bluuebunny/crossref_metadata_2025_split huggingface dataset:
2583. Short-term Impact of Antimicrobial Exposure on Fecal Carriage of Resistant Microorganisms
Authors: Ahmad Abdul , Amundson Carla , Clabots Connie , Porter Stephen , Johnson James R , Drekonja Dimitri M 
Published: October 2019

Abstract

Background
The relationship between antimicrobial use and subsequent resistance is complicated; this study assesses the short-term impact of antimicrobial use on fecal carriage of resistant microorganisms. This is a sub-study of an ongoing trial comparing 7 vs. 14 days of antimicrobial treatment for male urinary tract infection. This analysis quantifies the effect of 1–2 weeks of systemic antimicrobial use on the fecal flora within 1 week of completing therapy.

Methods
The parent study has enrolled 216 subjects, with 178 enrolled in the optional resistance sub-study. Subjects received either ciprofloxacin or trimethoprim/sulfamethoxazole (SXT), randomized to 7 vs. 14 days therapy. Subjects provided 2 stool specimens, 1 during treatment and 1 a week after completing study medication. Samples were plated on media for Gram-positive and negative growth, including T-7 plates with ciprofloxacin and SXT added to select for resistant organisms. Resistance to 22 antimicrobials was assessed, with resistance reported by: number of isolates with any antimicrobial resistance, total number of resistant drugs/isolate, and number of isolates with multi-drug resistance (resistance to 3 or more different antimicrobial classes).

Results
Overall, 143 (80%) subjects provided 2 stool samples, with 104 (73%) having growth from at least 1 of the samples. Fifty-one of 143 (36%) had microbial growth from both samples. From these 51 paired samples, there were 255 total strains isolated (117 from the first sample, 138 from the second), with some yielding multiple organisms (range, 1–5). From sample 1, 110/117 (94%) isolates had any antimicrobial resistance, vs. 131/138 (95%) from sample 2 (P = .79). Mean number of resistant drugs/isolate was 7.4 in sample 1 and 5.8 in sample 2 (P = .009). Multi-drug resistance was seen in 102/117 (87%) isolates from sample 1 vs. 85/138 (62%) isolates in sample 2 (P < .001).

Conclusion
The fecal flora of patients on antimicrobial therapy for UTI has a significant increase in resistant microorganisms compared with samples obtained shortly after antimicrobial completion. This may reflect repopulation of the fecal flora with less-resistant strains after the selection pressure of therapy has been removed. After unblinding, we will assess if differences in resistance are affected by therapy duration.

Disclosures
All authors: No reported disclosures.
2611. Enterotoxigenic Bacteroides fragilis Alters the Genome of Colon Epithelial Cells
Authors: Allen Jawara , Wu Shaoguang , Wu Xinqun , Sears Cynthia 
Published: October 2019

Abstract

Background
Individuals born in 1990 have twice the risk of developing colon cancer and four times the risk of developing rectal cancer as those born in 1950. The gut microbiome is being proposed as a potential contributor to this difference because of the surge in obesity in the United States, the link between obesity and gut dysbiosis, and the growing number of studies which have associated a dysbiotic gut microbiome with CRC. Enterotoxigenic Bacteroides fragilis (ETBF) is one of the bacteria most studied in relation to CRC development; it is found at a higher frequency in both the stool and mucosa of CRC patients, and it rapidly induces tumor formation in an Apcmin/+ mouse model of CRC. In this model, tumor formation typically occurs via loss of heterozygosity (LOH) of the Apc gene, the genetic mutation found in approximately 80% of sporadic CRC cases. ETBF produces a potent exotoxin (BFT) which induces E-cadherin cleavage, β-catenin nuclear localization and colonic epithelial cell proliferation. But we still do not understand how these downstream effects cause lasting changes in the genome of colon epithelial cells that then initiate tumor formation and growth. As cancer is ultimately a disease that arises and progresses via changes in the genome, understanding these interactions is essential.

Methods
We hypothesize that ETBF induces DNA mutations via BFT that encourage tumor formation, and enhance tumor growth. To test this hypothesis, we performed whole-exome sequencing on tumors and normal tissue isolated from Apcmin/+ mice after ETBF or sham inoculation. Additionally, we isolated colon organoids from Apcmin/+ mouse normal tissue (colonoids) and Apcmin/+ mouse tumors (tumoroids) after ETBF or sham inoculation. We performed in vitro DNA damage assays and qPCR for Apc LOH on these colon organoids.

