bluuebunny/crossref_metadata_2025 huggingface dataset:
2469. A National Intervention to Improve Infection Prevention Efforts in Hospitals with High Rates of Clostridioides difficile infection, Central Line-Associated Bloodstream Infection, Catheter-Associated Urinary Tract Infection and/or Methicillin-Resistant Staphylococcus aureus
Authors: Patel Payal K , Meddings Jennifer , Calfee David P , Popovich Kyle , Rohde Jeff , Rolle Andrew J , Fowler Karen E , Ameling Jessica , Ratz David , Greene M Todd , Forman Jane , Chopra Vineet , Saint Sanjay
Published: October 2019

Background

To strengthen state collaborative efforts and reduce common healthcare-associated infections (HAIs) in short-stay and long-term acute care hospitals, the Centers for Disease Control and Prevention (CDC) launched “States Targeting Reduction in Infections via Engagement” (STRIVE) - a national quality improvement program.

Methods

STRIVE consisted of a multimodal intervention implemented from November 2016 to May 2018 (Figure 1). Hospitals with excess Clostridioides difficile infection (CDI) and a high burden of at least one of the following HAIs - central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI) or methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection were targeted. Monthly aggregate HAI and device utilization ratios - according to CDC National Healthcare Safety Network definitions - were measured during the pre vs. post-intervention periods. Thematic analysis of qualitative interviews with state partners was conducted to understand the influence of the intervention.

Results

Overall, 387 hospitals from 23 states and the District of Columbia participated. Changes in HAI rates and catheter utilization are illustrated in Figure 2. From pre- to post-intervention, substantial changes in HAI rates above temporal trends were not observed (CDI, 7.0 to 5.7 per 10000 patient-days; CLABSI, 0.88 to 0.80 per 1000 catheter days; CAUTI, 1.12 to 1.04 per 1000 catheter days; MRSA bloodstream infection, 0.075 to 0.071 per 1,000 patient-days) Similarly, catheter utilization did not differ substantially between the pre- and post-intervention periods (24.05 to 22.07 central line days per 100 patient-days; 21.46 to 19.83 urinary catheter days per 100 patient-days). Qualitative analysis of 17 interviews with state partners showed that relationships among state partners and hospitals were strengthened, potentially facilitating collaboration on future infection prevention efforts.

Conclusion

Though HAI reductions were observed during STRIVE, these reductions were consistent with temporal trends. Hospitals struggling with high HAI rates may require additional novel approaches.

Disclosures

All authors: No reported disclosures.
2473. Trends in Methicillin Resistance Rate of Staphylococcus aureus among Medical Facilities Participating in Japan Nosocomial Infections Surveillance (JANIS)
Authors: Suzuki Yuka , Horikoshi Masaki , Ikeda Ai , Matsuura Hiroaki , Noda Hiroyuki , Ikeda Satomi , Tsuzuki Shinya , Nishiura Hiroshi , Yamagishi Kazumasa , Yahara Koji , Shibayama Keigo , Matsunaga Nobuaki , Hayakawa Kayoko , Ohmagari Norio
Published: October 2019

Background

The medical fee revision in 2014 economically motivated hospitals to join surveillance programs, such as Japan Nosocomial Infections Surveillance (JANIS), and rapidly increased JANIS member hospitals. The characteristics of the newly joined hospitals might have affected the reported resistance rate trends regardless of the effect of the policy itself. We examined the effect of the hospitals joining JANIS after 2014 on the trends in methicillin resistance rate of S. aureus.

Methods

We analyzed annual trends in methicillin resistance rate of S. aureus among inpatients, using JANIS datasets of 2007 to 2016, and defined oxacillin- or cefoxitin-resistant S. aureus as methicillin resistant. The dataset consisted of a total of 7,105 hospitals and 2,740,750 S. aureus test results. Hospitals were divided into two groups; joining JANIS A) before 2014 (751 hospitals), B) in and after 2014 (781 hospitals). A probit model examined their characteristics, and a panel data analysis calculated the resistance rate trends adjusted for age and sex, including interaction terms of hospitals group and year. Finally, we divided patients into quintile age groups, and conducted the same analysis by sex.

