprim/sulfamethoxazole, ciprofloxacin, nitrofurantoin, ampicillin, ampicillin/sulbactam, levofloxacin. The interpolation extends to the furthest health system point in each direction and is presented within state boundaries. Facility geocodes were masked from public display for confidentiality. City names were added for orientation. The mapping depicts regional differences, such as 2015 ampicillin susceptibilities ranging 55–64% (Figure 1). The maps provide a preliminary susceptibility prediction in areas where no AMR data were available. Average susceptibilities were compared across 2009, 2013, and 2015 to map areas with the highest rates of AMR change. Conclusion. The described mapping provides a novel visualization of AMR across Wisconsin. The maps created will be utilized in continued efforts to improve the functionality of AMR data in clinical practice to optimize antimicrobial choice.

Disclosures

All authors: No reported disclosures.
698. Nacubactam Inhibits Class A β-lactamases
Authors: Barnes Melissa D , Good Caryn E , Bajaksouzian Saralee , Taracila Magdalena A , Van Duin David , Kreiswirth Barry N , Jacobs Michael R , Papp-Wallace Krisztina M , Bonomo Robert A
Published: November 2018

Background

Nacubactam, formerly RG6080 and OP0595 (Figure 1A), is a bridged diazabicyclooctane (DBO) that inactivates class A and class C β-lactamases. Unlike avibactam, the DBO that is approved for use in combination with ceftazidime, nacubactam also inhibits penicillin binding proteins (i.e., PBP2) in Enterobacteriaceae. We set out to determine the effectiveness of meropenem-nacubactam against Klebsiella pneumoniae clinical strains and to elucidate the structure–function relationships.

Methods

Minimal inhibitory concentration (MIC) measurements using broth microdilution according to Clinical and Laboratory Standards Institute for meropenem (MERO) ± nacubactam (fixed concentration of 4 mg/L or fixed 1:1 ratio) was performed on 50 clinical K. pneumoniae strains (6 having OXA-48-like β-lactamases and 44 harboring KPC-2 or KPC-3) and 47 isogenic Escherichia coli strains harboring bla genes encoding K. pneumoniae carbapenemase (KPC) variants with single amino acid substitutions in residues that are involved in catalysis. IC50s for selected KPC-2 variants were determined on periplasmic extracts with varying concentrations of nacubactam using nitrocefin as a reporter substrate.

Results

The MERO combinations with either 4 mg/L or a 1:1 ratio of nacubactam effectively lowered the MERO MICs of K. pneumoniae strains (Figure 1B). Similarly, all E. coli strains expressing blaKPC-2 variants were susceptible to the MERO-nacubactam combinations based on the breakpoint of MERO. The strains harboring K73R, S130G, and K234R had slightly elevated MERO-nacubactam MICs relative to wild type but did not have corresponding increases in MERO MICs. Strains with pBC SK-KPC2, K73R or S130G had 0.015 mg/L MERO MICs. The pBR322-K234R strain had a twofold lower MERO MIC than pBR322-KPC-2 (Figure 1C). The IC50 of cell extracts containing the K234R variant is 781 µM, which is 12-fold higher than that for KPC-2 (66 µM) (Figure 1C). Extracts containing the S130G variant were not inhibited by nacubactam (IC50 > 2.6 mM).

Conclusion

Meropenem-nacubactam is an effective β-lactam β-lactamase inhibitor combination for Enterobacteriaceae with KPC or OXA-48 β-lactamases. The single amino acid substitutions K73R, S130G, and K234R in KPC-2 affect the inactivation mechanism.

Disclosures

M. R. Jacobs, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. K. M. Papp-Wallace, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. R. A. Bonomo, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant.
711. Molecular Epidemiology of Daptomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia
Authors: Sundaram Ayesha , Perri Mary Beth , Gurdziel Katherine , Hadid Hind , Herc Erica , Zervos Marcus J
Published: November 2018

Background

While methicillin resistance in S. aureus strains is prevalent, non-susceptibility to vancomycin and daptomycin, first-line treatments for bacteremia, has emerged as well. Little is known about the molecular epidemiology of daptomycin resistance in S. aureus strains.

