bluuebunny/crossref_metadata_2025 huggingface dataset:
889. Impact of an Infectious Disease Telehealth (IDt) Service on S. aureus Bacteremia (SAB) Outcomes in 15 Small Community Hospitals
Authors: Gabrellas Alithea D , Veillette John J , Webb Brandon J , Stenehjem Edward A , Grisel Nancy A , Vento Todd J
Published: October 2019

Background

Infectious diseases (ID) consultation improves SAB readmission rates, compliance with care bundles and mortality. Small community hospitals (SCHs) (which comprise 70% of US hospitals) often lack access to on-site ID physicians. IDt is one way to overcome this barrier, but it is unknown if IDt provides similar clinical benefits to traditional ID consultation. Our study aims to evaluate the impact of IDt on patient outcomes at 15 SCHs (bed range: 16–146) within the Intermountain Healthcare system in Utah.

Methods

Baseline demographics, Charlson Comorbidity Index (CCI), hospital length of stay (LOS), and mortality (in-hospital, 30- and 90-day) were collected using an electronic health record database and health department vital records on all patients with a positive S. aureus blood culture from January 1, 2009 through December 31, 2018. Data from January 2014 through Sep 2016 were excluded to avoid potential influence of a concurrent antimicrobial stewardship study. Starting in October 2016 an IDt program (staffed by an ID physician and pharmacist) provided consultation for SCH providers and patients using electronic consultation and encrypted two-way audiovisual communication.Statistical analyses were performed using Fisher’s exact test or χ 2 test for categorical variables and Mann–Whitney U test for nonparametric continuous data.

Results

In total, 625 patients with SAB were identified: 127 (20%) received IDt and 498 (80%) did not (non-IDt). The two groups (IDt vs. non-IDt) were similar in median age (66 vs. 62 years; P = 0.76), percent male (62% vs. 58%; P = 0.35), and median baseline CCI (4 vs. 4; P = 0.54). There were no statistically significant differences in median LOS (5 vs. 5 days; P = 0.93) or in-hospital mortality (2% in both groups). The IDt group had a lower 30-day (9% vs. 15%; P = 0.049) and 90-day mortality (13% vs. 21%; P = 0.034).

Conclusion

IDt consultation was associated with a decrease in 30- and 90-day mortality for SCH SAB cases. Early transfer of critically ill patients might have affected LOS and in-hospital mortality. Post-discharge care factors might also contribute to 30- and 90-day mortality. While more work is needed to identify other factors associated with the effect of IDt on SAB, these data support the use of IDt to increase access to care and improve SAB outcomes in SCHs.

Disclosures

All Authors: No reported Disclosures.
894. Universal Decolonization in Nursing Homes: Effect of Chlorhexidine and Nasal Povidone–Iodine on Prevalence of Multi-Drug-Resistant Organisms (MDROs) in the PROTECT Trial
Authors: Miller Loren G , McKinnell James A , Singh Raveena , Gussin Gabrielle , Kleinman Ken , Saavedra Raheeb , Mendez Job , Catuna Tabitha D , Felix James , Heim Lauren , Franco Ryan , Estevez Marlene , Lewis Brian , Shimabukuro Julie , Evans Kaye , Bittencourt Cassiana , Lee Eunjung , He Jiayi , Tjoa Thomas , Baesu Christine , Robinson Philip A , Tam Steven , Park Steven , Steinberg Karl , Beecham Nancy , Montgomery Jocelyn , Walters DeAnn , Stone Nimalie D , Huang Susan S
Published: October 2019

Background

The prevalence of MDROs in nursing homes (NH) is much higher than that of hospitals. Decolonization to reduce the reservoir of MDRO carriage in NH residents may be a strategy to address MDRO spread within and among healthcare facilities.

Methods

PROTECT is an 18-month cluster randomized trial of 1:1 universal decolonization vs. routine care in 28 NHs in California. Decolonization consists of chlorhexidine (CHG) bathing plus twice daily nasal iodophor on admission and Monday–Friday biweekly. We assessed pre- vs. post-intervention MDRO prevalence by sampling 50 randomly selected residents at each NH as an outcome unrelated to the trial’s primary intent (infection, hospitalization reduction). NH residents had nasal swabs cultured for methicillin-resistant S. aureus (MRSA), and skin (axilla/groin) swabs taken for MRSA, vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase producers (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models (GLM) assessed the difference in differences of MDRO prevalence using an arm by period interaction term, clustering by NH.

Results

Four NHs dropped from the trial. Among the 24 NHs that remained, MDRO colonization at baseline was 49.4% and 47.5% of residents in control (N = 650) vs. decolonization (N = 550) NHs, with no difference in MRSA, VRE, ESBL, and CRE (Table 1). Among remaining NHs, decolonization was associated with 28.8% raw decrease in MDRO prevalence in decolonization sites (GLM OR = 0.51, P < 0.001), 24.3% raw decrease in MRSA (OR = 0.66, P = 0.03), 61.0% raw decrease in VRE (OR = 0.17, P < 0.001), and 51.9% raw decrease in ESBL (OR = 0.40, P < 0.001). CRE increased, but numbers were small (Control arm: 10 in baseline, 4 in intervention; intervention arm: 1 in baseline, 2 in intervention, P = NS).

Conclusion

Universal NH decolonization with CHG bathing and nasal iodophor resulted in a marked decrease in Gram-positive and Gram-negative MDRO prevalence. This decrease may lower MDRO acquisition, infection, and antibiotic use within NHs, as well as regional MDRO spread to other healthcare facilities.

