bluuebunny/crossref_metadata_2025_split huggingface dataset:
1198. Measurement of Pre-transplant Anti-cytomegalovirus (CMV) Immunoglobulin G Titer to Predict Risk of CMV Infection in CMV-seropositive Kidney Transplant Recipients
Authors: Kirisri Similan , Vongsakulyanon Apirom , Kantachuvesiri Surasak , Bruminhent Jackrapong 
Published: January 2021

Abstract

Background
Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a lower risk of CMV infection compared with CMV-seronegative recipients, some patients remain at risk of CMV infection after transplant. Low pre-transplant anti-CMV immunoglobulin G (IgG) titer has been reported as a predictor of CMV infection in CMV-seropositive liver and heart transplant recipients, but this association in CMV-seropositive kidney transplant (KT) recipients has not been explored. We investigated the pre-transplant anti-CMV IgG titer and other CMV infection risk factors in CMV-seropositive KT recipients.

Methods
This retrospective study was conducted on CMV-seropositive KT recipients aged &gt;18 years old at Ramathibodi Hospital during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. The pre-transplant anti-CMV IgG titer was measured with an enzyme-linked fluorescent immunoassay. Risk factors for CMV infection were analyzed with Cox proportional hazards models.

Results
Of the 340 included CMV-seropositive KT recipients (37% female; age [mean±SD]: 43±11 years), 69% and 64% received deceased-donor allograft and induction therapy, respectively. The anti-CMV IgG titer was &lt; 20 and &gt;20 AU/ml in 7.1% and 92.9% of patients, respectively. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%, including both asymptomatic CMV infection (69%) and tissue-invasive disease (31%). A pre-transplant anti-CMV IgG titer of &lt; 20 AU/ml was significantly associated with CMV infection in both the univariate analysis (HR, 2.70; 95%CI, 1.21–6.05, [p=0.02]) and the multivariate analysis (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant risk factors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]).

Conclusion
A low pre-transplant CMV-specific humoral immunity is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. The universally available anti-CMV IgG titer test could potentially stratify those at risk and target preventive strategy appropriately.

Disclosures
All Authors: No reported disclosures
1205. Protectin D1 Induced by Clostridium butyricum MIYAIRI 588 Has an Anti-inflammatory Effects on Antibiotic-induced Intestinal Disorder
Authors: Ariyoshi Tadashi , Hagihara Mao , Egushi Shuhei , Aiki Fukuda , Oka Kentaro , Takahashi Motomichi , Mikamo Hiroshige 
Published: January 2021

Abstract

Background
The administration of Clostridium butyricum MIYAIRI 588 (CBM 588) upregulates protectin D1,the anti-inflammatory lipid metabolites, in colon tissue under the antibiotic therapy. However, how CBM 588 induces protectin D1 nor whether the metabolite has anti-inflammatory effects on antibiotic-induced enteritis are unclear. Therefore, we evaluated the effect of CBM 588 on lipid metabolism and protectin D1 on immunological functions in colon tissue.

Methods
Mice were divided into five groups and clindamycin (CLDM), CBM 588 and/or protectin D1 were administered for 4 days (1. Control, 2. CLDM group, 3. CBM 588 group, 4. CLDM plus CBM 588 group and 5. CLDM plus protectin D1 group). After 4 days of administration, mice were reared for an additional 4 days. On day 8, colon tissues were removed to measure lipid metabolites with LC-MS/MS. Also, cytokines, lipid metabolism relative genes, enzymes were measured with qRT-PCR and ELISA.

Results
In the CBM588 treatment group, protectin D1, α-linolenic acid, eicosapentaenoic acid (EPA) and autoxidation product of DHA (docosahexaenoic acid) were significantly increased, compared with CLDM group and control. At the same time, genes expression levels of polyunsaturated fatty acids (PUFAs) receptors, G-protein coupled receptor 120 (GPR120) and a DHA to protectin D1 metabolizing enzyme 15- lipoxygenase (LOX) in colon tissue increased. Il-4 produced by Th2 cells, also increased in CBM588 treated groups even under CLDM co-administration. In addition, similar to CBM 588, protectin D1 administration suppressed mice’s weight loss due to gut inflammation, decreased inflammatory cytokines, while anti-inflammatory cytokine IL-10 and TGF-β1 increased.
PUFAs metabolism cascade induced by CBM 588.

Lipid metabolism relative genes, pro/anti-inflammatory cytokines and body weight.