Results
Our preliminary data indicate that ETBF-induced tumors have lower rates of Apc LOH and that double-stranded DNA breaks are observed as soon as 3-hours after BFT treatment of colonoids and as soon as 72-hours after ETBF inoculation.

Conclusion
These data suggest that in vivo, ETBF may induce mutations in cancer-driver genes which cause tumor formation via pathways other than somatic recombination at the Apc locus, a result we are now testing with additional (N = 19) whole-exome tumor sequencing in-progress.

Disclosures
All authors: No reported disclosures.
2616. Genetic Susceptibility to Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants
Authors: Ferolla Fausto Martin , Acosta Patricio , Toledano Analia , Yfran Eduardo Walter , Giordano Ana Clara , Carrizo Barbara , Anselmino Cecilia , Feldman Florencia , Chiormi Agustina , Visingardi Gabriela , Retta Alejandra , Reyero Mariana , Dastugue Monica , Mascardi Normando , Neira Pablo , Caratozzolo Ana , Marta Contrini Maria , Lopez Eduardo Luis 
Published: October 2019

Abstract

Background
Differential expression of selected immunity genes may have a role in susceptibility to Respiratory Syncytial Virus (RSV). There are few data about some candidate gene single nucleotide polymorphisms (SNPs) associated with the severity of respiratory infections (e.g., Toll-like receptor 4 [TLR4], Toll-like receptor 8 [TLR8], macrophage receptor with colagenous structure [MARCO], myxovirus resistance 1 [MX1]). The aims of this study were to detect the presence of SNPs in selected genes of previously healthy infants infected with RSV, to assess viral load (VL) and to analyze their relationship with life-threatening disease (LTD)

Methods
Prospective cohort study including previously healthy full-term infants < 12 months, hospitalized with a first RSV infection during 2017–2018. RSV diagnosis, virus quantification and genotyping for SNPs (TLR4 rs4986790, TLR4 rs4986791, MARCO rs1318645, MX1 rs469390, TLR8 rs3761624) were performed by qRT–PCR in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit needing mechanical or non invasive ventilation

Results
75 patients, mean age 3.9 months (±2.8), 41 (54.7%) male. Fifteen developed LTD. Infants who were homozygous (−/−) or heterozygous (+/−) for MX1rs469390 and TLR8rs3761624 or MARCOrs1318645 and TLR8rs3761624 had significantly more risk of developing LTD (OR 3.45, P = 0.042; OR 3.63, P = 0.048, respectively). Multivariable logistic regression analysis showed that concurrent MARCOrs1318645, MX1rs469390 and TLR8rs3761624 SNPs increased the risk of LTD (aOR 4.7, P = 0.018), fig 1. These SNPs also associated with prolonged length of stay (LOS) (P = 0.026) and > 7 days of hypoxemia (P = 0.031). No differences were seen in VL of patients with LTD compared with those with better outcome (P = 0.737). No differences in VL were seen in patients with SNPs. VL did not correlate with LOS or days of hypoxemia. No other socioeconomic, pregnancy or infant variables associated with LTD

Conclusion
To the best of our knowledge, this is the first study assessing the presence of concurrent SNPs and their association with life-threatening disease in previously healthy infants with RSV infection. These findings provide evidence on the importance of the host and its immune response for the severity of RSV infection.

Disclosures
All authors: No reported disclosures.
2634. Human Metapneumovirus in a Children’s Hospital: It Should Get More Attention
Authors: Said Nellie , Gornick Wendi , Huff Beth , Singh Jasjit 
Published: October 2019

Abstract

Background
Viral respiratory infections are a major cause of hospitalization and intensive care unit (ICU) admission to children’s hospitals. Rates of respiratory syncytial virus (RSV) and influenza are closely tracked due to their known morbidity. We had previously observed over one season that human metapneumovirus (hMPV)-infected children have high rates of hospitalizations and ICU admissions, particularly those with chronic lung disease (CLD). We expanded our data to include an additional 5 seasons to compare rates of hospitalizations and hospital-acquired infections (HAIs) due to hMPV, RSV and influenza.

Methods
During the 2014–2019 winter viral seasons, hMPV, RSV and influenza infections were tracked through both PCR testing (Biofire Respiratory Panel) and DFA testing (D3 Ultra DFA Respiratory Virus Screening & ID Kit; Diagnostic Hybrids). For hMPV admissions, rates of hospitalizations, ICU admissions, HAIs and mortalities were assessed and compared with RSV and influenza admissions. Retrospective data were used to study patients infected with hMPV.

