bluuebunny/crossref_metadata_2025_split huggingface dataset:
1769. Viral Suppression Among Participants of the Patient-Centered HIV Care Model Project—A Collaboration Between Community-Based Pharmacists and HIV Clinical Providers
Authors: Byrd Kathy , Hou John , Clay Patrick , Bush Tim , Delpino Ambrose , Shankle Michael , Camp Nasima , Kirkham Heather , Hazen Ronald , Weidle Paul 
Published: November 2018

Abstract

Background
The patient-centered HIV care model was developed to integrate community pharmacists with HIV clinical providers to deliver patient-centered HIV care. The project required 10 clinics to share, with their partnered community-based pharmacists, patients’ medical histories, laboratory results, and medications. Pharmacists reviewed the clinic data and worked directly with participants and/or their partnered clinics to make recommendations and discuss potential intervention strategies for identified therapy-related problems.

Methods
We calculated the proportion of persons virally suppressed (&lt;200 copies/mL at the last test in each of two 12-month measurement periods), pre- and post-model implementation. Included in the analysis were persons with ≥1 HIV viral load in each measurement period. McNemar’s test was used to compare the proportion virally suppressed, pre- and postimplementation. Multivariable logistic regression was used to determine factors associated with viral suppression, postimplementation. Participant demographics and the proportion of days covered (PDC; a measure used to calculate adherence to medication therapy) were used as explanatory variables in the model. The PDC was modified to account for the time to the last viral load in the measurement period, and was stratified into 4 categories: ≥90%, &lt;90–80%, &lt;80–50%, and &lt;50%.

Results
With 765 persons enrolled, the plurality of those included in the analysis (n = 648) were non-Hispanic black (n = 286), male (n = 470), and had a median age of 49 years (IQR=38–56). Viral suppression improved 16.3% from 73.9% to 85.9%, pre- to postimplementation (P &lt; 0.001). Persons who had higher modified PDC (OR 1.9 per category level; 95% CI 1.4–2.6), were currently employed (OR 4.1; 1.6–12.8), or age &gt;50 years (OR 4.7; 2.1–11.8), had greater odds of being suppressed. Non-Hispanic black persons were less likely to be suppressed (OR 0.2; 0.1–0.6); however, viral suppression among this group improved from 62.5% to 77.6%, pre- to postimplementation (P &lt; 0.001).

Conclusion
Collaborations between community pharmacists and HIV clinic providers that seek to identify and address HIV therapy-related problems can lead to improved viral suppression among persons living with HIV.

Disclosures
P. Clay, Jaguar Health, Inc.: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Merck & Co., Inc.: Investigator, Research grant. A. Delpino, Walgreens: Employee and Shareholder, Salary.
1771. Gut Resistome Changes in Response to Prophylactic Antibiotic Administration During Chemotherapy in Children With Acute Lymphoblastic Leukemia
Authors: Margolis Ellie , Hakim Hana , Yao Jiangwei , Rosch Jason , Tang Li , Sun Yilun , Dallas Ronald , Wolf Joshua 
Published: November 2018

Abstract

Background
Antibiotic resistance harbored in gut microbiome contributes to the emergence of multi–drug-resistant organisms (MDRO). Pediatric leukemia patients typically receive extensive antibiotics and are at higher risk for infection due to MDRO.

Methods
A prospective cohort of children (n = 242) with acute lymphoblastic leukemia self-collected stool samples at diagnosis and after induction chemothearpy. A third of patients (n = 69) underwent protocol-driven antibiotic prophylaxis: Levofloxacin (LV) given once neutropenia develops. With neutropenic fever patients on prophylaxis stopped LV and all patients received cefepime. Using metagenomic sequencing, we identified bacterial community composition and after alignment to the Comprehensive Antibiotic Resistance Database were able to determine the presence of bacterial resistance genes in 168 stool samples from 49 patients.

Results
Expected changes in the community composition were discovered with LV prophylaxis, including the loss of many Enterobacteriaceae and Enterococcaceae species, offset by increases in Bacteroides species. Unexpectedly, LV prophylaxis reduced the acquisition of VanA cluster of vancomycin resistance genes and did not increase acquisition of β-lactamase or fluoroquinolone (FQ) resistance gene families.

Conclusion
LV prophylaxis during leukemia treatment imparts predictable changes in gut bacterial communities but counter intuitively decreases antibiotic resistance in the gut microbiome reservoir. The reduction in VanA cluster of genes is likely due to depletion of Enterococcaceae species via direct killing or loss of synergistic partners. The lack of increase in target (FQ) or off-target resistance suggests that prophylaxis altered community selective pressures or prophylaxis drug concentrations were sufficient to limit the outgrowth of resistant mutants.

