bluuebunny/crossref_metadata_2025_split huggingface dataset:
2845. Oral Antibiotic Use and Risk of Colorectal Cancer in the UK, 1989–2012: A Matched Case–Control Study
Authors: Zhang Jiajia , Haines Charles , Watson Alastair , Hart Andrew , Jane Platt Mary , Pardoll Drew , Cosgrove Sara E , Cosgrove Sara E , Gebo Kelly , Sears Cynthia 
Published: October 2019

Abstract

Background
Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and CRC risk is lacking.

Methods
A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders.

Results
In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (Ptrend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). In contrast, an inverse association was detected between antibiotic use and rectal cancers (Ptrend = 0.003), particularly with length of antibiotic exposure >60 days (adjusted odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, Pinteraction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]).

Conclusion
We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum.

Disclosures
Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
2855. Respiratory Syncytial Virus Neutralizing Antibodies in Cord Blood and Serum from Infants up to 2 Years of Age in a Multinational Prospective Study
Authors: Domachowske Joseph B , Bianco Veronique , Ceballos Ana , Cousin Luis , D’Andrea Ulises , Dieussaert Ilse , Englund Janet A , Gandhi Sanjay , Haars Gerco , Jose Lisa , Klein Nicola , Marie. Langley Joanne , Leach Amanda , Madhi Shabir A , Maleux Koen , Lien-Anh Nguyen Thi , Puthanakit Thanyawee , Silas Peter , Stoszek Sonia K , Tangsathapornpong Auchara , Teeratakulpisarn Jamaree , Virta Miia , Zaman Khalequ 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during infancy worldwide. High cord blood (CB) concentrations of anti-RSV neutralizing antibody (nAb) may attenuate, delay, or prevent infant infection. We report RSV A and B nAb concentrations in CB and serum from a birth cohort at different time points through 2 years of age.

Methods
Between 2013 and 2017, newborns from 8 countries were studied prospectively from birth to 2 years of age (NCT01995175). CB was collected at birth for the entire cohort. A subcohort of children was randomly assigned to have one blood sample collected again at either 2, 4, 6, 12, 18, or 24 months of age. Sera were analyzed for RSV A and B nAb concentrations by serum neutralization assay. Active surveillance was used to identify LRTIs during the 2-year follow-up as previously reported.

Results
In total, 2,401 newborns were enrolled and followed up. >99% of infants had detectable CB RSV A and B nAb. Geometric mean antibody titers (GMTs) varied by country, but were overall higher for RSV B than for RSV A (327 vs. 251; Figure 1). The lowest GMTs were seen from CB sera collected from South African newborns (197 RSV A, 255 RSV B); Canadian newborns had the highest RSV A GMT (383), while Hondurans had the highest RSV B GMT (460). 1380 infants provided follow-up serum nAb results as part of the subcohort (Figure 2). Dramatic waning of GMTs was evident, with a ~3-fold drop in GMTs at 2 months of age, and an additional ~2-fold drop between 2 and 4 months of age. At 6 and 12 months of age, 71% and 50% of infants had RSV A nAb and GMTs were at a nadir of 14. At 6, 12, and 18 months of age, RSV B nAb was detected in 98%, 69%, and 63% of infants, respectively. The RSV B nAb nadir GMT of 20 was observed at 12 months of age, while the 6- and 18-month RSV B nAb GMTs were 30 and 31, respectively. A total of 1,017 LRTIs were identified during the 2-year study period; of which, 94 (9%) were caused by RSV A and 132 (13%) by RSV B. Associations between CB nAb levels and RSV infection will be presented.

Conclusion
Neutralizing Ab to RSV A and B was present at birth in infants from 8 countries, and waned over time. GMTs were at a nadir at 6 to 12 months of age.
Funding. GlaxoSmithKline Biologicals SA.