Results

The methicillin resistance rate of S. aureus decreased from 59.4% (2007) to 48.6% (2016), and the decreasing trend kept significant through the study period but 2009 (mean annual decrease: 1.2%, P < 0.05). Inpatients of hospital B had higher age (β = 0.01, P < 0.001), and more male (β = 0.005, P < 0.05), but their resistance rate was not significantly higher (β = 0.05, p = 0.12) compared with hospital A. Age stratified analysis for all hospitals found the youngest group (younger than 35 years old) of both sex had steadily low resistance rates through the period, while the older groups had higher rates, but their rates decreased continuously.

Conclusion

The methicillin resistance rates of S. aureus decreased throughout 2007 to 2016 except 2009. The patients of the hospitals newly joining JANIS were higher in age, but the resistance rate of S. aureus was not statistically different from the hospitals having joined JANIS before 2014. Also, among JANIS member hospitals, older patients had higher resistance rates than younger patients, but their rates were continuously decreasing.

Disclosures

All authors: No reported disclosures.
2482. Clinical Outcomes of Once-Daily Darunavir in Treatment-Experienced Patients with Darunavir Resistance Associated Mutations Through 48 Weeks of Treatment
Authors: Rolle Charlotte-Paige M , Marquez Omar , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin
Published: October 2019

Background

Darunavir (DRV) is a well-tolerated, potent protease inhibitor used once-daily in patients with no DRV resistance-associated mutations (RAMs) and twice-daily in those with DRV RAMs. Treatment guidelines encourage use of once-daily regimens to optimize patient adherence, convenience and tolerability. Several studies suggest that once-daily DRV retains efficacy in the setting of 1–2 DRV RAMs whereas 3 or more DRV RAMs (with multiple background PI RAMs) is needed for DRV resistance. Currently, there is little clinical data to support the long-term use of once-daily DRV in patients with DRV RAMs.

Methods

This is a retrospective study evaluating the 48-week clinical outcomes of 22 treatment-experienced patients with DRV RAMs switched to once-daily DRV between 2014 and 2017 at the Orlando Immunology Center. The primary endpoint was the proportion with virologic suppression (HIV-1 RNA< 50 copies/mL) at Week 48. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study.

Results

The median age (range) of the sample was 53 (21–77) years, median baseline CD4+ count was 609 cells/mm3, 18 (82%) had baseline HIV-1 RNA <50 copies/mL, 15 (69%) had previously used 1 or more PIs and median number (range) of baseline DRV RAMs was 2 (1–5) (Table 1). At Week 48, 20 (91%) had HIV-1 RNA <50 copies/mL; 2 (9%) virologic non-responders had HIV-1 RNA of 82 and 59,637 copies/mL and reported noncompliance (Figure 1). There was no significant change in median CD4+ count from baseline to Week 48 (+22, 95% confidence interval (CI): [−116.5; 56.0]). Once-daily DRV was associated with a significant median increase in HDL cholesterol (+82, 95% CI: [37.0; 101.0]) and a significant median decrease in LDL cholesterol (-60, 95% CI: [-89.5; -31.0]). There were no significant changes in the proportion of patients on lipid lowering therapy at baseline and week 48 (p = 0.33). There were no self-reported AEs or Grade 3–4 lab abnormalities through Week 48.

Conclusion

Once-daily DRV maintained virologic control in this cohort of treatment-experienced patients with 1 or more baseline DRV RAMs and was safe and well-tolerated. This suggests that once-daily DRV may be effective in this population however further data are needed to validate this as a viable treatment option.

Disclosures

All authors: No reported disclosures.
2489. Adverse Events with Biktarvy: Post-Marketing Study
Authors: Hayes Edwin , Derrick Caroline , Smalls Danielle , Smith Hilary , Kremer Nicole , Weissman Sharon
Published: October 2019

Background

Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) was FDA approved in February 2018. There are no published post-marketing data evaluating safety and efficacy. After large uptake of BIC/FTC/TAF at our institution, reports of rash prompted a real-world review. The purpose of this study was to assess one year post-marketing safety and tolerability of BIC/FTC/TAF.

Methods

This retrospective, observational, pharmacoepidemiologic study was conducted one year post-approval of BIC/FTC/TAF, between February 2018 and March 2019 at the University of South Carolina Immunology Center. Adults receiving BIC/FTC/TAF were included. Drug discontinuation and treatment-related adverse effects were evaluated. Baseline demographics and serial laboratory data were collected.