Disclosures
J. Wolf, Karius Inc.: Investigator, Research support.
1775. Microbiome-Based Classifiers Accurately Differentiate Infectious Diarrhea From Functional Gastrointestinal Disorders and Provide Population-Scale Confidence Measures of Fecal Microbiota Restoration in Recurrent C. DifficileInfection
Authors: Wu Qinglong , Ross Cana , Jones Courtney , Blount Ken , Savidge Tor 
Published: November 2018

Abstract

Background
Fecal microbiota therapy is being actively pursued as treatment for recurrent C. difficile infection (rCDI), as well as for other GI disease indications associated with dysbiosis, for example, irritable bowel syndrome (IBS). RBX2660 is a microbiota-based drug designed to restore a healthier microbiome and has demonstrated clinical efficacy for preventing rCDI. Despite this and other treatment successes, our understanding of functional microbiota reconstitution at the population scale is still evolving, as is the ability to distinguish IBS from CDI recurrence. Herein we describe development of a Random Forest classifier for CDI diagnosis, and we evaluate microbiome restoration in participants of the Phase 2 trial of RBX2660.

Methods
Fecal 16S rDNA sequences from 2,129 subjects enrolled in diverse multi-center cohorts were analyzed (1,235 adults and 447 children with CDI, AAD, IBS, or controls). Technical variations due to different DNA extraction, primer region coverage, and sequencing platforms were addressed using closed-reference OTU picking with UCLUST. The RDP classifier and SILVA database assigned taxonomy for each OTU sequence. Stratified random sampling with 50 repeated tests of microbiota training sets was performed for supervised learning. Microbiota signatures of patients in the RBX2660 PUNCH CD2 trial were then assessed using classifiers built to predict CDI treatment outcomes and IBS misdiagnosis.

Results
Random Forest built the best classifiers accurately predicting 97.7% of CDI cases, and confidently distinguished CDI from IBS patients based on their microbiome signatures (figure). RBX2660 treatment significantly restored microbiota community composition in rCDI cases compared with placebo controls.

Conclusion
Random Forest classifiers built on a population-scale study of microbiota composition in patients with GI disease provide a highly accurate predictor of CDI cases versus potential IBS misdiagnosis in adults and children. RBX2660 significantly reduced disease classification scores in rCDI patients with a healthy-like microbiota reconstitution markedly accelerating after 30 days of treatment.
This study was funded by 1UO1 AI24290-01 and Rebiotix, Inc.

Disclosures
C. Jones, Rebiotix, Inc.: Employee, Salary. K. Blount, Rebiotix, Inc.: Employee, Salary. T. Savidge, Rebiotix: Grant Investigator, Research grant.
2553. Individual Patient-Level Data Meta-Analysis of Live Attenuated and Inactivated Influenza Vaccine Effectiveness Among US Children, 2013–2014 Through 2015–2016
Authors: Chung Jessie , Flannery Brendan , Begue Rodolfo , Caspard Herve , Demarcus Laurie , Fowlkes Ashley , Kersellius Geeta , Steffens Andrea , Fry Alicia M 
Published: November 2018

Abstract

Background
Quadrivalent live attenuated influenza vaccine (LAIV4) was not recommended for use in the United States for the 2016–2017 and 2017–2018 influenza seasons based on US observational studies of vaccine effectiveness (VE) from 2013–2014 to 2015–2016. We pooled individual patient data on children aged 2–17 years enrolled in 5 US studies during these 3 influenza seasons to further investigate VE by vaccine type.

Methods
Analyses included 17,173 children enrolled in the US Department of Defense Global Laboratory-based Influenza Surveillance Program, US Influenza Vaccine Effectiveness Network, Influenza Incidence Surveillance Project, Influenza Clinical Investigation for Children, and a Louisiana State University study. Participants’ specimens were tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR), culture, or a combination of rapid antigen testing and RT-PCR. VE was calculated by comparing odds of vaccination with either inactivated influenza vaccine (IIV) or LAIV4 among influenza-positive cases to test-negative controls and calculated as 100 × (1 − odds ratio) in logistic regression models with age, calendar time, influenza season, and study site (random effect). Patients were stratified by prior season vaccination status in a subanalysis.