Disclosures

All Authors: No reported Disclosures.
895. Impact of Measurement and Results Feedback of Chlorhexidine Gluconate (CHG) Skin Concentrations in Medical Intensive Care Unit (MICU) Patients Receiving CHG Bathing
Authors: Rhee Yoona , Hayden Mary K , Simms Andrew T , Yelin Rachel D , Lolans Karen , Bell Pamela B , Schoeny Michael , Baker Arthur W , Baker Meghan A , Gohil Shruti K , Rhee Chanu , Talati Naasha , Warren David K , Welbel Sharon F , Dangana Thelma E , Majalca Thelma , Bravo Heilen , Cass Candice , Nelson Alicia , Tolomeo Pam C , Wolf Robert , Lin Michael Y
Published: October 2019

Background

Higher CHG skin levels may be needed to adequately control infection and transmission of pathogens in the ICU. We assessed whether measurement and feedback of patient CHG skin concentrations could improve CHG bathing quality and identified factors associated with higher CHG skin concentrations.

Methods

We conducted 6 one-day surveys from January 2018 to February 2019 in 7 academic hospital MICUs with established daily CHG bathing. Adults admitted >1 day were assessed for CHG skin levels with a semi-quantitative colorimetric assay using swabbed 25 cm2 areas of anterior neck, axilla, and inguinal skin. Prior to survey 4, results from the first 3 surveys (baseline) were reported to ICU leadership and front-line staff to retrain and reeducate on bathing technique. Feedback of results from prior surveys also occurred before surveys 5 and 6. For statistical analysis, mixed-effects models accounted for clustering of CHG measurements within patients and ICUs. We categorized CHG product type as “cloth” for no-rinse 2% CHG-impregnated cloth and “liquid” for 4% CHG liquid or foam.

Results

In total, 681 of 704 (97%) patients were enrolled. Three ICUs used CHG cloth, 3 ICUs used CHG liquid, and 1 ICU switched from liquid to cloth after the second survey. Median CHG skin concentrations were higher in both the baseline and feedback period for institutions using CHG cloth, as compared with liquid (table). Across all time points, axillary and inguinal regions had higher skin CHG concentrations than the neck (median 39.1, 78.1, 19.5 µg/mL, respectively, P < 0.001). After controlling for age, mechanical ventilation, presence of a central venous catheter, body site, and hours since last CHG bath, institutions that used CHG cloth had a 3-fold increase in adjusted CHG skin concentrations in the feedback period compared with the baseline period (P = 0.001, Figure). There was no significant change in CHG skin concentrations from baseline to feedback period for institutions that used liquid CHG.

Conclusion

CHG skin concentrations on MICU patients receiving daily CHG bathing varied by body site and CHG product type. The use of CHG cloth was associated with higher CHG skin levels, compared with CHG liquid. For ICUs using CHG cloth, feedback of CHG skin concentration results to ICU staff improved CHG bathing quality.

Disclosures

All Authors: No reported Disclosures.
961. Prevalence and Macrolide Resistance of Mycoplasma genitalium After Initiation of HIV Preexposure Prophylaxis
Authors: Van Praet Jens , Steyaert Sanne , Vandecasteele Stefaan , Van Den Bergh Barbara , Mahieu Hilde , De Buyser Stefanie , Grootaert Veerle , Descheemaeker Patrick , Reynders Marijke
Published: October 2019

Background

Recent evidence shows that patients using HIV preexposure prophylaxis (PrEP) have an increased rate of bacterial sexually transmitted infections (STIs), including syphilis, chlamydia, and gonorrhea. The rate of Mycoplasma genitalium infections and the susceptibility of M. genitalium in patients on PrEP have been less well described.

Methods

We studied all patients who started on PrEP in the AZ Sint-Jan Hospital Bruges from January 6, 2017 to January 4, 2019. Patients were screened for M. genitalium and other bacterial STIs with rectal swabs, pharyngeal swabs, first-voided urine and blood collections at baseline and quarterly intervals after initiating PrEP. TaqMan array card technology was used to detect M. genitalium and determine macrolide-resistance mediating mutations in the region V of the 23S rRNA gene (A2058G, A2059G, A2058C, and others). Patients with an STI were treated based on a national guideline. Proportions were estimated using a Generalized Estimating Equations model with independent correlation structure.

Results

A total of 136 males and 1 female (median age, 40 years (interquartile range (IQR), 20–79)) were included in the study. All men were gay or bisexual. The median follow-up time was 11.3 months (IQR, 4.7–15.3). In total, 117 patients (85%) used PrEP daily at their last visit. The estimated proportion of patients with M. genitalium at baseline, 3 months, 6 months, 9 months, and 12 months was 7% (95% CI 4–13), 12% (95% CI 7–20), 7% (95% CI 4–15), 6% (3–15), and 6% (2–15). Thirty-two patients (23%) tested at least once positive for M. genitalium during the study period. The estimated percentage of macrolide resistance increased from 40% (95% CI 16–70) at baseline to 71% (95% CI 44–89), 67% (95% CI 27–92), 80% (95% CI 31–97), and 75% (95% CI 24–97) at 3 months, 6 months, 9 months, and 12 months, respectively.

Conclusion

After initiation of PrEP, the prevalence of M. genitalium in our cohort at quarterly screening was not increased compared with baseline. However, a nonsignificant trend of an increased percentage of macrolide-resistant strains was observed.