Results
During the winter seasons of 2014–2019, the rates of hospitalization due to hMPV were significantly higher than both RSV and influenza (Figure 1). ICU admissions and HAIs for hMPV were similar to RSV and influenza (Figures 2 and 3). There were 9 deaths over this time period; 5 due to RSV, 3 due to influenza and 1 due to hMPV. The proportion of deaths due to hMPV compared with RSV and influenza was similar (P = 0.54, 0.89, respectively). Of the 315 total admissions with hMPV, 43 (13.7%) had CLD and 13 (4.1%) were tracheostomy dependent. Among 67 hMPV ICU admissions from 2014–2019, 56 (84%) had an underlying medical diagnosis, 25 (37%) had CLD, 13 (19%) had tracheostomies, and 17 (25%) required mechanical ventilation. The average age of hMPV infected children in our ICU is 4 years 1 month.

Conclusion
Our large descriptive study of hMPV-infected children over 6 seasons showed higher rates of hospitalization compared with RSV and influenza, similar ICU and HAI rates, and similar rates of mortality. ICU admitted children often had associated co-morbidities, including CLD. Further studies for focused disease surveillance and potential vaccine development for high-risk children are needed.

Disclosures
All authors: No reported disclosures.
2646. Incidence of Myelosuppression Related to Valganciclovir Prophylaxis in Solid-Organ Transplant Recipients at High Risk of CMV Disease
Authors: Belga Sara , Hernandez Cristina , Kabbani Dima , Cervera Carlos 
Published: October 2019

Abstract

Background
Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence.

Methods
Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L.

Results
A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001).

Conclusion
VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis.

Disclosures
All authors: No reported disclosures.
2659. Retrospective Review of Biopsy Proven Acute Graft Pyelonephritis in Renal Transplant Patients
Authors: Powers Harry Ross , Hellinger Walter , Cortese Cherise , Wadei Hani M 
Published: October 2019

Abstract

Background
There are few studies of histologic acute graft pyelonephritis (HAGPN) following kidney transplant (KT). The goals of this study are to determine incidence, identify potential risk factors and describe outcomes of HAGPN in a large cohort of KT recipients.

Methods
Renal allograft biopsies of all patients undergoing first KT at our medical center between 2008 and 2017 were reviewed. HAGPN was defined as the presence of neutrophils within the interstitium and tubules (casts). Medical charts of patients with HAGPN were reviewed. Episodes of bacteriuria (≥10:5 cfu/mL growth in culture) were classified as urinary tract infection (UTI) or asymptomatic bacteruria (ASB) based upon documented symptoms. An episode of acute rejection was defined as pulse parenteral immunosuppressive therapy for histologic evidence of rejection.

Results
HAGPN was identified in 43 of 1,391 (3.1%) KT recipients at a median of 298 days post-transplant. There were no significant differences between recipient age or gender, donor age or transplant type (deceased, living related, living unrelated) between recipients with and without HAGPN. Urologic malformation was diagnosed in 14 (33%) by day 30 post-transplant. Twenty-five (58%), 17 (40%), and 13 (30%) sustained one or more episodes of acute rejection, UTI and ASB, respectively, prior to HAGPN. At diagnosis of HAGPN, 28 (65%), 7 (16%), and 16 (37%) had histologic evidence of rejection, UTI and ASB, respectively. Twenty-two (51%) and 37 (86%) were treated with pulse immunosuppression and antibiotics, respectively. Median nadir serum creatinine before HAGPN was 1.1 mg/day while median serum creatinine at 6 and 12 months after HAGPN were 1.5 and 1.6. Three patients (7%) developed graft failure within 1 year after HAGPN.

Conclusion
HAGPN is an infrequent complication of KT. A majority of patients with HAGPN have histologic evidence of rejection and either UTI or ASB at diagnosis, though over 40% have neither UTI nor ASB. When rejection accompanying HAGPN is routinely treated with pulse immunosuppression and antibiotic therapy is administered, graft function is preserved for most patients but a minority (7%) loses graft function within 1 year. Potential risk factors to be assessed in further study include post-transplant urologic dysfunction, acute rejection and UTI.

Disclosures
All authors: No reported disclosures.
2694. Incidence of Pneumocytis jiroveci (PJP) Infection with 3-Month Prophylaxis of Aerosolized Pentamidine (AP) in Autologous Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Perreault Sarah , McManus Dayna , Pulk Rebecca , Topal Jeffrey E , Foss Francine , Isufi Iris , Seropian Stuart , Bar Noffar 
Published: October 2019

Abstract

Background
HSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP.