Disclosures
All Authors: No reported Disclosures.
2886. Retrospective Case–Control Study of the Performance of the Karius Test, a Plasma Microbial Cell-free DNA Next-generation Sequencing test, to Detect Invasive Mold Infections in Hematopoietic Cell Transplant Recipients with Pneumonia
Authors: Hill Joshua A , Hong David K , Dalai Sudeb , Ho Carine , Hollemon Desiree D , Blair Lily , Stevens-Ayers Terry , Boeckh Michael , Fisher Cynthia E 
Published: October 2019

Abstract

Background
Pulmonary invasive mold infections (IMI) cause significant morbidity and mortality after hematopoietic cell transplant (HCT). Noninvasive diagnostic options are limited, particularly for non-Aspergillus (non-Asp) molds. Given differences in activity and toxicities of antifungals, early diagnosis and targeting of specific IMI is important. We evaluated the performance of the Karius Test, a plasma microbial cell-free DNA next-generation sequencing (NGS) test, for detecting IMI in HCT recipients.

Methods
We conducted a retrospective case–control study of 24 HCT recipients with proven non-Asp pulmonary IMI, 51 probable/proven Aspergillus pulmonary IMI, and 20 controls with nonfungal pulmonary infections. All subjects had plasma obtained within 14 days of diagnosis. Workup included bronchoalveolar lavage (BAL) and/or biopsy, with fungal stains/culture and galactomannan testing of BAL and serum. Plasma cell-free DNA was extracted and NGS performed (Karius, Redwood City, CA). Human reads were removed and remaining sequences aligned to a curated database including over 300 fungi. Organisms present above a predefined significance threshold were reported. A higher sensitivity research-use only pipeline was also used. Analysis of sequencing data was blinded to all clinical data.

Results
We identified pathogenic molds in 19/24 (79%) of subjects with proven non-Asp IMI, including Mucor, Rhizomucor, Scedosporium, Rhizopus, and Cunninghamella spp. In Aspergillus proven/probable IMI, A. fumigatus was identified in 13.7% (7/51) of subjects. In 3 other subjects with proven/probable aspergillosis, we also identified Rhizomucor miehei and R.pusillus, and Cunninghamella, consistent with clinical findings. The use of an optimal-sensitivity pipeline identified an additional 9 subjects with Aspergillus spp. and other pathogenic molds, increasing detection of molds to 37.3% (19/51). Specificity for molds in negative samples was 100% (20/20).

Conclusion
The Karius plasma NGS test is a noninvasive means of detecting IMI with high sensitivity for non-Aspmolds in HCT recipients with pulmonary disease. Further assay optimization may increase sensitivity for Aspergillus. This may be a useful adjunctive test for diagnosing IMI, and larger studies should be conducted.

Disclosures
All Authors: No reported Disclosures.
2890. Antibiotic Overuse at Discharge in Hospitalized Patients with Bacteriuria or Treated for Pneumonia: A Multi-Hospital Cohort Study
Authors: Vaughn Valerie M , Petty Lindsay A , Ratz David , Malani Anurag N , Mclaughlin Elizabeth , Patel Twisha S , Bernstein Steven J , Hsaiky Lama , Dumkow Lisa , Pogue Jason M , Flanders Scott A , Gandhi Tejal N 
Published: October 2019

Abstract

Background
Antibiotics prescribed at hospital discharge account for half of antibiotic use related to hospitalization for urinary tract infection or bacterial pneumonia. It is unclear how much antibiotic use at discharge represents overuse, and thus, could potentially be improved through antibiotic stewardship.

Methods
From July 2017 to December 2018, trained abstractors at 46 Michigan hospitals collected detailed data on a sample of adult, nonintensive care, hospitalized patients with bacteriuria or treated for community-acquired or healthcare-associated pneumonia (discharge diagnosis of pneumonia plus antibiotic treatment). Antibiotic prescriptions at discharge were assessed for overuse using a guideline-based hierarchical algorithm: evaluating first for unnecessary antibiotics (noninfectious/nonbacterial syndrome), then excess duration (antibiotics needed, but prescribed for longer than necessary), and finally avoidable fluoroquinolones (safer alternative antibiotic available) (Figure 1). For each disease state, descriptive results are shown with comparisons by t- or Fisher’s exact tests.