Conclusion
Our data suggested that CBM 588 stimulated PUFAs metabolism in the intestinal tract, and that PUFAs were signaled to Th2 cells as a ligand of GPR120. It was speculated that the stimulated Th2 cells produced IL4 and activated 15-LOX, resulting in the induction of protectin D1. Also, it became clear that protectin D1 induced anti-inflammatory cytokines in controlling antibiotic-induced gut inflammation. We provide as a new insight that lipid metabolism induction for the treatment of gut inflammatory diseases with CBM 588.
Anti-inflammatory pathway of protectin D1 induced by CBM 588.

Disclosures
Hiroshige Mikamo, M.D, Ph.D, Astellas Pharma Inc. (Grant/Research Support, Speaker’s Bureau)MSD Japan (Grant/Research Support, Speaker’s Bureau)Pfizer Japan Inc. (Grant/Research Support)Sumitomo Dainippon Pharma Co., Ltd (Grant/Research Support, Speaker’s Bureau)
1206. Association of Aging, Frailty and Place of Residence with Skin, Oral and Gut Microbiome Characteristics and Pathogenicity Reservoirs
Authors: Larson Peter J , Oh Julia , Robison Julie , Grady James , Kuchel George 
Published: January 2021

Abstract

Background
Despite their elevated risk for morbidity and mortality from infections, the microbiota of older adults remain understudied. While colonization resistance from resident microflora is a promising means to prevent infections, little is known about pathogenicity reservoirs and colonization resistance in this vulnerable population. Here we study the skin, oral, and gut microbiome dynamics of older adults in both community and Skilled Nursing Facility (SNF) settings, investigating relationships between age, frailty, environment, microbiota, and pathogenicity reservoirs.

Methods
We conducted a longitudinal metagenome survey of 47 adults age 65+ years of age; 22 residents of 3 different SNFs and 25 community dwelling individuals. We performed metagenomic whole genome shotgun sequencing on stool, oral, and skin samples from 8 sites, 1421 total. To correlate clinical and behavioral variables, we measured frailty, collected medical records, and interviewed participants on diet and lifestyle. We also draw comparisons with previous younger cohorts.

Results
• Compared to younger adults, the skin microbiota of older adults was characterized by
◦ High heterogeneity
◦ Decreased stability over time, suggesting increased susceptibility to colonization and pathogenicity
◦ Compositional differences including significantly lower levels of Cutibacterium acnes, with reciprocal increases in Staphylococci, Corynebacteria, and Malassezia
• In older adults, Frailty (Rockwood) was found to have linear correlation with relative abundance of species relevant to infection risk including acnes, staphylococci, streptococci, E. coli, Akkermansia mucinophila, and Enterococcus faecalis.
• The skin, oral, and gut microbiota of SNF residents had substantially elevated virulence factor and antibiotic resistance genes.

Conclusion
To the best of our knowledge, this is largest report to date of the skin metagenome in older adults. We demonstrate distinct and significant differences between cohorts with clinically relevant implications. We believe these results may inform infection control and prevention by increasing our understanding of colonization resistance and pathogenicity reservoirs, as well as advance our knowledge of the relationship between aging, the microbiome, and infections.

Disclosures
All Authors: No reported disclosures
1209. Impact of Respiratory Staphylococcus aureus Abundance on Risk for Ventilator-Associated Pneumonia During Long-Term Care
Authors: Harrigan James J , Abdallah Hatem , Clarke Erik , Lautenbach Ebbing , Reesey Emily , Wernovsky Magda , Tolomeo Pam C , Morawski Zygmunt , Jacob Jerry , Grippi Michael , Kelly Brendan 
Published: January 2021

Abstract

Background
Patients admitted to long-term acute care hospital (LTACH) for ventilator weaning are at high risk for ventilator-associated pneumonia, which may contribute to adverse ventilator-associated events (VAE). Staphylococcus aureus (Sa) is a common cause of VAP. We sought to evaluate the impact of respiratory Sa colonization and bacterial community dominance on subsequent Sa VAP and VAE during long-term acute care.

Methods
We enrolled 83 subjects dependent on mechanical ventilation at LTACH admission, collected endotracheal aspirates, performed 16S rRNA gene sequencing (Illumina HiSeq) and bacterial community profiling (QIIME2). Statistical analysis was performed with R and Stan; mixed effects models were fit to relate the abundance of respiratory Sa on admission to clinically-diagnosed VAP and VAE.

