bluuebunny/crossref_metadata_2025_split huggingface dataset:
2618. Determination of the Chemical Structure of a Novel Pneumococcal Serotype, 39X
Authors: Ganaie Feroze , Saad Jamil , McGee Lesley , van Tonder Andries , Bentley Stephen , Gladstone Rebecca , Turner Paul , Keenan Jeremy , Breiman Robert , Nahm Moon H 
Published: October 2019

Abstract

Background
Streptococcus pneumoniae produces a diverse group of capsular polysaccharides (serotypes) that are important for the virulence of the organism and for the serotype-specific prevention of pneumococcal disease. As a consequence of widespread PCV usage and pneumococcal genome plasticity, the distribution of pneumococcal serotypes is changing with an increase in non-vaccine serotypes post-vaccine introduction, a phenomenon known as serotype replacement. Recently, a potentially novel serotype was described and was provisionally named as serotype 39X. Genetic studies suggest that this novel serotype may be a hybrid of serotypes 6C and 39/10A.

Methods
Three 39X strains with the distinct serological and genetic description of the cps biosynthetic loci were obtained from the Global Pneumococcal Sequencing project (www.pneumogen.net). Capsular polysaccharide from one (Camb.853/MNZ2334) of the 39X strains was purified by sequential ethanol precipitation followed by ion-exchange chromatography. To detect polysaccharide fractions during purification, an inhibition ELISA assay was developed using factor serum 10d. The chemical structure of the 39X repeating unit was determined using one-dimensional (1D) and 2D nuclear magnetic resonance (NMR).

Results
All three isolates were confirmed to have the 39X genotype by PCR amplification and sequencing of the 39X specific region (wciN6c-wcrO-wcrC39) of the cps locus. (Figure 1). The 39X capsule PS fractions were detected during purification and pooled for structural studies (Figure 2). 1D-NMR for 39X showed it to be chemically distinct (Figure 3). 2D-NMR studies revealed that five of the sugar residues in 39X PS are identical to those in 39 PS, except the acetylation (Figure 4). The remaining part of the structure is being investigated.

Conclusion
The 39X capsular PS has a distinct chemical structure in addition to its distinct serologic and genetic properties. Given that serotype 39X is a new serotype, it becomes the 100th pneumococcal serotype. The chemical structure supports the genetic depiction of serotype evolution as a result of recombination between well-characterized and unrelated serotypes. Structural elucidation of the 39X capsule PS will help facilitate our understanding of serotype replacement and vaccine development.

Disclosures
All authors: No reported disclosures.
2627. Dynamics of Respiratory Viral Co-infections: Predisposition for and Clinical Impact of Viral Pairings in Children and Adults
Authors: Mandelia Yamini , Procop Gary W , Richter Sandra S , Worley Sarah , Liu Wei , Esper Frank 
Published: October 2019

Abstract

Background
The clinical relevance of respiratory viral co-infections is unclear. Few studies determine epidemiology and impact of specific co-infection pairings. Here we assess the dynamics of respiratory viral co-infections, determine any predisposition for specific pairings to occur and evaluate resulting clinical impact on hospitalization.

Methods
We reviewed respiratory viral panel results collected at The Cleveland Clinic between November 2013 to Jun 2018. Monthly prevalences, mono-infections and co-infections of 13 viral pathogens were tabulated. Employing a mathematical model which utilized each individual virus’ co-infection rate and prevalence patterns of concurrent circulating respiratory viruses, we calculated an expected number of occurrences for 132 viral pairing permutations. Expected vs observed co-infection occurrences were compared using binomial tests. For viral pairings occurring at significantly higher prevalence than expected, logistic regression models were used to compare hospitalization between patients with co-infection to ones with mono-infection.

Results
Of 30,535 respiratory samples, 9,843 (32.2%) samples were positive for at least 1 virus and 1,018 (10.82%) were co-infected. Co-infections occurred in 18% of pediatric samples and only 3% of adult samples (P < 0.001). Adenovirus C (ADVC had the highest co-infection rate (68.3%) while influenza B had the lowest (10.07%). Using our model, ADVC – rhinovirus (HRV), RSVA - HRV, and RSVB - HRV pairings occurred at significantly higher prevalence than expected (P < 0.05). In children, HRV-RSVB co-infection were significantly less likely to be hospitalized than patients with HRV mono-infections (ORmono/co = 2.3; 95% CI 1.1 to 4.7; P = 0.028). Additionally, HRV - ADVC co-infected children were less likely to be hospitalized than either HRV (ORmono/co = 3.3; 95% CI 1.6 to 6.8; P < 0.001) or ADVC (ORmono/co = 1.9; 95% CI 1.1 to 3.2; P = 0.024) mono-infected children. Regardless of the infecting virus, children were less likely to be hospitalized than similarly-infected adults.