Methods

A retrospective study was conducted at an 800-bed hospital in Detroit, Michigan. Blood isolates of S. aureus were obtained over time in patients with persistent bacteremia. Isolates were initially classified as MRSA/MSSA and MIC testing was done by the clinical microbiology laboratory; MICs were reconfirmed by a separate laboratory using Etest strips and microdilution broth testing. Non-susceptibility to daptomycin was defined as an MIC > 1 mg/mL. Isolates from each patient were also assessed for genomic similarity using pulse field gel electrophoresis (PFGE) and placed in the same PFGE group if they were 3 80% similar by Dice coefficient. Whole genome sequencing (WGS) on isolates and template strain ATCC29213 was done by the Applied Genomics Technology Center.

Results

There were 27 isolates from seven patients in the following distribution: six isolates each from Patients 1 and 2; three isolates each from Patients 3, 4, and 5; five isolates from Patient 6; and one isolate from Patient 7. All isolates from Patients 1 and 3 (n = 9) were classified as MSSA strains and the remainder were MRSA strains. Daptomycin nonsusceptible strains were found in the initial isolate on therapy in two patients and the MIC increased from first to last isolates in the other five patients. A PFGE dendrogram comparing isolates within each patient and with established CDC lineages determined that (1) each patient’s first and last isolate remained within the same strain type and (2) the PFGE groups were USA100 (n = 8), USA300 (n = 7), USA900 (n = 6), and USA1000 (n = 3). WGS revealed the presence of vraSR, mprF, dltA, cls2, and gdpD, genes implicated in resistance to both vancomycin and daptomycin. However, gdpD was not detected in isolates classified as MSSA.

Conclusion

No genetic modification of strains from each patient was seen between the first isolate obtained and the last. The presence of cell wall regulation genes in both daptomycin susceptible and nonsusceptible strains suggests gene upregulation.

Disclosures

M. J. Zervos, Merck: Consultant and Grant Investigator, Grant recipient.
712. Identification of a Novel Tedizolid Resistance Mutation in rpoB of Methicillin-Resistant Staphylococcus aureus
Authors: Werth Brian , Penewit Kelsi , Salipante Stephen , Shen Tianwei , Xu Libin , Nath Abhinav
Published: November 2018

Background

Tedizolid (TDZ) is an oxazolidinone antimicrobial with broad-spectrum activity against Gram-positive bacteria including methicillin-resistant S. aureus (MRSA). Resistance to TDZ is uncommon but mutations in the 23S rRNA target as well as in the transferable rRNA methyltransferase gene cfr, which also mediate resistance to linezolid and chloramphenicol have been implicated. The objective of this study was to determine whether other TDZ resistance pathways exist in MRSA.

Methods

Using a well-characterized MRSA strain, N315, we selected for TDZ resistance by serial passage in escalating concentrations of TDZ in Mueller Hinton broth (MHB) starting with 0.5× the MIC. Once visible growth was achieved a sample of the broth was diluted 1:1,000 into fresh MHB with twice the previous concentration of TDZ until an isolate with an MIC of ≥4 mg/mL was recovered. This MIC was selected since it is 1 dilution above the breakpoint for resistance ≥2 mg/L). This isolate was subjected to whole genome sequencing (WGS) and MICs to other antimicrobials were assessed. Homology modeling was performed to evaluate the potential impact of the mutation on target protein function.

Results

After 10 days of serial passage we recovered a stable mutant with a TDZ MIC of 4 mg/L. WGS revealed a single nucleotide variant (A1345G) in the rpoB gene corresponding to an amino acid substitution at D449N. The following table and figure summarize the changes in drug susceptibility between the parent and evolved strain and reveals the location of the amino acid substitution relative to the TDZ binding site.

Conclusion

We have identified a novel mutation in the RNA polymerase gene, rpoB, that mediates oxazolidinone and chloramphenicol resistance. This variant lies outside of the rifampin resistance determinant clusters of rpoB that span from 1,384 to 1,464 and 1,543 to 1,590, and as expected did not affect rifampin susceptibility. The underlying molecular mechanism by which this single nucleotide variant confers TDZ resistance remains unclear but may involve transcriptional modulation by altered sigma factor binding.

Disclosures

All authors: No reported disclosures.
713. Vancomycin Heteroresistance in Coagulase Negative Staphylococci (CoNS) Causing Central Line-Associated Bloodstream Infection (CLABSI) in Pediatric Patients with Leukemia
Authors: Dao Tina , Parsons Joshua , Hayden Randall , Rubnitz Jeffrey , Wolf Joshua , Rosch Jason
Published: November 2018

Background

Heteroresistance to vancomycin in Staphylococcus aureus may be associated with poor response to therapy. Although CoNS are the most important CLABSI pathogens in children with leukemia, and treatment failure is common, little is known about the frequency or clinical significance of heteroresistance. This is a retrospective study to evaluate frequency, risk factors and clinical impact of heteroresistance in CoNS CLABSI in immunocompromised children.

