bluuebunny/crossref_metadata_2025 huggingface dataset:
2603. Biofilm Formation as a Predictive Marker of Prognosis for Escherichia coli Sepsis
Authors: Zhang Kermit , Schneider Daniella , Biswas Rakesh , de la Espriella Mariana Gomez , Rao Jayasimha , Baffoe-Bonnie Anthony
Published: October 2019

Background

Escherichia coli is the Gram-negative organism most commonly associated with bloodstream infections and death due to sepsis. Timely administration of appropriate antibiotic(s) plays a significant role in improving patient outcomes. E. coli expresses virulence factors (VFs) such as biofilm formation and motility phenotypes which play a role in bacterial attachment and dissemination by enabling immune system evasion and host migration. The role of these VFs in bacteremia prognosis is not well characterized. Our study aims to evaluate the clinical characteristics and outcomes of E. coli bacteremia patients specifically in relation to biofilm forming isolates.

Methods

91 E. coli bacteremia clinical isolates were consecutively collected from patients between 2013 to 2015. Virulence factor phenotypes were determined by in vitro biofilm formation, motility, and milk hydrolysis. Clinical patient data associated with the isolates were abstracted from the electronic medical records database and blinded from research team throughout characterization. Descriptive statistics were used for clinical variables and analyzed in a dichotomized fashion based on biofilm formation. The chi-square or Fisher exact test were used for categorical data and the Mann–Whitney U or Student T-test for continuous variables as appropriate.

Results

Of the 91 isolates, 41 had a biofilm-forming phenotype. Of the 87 isolates tested for milk hydrolysis and motility a positive finding was seen in 61 (70%) and 67(77%) isolates, respectively. In the multivariate model, patients with E.coli bacteremia from biofilm producing isolates were at increased risk of death or going into hospice during that hospitalization. ([OR],9.8; 95% CI, 1.1,88.7, P = 0.041)

Conclusion

Patients with biofilm-forming E. coli bacteremia had worse clinical outcomes than their non-biofilm forming counterparts suggesting that this phenotype leads to a more pathogenic organism. A prospective study to confirm this finding is needed as is the design of rapid diagnostics to promptly identify this phenotype in septic patients.

Disclosures

All authors: No reported disclosures.
2605. Mixed Subpopulation of Hemolytic and Non-Hemolytic Phenotype in Clinical Staphylococcus aureus Blood Isolates
Authors: Bae Seongman , Cho Eunbeen , Yang Eunmi , Seo Hyeonji , Kim Eun Sil , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Jae Kim Min , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo , Chong Yong Pil
Published: October 2019

Background

Agr is a key regulator that controls expression of secreted exoproteins and surface protein in Staphylococcus aureus. It has been reported that mixed status of two different phenotypes including agr functional and nonfunctional subpopulations can coexist in vitro and in vivo. However, data on the natural course and clinical implication of the mixed agr status is limited. We thus investigated the frequency and characteristics of the mixed agr in clinical settings.

Methods

We evaluated isogenic paired MRSA isolates collected from patients with persistent S. aureus bacteremia (SAB) between October 2010 and April 2016, and then prospectively performed surveillance for the presence of mixed agr function in MRSA isolates from patients with SAB between May 2016 and December 2017. The mixed agr status was evaluated by single colony evaluation on sheep blood agar plate containing RN4220 supernatant (β-hemolysin) (Figure 1). Cross-streaking with RN4220 and RNAIII measurement were performed to confirm the agr functionality of each of hemolytic and non-hemolytic colonies, separately. The expression levels of RNAIII, hla, and saeS/saeR were measured by real-time reverse transcription polymerase chain reaction.

Results

A total of 161 first blood isolates were collected during study period, and 6 isolates (4%) displayed mixed phenotype by single colony test. The mixed hemolytic pattern was observed in 5 out of 52 ST72 isolates (10%) and 1 out of 82 ST5 isolates (1%) (Figure 1). No difference was found in the genotypes between hemolytic and non-hemolytic colonies from each isolate. Of the 6 isolates, three lost mixed hemolytic features in the follow-up blood cultures (Table 1). One ST72 and one ST5 isolate showed agr mixed pattern determined by different RNAIII levels, but remaining four ST72 isolates had mixed hemolytic pattern due to different expression of hla correlated with saeS/saeR expression (Figure 2).