Results
Of 17,157 patients (7,283 with bacteriuria; 9,874 treated for pneumonia), 30.1% of patients with bacteriuria had asymptomatic bacteriuria and 11.4% of patients treated for pneumonia did not meet diagnostic criteria for pneumonia. The most common antibiotics prescribed at discharge were fluoroquinolones. Nearly half (43.6%) of patients had antibiotic overuse at discharge (33.8% bacteriuria, 50.9% pneumonia), with a median 4 days of overuse after discharge (Table 1). For bacteriuria, 45.0% of overuse days at discharge were due to unnecessary antibiotics; for pneumonia, 61.2% were due to excess antibiotic duration (Figure 2). Patients with community-acquired pneumonia and those with sepsis on admission had the highest rates of antibiotic overuse at discharge (Table 2).

Conclusion
In the largest assessment of antibiotics at discharge to-date, antibiotic overuse at discharge was extremely common. Specific targets for discharge stewardship vary by disease state. Notably, interventions may be more effective at reducing fluoroquinolone prescribing at discharge indirectly by stopping treatment for asymptomatic bacteriuria and reducing excess duration in pneumonia.

Disclosures
All Authors: No reported Disclosures.
2899. Decreased Hepatitis C Virus-Associated Mortality in the US 2014–2017 After New Oral Direct-Acting Antiviral Era
Authors: Wasti Zainab , Coppock Dagan , Chou Edgar , Heun Lee Dong 
Published: October 2019

Abstract

Background
Due to the ease of use and low side effect profile of new direct-acting antivirals (DAA), cure rates for hepatitis C virus (HCV) infection have increased in recent years. However, limited data exist addressing the mortality associated with HCV infection since the advent of DAAs. This study examines multiple-cause-of-death (MCOD) data from 2014 to 2017 to describe changes in HCV-associated mortality in the United States.

Methods
We examined death certificate information from public use MCOD data obtained from the National Center for Health Statistics. All-cause mortality associated with HCV, as defined by ICD-10 codes (B17.1 and B18.2), was evaluated. The age-adjusted crude mortality rate was calculated. Overall HCV-associated mortality, stratified by race and gender, was analyzed.

Results
From 2014 to 2017, the number of deaths associated with HCV, as listed in death certificates decreased from 19,613 to 17,253. This represents an average of 4% decrease in mortality each year. Crude age-adjusted mortality decreased from 5.01 (95% CI 4.93–5.08) deaths per 100,000 people in 2014 to 4.13 (95% CI 4.07–4.20) deaths per 100,000 people in 2017. Males had age-adjusted mortality of 6.82 (95% CI 6.76–6.88) and females had age-adjusted mortality of 2.59 (95% CI 2.55–2.63). African Americans had age-adjusted mortality of 7.50 (95% CI 7.37–7.63), and whites had age-adjusted mortality of 4.39 (95% CI 4.35–4.42) during the three-year period.

Conclusion
After the introduction of DAAs in 2014, mortality associated with HCV significantly decreased in the United States. There were differences in mortality rates by gender and race, which may reflect differences in HCV seroprevalence. With the availability of effective, well-tolerated HCV treatment, aggressive HCV screening and linkage to care is warranted, especially in high-risk populations.

Disclosures
All Authors: No reported Disclosures.
2902. Pertussis Antibody Levels in Preterm Infants After Maternal Tdap Immunization During Pregnancy
Authors: Healy C Mary , Rench Marcia , Swaim Laurie , Rajam Gowrisankar , Havers Fiona , Hariri Susan , Schiffer Jarad , Baker Carol J 
Published: October 2019

Abstract

Background
Maternal immunization with tetanus, diphtheria, acellular pertussis vaccine (Tdap) in the third trimester reduces infant pertussis, but data are lacking on how this strategy impacts pertussis antibody levels in large cohorts of preterm infants

Methods
We collected paired maternal delivery-cord sera from infants of women who received Tdap ≥7 days before birth. IgG to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by Luminex assay (IU/mL). Geometric mean concentrations (GMC) with 95% confidence intervals (CI) for pertussis antibodies were calculated. Four infant groups were compared by weeks of gestation: very (<32), moderate (32–33) and late preterm (34–36), and term (≥37).