Methods

The study was approved by the Institutional Review Board. All patients undergoing treatment for leukemia at St. Jude Children’s Research Hospital with CoNS isolated from blood between 2010 and 2016 were eligible. The first available isolate from each blood culture episode was obtained from the clinical laboratory and tested for vancomycin heteroresistance by population analysis profiling in comparison to the hVISA strain Mu3. Clinical data were collected from the medical record for up to 9 months after the episode. Episodes with ≥2 positive cultures or a single positive culture from a single lumen CVC were classified as CLABSI. Outcomes of interest included treatment failure (death or relapse of infection) or poor response to vancomycin therapy (persistence of bacteremia ≥1 day after initiation of vancomycin or treatment failure). Logistic regression was used to test associations between heteroresistance and exposures, and cumulative incidence analyses were used to test the effect on outcomes.

Results

A total of 74 CoNS isolates were obtained from 65 participants, 39 with ALL and 26 with AML; 25/74 (33.8%) of isolates showed showed heteroresistance. The strongest identified risk factor for infection with a heteroresistant organism was number of days of vancomycin in the preceding 60 days (OR = 1.05/day; P = 0.035). In the 40 CLABSI episodes, heteroresistant isolates had a higher cumulative incidence of poor response and of treatment failure (P = 0.006 and P = 0.003, respectively).

Conclusion

Vancomycin heteroresistance is common in CoNS causing CLABSI in children undergoing treatment for leukemia, and is associated with an increased risk of Treatment Failure. Further research should aim to validate this finding in an independent cohort and identify strategies to improve the diagnosis and treatment of these infections.

Disclosures

R. Hayden, Roche Molecular: Scientific Advisor, Consulting fee. Abbott Molecular: Scientific Advisor, Consulting fee. Quidel: Scientific Advisor, Consulting fee. J. Wolf, Karius Inc.: Investigator, Research support.
716. Molecular Epidemiology of Respiratory Syncytial Virus in Children and Adults in Seattle, WA
Authors: Scott Emily , Kuypers Jane , Jackson Michael L , Chu Helen
Published: November 2018

Background

Respiratory syncytial virus (RSV) is the most important cause of pneumonia in children <5 years worldwide and may cause severe disease in elderly and high-risk adults. Multiple RSV strains co-circulate and evolve over seasons. We seek to describe the evolution of RSV over five seasons in Seattle, WA, USA with two seasons reported here.

Methods

From 2014 to 2016, subjects 6 months and older seeking outpatient care for acute respiratory illness at Kaiser Permanente Washington were enrolled in the Influenza Vaccine Efficacy Network (Flu VE Network) and a respiratory swab was collected. Real-time polymerase chain reaction (RT-PCR) was performed to test and quantify RSV and subtype positive samples. A subset of RSV samples with cycle threshold (CT) value <30 will be sequenced using a metagenomic next-generation sequencing (NGS) approach. Specific RSV genotypes will be associated with severe disease, defined as requiring emergency department care or hospitalization, or chest radiographic findings.

Results

A total of 8,730 patients were enrolled in the Flu VE Network and PCR testing of seasons 2014/2015 and 2015/2016 resulted in 562 of 4,137 (13.6%) RSV-positive specimens. Of patients with RSV-positive specimens, 204 (36.5%) were adults 18–64 years and 112 (20.0%) were 65+ years. RSV-B predominated in the 2014/2015 season (n = 298; 83.7%), whereas RSV-A was more common in the 2015/2016 season (n = 154; 79.8%) (Figure 1). The median (IQR) CT value for RSV-A specimens was 26.7 (23.3–29.9) compared with 27.9 (25.2–31.3) for RSV-B.

Conclusion

One RSV subtype predominated within each season. Similar RSV subtype distributions were seen across age categories. With multiple RSV vaccine candidates in development, understanding the genetic diversity and circulation of RSV various viruses within a population is important for analyzing the effects of a vaccine on the evolution of RSV.