Conclusion
Respiratory viral co-infections are largely a pediatric phenomenon. Select viral pairings occur more often than predicted by our model, many of which are associated with altered severity of resultant disease.

Disclosures
All authors: No reported disclosures.
2630. Treatment of RSV Lower Respiratory Tract Infection in Two Immunocompromised Children with Polyclonal Immunoglobulin Containing Standardized Levels of Neutralizing Anti-RSV Antibody
Authors: Levy Emily Ruth , Madigan Theresa , Binnicker Matthew , mond jimmy , Huskins W Charles 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRTI) in immunocompromised children. There is no standard effective treatment, though ribavirin (inhaled or oral), pooled human intravenous immunoglobulin (IVIG), and monoclonal anti-RSV antibody (palivizumab) have been described. RI-002 (ADMA Biologics Inc.) is a pooled human polyclonal IVIG that contains standardized levels of neutralizing anti-RSV antibodies. It was recently FDA-approved for prophylaxis in primary immunodeficiency patients and has been used as compassionate treatment for RSV LRTI in stem cell transplant patients.

Methods
Two children with T-cell lymphoblastic lymphoma, both undergoing delayed intensification chemotherapy, were diagnosed with RSV LRTI. They were both treated with RI-002 under an emergency FDA Investigational New Drug protocol.

Results
Patient 1, a 4-year-old boy, was admitted with fever, neutropenia and nasal congestion, and diagnosed with RSV infection on hospital day (HD) 5. On HD17, he was intubated for respiratory failure. IVIG, palivizumab, and daily oral ribavirin were administered. On HD18, he required high frequency oscillator ventilation, nitric oxide, and paralysis. He was given RI-002 (1.5 g/kg on HD20 and 0.75 g/kg on HD22). He was placed on veno-venous extracorporeal membrane oxygenation (ECMO) on HD23. RSV PCR crossing point (Cp) values trended higher, but remained positive (table). On HD33, RI-002 was re-dosed (0.75 g/kg). Pulmonary compliance and chest CTs improved (figure). On HD52, ECMO support was discontinued. He was discharged on HD88, and currently requires no respiratory support. Patient 2, a 5-year-old boy, was admitted with fever, neutropenia, nasal congestion, cough, and stridor and diagnosed with RSV infection (HD1). He required nasal cannula oxygen. IVIG and daily oral ribavirin were administered. He was given RI-002 (1.5 g/kg on HD3 and 0.75 g/kg on HD5). By HD5, he was afebrile; oxygen was discontinued. He was discharged HD6.

Conclusion
Human polyclonal IVIG containing standardized levels of neutralizing anti-RSV antibodies may be useful in the treatment of RSV LRTI in immunocompromised children. Future studies on the role of RI-002 in treatment of RSV infection in immunocompromised children are warranted.

Disclosures
All authors: No reported disclosures.
2633. Influenza and Tdap Vaccination Coverage among Pregnant Women in the PREVAIL Cohort
Authors: Schlaudecker Elizabeth P , Conrey Shannon , Gelvin Brady J , Cline Allison R , DeFranco Emily A , Campbell Angela P , Piasecki Alexandra , Beacham Lauren , Bardenheier Barbara , Payne Daniel C , Morrow Ardythe L , Staat Mary A 
Published: October 2019

Abstract

Background
The ACIP recommends influenza and Tdap vaccination during pregnancy to reduce the risk of influenza and pertussis in the mother and her infant. We assessed influenza and Tdap vaccination coverage and associated factors among pregnant women enrolled in PREVAIL, a prospective birth cohort study in Cincinnati, OH. We assessed sensitivity and specificity of self report for both vaccines against state registry, maternal healthcare provider, and work-place records.

Methods
We enrolled and interviewed 265 pregnant women regarding self-reported receipt of influenza and Tdap vaccines, and obtained vaccine records from registry, electronic medical record, provider, employer, or pharmacy. We grouped subjects by documented vaccination status and analyzed demographic variables and vaccine attitudes regarding efficacy, safety, and hesitancy using unadjusted Fisher exact tests. We analyzed sensitivity and specificity of maternal recall.