Conclusion

The mixture of agr function status among the clinical blood isolates of MRSA was rarely observed and isolates displaying heterogeneous hemolytic phenotype were largely due to differential expression of α-hemolysin. Further investigation is needed to unveil the clinical significance of mixture of different hemolytic phenotypes.

Disclosures

All authors: No reported disclosures.
2609. Escherichia coli Clonal Lineages and Virulence Factors Predict Fecal Colonization within Households
Authors: Fox Teresa C , Thuras Paul , Clabots Connie , Porter Stephen , Johnson James R
Published: October 2019

Background

Extraintestinal Escherichia coli infections are an ever-growing threat, to which specific clonal lineages and virulence factors contribute disproportionately. Despite the gut being the main reservoir for such E. coli strains, relationships between clonal lineages, virulence factors, and fecal colonization patterns are poorly understood. Accordingly, we defined E. coli fecal colonization patterns within households (HHs) and assessed specific lineages and virulence genes (VGs) as predictors of colonization behaviors.

Methods

Veterans with an E. coli clinical isolate (n = 22: 11 fluoroquinoline [FQ]-resistant, 11 FQ-susceptible) and their HH members provided stool samples on 2–6 occasions each. Stools were screened for total and FQ-resistant E. coli. Distinct E. coli strains were resolved by genomic profiling of 10 colonies/sample. Strains underwent molecular lineage identification, VG detection, and comparison with the veteran’s clinical isolate. Clonal lineages and VGs were assessed (Wilcoxon rank-sum test) as predictors of strains’ (i) predominance within the fecal sample, (ii) persistence across serial fecal samples, (iii) within-HH strain sharing, and (iv) overall within-HH colonization prevalence.

Results

From the 22 veterans and 46 HH members (27 humans, 19 pets) we recovered 139 unique-by-household fecal E. coli strains. Sixty-four traits were evaluated (16 clonal lineages, 48 VGs). Of these, 44 exhibited n ≥ 5, so could be analyzed statistically. Among these 44 traits, the proportion significantly associated with ≥ 1 outcome variable was 5/6 (83%) for clonal lineages and 18/38 (47%) for VGs. Additionally, fecal strains that matched the veteran’s clinical isolate exhibited significantly greater sharing, persistence, and overall colonization.

Conclusion

The studied E. coli traits – known for their associations with clinical infections –here were significantly associated with within-HH colonization behavior. These findings support that “virulence factors” may be regarded also (or perhaps best) as “colonization factors,” and “virulent lineages” as “colonizing lineages.” This suggests the possibility that future interventions that disrupt colonization behavior also could prevent E. coli infections.

Disclosures

All authors: No reported disclosures.
2612. Molecular Evidence of Ureaplasma urealyticum and Ureaplasma parvum Colonization in Preterm Infants with Respiratory Distress
Authors: Kumar Surinder , Kashyap Priyanka , Kumar N B , Kashyap Bineeta , Garg Indu Bala , Saigal Sanjeev R
Published: October 2019

Background

Ureaplasma urealyticum and Ureaplasma parvum have been associated with respiratory diseases in premature newborns, but their role in the pathogenesis of the respiratory distress syndrome (RDS) is unclear. The present study was conducted to investigate preterm newborns with respiratory distress for colonization of U. urealyticum and U. parvum in endotracheal fluid (TF)/nasopharyngeal aspirates (NPA) specimens employing culture and polymerase chain reaction (PCR).

Methods

Sixty preterm infants, presenting with respiratory distress persisting for more than 24 hours were investigated. Endotracheal fluid or nasopharyngeal aspirates specimens were inoculated in 2mL Ureaplasma broth and Ureaplasma agar for culture identification assay and PCR. DNA extracts were processed for a genus specific PCR (429 base pair region) on urease gene of U. urealyticum/U. parvum and species specific PCR (1305 base pair region) on 16S rRNA gene in U. parvum.