Results
344 preterm and 688 term mother-infant pairs were included. Among preterm infants, mean maternal age was 31.2 years (range 15.1–39.3); 37% were white, 37% Hispanic, 17% Black, 8% Asian and 1% other. Fifty-six were very preterm infants (16%, mean gestation 30.5 weeks), 82 moderate (24%, 33.1 weeks), and 206 late (60%, 35.4 weeks); 17 (5%) were born at <30 weeks. For preterm infants, Tdap was administered at a mean gestation of 29.9 weeks (very 27.9; moderate 29.7; late 30.4; [P < .001]), and at a mean interval of 29.3 days before delivery (very 17.9; moderate 24; late 34.5 [P <.001]). Eleven (3%) women received Tdap during the second trimester (8 very, 2 moderate, 1 late). GMCs (95% CI) of pertussis-specific IgG at birth varied by gestation (table). Infant antibody levels as a proportion of maternal antibodies increased from 24 to 32% in infants < 30 weeks to 117 to 132% in those ≥37 weeks (P<.001).

Conclusion
Although levels are lower than in term infants, maternal immunization with Tdap results in substantial pertussis-specific antibodies in most preterm infants, especially late preterm infants.

Disclosures
All Authors: No reported Disclosures.
1143. Measuring Up! Benchmarking Antimicrobial Use in Canadian Children’s Hospitals
Authors: Blackburn Julie , Bowes Jennifer , Harrison Mary-Ann , Barrowman Nick , Roy Hélène , Science Michelle , Timberlake Kathryn E , Tse-Chang Alena , Roberts Ashley , Paquette Vanessa C , Kwan Natasha , Vayalumkal Joseph V , Constantinescu Cora , Dersch-Mills Deonne , Mertz Dominik , Khan Sarah , Al Matawah Yameen , Thibeault Roseline , Gosselin Louise , Lefebvre Marie-Astrid , Fanella Sergio , Walus Ashley N , Barton Michelle , Harris Venita , Comeau Jeannette L , Slayter Kathryn , Foo Cheryl , McConnell Athena , Seifert Blair , Leifso Kirk , Viel-Thériault Isabelle , Le Saux Nicole 
Published: October 2019

Abstract

Background
Inappropriate antimicrobial use (AU) is recognized as a leading cause of antimicrobial resistance. However, quantifying AU in hospitals is challenging due to variability in information systems. Point prevalence surveys (PPS) provide a means to quantify AU in a cross-sectional manner within and between institutions. The aim of the study was to describe and compare the prescription patterns of AU across pediatric hospitals in Canada using PPS.

Methods
Two PPS (November 2018 and February 2019) were conducted at each of the 15 Canadian pediatric hospitals. For each PPS, AU data were collected for all inpatients ≤ 18 years (excluded mental health and birthing units) on the survey date. Data, including admitting diagnosis, age, comorbidities, Infectious Diseases consult, admitting service, documented pathogen(s), and antimicrobial(s) prescribed, was collected and entered into a RedCap database.

Results
In total, we surveyed 3826 patient-days. The mean proportion of children receiving at least one antimicrobial was 35.2% [range 25.1% to 42.9%]. Of the 1951 antimicrobials prescribed, the most common were third-generation cephalosporins [3GC] (16%; 321), aminopenicillins (15%; 297), TMP-SMX (11%; 207), piperacillin–tazobactam (10%; 193) and first-generation cephalosporins (9%; 181). Overall, the frequency of carbapenems, quinolones and vancomycin use was 4% (79), 3% (65) and 8% (151), respectively. Of the antimicrobials used for targeted or empiric therapy (n = 1541), 373 (24.2%) were for pneumonia, 278 (18%) for intra-abdominal infections and 251 (16.3%) for fever without a source. For the treatment of community-acquired pneumonia (CAP) (n = 178), aminopenicillins and 3GC use was 31% and 37%, respectively.

Conclusion
Our study used a standardized approach to assess AU to obtain benchmarking data for Canadian pediatric hospitals. About one-third of children hospitalized in Canadian pediatric hospitals are prescribed at least one antimicrobial. Of patients on treatment for CAP, only 31% were prescribed aminopenicillins. More detailed analysis of the rationale for AU, and assessment of appropriateness is required to fully understand antimicrobial prescribing practices in pediatric hospitals and develop stewardship initiatives.