Results

A total of 201 patients were assessed. Of those, the majority were treatment experienced (181, 90%), African American (137, 68%) males (132, 65%) with a mean age of 46 years (range 20–76 years). Four patients were transgender. 135 (67%) had a BMI of ≥ 25 kg/m2 and 77 (38%) had a BMI of ≥ 30 kg/m2. At baseline, 146 (72.6%) had virologic suppression (VS) (< 200 copies/mL) with a mean CD4 count of 529 cells/mm3 (range < 35–1573 cells/mm3). VS was maintained in 145/146 and subsequently reached in 47/55 (85.5%) at first follow-up. Of the 201, 18 (8.9%) patients reported adverse drug events (ADEs) for a total of 19 events (10 rash, 2 dizziness, 1 nausea/vomiting, 1 headache, 1 diarrhea, 1 loss of appetite, 1 weight gain, 1 fatigue, 1 insomnia). Eleven (5%) patients discontinued therapy; nine (4%) due to ADEs (7 rash, 1 insomnia and loss of appetite, and 1 feeling unwell). One patient with high AST/ALT at baseline increased from 129/243 U/L to 234/394 U/L, respectively. No other laboratory abnormalities were reported.

Conclusion

In a southern, predominantly African American overweight population, our results demonstrate low discontinuation rates associated with BIC/FTC/TAF, with rash being the predominate cause. Overall, 4% discontinued BIC/FTC/TAF due to ADEs compared with 1% as reported in the package insert. VS rates were high throughout the evaluation period. Ongoing post-marketing evaluation is important for early recognition of unexpected adverse outcomes.

Disclosures

All authors: No reported disclosures.
2512. Decreasing Adherence to Antiretroviral Therapy over 4 Years of Follow-up in a Commercially-Insured Population of Patients with HIV
Authors: Priest Julie , Bhak Rachel , DerSarkissian Maral , Garris Cindy , Oglesby Alan , Kunzweiler Colin , Fuqua Ellie , Park Suna , Sheng Duh Mei
Published: October 2019

Background

This study compared yearly and longer term antiretroviral (ARV) adherence among HIV patients overall and by single-tablet regimens (STRs) vs. multi-tablet regimens (MTRs).

Methods

A retrospective study using Optum Clinformatics US-based claims data was conducted. Patients with an HIV-1 diagnosis during 2011–2017, age ≥ 18 years at index (date of first complete ARV regimen during the study period), and continuous enrollment for ≥ 3 months before index (baseline) and ≥ 12 months after index (observation) were included. MTRs were required to be comprised of 3 or more agents across at least 2 classes. Adherence was measured as the proportion of days covered (PDC) and compared using a Chi-square test. PDC was examined in the 1-year observation period for the overall analysis, and each year following index among patients with at least 4 years of continuous data. A subgroup analysis was conducted among patients with index during 2014–2016 to evaluate modern ARV adherence.

Results

Among the 15,153 included patients, median age was 45 years, the majority were male (88%), and 53% were in the South. At baseline, 58% (n = 8,715) were receiving an STR and 43% (n = 6,438) an MTR. Compared with STR patients, MTR patients had higher prevalence of hyperlipidemia (36% vs. 29%), cardiovascular disease (27% vs. 21%), and hypertension (25% vs. 20%). During year 1, the proportion of patients with PDC ≥ 0.90 was 63% overall (Table 1), and greater for STR than MTR (67% vs. 58%, P < .001). Among patients with at least 4 years of observation, PDC ≥ 0.90 decreased over time (from 67% in year 1 to 53% in year 4). In the subgroup of patients with index during 2014–2016 (Table 2), similar but slightly worse trends were observed, with PDC ≥ 0.90 for 57% of patients overall, and decreasing over time for those patients with at least 3 years of observation (59% in year 1 to 42% in year 3).

Conclusion

Adherence in this population of patients with HIV showed room for improvement in the first year of observation overall and in the modern ARV era, with those receiving STRs having higher adherence when compared with those receiving MTRs. For the patients with 4 years of follow-up, adherence tended to decrease year on year. Maintaining high rates of ARV adherence is a critically important aspect of therapy for patients with HIV.