Results
Overall, 38% of patients (N = 6,558) were vaccinated in the current season, of whom 30% (N = 1,979) received LAIV4. Pooled VE of IIV against any influenza virus was 51% (95% CI: 47, 54) versus 26% (95% CI: 15, 36) for LAIV4. Point estimates for pooled VE against any influenza by age group ranged from 45% to 58% for IIV and 19% to 34% for LAIV4 during the 3 seasons (Figures 1 and 2). Pooled VE against influenza A(H1N1)pdm09 was 67% (95% CI: 62, 72) for IIV versus 20% (95% CI: −6, 39) for LAIV4. Pooled VE against influenza A(H3N2) was 29% (95% CI: 14, 42) for IIV versus 7% (95% CI: −11, 23) for LAIV4, and VE against influenza B was 52% (95% CI: 42, 60) for IIV and 66% (95% CI: 47, 77) for LAIV4. VE against influenza A(H1N1)pdm09 was lower for LAIV4 versus IIV across all strata of prior season vaccination (Figure 3).

Conclusion
Consistent with individual studies, our pooled analyses found that LAIV4 effectiveness was reduced for all age groups against influenza A(H1N1)pdm09 compared with IIV. This result did not vary based on prior vaccination status.

Disclosures
H. Caspard, AstraZeneca: Employee, Salary.
2555. Predicting Risk of Breakthrough Invasive Pneumococcal Disease in Children After 13-Valent Pneumococcal Conjugate Vaccination
Authors: Yildirim Melike , Pelton Stephen I , Keskinocak Pinar , Yildirim Inci 
Published: November 2018

Abstract

Background
Thirteen-valent-pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the childhood immunization schedule in Massachusetts beginning in April 2010. We evaluated the predictors of vaccine-type (VT) invasive pneumococcal infection (IPD) occurrence despite vaccination.

Methods
Cases of IPD in children &lt;18 years of age were detected through an enhanced surveillance system in MA since 2001. All cases and Streptococcus pneumoniae (SP) isolates are submitted to Department of Public Health (MDPH) and parents/physicians are interviewed for confirmation of demographic and clinical data. All available isolates are serotyped by Quellung reaction. Children who received any dose of PCV7 were excluded from this study. We used 4-layer, feed-forward, neural network with backpropagation learning algorithm, random forest algorithm with 150 classification trees, and extreme gradient boosting (XGBoost) algorithm based on boosted trees with over than 200 iterations to make prediction about risk of nonvaccine serotype (NVST) causing IPD.

Results
Overall, 144 IPD cases have been identified between April 1, 2010, and March 31, 2017, and 27 (19%) were VT IPD. Compared with children with complete PCV13 vaccination, IPD among those with incomplete immunization was more likely to be due to VT (9%, 95% CI 4–18% vs. 19%, 95% CI 10–31%, respectively). Despite complete immunization, 80 of 144 (55.6%) of all IPD in &gt;60 months was breakthrough IPD (Figure 1). Among children with ≥1 comorbid condition and incomplete PCV13, 4 of 18 (22%) IPD were due to VT. Children with incomplete vaccination and pneumonia were most likely (11/17, 65%) to have VT; however, bacteremia without focus cases with incomplete vaccination were most likely (44/45, 3%) to have NVST (Figure 2). Our algorithm performs with 85% accuracy and 92% precision scores.

Conclusion
IPD due to VT after PCV13 vaccination mostly occurs in older children with incomplete PCV13 immunization, among those with underlying comorbidity, and among those who present with pneumococcal pneumonia. Evaluating the immune response following PCV13 vaccination in children with comorbidity could increase our understanding of breakthrough pneumococcal infections despite vaccination with PCV13.

Disclosures
All authors: No reported disclosures.
2558. Predicting β-Lactam Resistance Using Whole Genome Sequencing (WGS) in Klebsiella pneumoniae: The Challenge of β-Lactam Inhibitors
Authors: Hujer Andrea , Long Wesley , Olsen Randall , Kreiswirth Barry N , Evans Scott R , Musser James , Bonomo Robert 
Published: November 2018

Abstract

Background
Antimicrobial susceptibility testing (AST) is the major driver in designing effective therapy. As multiple resistance determinants can demonstrate the same phenotype (e.g., inhibitor resistant [IR], extended spectrum [ES], and carbapenem hydrolyzing [CH] β-lactamases), critical information provided from AST for therapy, stewardship, and infection control is currently lacking. WGS provides more comprehensive genetic data, explaining phenotype, and provides insight into clonality. Efforts are in development that apply novel statistical methods (e.g., PRIMERS I-IV) and machine learning (Sci Reports, 2108, 8, 421) to interpret results accurately and anticipate AST. Using a collection of clinical strains that spanned a 3.5-year period, we tested how well the detection of problematic IR, ES, and CH bla resistance genes predicted phenotype.