Disclosures

All Authors: No reported Disclosures.
970. Antibiotic Use Variability Among US Nursing Homes—2016
Authors: Kabbani Sarah , Wang Stanley , Ditz Laura , Palms Danielle , Rowe Theresa , Hyun David Y , Chi Nancy , Stone Nimalie D , Hicks Lauri
Published: October 2019

Background

Antibiotics are frequently prescribed in nursing homes (NH). National data describing facility-level antibiotic use (AU) in NH are lacking. The objectives of this analysis were to use NH electronic health records (EHR) to describe AU in NH and variability in AU rates across NH.

Methods

We analyzed antibiotic orders for 309,884 residents in 1,664 US NHs using one EHR company in 2016. We calculated AU rates as antibiotic days-of-therapy (DOT) per 1,000 resident-days and compared by the type of stay (short-stay (SS) ≤ 100 days vs. long-stay (LS) >100 days). We also examined prescribing indications and the duration of nursing home-initiated antibiotic orders. We assessed facility-level correlates of AU using resident health and NH facility characteristics publically available through NH Compare and LTCfocus using a univariate linear regression.

Results

In 2016, 57% of NH residents received at least one systemic antibiotic; overall rate of AU was 90 DOT/1,000 resident-days. The median facility-level AU rate was 64 DOT/1,000 resident-days (IQR 36–104). The median proportion of SS residents at a facility was 74% (IQR 60–84%). The SS and LS AU rates were 241 DOT/1,000 resident-days (IQR 173–342) and 24 DOT/1,000 resident-days (IQR 14–37), respectively. Overall, the three most common antibiotic classes prescribed were fluoroquinolones (18%), cephalosporins (18%), and extended-spectrum β-lactams (10%). Antibiotics were most frequently prescribed for urinary tract infections, and the mean duration of an antibiotic order was 9 days (range 1–365). Higher facility AU rate correlated positively with the following facility characteristics; proportion of SS residents, urban location, proportion of residents with mild cognitive impairment and lower activities of daily living scores, presence of ventilator beds, proportion of LS residents with urinary catheters or pressure ulcers, facility case-mix index, and not-for-profit ownership and multiorganization facilities.

Conclusion

Significant variability in NH AU rates exist, and SS residents have higher AU rates. Identifying NH with high rates of AU after adjusting for facility-level predictors of AU may identify opportunities for targeting efforts to improve prescribing practices.

Disclosures

All Authors: No reported Disclosures.
973. Single-cell RNA Sequencing Analysis of Zika Virus Infection in Human Stem Cell-Derived Cerebral Organoids
Authors: Ocwieja Karen , Stanton Alexandra , Richards Alexsia , Antonucci Jenna , Hughes Travis , Shalek Alex , Jaenisch Rudolph , Gehrke Lee
Published: October 2019

Background

The molecular mechanisms underpinning the neurologic and congenital pathologies caused by Zika virus (ZIKV) infection remain poorly understood. One barrier has been the lack of relevant model systems for the developing human brain; however, thanks to advances in the stem cell field, we can now evaluate ZIKV central nervous system infections in human stem cell-derived cerebral organoids which recapitulate complex 3-dimensional neural architecture.

Methods

We apply Seq-Well—a simple, portable platform for massively parallel single-cell RNA sequencing—to characterize cerebral organoids infected with ZIKV. Using this sequencing method, and published transcriptional profiles, we identify multiple cellular populations in our organoids, including neuroprogenitor cells, intermediate progenitor cells, and terminally differentiated neurons. We detect and quantify host mRNA transcripts and viral RNA with single-cell resolution, defining transcriptional features of uninfected cells and infected cells.

Results

In this model of the developing brain, we identify preferred tropisms of ZIKV infection and pronounced effects on cell division, differentiation, and death. Our data additionally reveal differences in cellular populations and gene expression within organoids infected by historic and contemporary ZIKV strains from a variety of geographic locations. This finding might help explain phenotypic differences attributed to the viruses, including variable propensity to cause microcephaly.

Conclusion

Overall, our work provides insight into normal and diseased human brain development, and suggests that both virus replication and host response mechanisms underlie the neuropathology of ZIKV infection.

Disclosures

All Authors: No reported Disclosures.
976. Development and Validation of a Risk Score for Predicting Cardiovascular Events in HIV-Infected Patients
Authors: Karanika Styliani , Karantanos Theodoros , Carneiro Herman , Assoumou Sabrina A
Published: October 2019

Background

HIV-infected individuals are at higher risk for developing cardiovascular disease (CVD). We aimed to develop a model to predict 10-year cardiovascular (CV) risk given that commonly used CVD risk assessment tools might not be accurate for HIV-infected patients.

Methods

We conducted a retrospective cohort study of HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017. Exclusion criteria are shown in Figure 1. Patients were divided into model development and validation cohorts. Logistic regression was used to create a risk model for CV events using data from the development cohort. The relationship between risk factors and CVD risk was summarized using a point-based risk-scoring system. Areas under the receiver-operating-characteristics curve (AUC) were used to evaluate model discrimination. The model was subsequently tested using the validation cohort.

Results

Of 3,867 eligible HIV-infected patients, 1,914 individuals met inclusion criteria (Figure 1). There were 256 CV events in the development cohort. Ten independent prognostic factors were incorporated into the prediction function (Pmodel < 0.001). The model had excellent discrimination for CVD risk [AUC 0.94; (95% CI:0.93–0.96)] (Figure 2) and included the following variables: male sex (P < 0.001), African-American ethnicity (P = 0.023), current age (P = 0.020), age at HIV diagnosis (P = 0.006), peak HIV viral load (P = 0.012), nadir CD4 lymphocyte count (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P = 0.001), diabetes (P < 0.001), and chronic kidney disease (P < 0.001). Scoring system and score sheets of risk estimates were developed to predict CV events in a 10-year follow-up period (Figures 3 and 4). The 10-parameter multiple logistic regression model also had excellent discrimination [AUC 0.96; (95% CI: 0.89–0.99)] when applied to the validation cohort.