Results
We identified documentation of influenza and Tdap vaccine receipt during pregnancy in 172/265 (64.9%) and 238/265 (89.8%) of women, respectively (Figure 1); by self report, 177/265 (66.8%) reported receiving influenza and 221/265 (83.4%) Tdap vaccine. The two most common primary reasons cited for receiving influenza vaccine were “to protect my baby” (36.7%) and “to protect myself” (26%; Figure 2). Pregnant women were more likely to get Tdap vaccine if a healthcare worker recommended it (OR 5.4). Subjects were more likely to get influenza vaccine if they believed it was effective in preventing influenza in themselves (OR 9.0) or their babies (OR 8.1). While positive recall had a high concordance (95.2% and 93.4% for influenza and Tdap, respectively), 12.5% and 32.1% of mothers incorrectly recalled not receiving an influenza or Tdap vaccine, respectively, that was documented as received in the records (Figure 3).

Conclusion
We found high concordance between maternal recall and verification for both influenza and Tdap vaccines. In this single-site cohort of 265 women, self report was a reliable measure of vaccination status among pregnant women. Provider communication to pregnant women regarding effectiveness of influenza and Tdap vaccinations for themselves and their infants may lead to higher maternal vaccination rates.

Disclosures
All authors: No reported disclosures.
2638. Respiratory Syncitial Virus Hospitalizations (RSVH) and All-Cause Bronchiolitis Hospitalizations (BH) Among 29–34 Weeks Gestational Age (wGA) Preterm Infants Before and After the 2014 American Academy of Pediatrics (AAP) Immunoprophylaxis Policy Change Using the Children’s Hospital Association’s Pediatric Health Information System (PHIS)
Authors: Fergie Jaime , Gonzales Tara , Jiang Xiaohui , Fryzek Jon 
Published: October 2019

Abstract

Background
In 2014, the AAP stopped recommending RSV immunoprophylaxis for otherwise healthy 29–34 wGA preterm infants. This study examined the risk of RSVH and BH among 29–34 wGA infants before the AAP policy change (November 1, 2010–March 31, 2014) and after (November 1, 2014–March 31, 2017) using PHIS hospital-level encounter data from 51 US children’s hospitals.

Methods
The study population included the first November to March RSVH (ICD9 = 79.6, 480.1, 466.11, ICD10 = B97.4, J12.1, J21.0) or BH (RSVH or unspecified bronchiolitis [ICD9 = 466.19, ICD10 = J21.1, J21.8, J21.9]) among infants 6 months of age or younger admitted to a PHIS hospital between November 1, 2010 and March 31, 2017. The proportion of RSVH and BH by wGA categories (22–28 wGA, 29–34 wGA, 35–36 wGA, and term infants [37+ wGA]) were compared in the time period before and after 2014. Frequencies and proportions were calculated overall for all infants and by demographic and clinical factors for 29–34 wGA infants for RSVH and BH, separately. Statistically significant differences before and after the AAP policy were compared using χ 2 test or Wilcoxon rank-sum test, as appropriate.

Results
96,281 infants with BH, including 67,570 with RSVH, were studied. Among infants with known gestational age, the proportions of hospitalizations for RSVH and BH increased after the AAP policy change for all wGA categories, except for term infants (table). Infants 29–34 wGA represented 8.7% of all RSVH before the policy change and 14.2% of all RSVH after the policy change (P < 0.0001). No significant differences were found by gender or co-morbidity for infants 29–34 wGA. Among infants 29–34 wGA, the intensive care unit admission rate increased significantly for RSVH (from 54.5% to 64.2%, P < 0.0001) and BH (from 46.7% to 54.5%, P < 0.0001) after the policy change. The median RSVH length of stay (from 6 to 7 days, P = 0.047) and median adjusted estimated cost (from $14,077 to $16,058, P = 0.038) increased significantly after the policy change.

Conclusion
RSV and all-cause bronchiolitis hospitalizations and their severity increased among preterm infants 29–34 wGA in the 3-year period following the 2014 AAP policy change on RSV immunoprophylaxis.

Disclosures
All authors: No reported disclosures.
2640. Aerosol vs. Oral Ribavirin for the Treatment of Community-Acquired Respiratory Virus Infections in Lung Transplant Recipients
Authors: Mui Emily , Holubar Marisa , Lee Roy , Pham Danielle , Meng Lina , Nguyen Vinhkhoa , Blackburn Brian G , Desai Janjri , Gombar Saurabh , Ohgami Robert , Pinksy Benjamin A , Chang Amy , Deresinski Stan 
Published: October 2019

Abstract

Background
Community-acquired respiratory virus (CARV) infections are associated with an increased risk of chronic lung allograft dysfunction (CLAD) and graft loss in lung transplant recipients (LTR). Administration of ribavirin by aerosol was the standard of care at Stanford Health Care in the management of CARV infections. Given the sparse evidence of benefit with aerosol ribavirin (AR) and its increasing cost and teratogenic risk for exposed healthcare personnel, AR was restricted to the treatment of respiratory syncytial virus (RSV) in 2016 and was ultimately removed from formulary in 2017. Oral (PO) ribavirin was used at the discretion of the transplant team. The objective of this study was to evaluate the clinical outcomes of AR compared with PO ribavirin in lung transplant recipients.