Disclosures

All authors: No reported disclosures.
2516. Persistence of Anti-HIV Antibodies in HIV-1-infected Patients on Combination Antiretroviral Therapy (cART) with Prolonged Viral Suppression
Authors: Singh Kanal , Davis Ivery , Dewar Robin L , Imamichi Hiromi , Lane H Clifford
Published: October 2019

Background

Despite years of cART with sustained HIV-RNA plasma viral load (pVL) < 50 copies/mL, antibodies (Abs) to HIV-1 proteins persist. The reasons for this are unknown but may reflect long-lived B cell responses and/or persistence of antigen. To address which of these may be the case, we compared decay rates of anti-HIV Abs to those of anti-Measles Abs.

Methods

A cohort of 10 HIV-infected patients on cART with pVL < 50 (average 3 years, range 0–7.1 years) were studied. Baseline and 5-year follow-up serum were collected and assessed for anti-HIV-1 Abs via western blot (Cambridge Biotech WB kit), with additional densiometric analysis used for quantitative calculation of a western blot “score” that was normalized to control specimens. The kinetics of measles Abs titers over the same 5-year period were also analyzed by the quantitative Serion Measles IgG ELISA kit, given a history of prior vaccination in these participants. McNemar’s and paired t-tests were used for analysis.

Results

All 10 patients exhibited persistence of anti-HIV-1 Abs at ≥ 5 year follow-up as determined by persistence of ≥ 2 diagnostic bands on WB (P = 0.003). The patterns for all 10 participants varied individually by patient with each exhibiting a unique profile (representative figure); 7/10 patients had WBs that could be analyzed quantitatively and showed no significant change over the study period (average baseline score 5.9 vs 5.3 at follow-up, P = 0.26). 7/9 patients had valid measles IgG measurements showing a consistent but nonsignificant decline over the same 5-year study period (measles titer 55–2800 mIU/mL at baseline vs 50–1300 mIU/mL at follow-up, n = 9, P = 0.18).

Conclusion

The mechanism leading to the persistence of anti-HIV-1 Abs in HIV-infected individuals with prolonged viral suppression has been unclear. The general decline in anti-Measles IgG titer over the 5-year observational period in 7/9 patients is likely to be explained by waning B cell-mediated humoral immunity in these vaccinated individuals and consistent with their lack of ongoing exposure to this pathogen. The persistence of anti-HIV-1 Abs over the same 5-year period, on the other hand, may indicate persistent HIV-1 viral protein production either from active reservoirs or by transcription of “defective” HIV-1 proviruses as recently reported.

Disclosures

All authors: No reported disclosures.
2520. Resource utilization in adolescents and young adults with HIV in the HIV Research Network
Authors: Neilan Anne M , Lu Frances , Gebo Kelly , Diaz-Reyez Rebeca , Huang Mingshu , Parker Robert , Karalius Brad , Patel Kunjal , Voss Cindy , Ciaranello Andrea , Agwu Allison
Published: October 2019

Background

Adolescents and young adults (AYA) with HIV experience worse health outcomes than adults with HIV in the United States. Little is known about AYA patterns of utilization of costly healthcare resources.

Methods

We estimated utilization of outpatient, emergency department (ED), and inpatient care among 13–30 year-olds from 2006–2015. We stratified outpatient visits, ED visits and inpatient days per person-year (PY) by transmission mode (perinatal (PHIVY), non-perinatal (NPHIVY), age (13–17, 18–23, 24–30 years), CD4 strata (< 200, 200–499, ≥ 500 cells/µL) and presence or absence of viral load (VL) suppression (<, ≥ 400 copies/mL[c/mL]) combined with antiretroviral (ARV) use. We also quantified outpatient, ED, and inpatient care associated with specific AIDS-defining conditions.