Conclusion

We developed and validated a risk-scoring system based on 10 clinical factors that accurately predict the 10-year risk for CV events in an HIV-infected population. This assessment tool may provide clinicians with a rapid assessment of cardiovascular disease risk among HIV-infected patients and inform prevention measures during the era of effective antiretroviral therapy.

Disclosures

All Authors: No reported Disclosures.
977. The Prevalence and Burden of Non-AIDS Co-Morbidities in Women with or At-risk for HIV Infection in the United States
Authors: Collins Lauren F , Sheth Anandi N , Mehta C Christina , Golub Elizabeth T , Tien Phyllis C , Anastos Kathryn , French Audrey L , Kassaye Seble , Taylor Tonya , Kempf Mirjam-Colette , Fischl Margaret A , Adimora Adaora A , Palella Frank J , Ofotokun Igho
Published: October 2019

Background

Age-related non-AIDS comorbidities (NACM) increasingly account for morbidity and mortality in persons living with HIV. The burden of NACM and its association with HIV is poorly described in women.

Methods

We analyzed data from HIV+ and at-risk HIV− participants who were followed in the Women’s Interagency HIV Study (WIHS) after 2009 (when >80% of participants used antiretroviral therapy). The prevalence of each NACM (defined by a combination of self-report, clinical measurements, and laboratory data) and the number of NACM were summarized at a most recent follow-up visit and were compared by age and HIV serostatus using unadjusted linear regression models.

Results

There were 3232 women (2309 HIV+, 923 HIV–) with a median follow-up of 15.3 years. The median age was 50 years, 65% were black, 38% currently smoked, 71% had ever used illicit drugs, 50% had annual income < $12,000, and median body mass index was 30 kg/m2. HIV+ women had a median CD4 count of 618 cells/mm3 and 66% had HIV viral suppression. Among 10 NACM evaluated, the following were more prevalent in HIV+ vs. HIV– women (all P < 0.01): psychiatric illness (57%/48%), liver disease (45%/26%), hyperlipidemia (40%/35%), bone disease (40%/33%), chronic kidney disease (15%/7%), and non-AIDS cancer (11%/7%). There was little difference in the prevalence of hypertension (66%/64%), lung disease (41%/43%), diabetes (22%/24%), and cardiovascular disease (19%/19%). Mean number of NACM was higher in HIV+ vs. HIV– women (3.6 vs. 3.0, P < 0.0001). Regardless of HIV serostatus, NACM burden significantly increased with age (P < 0.0001). Compared with women aged <40 of the same HIV serostatus, the estimated mean difference in NACM (HIV+/HIV–) for those 40–49, 50–59, ≥60 years was 1.1/0.7, 2.3/2.3, and 3.6/3.2, respectively (P < 0.0001 for all). Within-age-group comparisons revealed significantly greater NACM burden in HIV+ vs. HIV− women aged 40–49 years (P < 0.0001) and ≥60 years (P = 0.003), but not in those aged <40 or 50–59 years (HIV*age interaction P = 0.02) (figure).

Conclusion

NACM burden was high in both HIV+ and at-risk HIV– women, but higher in HIV+ women overall and in certain age groups. Accumulation of NACM has complex implications for clinical care, medication management, and healthcare screening that must be further examined in this population.

Disclosures

Anandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant.
1824. Herpes Simplex Encephalitis: Outcomes from a 10-Year Retrospective Single-Center Case Series
Authors: Snider Christina A , Banzon Jona , Bhimraj Adarsh , Procop Gary W , Goldfarb Johanna
Published: October 2019

Background

Herpes simplex virus (HSV) is the most common cause of infectious encephalitis in the United States. While early treatment with acyclovir has improved acute management, long-term morbidity and mortality remain high and warrant further characterization.

Methods

We retrospectively identified adult patients (≥18 years) with HSE admitted to the Cleveland Clinic Main Campus and affiliated regional hospitals from April 2006 to June 2016. HSE diagnosis was concordant with Infectious Disease Society of America Encephalitis Guidelines. HSE diagnosis was confirmed in that HSV-1 DNA was detected in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) assay for all patients included in this study. Patients for which HSV-2 was detected in the CSF were excluded to avoid inclusion of HSV meningitis. Clinical information was collected in a REDCap database and analyzed by descriptive statistics. Patients were indexed at the date of admission, and Kaplan–Meier analysis was used to estimate overall survival.

Results

We identified 32 patients with confirmed HSE. The median patient age was 62 years (interquartile range [IQR] 45–72). All patients received treatment with intravenous (IV) acyclovir, with a median treatment duration of 24 days (IQR 19–30). The median time from initial symptom onset to IV acyclovir treatment was 5 days (IQR 3–8). Three patients (9%) died during the hospitalization course, 16 (50%) were discharged to a nursing facility, 11 (35%) returned home, and two (6%) transitioned to an acute care facility (Figure 1). Within three months of discharge, 15 (47%) patients were readmitted, six (19%) of which readmitted for HSE relapse. The overall survival rate at one month was 84% and 74% at 12 months (Figure 2). At outpatient follow-up, cognitive deficits were self-reported by 19 (66%) patients, followed in frequency by motor (31%) and sensory deficits (7%).