Methods
We performed a retrospective cohort analysis of adult lung transplant recipients diagnosed with CARV (metapneumovirus, parainfluenza virus, and RSV) infections treated with either AR or PO ribavirin. The analysis included the first treatment course of ribavirin by either route and patients were excluded if they received ribavirin in the prior 12 months. The primary outcome was the development/progression of CLAD, acute organ rejection, and overall mortality.

Results
Of 85 patients, 41 received AR and 44 received PO ribavirin. There was no significant difference in the following clinical outcomes with AR and oral ribavirin, respectively: development or progression of CLAD (30 days: 9.7% vs. 4.5%, P = 0.4227; 90 days: 14.6% vs. 6.8%, P = 0.303; 6 months: 17% vs. 9%, P = 0.3413; 12 months: 24% vs. 15.9%, P = 0.4188), acute organ rejection (90 days: 7.3% vs. 4.5%, P = 0.6689; 6 months: 12.1% vs. 9%, P = 0.7329; 12 months: 19.5% vs. 13.6%, P = 0.5635), and overall mortality (30 days: 0% vs. 4.5%, P = 0.4947; 90 days: 7.3% vs. 4.5%, P = 0.6689; 6 months: 7.3% vs. 9%, P = 1.0; 12 months: 7.3% vs. 13.6%, P = 0.4858). There was no observable difference in reported adverse effects between AR and PO ribavirin.

Conclusion
Lung transplant recipients with CARV infections had similar outcomes when treated with AR or PO ribavirin. Oral ribavirin is a less costly treatment than AR, but the efficacy of ribavirin by any route remains questionable.

Disclosures
All authors: No reported disclosures.
2643. Oral Nitazoxanide for Viral Gastroenteritis: A Single-Center Experience
Authors: Shweta Fnu , Saleh Omar Abu 
Published: October 2019

Abstract

Background
Norovirus and serotypes (40/41) of adenoviruses are the leading cause of viral acute gastroenteritis in adults. The lack of therapeutic options can be devastating especially in the immunocompromised population. Nitazoxanide (NTZ), first designed as an antifolate anti-parasitic agent, is also known to have a broad-spectrum antiviral activity. Efficacy of NTZ in decreasing duration of symptomatic diarrhea in adults was first reported in a placebo controlled trial in 2006. Subsequent reports showed some promise as a possible therapeutic agent for viral gastroenteritis in the immunocompromised hosts.

Methods
Utilizing the inpatient pharmacy database we identified patients, who received NTZ for documented viral gastroenteritis, from January 1, 2008 to April 15, 2019. Chart review of cases was done to determine demographics, comorbidities, length of stay (LOS) in hospital, LOS in intensive care unit (ICU), duration of therapy, improvement in symptoms, and mortality.

Results
We identified 48 unique adult patients who were administered NTZ in the period under review. Of these 10 were prescribed NTZ specifically for viral gastroenteritis. 40% of the patients were females. The median age was 59 years (Interquartile Range [IR]: 47.75–69.25). Median LOS in hospital was 9.5 days (IR: 6.75–41.75). None of the patients required admission to the ICU. 4/10 patients had an active concomitant malignancy, of these 3 were receiving ongoing chemotherapy. 9/10 patients were recipients of stem cell (2) or solid-organ transplants (7). 7/10 patients were also on some form of immunosuppressive medications. Most common virus isolated was Norovirus (7/10). All patients received a standard dose of 500mg twice daily NTZ. The median duration of therapy was 7 days (range: 3–21). 6/10 patients had documented improvement in diarrhea at the end of treatment. 1/10 patients died within 30 days of diagnosis from causes unrelated to diarrheal illness (Table 1).

Conclusion
Our limited data set presents interesting insights into treatment of viral gastroenteritis in immunocompromised hosts, in particular transplant recipients. All of the cases identified were treated in second half of study period after January 1, 2015, signaling an increasing interest in this therapy, especially in cases with prolonged symptoms or viral shedding. Our observations indicate a need for larger studies into this application of NTZ in adult immunocompromised hosts.