Methods
A single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: <18 years of age, received < or >3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT.

Results
A total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year.

Conclusion
Three months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen.

Disclosures
All authors: No reported disclosures.
2704. Molecular Technology to Detect Pneumococcal Colonization in Young Children Reveals Increased Prevalence of Vaccine Serotypes as Compared with Enhanced Culture Methods
Authors: Pelton Stephen I , Shea Kim , Shaik-Dasthagirisaheb Yazden , Little Brent 
Published: October 2019

Abstract

Background
Human challenge studies demonstrate enhanced sensitivity of molecular technology for identification of vaccine serotype pneumococcal (SP) carriage in PCV13 immunized adults. We hypothesized that PCV13 immunized children would similarly harbor vaccine serotypes in their nasopharynx (NP) that could only be identified by molecular technology.

Methods
We compared use of enhanced microbiologic culture vs. molecular technology to characterize SP colonization among NP swabs collected from 995 healthy or sick children <5 years old at Boston Medical Center from November 2015 to May 2017. NP specimens were broth enriched for 4 hours and cultured on selective blood agar. Specimens were evaluated for presence of SP using both routine microbiologic methods and RT–PCR. RT–PCR assays targeted the lytA, and piaB (SP membrane permease) genes, and 26 SP serotypes: all serotypes included in 13-valent pneumococcal conjugate vaccine and 13 prevalent non-vaccine serotypes

Results
A total of 162 (16.3%) NP specimens were positive for SP via enhanced culture, and an additional 163 (16.3%) were SP positive via lytA+ RT–PCR molecular technology. Prevalence of SP carriage was equivalent in children aged 0<2 years and 2≤5 years, but greater in children with respiratory tract infections (RTI) compared with children without RTI (26.5% vs. 9.6% among culture+ specimens only; and 43.2% vs. 25.8% among combined culture+ and molecular+ specimens). Using enhanced culture only, vaccine serotypes (VST) were identified in 4 (1%) of 450 children <2 years and 14 (2.6%) of 545 children 2 ≤5 years; adding molecular positive specimens increased the prevalence of VST to 2.9% in children <2 years and 4.6% in children 2 ≤5 years (table). Serotypes 3 and 19A were the two most commonly identified VST.

Conclusion
Combining molecular technology with enhanced culture reveals an increased prevalence of vaccine serotype colonization in young children. The ability of sensitive molecular methods to detect vaccine serotypes in culture-negative specimens suggests low-density vaccine serotype carriage persists in a highly immunized pediatric population. The importance of culture negative but RTPCR positive carriage for transmission requires further evaluation.

Disclosures
All authors: No reported disclosures.
2705. Serotype Replacement Following Childhood Pneumococcal Conjugate Vaccination Programs in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah 
Published: October 2019

Abstract

Background
Pneumococcal conjugate vaccines have substantially reduced the incidence of invasive pneumococcal disease (IPD); however, the impact of the vaccine on non-vaccine serotypes (NVT) remains unclear. We evaluated the effect of PCV13 use in British Columbia, Canada.

Methods
The annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) was calculated using provincial laboratory surveillance data. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–10) and pre-PCV7 (2002–03) baselines using Poisson regression for non-conjugate vaccine type IPD.

Results
A total of 4,490 cases were reported over the 14 year period. The overall annual incidence increased from 5.73 cases per 100,000 population in 2002 to 7.90 cases per 100,000 population in 2015. Compared with baseline, PCV7 reduced VT-IPD (IRR: 0.49; 95% CI: 0.42–0.56), but the additional 6 serotypes in the PCV13 vaccine caused 214% increase in IPD (IRR: 2.65; 95% CI: 2.12–3.39). The majority of this increase is related to an increase in NVT disease (IRR: 3.17; 95% CI: 2.62–3.87) such as 23B, 23A, 9N, 20, 33F, 15C, 17F and 6C. IPD from PCV13 vaccine serotypes 19A and 7F which emerged after PCV7 continue to be high.

Conclusion
The introduction of PCV13 has a modest impact on IPD rates, due to inadequate control of serotypes 19A and 7F, and, of concern, IPD rates continue to escalate due to serotype replacement by non-vaccine serotypes.

Disclosures
All authors: No reported disclosures.