Conclusion

Despite appropriate treatment with IV acyclovir, HSE survivors frequently experienced severe morbidities after initial hospitalization, including HSE relapse, discharge to long-term care facilities, and neurocognitive impairment. Risk of death was highest within one month of admission. Further investigation is needed to optimize treatment of HSE to improve mortality and to reduce permanent neurologic deficits.

Disclosures

All Authors: No reported Disclosures.
1835. High Burden of Invasive Staphylococcus aureus Disease Among Native Americans on the White Mountain Apache Tribal Lands
Authors: Sutcliffe Catherine , Grant Lindsay , Reid Angelina , Douglass Grace K , Brown Laura B , Kellywood Kamellia , Weatherholtz Robert , Hubler Robin , Quintana Alvaro , Close Ryan M , McAuley James , Santosham Mathuram , O’Brien Katherine , Hammitt Laura
Published: October 2019

Background

Native Americans in the southwestern United States (US) have a higher risk of many infectious diseases than the general US population. The objective of this study was to determine the burden of invasive Staphylococcus aureus disease among Native Americans on the White Mountain Apache (WMA) Tribal lands.

Methods

Prospective population and laboratory-based surveillance for invasive S. aureus infections was conducted from May 2016 through April 2018. A case was defined as a Native American individual living on or around the WMA Tribal lands with S. aureus isolated from a normally sterile site. Incidence rates were calculated using the Indian Health Service User Population as the denominator. Age-standardized incidence rates were calculated by direct standardization methods using US Census data from 2015 as the reference.

Results

Fifty-three cases were identified (Year 1: 24; Year 2: 29). Most cases were adults (90.6%; median age: 47.4 years) and had ≥1 underlying medical condition (86.8%), of which the most common were obesity (50.0%) and diabetes (50.0%). 26.4% of cases were categorized as community acquired. Most infections were methicillin-resistant (MRSA; 75.5%). 88.7% of cases were hospitalized, 7.5% required amputation, and 7.7% died within 30 days of the initial culture. The overall incidence of invasive S. aureus was 156.3 per 100,000 persons (95% confidence interval [CI]: 119.4, 204.5) with no significant difference in the incidence by year (Year 1: 141.5; Year 2: 171.1; incidence rate ratio: 1.21; 95% CI: 0.70, 2.08). The overall incidence of invasive MRSA was 118.0 per 100,000 persons (95% CI: 86.5, 160.8) with no significant difference by year (Year 1: 106.1; Year 2: 129.8; incidence rate ratio: 1.22; 95% CI: 0.66, 2.28). The incidence of invasive S. aureus and MRSA increased with age and was highest among individuals 50–64 years of age. The overall age-adjusted incidence of invasive MRSA was 138.2 per 100,000 persons (Year 1: 125.2; Year 2: 150.9, for comparison US 2015 general population: 18.8 per 100,000 persons).

Conclusion

The WMA community has one of the highest reported incidence rates globally of invasive MRSA. Interventions are urgently needed in this community to reduce the morbidity and mortality associated with these infections.

Disclosures

All Authors: No reported Disclosures.
1872. Neurodevelopment in Apparently Normal Infants from Zika Virus Positive Pregnancies
Authors: Mulkey Sarah B , Arroyave-Wessel Margarita , Peyton Colleen , Bulas Dorothy , Vezina Gilbert , Fourzali Yamil , Morales Armando , Swisher Christopher , Cristante Caitie , Russo Stephanie , Kousa Youssef , Jiang Jiji , Msall Michael , McCarter Robert , du Plessis Adre , Cure Carlos , DeBiasi Roberta
Published: October 2019

Background

Congenital Zika syndrome (CZS) is seen in 5–12% of newborns from Zika virus (ZIKV)-infected pregnancies and includes severe neurologic abnormalities. However, the majority of ZIKV-exposed newborns do not have CZS. The risk for neurodevelopmental impairment for infants without CZS following in utero ZIKV is not well known. The objective was to determine whether infants without CZS exposed to ZIKV in utero, have normal neurodevelopment.

Methods

We performed a longitudinal study of neurodevelopment in Colombia for infants exposed to ZIKV in utero who had a normal fetal brain MRI (Mulkey et al, JAMA Peds 2019) and normal head circumference at birth. Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) between 6 and 18 months of age. In-person training was done by a neurologist. The AIMS were video-recorded and scored centrally. Interrater reliability for the novel method of video-based AIMS was determined. WIDEA and AIMS scores were converted to Z-scores compared with normative samples. We also compared development between infants with normal and nonspecific findings on cranial ultrasound (US).

Results

Seventy-two non-CZS infants had neurodevelopmental tests; 40 were at a mean (SD) of 5.7 (0.9) months and 66 were at 13.5 (3.2) months of age. Thirty-four had two assessments. The total WIDEA, social cognition, and mobility domain scores became more abnormal with postnatal age (figure). The AIMS scores were similar to the normative sample. Three infants had an AIMS score < 2 SD’s below the norm. On cranial US, 19 infants (26%) had a nonspecific finding (lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts, and/or calcification). Infants with a US finding had a lower WIDEA mobility score than infants with normal US (P = .054). There was a trend toward lower AIMS scores in infants with US findings compared with infants with normal US (P = .26). AIMS Interrater agreement on video-based scoring was good (ICC = 0.73, 95% CI 0.42, 0.87).