Results

Ureaplasma species colonization was positive in 11 (61.11%) male patients and7 (38.89%) females but there was no statistical association between sex and Ureaplasmaspecies colonization (P = 0.771). Ureaplasma spp. culture identification assay was positive in 7 (11.67%).Ureaplasma genus specific PCR was positive in 14 (23.33%) cases; species specific PCR in 9 (64.28%) infants were identified as U. parvum. Considering culture as diagnostic standard, sensitivity of PCR was 42.86%; specificity 79.24%; positive predictive value 21.43% and negative predictive value 91.30 %; with overall percentage agreement at 75%. Septicemia was positive in 12 (66.67%) infants colonized with Ureaplasmaspecies than in 5 (11.9%) of non colonized infants which was found to be significant (P = 0.00). Twelve (66.67%) patients with Ureaplasmaspecies colonization had lethargy with statistically significant association(P = 0.04).

Conclusion

This study confirms that Ureaplasma species and particularly U. parvum colonization in preterm infants was related to respiratory distress.

Disclosures

All authors: No reported disclosures.
2613. The Epidemiology of Respiratory Syncytial Virus (RSV) in People with Immune Dysfunction Seen at a Tertiary Hospital Between 2010 and 2017
Authors: Li Qiuju , Reekie Joanne , Helleberg Marie , Sengeløv Henrik , Sørensen Søren Schwartz , Jacobsen Søren , Daugaard Gedske , Mocroft Amanda , Lundgren Jens
Published: October 2019

Background

Persons with a compromised immune system are at increased risk of complications related to respiratory syncytial virus (RSV) but the risks are not well defined. We aimed to investigate the prevalence of RSV infection, associated risk factors and complications in a large population of people with immune dysfunction.

Methods

Persons with immune dysfunction, first seen at Copenhagen University Hospital, Rigshospitalet, between January 1, 2010 and February 21, 2017, aged ≥18 were included. RSV testing and positivity (positive PCR or antigen test) was determined through the Danish Microbiology Database. Generalized estimating equations logistic regression was used to investigate the risk factors for RSV positivity; Cox regression was used to assess the impact of RSV positivity (time-updated) on mortality in the first 12 months after first visit.

Results

The study included 42,567 persons, of which 3,356 (7.9%, 95% CI 7.6%-8.1%) were tested for RSV at least once during follow-up, with 2,374 (71%) tested in the first 12 months. Stem cell transplant (HSCT) and solid-organ transplant (SOT) recipients had the highest proportion of persons tested for RSV (66.0%, 95% CI 62.9%–69.1% and 31.6%, 95% CI 29.0%–34.2%, respectively). Of those tested, 256 (7.6%, 95% CI 6.7%–8.5%) had ≥1 positive RSV test (figure). After adjustment, HSCT and SOT recipients, as well as other hematologic and rheumatologic patient groups were more likely to have a positive RSV test compared with persons seen in the infectious disease department. Fifty-seven RSV-related complications were identified in 53/256 (20.7%, 95% CI 15.7%-25.7%) persons positive for RSV (table), of which 24 (45.3%) were HSCT recipients and 18 (34.0%) were other hematologic patients. In the 12 months after first department visit, 9,451 (22%) patients died; persons with RSV had an increased risk of short-term mortality (aHR 1.77, 95% CI 1.19–2.64), adjusting for sex, age, patient group and flu positivity.

Conclusion

Patients with a hematological or rheumatological condition and SOT recipients had the highest odds of contracting RSV, with hematological patients in particular at an excess risk of RSV-related complications. RSV was associated with an increased risk of death in the first 12 months of patient follow-up.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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.
160. Could Reducing Time to Bacterial Identification From Positive Blood Cultures Improve Outcomes in Bacteremic Patients?
Authors: Forbes Jessica D , Haj Reem , Taggart Linda R , Fattouh Ramzi , Leung Elizabeth , Friedrich Jan , Matukas Larissa M
Published: October 2019

Background

Survival of patients with septic shock is dependent on the timing of effective antibiotic administration. The initial notification by the microbiology lab of a positive blood culture is a key factor in improving patient outcomes. It can take >24 hours to definitively identify bacteria from positive blood cultures. Accordingly, we employed rapid organism identification and studied the impact of this on patient management from a quality improvement perspective.

Methods

Rapid organism identification was performed for bacteremic patients admitted to an ICU at St. Michael’s Hospital in Toronto, ON, by creating a pellet from positive blood culture bottles using a lysis centrifugation technique. MALDI-TOF was then used to obtain an organism identification. The microbiology lab verbally notified the ward clerk of the identification and surveys were conducted with treating physicians within 24–48 hours to evaluate the downstream impact of the rapid identification including changes to antibiotics, diagnostic testing, central line management and requests for specialty consultations.