Results
Of the 83 subjects, 8 were diagnosed with Sa pneumonia during the 14 days prior to LTACH admission (“Known Sa”), and 17 additional subjects received anti- Sa antibiotics within 48 hours of admission (“Suspected Sa”); 58 subjects had no known or suspected Sa (“Unknown Sa”). Among the Known Sa group, all 8 had Sa detectable by 16S sequencing, with elevated admission Sa proportional abundance (median 0.36; range 0.0013 - 1). Among the Suspected Sa group, only 7 had Sa detectable by 16S sequencing, with a wide range of admission Sa proportional abundance (median 0; range 0 - 0.96). 25 of 58 subjects in the Unknown Sa group also had detectable respiratory Sa, and a wide range of Sa proportional abundance at admission (median 0; range 0 - 0.93). Incident Sa VAP was observed within 30 days among 2 (25%) of the Known Sa subjects, 0 (0%) of the Suspected Sa subjects, and 3 (5.17%) of the Unknown Sa subjects. VAE was observed within 30 days among 0 (0%) of the Known Sa subjects, 3 (18%) of the Suspected Sa subjects, and 1 (1.7%) of the Unknown Sa subjects. Admission Sa abundance was positively associated with 30-day VAP risk in the Suspected Sa (type S error &lt; 0.001) and Unknown Sa (type S error &lt; 0.001) groups.

Conclusion
Among patients admitted to LTACH for weaning for mechanical ventilation, we observed a high prevalence of respiratory Sa colonization. Respiratory Sa abundance was associated with risk of incident Sa VAP, particularly among subjects without recognized Sa colonization.

Disclosures
All Authors: No reported disclosures
1213. A TRAIL/IP-10/CRP Signature Distinguishes between Viral and Bacterial Infection in Chronic Obstructive Pulmonary Disease Patients
Authors: Paz Meital , Halabi Salim , Shiber Shachaf , Neuberger Ami , Petersiel Neta , Grupper Mordechai , Kirshner Dani , Avni Noa , Stein Michal , Kronenfeld Gali , Shani Liran , Gottlieb Tanya , Lishtzinsky Ynon , Maor Yasmin , Yanai Shirly , Oved Kfir , Eden Eran , Drescher Michael , Paul Michal 
Published: January 2021

Abstract

Background
Challenges in determining the etiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant overuse of antibiotics. A new host-response assay that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind pediatric validation studies. Here we sought to evaluate its ability to differentiate bacterial from viral infection in adult COPD patients with suspicion of lower respiratory tract infection (LRTI).

Methods
The study population included 492 febrile adult patients prospectively recruited in “Observer”, an EU Horizon 2020 funded study (grant #684589). Patient etiology was determined by majority expert panel based on clinical, laboratory, multiplex PCR, radiological and follow-up data. We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal.

Results
45 out 492 adult patients prospectively recruited with suspicion of LRTI had a medical history of COPD. Of these, 20 cases were assigned as suspected viral infections and 19 as suspected bacterial infections (Figure 1). Antibiotics were prescribed to 19/19 bacterial infections and 16/20 viral infections. The assay correctly classified 19/19 bacterial infections and 12/20 viral infections, with 2 viral cases classified by the assay as bacterial and 6 receiving an equivocal outcome. These data support the assay’s potential to reduce antibiotic overuse from 16/20=80% to 8/20=40% (P=0.01).
FIgure 1: Flow through of COPD patients in prospective performance validation study “Observer”

Conclusion
A new TRAIL/IP-10/CRP signature has potential to significantly reduce antibiotic overuse for patients with suspected LRTI and a history of COPD without missing bacterial infection.

Disclosures
Meital Paz, MD, MeMed Ltd. (Employee) Noa Avni, PhD, MeMed (Employee) Michal Stein, MeMed Ltd. (Employee) Liran Shani, MD, MeMed Ltd. (Employee) Tanya Gottlieb, PhD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Employee) Eran Eden, PhD, MeMed (Employee)
1219. Diagnosing vaginal discharge syndrome and its potential impact on clinical practice in a regional hospital in Taiwan
Authors: Huang Sung-Hsi , Hsu Heng-Cheng , Lee Tai-Fen , Fan Hui-Ming , Tseng Chi-Wei , Hsu Hong-Ming , Hung Chien-Ching 
Published: January 2021

Abstract

Background
Vaginal discharges are frequently encountered in clinical practice and usually managed empirically. We aimed to investigate the prevalence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomoniasis among adult women of reproductive age and evaluate the appropriateness of empirical treatment.

Methods
Non-pregnant women between the age of 20 and 49 years who presented with vaginal discharge were prospectively enrolled in a teaching hospital since Oct 2018. Vaginal swabs were collected for determination of Nugent score, culture for Trichomonas vaginalis (TV) and Candida species, and multiplex polymerase chain reaction (PCR) for BV, VVC and TV. Demographics, symptoms, physical findings, and the empirical treatment were recorded.