Methods
Fourty-one isolates were chosen for AST from a collection of 1,777 WGS K. pneumoniae. Isolates chosen possessed the following β-lactamases: (9 isolates) NDM; (3) NDM and OXA-48; (5) KPC-8 or KPC-14; (24) with a very complex β-lactamase background (all possessed an inhibitor resistant TEM (IRT), SHV ESBL, +/− CTX-M, and/or +/− KPC). AST was performed using CLSI methods for piperacillin/tazobactam (PIP/TAZO), ceftazidime (CAZ), aztreonam (ATM), ceftazidime/avibactam (CAZ/AVI), CAZ/AVI/ATM, and ceftolozane/tazobactam (TOL/TAZO) by disk diffusion assay.

Results
Presented below.

Conclusion
In all cases, blaNDM-1 and blaNDM-1/OXA-48 containing isolates were resistant to CAZ/AVI; the addition of ATM fully restored susceptibility to CAZ/AVI. Surprisingly, clinical K. pneumoniae isolates bearing KPC-8 (V240G) and KPC-14 did not test fully resistant to CAZ/AVI, suggesting a more complex mechanism than the D179Y variant of KPC-3. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Interestingly, TOL/TAZO maintained efficacy in these same complex backgrounds in the absence of NDM, KPC, and SHV-12. As previously shown in PRIMERS I-II, PIP/TAZO resistance was not observed in the majority of isolates as was predicted by the genotype. WGS in K. pneumoniae to predict AST results and potentially guide clinical decisions is improved for novel combinations like CAZ/AVI.

Disclosures
All authors: No reported disclosures.
2561. Using Whole Genome Sequencing to Assess the Emergence of Antibiotic Resistance During Treatment of Enterococcus faecium and Enterococcus faecalis Bacteremia at Mount Sinai Hospital
Authors: Chacko Kieran , Beckford Colleen , Molina Carlotta Calvi , Van Bakel Harm 
Published: November 2018

Abstract

Background
Multidrug-resistant Enterococci are a major cause of nosocomial infections, yet our understanding of how resistance emerges during antibiotic treatment remains incomplete. We performed whole- and complete-genome sequencing of all paired isolates from 11 Enterococcus faecium and 10 Enterococcus faecalis cases that acquired resistance during hospitalization at Mount Sinai Hospital. Comparative and phylogenetic genomic analyses identified novel mechanisms of resistance and heteroresistance.

Methods
2.5 years of electronic health records were analyzed to identify cases of bacteremia that acquired resistance to at least 1 of the 8 antibiotics. Core genome phylogenetic analyses of paired susceptible and resistant isolates was performed to confirm persistent single clone infections. Long read sequencing data, with Illumina error correction, were used to assemble and align complete genomes. Population analysis profile (PAP) assays were performed to assess the prevalence of heteroresistance.

Results
Among the 102 persistent enterococcal bacteremia cases, 57 isolates from 21 cases (20.6%) cases experienced a gain in resistance. Phylogenetic analyses confirmed that 80% of cases had single clone blood infections, with maximum of 138 days separating paired isolates. Known genetic determinants were responsible for emerging linezolid (LIN), vancomycin (VAN), and gentamicin synergy resistance in almost all cases. In 2 instances, emerging daptomycin (DAP) resistance was not accounted for by known resistance determinants. Notably, PAP assays revealed that LIN-, VAN-, and DAP-resistant subclones were present in only a subset of bacteria in clinical isolates. Longitudinal pairwise analyses of complete genomes revealed novel candidate SNPs for DAP resistance, both located in genes involving cell wall metabolism and maintenance, as well as multiplasmid recombination events that led to VAN heteroresistance.

Conclusion
Our study demonstrates the high prevalence of emerging antibiotic resistance during treatment. We find previously unreported single and structural genomic events that contribute rapid adaptation to antibiotic treatment.

Disclosures
All authors: No reported disclosures.
2570. HCV Screening Practices Among Adolescents and Young Adults in a National Sample of Federally Qualified Health Centers in the United States
Authors: Epstein Rachel L , Wang Jianing , Mayer Kenneth , Puro Jon , Horsburgh C Robert , Linas Benjamin P , Assoumou Sabrina A 
Published: November 2018

Abstract

Background
The opioid crisis has been associated with an increase in hepatitis C virus (HCV) infections among 15–30 year olds. Federally Qualified Health Centers (FQHCs) provide comprehensive healthcare to diverse and underserved communities. However, little is known about HCV screening practices among adolescents and young adults seen at FQHCs across the United States.
Objective. To characterize the continuum of HCV testing and care among adolescents and emerging adults in a large national sample of US FQHCs.