Disclosures
All authors: No reported disclosures.
1162. An Evaluation of Metrics for Catheter-Associated Urinary Tract Infections (CAUTIs): A Statewide Comparison
Authors: Pepe Dana , Maloney Meghan , Leung Vivian , Harizaj Adora , Banach David , Dembry Louise , Dembry Louise , Advani Sonali D 
Published: October 2019

Abstract

Background
The Standardized Infection Ratio (SIR) is a metric used to gauge catheter-associated urinary tract infection (CAUTI) prevention, both locally and nationally. The device utilization ratio (DUR) is a process metric that captures catheter harm. More recently, the cumulative attributable difference (CAD) was introduced, which identifies the number of excess infections that need to be prevented to reach the desired goal. Our objective was to evaluate these metrics across all acute care hospitals in Connecticut (CT) by facility size.

Methods
A CAUTI Targeted Assessment for Prevention (TAP) Report for acute care hospitals across CT was generated from 1/1/2018 to December 31/2018, using the National Healthcare Safety Network (NHSN) database. CAUTI events, SIR, DUR, and CAD were compared across all hospitals. The SIR goal of 0.75 was used to calculate the CAD. Hospitals were stratified into large ( >425 beds), medium (250 to 424 beds), and small ( <249 beds) based on the Healthcare Cost and Utilization Project NIS Description of Data Elements, Agency for Healthcare Research and Quality for urban hospitals in the northeast region.

Results
A comparison of CAUTI metrics for 29 acute care hospitals across CT is shown in Table 1. Median SIR and DUR were 0.97, 1.02, 0.77, and 22%, 14%, 14.5% for large, medium and small hospitals, respectively. Of the 20 small hospitals, SIR could not be calculated for 5 hospitals, while 2 hospitals had an SIR = 0, as they had no reported infections. Median CAD for large, medium and small hospitals was 6.17, 1.3 and 0.25, respectively. Of note, 40% of small hospitals (J – CC, as in Table 1) had a negative CAD. Interestingly, 5 of these 8 hospitals with a negative CAD had a DUR higher than 16%.

Conclusion
Based on CT hospital data, metrics like CAD and SIR may be more suitable for larger hospitals or hospitals with higher CAUTI events, whereas DUR may be a more useful metric for smaller hospitals or hospitals with rare events. Hospitals with high SIR and low DUR may represent a population with high-risk catheter use, poor catheter care or higher rates of urine culturing. On the other hand, hospitals with high DUR and low SIR may represent low-risk populations, better catheter care practices or lower rates of urine culturing. Ultimately, we need a combination of metrics to measure preventable catheter harm.

Disclosures
Louise Dembry, MD, MS, MBA, ReadyDock: Consultant, Stock options.
1165. Risk Factors for Bloodstream Infections During Extracorporeal Membrane Oxygenation (ECMO)
Authors: In Hong Sun , You Shinae , Ryu Byung-Han , Hong Kyung-Wook , Cho Oh-Hyun , Bae In-Gyu 
Published: October 2019

Abstract

Background
Although bloodstream infections (BSIs) are important complications of ECMO, data on clinical characteristics of ECMO-associated BSIs remain limited. This study aimed to investigate clinical characteristics of ECMO-associated BSIs and evaluate the role of routine active surveillance cultures (ASCs) in predicting subsequent BSIs.

Methods
We reviewed the medical records of adult patients who received ECMO for >48 hours in 2 teaching hospitals between January 2013 and March 2019. ECMO-associated BSIs were defined as bacteremia occurring from 48 hours after ECMO initiation. ASCs for multidrug-resistant organisms were obtained from nasal, axillary, inguinal, and rectal swabs when patients were admitted to the ICUs.

Results
Overall, 28 of 110 (25.4%) patients had BSIs within the median 7 days after ECMO initiation. Table 1 shows the clinical characteristics of patients with ECMO-associated BSIs. Among BSI cases, the most common pathogens were Candida spp. (25%). Longer ECMO days (P < 0.01), steroid use (P = 0.02), and more blood transfusions (P < 0.01) were associated with BSIs. However, there was no association between the results of ASCs and subsequent pathogens of BSIs.

Conclusion
BSIs during ECMO were associated with longer ECMO duration, steroid use and blood transfusion. The pathogens of BSIs could not be related to ASCs.

Disclosures
All authors: No reported disclosures.