Results
From Oct 2018 to May 2020, 172 women were included (median age, 37 years). The prevalence of laboratory confirmed BV, VVC, and TV was 21.5% (n=37), 20.3% (35), and 0.6% (1), respectively. Ten (5.8%) women had concurrent BV and VCC. Among 38 women who had bacterial vaginosis or trichomoniasis, only 8 (21.1%) received metronidazole empirically while more than half (11/19, 57.9%) of women who received metronidazole empirically did not have laboratory-confirmed bacterial vaginosis or trichomoniasis. Among 35 women who had candidiasis, 10 (28.6%) received antifungal agents. Antifungal agents were prescribed to more than two thirds (21/31, 67.7%) of women who did not have laboratory confirmed candidiasis. Overall, 58.7% (101/172) of empirical treatment was deemed optimal. Multiplex PCR test has an overall diagnostic accuracy of 86.0% (148/172) as compared to the composite gold standard.

Conclusion
The empirical treatment for vaginal discharge syndrome is suboptimal. Better diagnostic assays have a potential to improve clinical patient care.

Disclosures
All Authors: No reported disclosures
96. Assessing the Impact of the Meningitis/encephalitis Diagnostic Panel on Antimicrobial Stewardship
Authors: Garellek Jonathan , Doan Thien-Ly , Varghese Shawn , Schwartz Rebecca , Rasul Rehana , Donaghy Henry 
Published: January 2021

Abstract

Background
The multiplex polymerase chain reaction (PCR) test for meningitis/encephalitis (ME) is an assay that is available to detect 14 organisms in 2 hours from the cerebral spinal fluid. The primary objective was to assess the clinical impact of this assay on antimicrobial stewardship.

Methods
This is an IRB-approved, retrospective cohort study of a random sample of patients admitted between 7/2015 - 12/2018, stratified by season. A chart review was performed to collect: demographics, microbiology/treatment data, length of stay, hospital readmissions, and mortality. Differences for ME PCR versus culture only were assessed using Chi-square test or Fisher’s exact test. Time to de-escalation of empiric therapy was compared using the log-rank test.

Results
The study consisted of 241 patients, of whom 161 (66.8%) had CSF-PCR testing performed. Mean age was 51.76. There was an even distribution of males and females. Aside from patients with HIV, who were more represented in the standard period, there were no differences by comorbidity. The etiology of meningitis was greater in the PCR compared to the non-PCR group (10.5% vs. 2.5% in PCR and non-PCR respectively). Time to de-escalation of empiric therapy was significantly shorter in the PCR period (median [IQR]: 43.06 [26.9–47.7] vs. 64.62 [37.18–83.33], P&lt; 0.004). Total days of therapy of antibiotics was longer among the PCR group, but not statistically significant (median [IQR] = 4 [1–7] vs. 2 [1–4], P=0.121). Median length of stay was higher in the PCR period compared to the standard group (median [IQR]: 9 [6 - 15] vs. 5.5 [3 - 8.5], P&lt; 0.004). Readmission rates did not differ (PCR 13.7% vs. non-PCR 16.3%, P=0.592). More died during the PCR period (8.6% vs. 3.8%, P=0.16) but this was not statistically significant.

Conclusion
The ME PCR was associated with an earlier time to antibiotics de-escalation. Patients that had the PCR test performed had more days of therapy and longer length of stay, but this is likely due to a higher rate of pathogen diagnosed. There was no association in readmissions. The initiation of rapid diagnostic testing in a healthcare settings has the potential to improve patient outcomes and may help antimicrobial stewardship by shortening the time to de-escalating antimicrobials and offering appropriate targeted therapy.

Disclosures
All Authors: No reported disclosures
1227. Plazomicin Susceptibility Testing using ETEST® MIC for Enterobacterales
Authors: Ying Yun , Armstrong Tom , Blanchard Laurine , Kresken Michael , Zambardi Gilles , Pompilio Marion 
Published: January 2021

Abstract

Background
Plazomicin (PLZ) approved by FDA in June of 2018, is an aminoglycoside class antibacterial indicated for the treatment of adults with complicated urinary tract infections (cUTI) including pyelonephritis caused by Enterobacterales. It is used in patients who have limited or no alternative treatment options, e.g. CRE and MDRO patients. The drug has bactericidal activity, it is active against organisms producing ESBL, Carbapenemase and aminoglycoside-modifying enzymes. The purpose of this study was to compare ETEST® PLZ bioMérieux to the broth microdilution reference method (BMD) for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and pneumoniae, Morganella morganii, Providencia stuartii, Proteus mirabilis and vulgaris and Serratia marcescens isolates.