Figure 1, Total counts (A) and proportions (B) of RSV-A and RSV-B specimens collected from study patients in Seattle, WA during 2014/2015 and 2015/2016 seasons, by age category.

Disclosures

M. L. Jackson, sanofi pasteur: Grant Investigator, Research support. H. Chu, Sanofi-Pasteur: Grant Investigator, Grant recipient.
720. Respiratory and Nonrespiratory Complications Among Patients Hospitalized with Influenza, FluSurv-NET, 2016–2017
Authors: Garg Shikha , Cummings Charisse Nitura , O’Halloran Alissa , Kirley Pam Daily , Herlihy Rachel , Yousey-Hindes Kimberly , Monroe Maya , Eckel Seth , McMahon Melissa , Angeles Kathy , Muse Alison , Bennett Nancy M , Billing Laurie , Thomas Ann , Talbot H Keipp , George Andrea , Anderson Evan J , Reed Carrie
Published: November 2018

Background

Influenza is most commonly associated with respiratory complications; however, nonrespiratory complications occur frequently among patients hospitalized with influenza. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) to describe complications recorded on discharge summaries of patients hospitalized with influenza.

Methods

We included children (0–17 years) and adults (≥18 years), who resided within a FluSurv-NET catchment area and were hospitalized with laboratory-confirmed influenza during 2016–2017. We abstracted data on underlying conditions and discharge diagnoses from medical charts. We calculated the frequency of respiratory and nonrespiratory complications in all age groups and used univariate and multivariable logistic regression to examine factors associated with select complications among adults.

Results

Among 17,489 patients, the most common respiratory complications were pneumonia (26%) and acute respiratory failure (23%) and the most common nonrespiratory complications were sepsis (16%) and acute renal failure (ARF) (12%). Complications varied by age group (figure). Pneumonia was the most common respiratory complication in all age groups except 0–4 years; among children aged 0–4 years bronchiolitis was most common (104/712; 15%). Among 97 children aged 0–4 years with bronchiolitis who underwent testing for respiratory syncytial virus (RSV), 37% had RSV. The most common nonrespiratory complication was seizures in children aged 0–17 years (17% had a history of prior seizures) and sepsis in adults. Among adults (n = 16,057), factors most strongly associated with ARF included chronic renal disease (adjusted odds ratio (AOR) 2.5; 95% confidence interval (95% CI) 2.2–2.8), male sex (AOR 1.5 95% CI 1.4–1.7) and age ≥65 years (AOR 1.4 95% CI 1.2–1.7); the factor most strongly associated with sepsis was chronic neuromuscular disease (AOR 1.5 95% CI 1.3–1.8).

Conclusion

Influenza hospitalizations are associated with a broad spectrum of complications including pneumonia, respiratory failure, sepsis, ARF and seizures. During the influenza season, astute clinicians should keep influenza in the differential diagnosis for patients with a wide range of presentations.

:Disclosures. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support.
721. Clinical Respiratory Syndromes and Association with Influenza Clinical Diagnostic Testing and Antiviral Treatment among Children Hospitalized with Acute Respiratory Illness, 2015–2016
Authors: Campbell Angela P , Rha Brian , Ogokeh Constance , Englund Janet , Halasa Natasha B , Selvarangan Rangaraj , Staat Mary A , Weinberg Geoffrey A , Azimi Parvin H , Boom Julie A , McNeal Monica , Sahni Leila C , Singer Monica Nayakwadi , Szilagyi Peter G , Harrison Christopher J , Klein Eileen J , Yu Joana , Figueroa-Downing Daniella , Payne Daniel C , Fry Alicia M
Published: November 2018

Background

We investigated clinical influenza testing and treatment in children hospitalized with acute respiratory illness (ARI) who had distinct respiratory syndromes.

Methods

Children <18 years old with ARI were enrolled at seven hospitals in the New Vaccine Surveillance Network (NVSN) between November 1, 2015–June 30, 2016. ICD10 admission diagnosis codes were grouped to define syndromes of bronchiolitis, asthma, pneumonia, and croup. At clinician discretion, influenza testing with a rapid influenza diagnostic test or molecular assay was performed on respiratory samples. As part of the study, each site performed influenza testing using molecular assays on mid-turbinate nasal and throat swabs from all enrolled children. Analysis was restricted to influenza season; children who received antivirals before hospitalization were excluded.