Results

Between January 28 and April 28, 2019, 17 rapid blood culture results were included for study. When asked how physicians received the result, in 7 cases the physician did not remember; other responses included microbiology report (2), nurse (2), pharmacist (1), antimicrobial stewardship or lab (1), on-call team (1) and residents (1). Antibiotics were adjusted in 13 patients; 3 of which may have changed antibiotics for reasons other than the organism identification. Reasons for not changing therapy include: appropriate empiric treatment, likely contaminants, or physician not being notified of the result. In 5 cases, all antibiotics were discontinued, in another 2 cases the antibiotics were broadened and a further 5 narrowed to cover the organism; the remaining 5 continued the same empiric therapy. Repeat blood cultures were obtained for 5 cases, follow-up imaging in 5 cases and lines were changed/removed in 5 cases. Consultation was requested for 7 cases.

Conclusion

Based on preliminary data, rapid organism identification shows promise of improved patient management with line removal and antibiotics adjustments occurring 1 day sooner with rapid results.

Disclosures

All authors: No reported disclosures.
2672. Clostridioides difficile Infection Among Bone Marrow Transplant Recipients: Findings From a Single Institution
Authors: Thomas Christine , Hagen Patrick , Henry Elizabeth , Joyce Cara J , Berg Stephanie
Published: October 2019

Background

Clostridioides difficile infection (CDI) is increasingly common among hematopoietic stem cell transplantation (HSCT) recipients and efforts to define CDI risk have shown variable results. The primary objective of this study was to further characterize CDI incidence and risk factors in HSCT recipients.

Methods

All allogeneic and autologous HSCT recipients at Loyola University Chicago between January 2011 and May 2017 were retrospectively reviewed for development of CDI within 6 months prior to 2 years following HSCT. Collected data include comorbid conditions, statin or proton pump inhibitor (PPI), and antimicrobial use. HSCT baseline information was also obtained and include underlying malignancy, prior chemotherapy, graft type, conditioning regimen consisting of total body irradiation (TBI) use, and donor source (matched related or unrelated and umbilical cord blood). Among those with diagnosed CDI, data pertaining to CDI severity, treatment, and recurrence was collected. Logistic regression analyses were performed to estimate odds ratios for factors associated with development of CDI.

Results

Six hundred eighty-nine patients met our inclusion criteria. Of these, 367 (53%) underwent autologous HSCT and 322 (47%) allogeneic HSCT. Among all patients, 132 (19.1%) had CDI of which 26 (19.7%) had recurrence within 60 days. In univariable analysis, any type of leukemia was associated with increased odds of CDI compared with lymphoma (OR = 2.44, 95% CI: 1.49- 4.00, P < 0.01) as was allogeneic HSCT compared with autologous (OR = 2.51, 95% CI: 1.63–3.88, P < 0.01 for matched and OR = 3.96, 95% CI: 2.31–6.79, P < 0.01 for cord blood) and use of TBI (OR = 1.63, 95% CI: 1.10 – 2.40, P < 0.05). Exposure to any cephalosporin or intravenous vancomycin within 100 days of HSCT was associated with CDI (OR = 1.55, 95% CI: 1.03–2.32, P < 0.05 and OR = 1.75, 95% CI: 1.19–2.58, P < 0.01 respectively). No significant differences in the odds of developing CDI were identified by patient comorbidities, statin or PPI use.

Conclusion

In our population there was a 19% incidence of CDI. Underlying leukemia, TBI exposure, and allogeneic HSCT appear to be risk factors for CDI and further research is needed to evaluate whether exposure to cephalosporin or vancomycin may be modifiable risk factors.

Disclosures

All authors: No reported disclosures.
2678. Characterizing Hospitalizations and Infections Among Older Adults Receiving Palliative Chemotherapy for Hematologic Malignancies
Authors: Uy Natalie , Datta Rupak , Bar Noffar , Juthani-Mehta Manisha
Published: October 2019

Background

As cancer survivorship improves, the number of patients with hematologic malignancies receiving palliative chemotherapy will grow. Older adults with hematologic malignancies often carry poor prognoses and experience high risks of infection. We evaluated the frequency of CDC criteria confirmed infection and antimicrobial use during hospitalizations following initiation of palliative chemotherapy.