Methods
A total of 598 isolates were tested by ETEST® (PLZ) and BMD at four clinical trial sites.
Isolates were subcultured on tryptic soy or Columbia agar plates supplemented with 5% sheep blood. Suspensions of the isolates were prepared in 0.85% saline, which were used to inoculate BMD and Mueller Hinton agar for ETEST®. Results were read after 16-20 hours incubation at 35°C +2°C in ambient air. QC organisms were tested with each run following CLSI QC guidelines.
Results were analyzed using FDA breakpoints for PLZ (Susceptible &lt;2 µg/mL, Intermediate 4 µg/mL, Resistant &gt;8 µg/mL).
Performance was evaluated using FDA performance criteria, EA and CA (≥ 90%), major error rate (≤3.0%) and very major error rate (≤2.0%).

Results

Conclusion
ETEST® PLZ clinical performance met the FDA acceptance criteria and was found useful for determining Plazomicin MIC of Enterobacterales, including ESBL, CRE (MBL, KPC, Oxa-48), high level AmpC and aminoglycoside resistant strains. Percent susceptibility of Plazomicin is at 80% among the 598 isolates tested, the mode MIC is 0.5 ug/ml as Susceptible.

Disclosures
Tom Armstrong, BS, bioMérieux (Employee) Laurine Blanchard, PhD, bioMérieux (Employee) Michael Kresken, PhD, bioMérieux (Scientific Research Study Investigator, Research Grant or Support) Gilles Zambardi, biomerieux (Employee) Marion Pompilio, BioMérieux (Employee)
1232. Efficacy and Safety of Intravenous Sulopenem Followed by Oral Sulopenem etzadroxil/Probenecid Versus Intravenous Ertapenem Followed by Oral Ciprofloxacin or Amoxicillin-clavulanate in the Treatment of Complicated Urinary Tract Infections (cUTI): Results from the SURE-2 Trial
Authors: Dunne Michael W , Aronin Steven I 
Published: January 2021

Abstract

Background
Sulopenem is a broad-spectrum IV and oral penem antibiotic being developed for the treatment of infections caused by multidrug-resistant bacteria to allow for earlier discharge of hospitalized patients.

Methods
1,395 hospitalized adults with pyuria, bacteriuria, and clinical signs and symptoms of cUTI were randomized to sulopenem IV once daily for 5 days followed by a bilayer tablet of sulopenem-etzadroxil and probenecid bid or ertapenem IV once daily for 5 days followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on susceptibility of the baseline uropathogen. The primary endpoint was overall (clinical and microbiologic) response at Day 21 [Test of Cure (TOC)] in the micro-MITT population.

Results
The sulopenem and ertapenem treatment arms were well-balanced at baseline.
The difference in overall response was driven by a difference in asymptomatic bacteriuria occurring between the end of treatment (EOT) and TOC in the subgroup of patients with a ciprofloxacin susceptible uropathogen at baseline who received ertapenem IV followed by oral ciprofloxacin. No difference in overall response was identified at EOT [86.7% vs 88.9%, sulopenem and ertapenem, respectively; difference, 95% CI: -2.2% (-6.5, 2.2)].
19% of patients remained on ertapenem IV as the baseline pathogen was both resistant to quinolones and ESBL positive; overall response for patients with these resistant pathogens on IV sulopenem who stepped down to oral sulopenem was higher [64/80 vs 55/84 on sulopenem IV/oral and ertapenem IV, respectively; difference, 95% CI: 14.5% (0.8, 27.8)].
Treatment emergent adverse events (all, 14.8% vs 16.1%; related, 6.0% vs 9.2%) and serious adverse events (2.0% vs 0.9%) were similar for patients on sulopenem and ertapenem, respectively.
Overall Response at Test of Cure, micro-MITT Population

Conclusion
Sulopenem followed by oral sulopenem-etzadroxil probenecid was not non-inferior to ertapenem followed by oral step-down therapy for the treatment of cUTI driven by a lower rate of asymptomatic bacteriuria in patients receiving oral ciprofloxacin. Sulopenem, both IV and oral, was well-tolerated; its oral formulation allowed patients with baseline pathogens resistant to both quinolones and β-lactams an opportunity to successfully step down from IV therapy.

Disclosures
Michael W. Dunne, MD, Iterum Therapeutics (Employee, Shareholder) Steven I. Aronin, MD, Iterum Therapeutics (Employee, Shareholder)