Results

Among 4,450 AYA (PHIVY: 15%; NPHIVY: 85%), mean (SD) follow-up was 2.8 years (2.5) [PHIVY: 4.2 years (3.1); NPHIVY: 2.5 years (2.3)]. Mean age was 21.4 years (PHIVY: 16.9 years; NPHIVY: 22.3 years) and female sex was 28% (PHIVY: 52%; NPHIVY: 23%). Among PHIVY, most person-time (PT) was spent between ages 13–23 years (13–17 years: 43%; 18–23 years: 45%), CD4 ≥ 500/µL (61%), and VL < 400 c/mL (69%). Among NPHIVY, most PT was spent between ages 24 and 30 years (56%), CD4 ≥ 500/µL (54%), and VL < 400 c/mL (66%). PT spent while prescribed ARVs and VL ≥ 400 c/mL was 30% (PHIVY) and 24% (NPHIVY). For both PHIVY and NPHIVY, outpatient visit rates were higher at younger ages (13–17 years and 18–23 years), lower CD4 (< 200, 200–499/µL), and among those prescribed ARVs (Figure 1). Rates of ED visits and inpatient days were higher during PT spent at older ages (18–23 years, 24–30 years), lower CD4 (< 200, 200–499/µL), and VL ≥ 400 c/mL (Figures 2 and 3). Overall, utilization was higher among PHIVY than NPHIVY (outpatient: 12.1 vs. 6.0/PY; ED: 0.4 vs. 0.3/PY; inpatient: 1.5 vs. 0.8/PY). The overall rate of AIDS-defining conditions was 4.5/100 PY (Figure 4).

Conclusion

Among AYA with HIV, more ED visits and inpatient days were observed during time spent at older ages, lower CD4 counts, and VL ≥ 400 c/mL. While AIDS-defining conditions were rare, associated resource utilization was substantial. Interventions to improve retention in care, virologic suppression, and immune response may improve outcomes, and thus decrease costly resource utilization, for AYA with HIV as they transition to adulthood.

Disclosures

All authors: No reported disclosures.
2545. Needs Assessment for a Presentation Skills Curriculum in an Infectious Diseases Fellowship Program
Authors: Bares Sara H , Van Schooneveld Trevor C , Marcelin Jasmine R , Marcelin Jasmine R , Nada Fadul , Zimmer Andrea
Published: October 2019

Background

Presentation skills are critical for infectious diseases fellows regardless of their ultimate career path. Despite this, there is little emphasis on training in presentation skills within the infectious diseases (ID) fellowship curricula.

Methods

To determine the perceived need for a presentation skills curriculum for ID fellows, faculty and fellows were asked to complete a brief online needs assessment. The survey included questions on demographics, prior presentation experience and skills training, perceived need for and interest in a presentation skills curriculum, and the preferred modality for such a curriculum. Descriptive statistics were calculated for each theme.

Results

In April 2019, 4/4 fellows and 15/22 faculty members completed the online survey. While all fellows (100%) agreed or strongly agreed their presentation skills could be improved, only 50% wanted more feedback about their presentation skills and only 50% were interested in training to improve their presentation skills (Figure 1). Concerns about time constraints were noted in the optional comments. Most faculty (87%) agreed or strongly agreed that fellow presentation skills could be improved and most felt empowered (73%) and were willing (73%) to provide the fellows with feedback. Only 27% of faculty reported prior training in presentation skills and 60% expressed an interest in receiving training before providing the fellows with feedback. Regarding presentation skills feedback modalities (Figure 2), fellow respondents expressed a preference for written feedback (75%) and in-person, one-on-one feedback (75%); faculty respondents were willing to provide written feedback (93%), in-person, one-on-one feedback (80%) and in-person feedback with a group of other faculty (73%).

Conclusion

This study provides a framework for ID fellowship programs interested in developing a presentation skills curriculum. The results support the need for a presentation skills curriculum, but interest in such a curriculum is not universal. Our findings will guide the development and structure of a curriculum that will target interested faculty and aim to benefit the fellows without putting an undue onus on their time and other commitments.

Disclosures

All authors: No reported disclosures.
2577. Periodontal Disease and the Oral Microbiome in Alcohol-Dependent Individuals
Authors: Meeks Brianna K , Barb Jen , Mudra Sarah E , Kazmi Narjis , Tuason, Ralph T S , Schuebel Kornel , Brooks Alyssa T , Krumlauf Michael , Brenchley Laurie , Gardner Pamela J , Goldman David , Wallen Gwenyth R , Ames Nancy J
Published: October 2019

Background

Periodontal disease results from a polymicrobial infection composed of pathogenic bacteria that colonize the oral cavity, resulting in loss of periodontal attachment and alveolar bone. Periodontitis can increase the risk or exacerbate other comorbidities. Alcohol use increases the risk of periodontitis, but there is little knowledge about periodontitis among people who misuse alcohol.