Methods

We conducted a cohort study of patients aged ≥65 years who received non-curative palliative chemotherapy between January 1, 2016 and September 30, 2017 and were subsequently hospitalized by January 31, 2018. Hematologic malignancies were verified with medical record review. Infections were identified using CDC criteria, and antimicrobials were categorized by indication for use.

Results

We identified 268 patients receiving palliative chemotherapy for hematologic malignancies (Table 1) who had a total 591 hospitalizations (Table 2) during follow-up. There were 162 readmissions (27%) among 92 patients. Among all patients, 128 (48%) died during follow-up. Forty-one (15%) deaths were within 30 days of discharge. The most common site of death was hospice, in and outpatient (27%). Two hundred forty-nine (42%) admissions were for infectious causes; of the 34 patients who died inpatient (non hospice), 56% had been admitted for infectious causes. Antimicrobials were prescribed for prophylaxis in 57% (n = 337/591) of hospitalizations. Antimicrobials were prescribed for suspected infection in 48% (n = 282/591) of hospitalizations. Only 30% (n = 178/591) of hospitalizations had antimicrobials given for CDC confirmed infections. Figure 1 shows the most common indications for antimicrobial use.

Conclusion

Infections are an important cause of the morbidity and mortality in older adults receiving palliative chemotherapy for hematology malignancies. Hospitalizations for infectious causes were frequent in our cohort. Nearly half of hospitalizations involved antimicrobial use for suspected infection, but CDC confirmed infections were less common. This population warrants further investigation to improve antimicrobial use. Future studies should identify the subset of patients at high risk for recurrent admissions to optimize medical care.

Disclosures

All authors: No reported disclosures.
2682. Prophylaxis-Driven Molecular Epidemiology of Pseudomonas aeruginosa Bloodstream Infections in Adults With Leukemia
Authors: Endres Bradley T , Buege Michael J , Marx Kayleigh , Sahasrabhojane Pranoti V , Galloway-Peña Jessica , Garey Kevin W , Kim Jiwoong , Greenberg David E , Zhan Xiaowei , Shelburne Samuel A , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L
Published: October 2019

Background

Fluoroquinolones (FQs) are routinely used as antimicrobial prophylaxis in leukemia patients receiving chemotherapy to prevent Pseudomonas aeruginosa infections. Patients who are intolerant to FQs may receive cefpodoxime (CPD) or other agents. How FQ use affects the resistance profile and epidemiology of breakthrough P. aeruginosa infections is unknown. To determine this, we performed a whole-genome sequencing (WGS)-driven epidemiologic study of leukemia patients with P. aeruginosa bloodstream infections.

Methods

All adult (age > 17 years) inpatients with leukemia and a first episode of monomicrobial P. aeruginosa bloodstream infection were included. Clinical data were extracted from the electronic medical record. Isolates were sequenced using an Illumina NextSeq and phylogenomics was performed using an in-house analysis pipeline consisting of Bowtie2, SAMtools and bcftools.

Results

110 patients were included and most had a diagnosis of acute myeloid leukemia (n = 66). Twenty (18%) patients received FQ prophylaxis, 56 (54%) received CPD, and the remaining 34 (31%) received other agents. 9 (8%) isolates were multidrug-resistant (MDR). MDR was more common in those receiving FQ prophylaxis (20% vs 6%, P = 0.06). 76 sequence types (STs) were represented with ST235 (n = 8) being most common followed by ST244 (n = 7). ST235 strains were genetically distinct, but closely related (>10 but < 250 SNPs) in comparison to other STs. 2 ST244 strains were genetically identical despite being isolated 4 months apart, suggesting horizontal transmission. MDR was more common among ST235 isolates compared with other STs (38% vs 6%, P = 0.02). ST235 strains were more common in patients receiving FQ vs other prophylaxis (20% vs 4%, P = 0.04). 1 ST244 isolate harbored a VIM-2 β-lactamase. In 20 FQ-resistant isolates, 80% had mutations in either parC (S87L) or gyrA (T83I) and 50% had both. FQ-resistance mutations were more common in FQ recipients (50% vs 8%, P < 0.01).

Conclusion

Most P. aeruginosa infections occurred in non-FQ recipients, while MDR P. aeruginosa infections were more common in FQ recipients. These data suggest that decisions on empiric treatment of patients with P. aeruginosa bacteremia must take antimicrobial prophylaxis history into account.

Disclosures

Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.