Conclusion

ZIKV-exposed infants without CZS are at risk for neurodevelopmental delay. Nonspecific cranial US findings may represent mild ZIKV-related injury. Long-term neurodevelopmental follow-up is important for all ZIKV-exposed infants.

Disclosures

All Authors: No reported Disclosures.
1881. The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use: Results From a National Antibiotic Stewardship Intervention of 402 United States (US) Hospitals
Authors: Tamma Pranita , Tamma Pranita , Miller Melissa A , Dullabh Prashila , Ahn Roy , Speck Kathleen , Gao Yue , Cosgrove Sara E , Cosgrove Sara E
Published: October 2019

Background

The AHRQ Safety Program for Improving Antibiotic Use aims to improve antibiotic (abx) use in acute, long-term, and outpatient care settings by enhancing abx stewardship programs (ASP) and engaging frontline providers to incorporate stewardship into daily abx decision-making, with an emphasis on viewing appropriate prescribing as a patient safety issue. We report on the impact of implementation of the Acute Care Safety Program on abx use and Clostridioides difficile in a cohort of US hospitals.

Methods

The Acute Care Safety Program was implemented from December 2017 to November 2018. At least one unit from each hospital participated. The Safety Program trained local ASP leaders and assisted ASPs and frontline staff to: (a) address attitudes and culture that pose challenges to judicious abx use and (b) incorporate best practices for the management of common infections into daily practice using the Four Moments of Antibiotic Decision Making framework (Figure 1). Education occurred via 17 live Webinars and an online toolkit that included recorded Webinars, narrated presentations, and other tools to assist with the development and dissemination of syndrome-specific local guidelines (Table 1). Units submitted days of abx therapy (DOT) per 1,000 patient-days (PD), C. difficile LabID events per 10,000 PD, and 10 review forms per month documenting structured discussions between the ASP and frontline staff about patients on abx. Linear and generalized linear mixed-effects models were employed to calculate pre-post intervention changes in abx use and C. difficile LabID events, respectively.

Results

402 hospitals completed the Safety Program, including 28 (7%) academic medical centers (AMC), 289 (72%) community hospitals, and 85 (21%) critical access hospitals. 476 participating units consisted of 165 (35%) ICUs, 300 (63%) medical-surgical floors, and 11 (2%) other units. Both abx use and C. difficile LabID events decreased when comparing pre-post data (−41 DOT per 1,000 PD, [from 886.56, Figure 2], P = 0.001 and −1.2 LabID events per 10,000 PD [from 6.3], P = 0.027), respectively.

Conclusion

By targeting both improving abx prescribing culture and knowledge of best practices, the AHRQ Safety Program led to reductions in abx use across a diverse cohort of hospitals.

Disclosures

Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
1884. Clinical Outcomes Among Patients with Drug-Resistant Tuberculosis Receiving Bedaquiline or Delamanid Containing Regimens
Authors: Kempker Russell R , Mikiashvili Lali , Zhao Yuan , Benkeser David , Barbakadze Ketino , Bablishvili Nino , Peloquin Charles , Blumberg Henry , Kipiani Maia
Published: October 2019

Background

Bedaquiline and delamanid are new and much-needed treatment options for drug-resistant tuberculosis (TB); however, there are limited data guiding their use and no direct comparison of the two drugs. We thus sought to compare the clinical outcomes of patients with drug-resistant tuberculosis receiving either a bedaquiline- or delamanid-based treatment regimen.

Methods

This is a prospective observational study among patients with drug-resistant pulmonary TB in the country of Georgia from 2015 to 2017. Patients receiving bedaquiline or delamanid were eligible to be enrolled. Monthly sputum cultures and MIC testing on Mycobacterium tuberculosis isolates were performed. Clinical outcomes included time to culture conversion, rate of acquired drug resistance and treatment outcomes.

Results

Among 156 patients with MDR-TB who were approached, 100 were enrolled, and 95 were receiving a bedaquiline (n = 64) or delamanid (n = 31) based regimen and included in the study. Patients receiving bedaquiline or delamanid were similar with regards to age, BMI, substance use, comorbidities, rate of cavitary disease, and extensively drug-resistant (XDR) TB. Rates of additional Class A drug use including linezolid (78 vs. 81%) and a fluoroquinolone (39 vs. 36%) were similar and the mean effective drugs received per group was 4 (IQR 3–4, P = 0.33). Median drug duration was 171 days for bedaquiline and 182 days for delamanid; no patient discontinued due to QTC prolongation. Adjusted cumulative culture conversion rates at 60 days (64% vs. 48%, P = 0.14) and 180 days (95% vs. 77%, P = 0.02) were higher in patients receiving bedaquiline compared with delamanid (see figure). Rates of acquired drug resistance were higher in patients receiving delamanid compared with bedaquiline (35 vs. 12%, P < 0.01). Lastly, patients receiving a bedaquiline-based regimen had higher rates of favorable outcomes as compared with patients receiving delamanid (94% vs. 67%, P < 0.01).

Conclusion

Patients receiving bedaquiline- and delamanid-based treatment regimens for drug-resistant TB had similar characteristics and those receiving bedaquiline had better clinical outcomes. Our results provide an important first comparison of bedaquiline vs. delamanid containing regimens.