Results

Among 2,134 children with available ICD10 codes, on preliminary analysis 1,119 (52%) had influenza testing ordered by a clinician: 111 (10%) were positive, and 57 (51%) of 111 received antiviral treatment. Of the 2,134, 858 (40%) had one of the four mutually exclusive syndromes (table). Hospital clinical testing per clinician discretion was influenza positive in 16 of the 858 children (percent positivity per syndrome ranged from <1% to 38%; table). Research study testing of children not undergoing clinical influenza testing identified 11 additional positives. Antiviral treatment was highest for pneumonia patients.

Conclusion

Understanding testing and treatment practices by clinical syndrome may help to identify missed opportunities for influenza diagnosis and treatment.

Table:

Disclosures

J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. N. B. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.
728. Regional Validation of Distinct RSV Seasonality Thresholds for Antigen and PCR Testing
Authors: Ambrose Christopher S , Steed Lisa L , Brandon Michael , Frye Kara , Thomson Gina
Published: November 2018

Background

Respiratory syncytial virus (RSV) produces annual epidemics that vary in the timing of season onset, peak, and duration by season and by geographic region. Recent analyses by the US Centers for Disease Control at the national level have demonstrated that polymerase chain reaction (PCR) testing has largely replaced rapid antigen testing as the predominant test type and that the traditional 10% positivity threshold for defining an RSV season based on antigen testing should not be applied to PCR testing, for which the comparable threshold for real-time surveillance was 3%. The aim of this study was to validate and model implementation of the antigen (10%) and PCR (3%) positivity thresholds at regional, state, and local levels in a large national dataset of RSV testing results from US hospitals.

Methods

RSV test results were obtained from 599 laboratories that participated from 2011 to 2016 in RSVAlert®, a national RSV surveillance program. For laboratories that provided consistent weekly data (≥10 tests for ≥30 weeks of a season), regional test numbers and positivity were summarized weekly by test type within each season. Season onset and offset were calculated for the 10 US Department of Health and Human Services (HHS) regions and 10 large states plus Hawaii based on (1) antigen only for all seasons, (2) PCR only for all seasons, and (3) the predominant test type used in a specific geography in a season (either antigen or PCR).

Results

An average of 543,340 RSV tests was reported each season. At the regional and state levels, there were fewer outlier estimates of RSV season length when the predominant regional test type was used to define the season (Figures 1 and 2). Exceptions were few and occurred with antigen testing data.

Conclusion

Overall, PCR positivity of 3% was comparable to antigen positivity of 10% at the regional and state levels. Local RSV season determination was most reliable when based on the predominant test type utilized.

Funded by AstraZeneca

Disclosures

C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks.
731. Investigating Clinical Factors Contributing to Continued Antibiotic Therapy in Patients with Viral Upper Respiratory Tract Infections
Authors: Lawandi Alexander , Frenette Charles
Published: November 2018

Background

It has previously been demonstrated that upwards of 50% of patients presenting to Emergency Departments with symptoms of an upper respiratory tract infection receive empirical antibiotics, and that even with a demonstrated viral infection, 70% of these patients are continued on antibiotics. However, the clinical and biochemical factors contributing to this continued therapy is unclear. This study assessed parameters that may impact antibiotic prescriptions in patients with a confirmed viral respiratory infection. Methods. Positive respiratory virus PCRs (RVPs) from nasopharyngeal aspirates performed on adult patients presenting to the McGill University Health Centre Emergency Departments and outpatient clinics over a period of 10 days during the peak of influenza season were included. For each patient, antibiotic administration pre- and post-PCR result were determined, as were the presence of leukocytosis, neutrophilia, an abnormal chest X-ray, and sepsis. Each parameter’s effect on antibiotic use was then determined. Results. During the study period, there were 123 positive RVPs included. These consisted of 34% Flu A, 43% Flu B, and 23% were a mixture of other common respiratory viruses. Antibiotics were administered in 38% of patients before the test was resulted and continued in 79% of these patients afterwards. There was no correlation between the presence of leukocytosis, neutrophilia, signs of sepsis or abnormalities on chest X-ray and continued antibiotic therapy. Conclusion. Despite identification of a respiratory virus infection, patients are routinely treated with antibiotics even without significant evidence of a bacterial process. The impact of testing for respiratory viruses in limiting antibiotic therapy could be improved by education and direct antibiotic stewardship interventions in this population.

Disclosures

All authors: No reported disclosures.