Methods

As part of a larger oral and gut microbiome study, this analysis examines the oral microbiome in the occurrence and severity of periodontitis among alcohol-dependent (AD) subjects undergoing a 28-day inpatient alcohol treatment program. Tongue brushings were collected from 22 subjects within the first week of admission, and 16S rDNA sequencing was performed. All subjects had a dental examination during the inpatient stay. This analysis divided periodontal disease status into three major groups–no disease, mild or moderate disease, and severe disease. One-way ANOVA was used to compare microbial genera across the 3 groups.

Results

Nineteen (86%) of the subjects had periodontitis: 16 had mild or moderate disease, and 3 had severe disease. Statistically different microbial genera in at least one of the three groups (P ≤ 0.05 corresponding to FDR ≤ 0.25) that had a relative abundance of at least 0.5% include: Bifidobacterium, Lactobacillus, Parvimonas, Peptostreptococcus, Porphyromonas, and Treponema. Surprisingly, the subjects with no periodontitis had increased abundances of genera that are often pathogens, Porphyromonas and Peptostreptococcus. Subjects with severe periodontitis had increased abundances of known pathogens Treponema and Parvimonas, as well as Lactobacillus, which has been associated with dental caries.

Conclusion

We observed that periodontitis accompanies chronic AD, given that 86% of our subjects had the disease. While some microbiome differences for individuals with and without periodontitis were not consistent with the existing literature, this may have many explanations. Future studies should consider how chronic AD could change the microbial ecology of the mouth and lead to further infection as well as utilizing multiple oral sites and a larger sample size to better understand the relationship between AD and periodontal disease.

Intramural funds from NIH

Disclosures

All authors: No reported disclosures.
2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France
Authors: Levast Benoit , Batailler Cécile , Pouderoux Cécile , Boucihna Lilia , Lustig Sébastien , Boutoille David , Dauchy Frederic-Antoin , Zeller Valérie , Senneville Eric , Maynard Marianne , Laurent Frederic , Ferry Tristan
Published: October 2019

Background

There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not.

Methods

Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation.

Results

Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI.

Conclusion

The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation.

Disclosures

All authors: No reported disclosures.
2580. Serial Microbiome Analysis in a Patient with Multiple Failed Fecal Microbiome Transplantations
Authors: Gonzales-Luna Anne J , Lancaster Chris , Khan M A Wadud , Begum Khurshida , Endres Bradley T , Rashid Tasnuva , Carlson Travis J , Alam M Jahangir , Garey Kevin W
Published: October 2019

Background

Fecal microbiota transplantation (FMT) is recommended to treat refractory or recurrent cases of Clostridioides difficile infection (CDI) through restoration of a healthy intestinal microbiome. The procedure has reported success rates of 90% or higher for CDI, but several risk factors for FMT failure have been identified. Here we present a case of a patient failing four FMT procedures over a 2-year period, with accompanying microbiome and metagenomic analyses.

Methods

Seven serial C. difficile-positive stool samples were collected as part of an ongoing surveillance system in Texas. Samples, including the index case, represented independent CDI episodes interspersed between four separate FMT procedures between 2016 and 2018. PCR ribotype (RT) testing, 16S rRNA gene sequencing, MIC testing, multidrug-resistant organism (MDRO) screening, and shotgun metagenome sequencing were conducted for each of the samples.

Results

The patient was a 42-year-old female with various comorbidities, including systemic lupus erythematosus. She received continuous non-CDI antibiotic courses throughout her CDI therapy for a variety of infections. The vancomycin MICs in infecting C. difficile strains increased with cumulative vancomycin exposure. Multidrug-resistant organisms were detected in stool, including Enterococcus spp., MRSA, and Candida glabrata. The first five of the seven strains were RT 078–126, one was mixed RT 002 and RT 054, and one was RT 002. The analysis of 16S rRNA gene sequences demonstrated that microbial diversity was never restored after FMT procedures. A strong correlation between microbial and functional gene compositions suggests that fecal samples share many microbial species with associated functional genes.

Conclusion

A number of systems biology changes were observed in a patient with persistent CDI despite multiple FMTs. The lack of FMT engraftment was most likely due to continuous broad-spectrum antibiotic exposure in an immunocompromised patient.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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.