Disclosures

All Authors: No reported Disclosures.
1885. T-helper 1 (Th1) Production of Interferon Gamma (IFNγ) Is Directly Inhibited by TGFβ Within Pulmonary Mycobacterium tuberculous (Mtb) Granulomas
Authors: Gern Benjamin H , Adams Kristin , Stoltzfus Caleb , Plumlee Courtney , Gerner Michael , Urdahl Kevin
Published: October 2019

Background

CD4 T-cell production of IFNɣ is essential to prevent dissemination of pulmonary Mtb, though is less effective at controlling infection within the lung. Because T cells are most effective in the context of direct interactions with Mtb-infected cells, we sought to determine the location of CD4 T-cell antigen sensing and IFNɣ production within granulomas.

Methods

We used a murine ultra-low-dose aerosol infection, developed by our lab, where most mice are infected by a single bacillus, resulting in a solitary granuloma that is more similar to human granulomas. We examined the lungs of wild-type mice 35 days later for patterns of T-cell activation with quantitative confocal imaging. This analysis was next performed following adoptive co-transfer of Th1 polarized Mtb-specific cells and control cells of irrelevant specificity (OVA). To determine the effect of TGFβ on IFNɣ production, we examined mice that lack the TGFβR on T cells (TGFβR.KO). Finally, we examined whether this effect was Th1 cell-intrinsic with an adoptive transfer of Th1-polarized Mtb-specific cells with (Tg.WT) and without (Tg.KO) the TGFβR.

Results

Despite many CD4 T cells localizing to the granuloma and undergoing T-cell receptor (TCR) activation (pS6), IFNɣ production was not significantly increased in the granuloma compared with a distal lung site (Figure 1). This pattern of localization and activation was found to be similar in the Mtb-specific (but not control) Th1 cells (Figure 2). In contrast, CD4 T cells from TGFβR.KO mice produced more IFNɣ within the granuloma (Figure 3). Lastly, Tg.KO cells transferred into wild-type mice produced increased IFNɣ compared with Tg.WT, mirroring the findings in TGFβR.KO mice (Figure 4).

Conclusion

CD4 T cell production of IFNɣ is decreased within the granuloma, where it can be most effective, despite evidence of ongoing TCR stimulation in Mtb-specific cells. We have shown that by alleviating the effects of TGFβ signaling, even terminally-differentiated Mtb-specific Th1 cells can produce more IFNɣ within the granuloma. While this modest increase suggests that there are additional mechanisms at play which warrant further exploration, these findings have the potential to guide immunotherapeutic development, especially given that TGFβ inhibitors are already in phase III clinical trials for other purposes.

Disclosures

All Authors: No reported Disclosures.
1886. N1,N12-Diacetylspermine as Potential Urinary Biomarker to Monitor Treatment Response and Bacterial Load in Pulmonary Tuberculosis
Authors: Xia Qianjing (Jenny) , Hee Lee Myung , Rhee Kyu , Isa Flonza
Published: October 2019

Background

Adequate control of the global tuberculosis (TB) burden is limited by a lack of accurate measures of treatment efficacy. Current gold standard relies on sputum cultures, which often lag weeks behind time of sample collection. Previous studies have identified urinary N1,N12-diacetylspermine (DiAcSpm) as a potential biomarker of active pulmonary TB (ATB). We aimed to quantify urinary DiAcSpm in participants being treated for ATB and identify its relationship to treatment response.

Methods

Longitudinal urine samples were obtained from two separate cohorts of participants treated for ATB. Cohort one consisted of 34 successfully treated ATB cases with urine collected at weeks 0, 2, 4, 8, 17, 26, and 52. Cohort two consisted of 35 ATB cases under two treatment arms: one arm was successfully treated with the standard therapy of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), and the other arm received an experimental drug, which was later found to be ineffective against ATB. Urine from cohort two was collected at days 0, 2, 4, and 14. All samples were blinded, randomized, normalized to osmolality and urinary creatinine, and analyzed using high-performance liquid chromatography-mass spectrometry. DiAcSpm concentrations were further tested using ELISA.

Results

Using linear-mixed modeling that adjusted for age, sex, and participant weight, we found that urinary DiAcSpm significantly decreased by week 2 of successful treatment in both cohorts (P < 0.0001). DiAcSpm levels remained unchanged in the ineffective experimental drug group (cohort two), significantly differentiating treatment success and failure by day 14 (P < 0.0001). Additionally, concentrations of urinary DiAcSpm positively correlate with sputum mycobacterial burden (P = 0.0002).These findings were consistent across both methods of detection.

Conclusion

Our results suggest that urinary concentrations of DiAcSpm correlate with TB treatment outcome and mycobacterial disease burden, and have the potential to serve as an early biomarker of TB treatment efficacy.

Disclosures

All Authors: No reported Disclosures.
1891. Invasive Group A Streptococcus Infections Among Residents of Multiple Nursing Homes—Denver, Colorado, 2017–2018
Authors: Idubor Osatohamwen , Alden Nisha B , Nanduri Srinivas , Ogundimu Abimbola , Tanwar Sukarma S S , Reese Heather , Odongo Wycliffe , Herlihy Rachel , Johnston Helen , Burakoff Alexis , Burdorf April , Dale Ariella P , Nichols Janell , Bamberg Wendy M , Cilwick Alana , Barter Devra , Brousseau Geoff , Chochua Sopio , Stone Nimalie D , Van Beneden Chris
Published: October 2019

Background

Older adults residing in nursing homes (NH) are at increased risk for invasive group A Streptococcus (GAS) infections due to advanced age, presence of wounds, and comorbidities; approximately one-third of infected patients die. Beginning in 2015, increasing numbers of GAS infections in NH residents and several NH clusters were reported from the Denver metropolitan area. Colorado Department of Public Health and Environment (CDPHE) and CDC investigated to characterize cases and assess if outbreaks resulted from interfacility transmission.