Methods
We used the OCHIN electronic medical record to create a retrospective cohort of 13 to 21 year olds who had a least 1 outpatient visit at any of 98 participating US FQHCs across 19 states from 2012 to 2017. Primary outcome was HCV testing during this timeframe. We also identified predictors of HCV screening using multivariable logistic regression adjusting for age, sex, race/ethnicity, and substance use.

Results
Among 269,287 youth who met inclusion criteria, 54.7% were female, 37.6% White, 33.5% Hispanic, 17.6% Black, and 11.3% other. Mean [SD] age at first HCV screening was 18.5 [2.2] years. Over the study period, 2.5% (6849/269,287) were tested for HCV and 153 (2.2%) had reactive HCV testing. Of those, 117 (76.5%) had confirmatory RNA testing and 65 (55.6%) had detectable RNA. Thirty-five percent (325/933) with ICD-9 codes for opioid-use disorder (OUD) and 8.9% (2080/23,345) with any ICD-9 code for drug use were tested for HCV. Only 10.6% (728/6,849) of individuals tested for HCV had also been tested for human immunodeficiency virus (HIV). Older age (19–21 vs. 13–15 years old at study end, aOR 5.64, 95% CI 5.13–6.19), Black race (aOR 1.88, 95% CI 1.76–2.00), and ICD-9 codes for substance-use disorder, in particular amphetamine (aOR 5.82, 5.10–6.64), opioids (aOR 3.50, 2.92–4.19), cocaine (aOR 2.90, 2.43–3.47), or cannabis (aOR 2.46, 2.31–2.62) were independently associated with HCV testing in multivariable analysis.

Conclusion
During the current opioid crisis, only a third of adolescents/young adults diagnosed with OUD in a large national sample of FQHCs were tested for HCV. In addition, only 10% of those tested for HCV were also screened for HIV. Initiatives are needed to increase HCV and HIV screening among at-risk youth at FQHCs.

Disclosures
All authors: No reported disclosures.
1169. Surveillance of Antibiotic-Resistant Bacteria Reported Among Healthcare-Associated Infections, California, 2011–2017
Authors: Rizzo Kyle , Horwich-Scholefield Sam , Epson Erin 
Published: November 2018

Abstract

Background
Antibiotic-resistant healthcare-associated infections (HAI) threaten patient safety and public health. HAI reported by California hospitals to the National Healthcare Safety Network include pathogen and antibiotic susceptibility information. We analyzed HAI data to measure regional changes in antibiotic resistance (AR) over time among select bacteria.

Methods
We analyzed central line-associated bloodstream infection (CLABSI) data using log binomial regression models to estimate annual change in the proportion of pathogens resistant to carbapenems, extended-spectrum cephalosporins, methicillin/oxacillin, and multidrug (MDR) combinations for the reporting years 2011–2017. We aggregated HAI CLABSI, catheter-associated urinary tract infection (CAUTI), and surgical site infection (SSI) data in 2-year increments (i.e., 2014–2015, 2016–2017) to assess changes in percent resistance by county when data for 30 or more pathogens were available.

Results
Among CLABSI reported from 2011 to 2017, there were no significant changes in the proportion of carbapenem-resistant Enterobacteriaceae (CRE) (Figure 1; risk ratio [RR]: 0.97, 95% CI: 0.92, 1.03; P = 0.32), methicillin/oxacillin-resistant S. aureus (MRSA) isolates (RR: 0.98, 95% CI: 0.96, 1.00; P = 0.06) or Pseudomonas aeruginosa with an MDR phenotype (RR: 1.02, 95% CI: 0.95, 1.10; P = 0.54). The proportion of E. coli with MDR and extended-spectrum β-lactamase (ESBL) phenotypes increased by 7% (RR: 1.07, 95% CI: 1.02, 1.12; P &lt; 0.01) and 4% (RR: 1.04, 95% CI: 1.01, 1.08; P = 0.02) per year, respectively. Percentages of AR among aggregated CAUTI, CLABSI and SSI pathogens varied by county and time period (Figures 2 and 3).

Conclusion
Increases in antibiotic resistant phenotypes among E. coli, and unchanged prevalence of MDR Pseudomonas aeruginosa, CRE, and MRSA among reported HAI underscore the need for continued infection prevention and antibiotic stewardship efforts in California. Local public health departments can use these analyses to target coordinated AR prevention initiatives with healthcare facilities in their regions.

Disclosures
All authors: No reported disclosures.