Disclosures
All authors: No reported disclosures.
2645. Clinical Outcomes of Oseltamivir vs. Baloxavir in Patients Hospitalized with Influenza A
Authors: Shah Sunish , McManus Dayna , Bejou Nika , Tirmizi Samad , Rouse Ginger , Lemieux Steven , Gritsenko Diana , Topal Jeffrey E 
Published: October 2019

Abstract

Background
Baloxavir marboxil is a new antiviral agent for the treatment of acute uncomplicated influenza in patients > 12 years of age who have been symptomatic for no more than 48 hours. However, clinical trials to date have excluded patients hospitalized with influenza infection.

Methods
This study was a multi-center, retrospective chart review of adult patients admitted to the hospital who received oseltamivir or baloxavir for the treatment of influenza A. Patients were screened for inclusion between January 2018 and February 2018 in the oseltamivir group while patients in the baloxavir group were screened for inclusion between January 2019 and February 2019. Patients who had influenza diagnosed after 48 hours from hospital admission, were not admitted to the hospital, received baloxavir and > 2 doses of oseltamivir during their hospital stay, received > 1 dose of baloxavir during admission for influenza, received influenza therapy prior to admission, died within 48 hours of presentation to the hospital, were asymptomatic at the time of antiviral therapy, or who had left the hospital against medical advice were excluded. Influenza A diagnosis was confirmed by RT–PCR using a nasopharyngeal swab specimen. The primary outcome was hospital length of stay (LOS).

Results
Of the 699 patients reviewed, 359 met inclusion criteria. There were 221 patients who received baloxavir and 138 patients who received oseltamivir. Patients who received oseltamivir were older (65 years [55–78] vs. 82 years [69–88], P < 0.01) and were less likely to have a Body Mass Index > 40 kg/m2 (26 [12%] vs. 7 [5%], P = 0.03) compared with the baloxavir group. For the primary outcome of LOS, the baloxavir group had a shorter LOS compared with oseltamivir (4 days [3–6] vs. 5 days [3–8], P = 0.02). Of the 272 patients who were hypoxic at the time of antiviral administration, the baloxavir group was more likely to resolve their hypoxia (145 [88%] vs. 84 [79%], P = 0.04) and had a shorter time to resolution of hypoxia (43 hours [22–78] vs. 81 hours [33–135], P < 0.001) compared with oseltamivir.

Conclusion
This study supports the use of baloxavir for the treatment of influenza A in hospitalized patients with possible benefits of reduced length of stay and faster time to resolution of hypoxia compared with oseltamivir.

Disclosures
All authors: No reported disclosures.
2662. Methenamine Hippurate Decreases the Incidence of Urinary Tract Infections in Adult Renal Transplant Recipients
Authors: Quintero Orlando , Puius Yoram , Hemmige Vagish 
Published: October 2019

Abstract

Background
Urinary tract infections (UTIs) are a common complication of renal transplantation. Methenamine hippurate is a non-antibiotic alternative that reduces the frequency of UTIs in selected non-transplant patients, but which is not recommended in renal insufficiency. We conducted a retrospective study to determine the efficacy of methenamine prophylaxis in our kidney transplant population, and identify subgroups for which efficacy is greatest.

Methods
Retrospective chart review of adult kidney transplant patients at Montefiore Medical Center who were prescribed methenamine during January 1, 2016–December 31, 2017, with extraction of clinical data in the year before and after prophylaxis. Variables included demographics, creatinine clearance and hemoglobin A1c levels at the time of prescription, incidence of UTIs as determined by standardized literature definitions, hospital admissions for infections, and antibiotic use.

Results
The incidence of UTIs per 1000 patient-days decreased significantly, from 9.66 (95% CI 7.53–12.40) the year before to 3.24 (95% CI 2.00–5.24) the year after (P < 0.001). The effect was significantly more pronounced in patients who were transplanted due to diabetic nephropathy, with a decreased incidence of 13.05 (95% Cl 10.00–17.02) UTIs/1000 patient-days to 2.90 (95% Cl 1.58–5.32) in diabetics (P < 0.001), vs. 5.50 (95% Cl 3.65–8.28) UTIs/1000 patient-days to 3.81 (95% Cl 1.70–8.55) in non-diabetics (P = 0.44). The number of days of antibiotics for UTIs per 1000 days also decreased significantly for all patients, from 128.58 (95% CI 94.87–174.28) the year before to 49.78 (95% CI 31.74–78.07) the year after (P = 0.001). No significant differences in efficacy were seen based on sex or renal function. Three patients with indwelling urinary catheters or who required intermittent catheterization did not appear to benefit

Conclusion
Methenamine prophylaxis decreases the incidence of UTIs and number of antibiotic days in adult renal transplant recipients. This effect was seen even in patients with reduced creatinine clearance. Patients with diabetes benefited the most. The small number of patients who required catheterization did not appear to benefit.

Disclosures
All authors: No reported disclosures.