Methods

We reviewed data from Active Bacterial Core surveillance (ABCs) in the 5-county Denver area from January 2017 to June 2018. We defined a case as isolation of GAS from a normally sterile site in an NH resident. GAS isolates underwent whole-genome sequencing (WGS) at CDC’s Streptococcus Laboratory to determine emm types for genotyping. Among isolates with the same emm type, pairwise single-nucleotide polymorphism (SNP) distances were calculated using Nucmer software. In October 2018, a CDPHE-CDC team assessed infection control at NHs with cases of the most common emm type.

Results

Over 18 months, among >100 NHs in the Denver area, ≥1 GAS case was identified in 29 NHs, with 6 having ≥3 cases. During this period, 68 cases in NH residents were identified. WGS identified 17 emm types among isolates from these cases; most common was emm11.10 (34%, n = 22), a rare subtype in ABCs. All emm11.10 isolates had nearly identical genomes (average pairwise SNP distance: 3.2), and were isolated from 10 NHs, with 2 NHs having ≥ 4 cases. Multiple infection control lapses were noted during site visits to 8 NHs.

Conclusion

Multiple outbreaks due to GAS were noted in 5-county Denver area NHs in 2017–2018. WGS of surveillance isolates identified a rarely seen emm subtype 11.10 from multiple facilities with temporal and genomic clustering suggesting interfacility GAS transmission.

Disclosures

All Authors: No reported Disclosures.
1946. An Exploratory Study of the Therapeutic Reasoning Underlying Antimicrobial Selection
Authors: Abdoler Emily , O’Brien Bridget , Schwartz Brian , Schwartz Brian
Published: October 2019

Background

Clinical reasoning research has helped illuminate how clinicians make diagnoses but offers less insight into management decisions. The need to understand therapeutic choices is particularly salient within infectious diseases (ID), where antimicrobial prescribing has broad implications given increasing rates of resistance. Researchers have examined general factors underlying antibiotic prescribing. Our study advances this work by exploring the factors and processes underlying physician choice of specific antimicrobials.

Methods

We conducted individual interviews with a purposeful sample of Hospitalists and ID attendings. Our semi-structured interview explored the reasoning underlying antimicrobial choice through clinical vignettes. We identified steps and factors after 12 interviews then conducted 4 more to confirm and refine our findings. We generated a codebook through an iterative, inductive process and used Dedoose to code the interviews and facilitate analysis.

Results

We identified three antibiotic reasoning steps (Naming the Syndrome, Delineating Pathogens, Antimicrobial Selection) and four factors involved in the reasoning process (Host Features, Case Features, Provider and Healthcare System Factors, Treatment Principles) (Table 1). Participants considered host and case features when determining likely pathogens and antimicrobial options; the other two factors influenced only antimicrobial selection. From these data, we developed an antimicrobial reasoning framework (Figure 1). We also determined that participants seemed to have a “script” with specific content for each antimicrobial they considered, functioning much like the illness scripts common to diagnostic reasoning (Table 2).

Conclusion

Our antimicrobial reasoning framework details the cognitive processes underlying antimicrobial choice. Our results build on general therapeutic reasoning frameworks while elaborating factors specific to ID. We also provide evidence of the existence of “therapy scripts” that mirror diagnostic reasoning’s “illness scripts.” Our framework has implications for medical education and antimicrobial stewardship.

Disclosures

All Authors: No reported Disclosures.
1952. Bacteriophage Treatment Improves Survival of Mice Infected with Carbapenem-Resistant Klebsiella pneumoniae
Authors: Hesse Shayla , Malachowa Natalia , Porter Adeline , Freedman Brett , Kobayashi Scott , Adhya Sankar , DeLeo Frank
Published: October 2019

Background

Bacteriophage (phage) therapy is being considered as a treatment option for patients with multi-drug-resistant bacterial infections. However, there is a dearth of controlled clinical data to support therapeutic phage efficacy. As a first step toward addressing this deficiency, we tested the ability of two well-characterized phages, alone and in combination, to kill carbapenem-resistant Klebsiella pneumoniae (ST258) in blood in vitro and rescue mice from lethal ST258 infection.

Methods

Wild-type C57BL/6J mice were infected with a lethal inoculum of ST258 by intra-peritoneal (IP) injection followed 1 hour later by IP administration of lytic phage P1, P2, or P1+P2 at a multiplicity of infection (MOI) estimated at 1. Survival of each group of mice was tracked for 10 days. In separate experiments, mice were sacrificed at 1 hour, 24 hours, and 48 hours post-phage treatment. Mouse blood and tissues were collected at each timepoint for enumeration of bacteria and phage, screening for phage resistance, and histopathology.

Results

ST258 survival in mouse blood in vitro was significantly less after 1 hour of incubation with P1 or P1+P2 (MOI 1) compared with the control group (no phage). Consistent with the in vitro data, none of the mice (0/15) in the control group (no phage) survived to 10 days post-infection, whereas 12/15, 14/15, and 15/15 mice survived in the P2, P1, and P1+P2-treated groups, respectively (P < 0.0001).

Conclusion

Prompt, systemic administration of lytic bacteriophages rescued mice from lethal ST258 infection. These data support the potential of phage therapy to effectively treat infections caused by ST258. It will be important to assess whether, for other phage-bacteria combinations, in vitro lysis in blood correlates with in vivo treatment efficacy and therefore may have predictive utility.

Disclosures

All Authors: No reported Disclosures.