bluuebunny/crossref_metadata_2025_split huggingface dataset:
1005. COVID-19 At-Home Capillary Blood Specimen Collection Pilot – Gaining Insight into Independent Self- Collection of Blood Specimens and COVID-19 Within the Veteran Population
Authors: Mohammed Tseli , Brewer Jessica V , Pyatt Mary E , Romero Casas Juan P , Whitbourne Stacey , Michael Gaziano J , Edson Connor W , Holodniy Mark 
Published: December 2021

Abstract

Background
The VA Million Veteran Program (MVP) studies what factors influence Veteran health. Current procedures involve collection of venous blood at MVP enrollment sites. To examine home specimen collection options, MVP performed a pilot study comparing two blood specimen collection devices and evaluated SARS-CoV-2 antibody assays to determine known COVID-19 infection or vaccination.

Methods
A sub-sample of MVP Veteran participants were asked to self-collect a capillary blood specimen using the Neoteryx Mitra Clamshell (up to 120uL dried blood) or Tasso-SST (up to 200uL liquid blood) per the vendor instructions. Veterans were randomly assigned to a device prior to consent. Eligibility included 30% of Veterans with known COVID-19 diagnosis or vaccination and sampling time was variable from these events. Veterans rated their device experience and shipped collected specimens directly to an MVP laboratory. Mitra tip (4) blood was eluted in 1 mL of 0.9% normal saline for 1 hour at room temperature shaking at 300 rpm. Tasso tubes were centrifuged per vendor instructions. All samples were stored at -80°C until tested with SARS-Cov-2 antibody (Ab) assays (InBios Spike IgG, BioRad Nucleocapsid (NC) Total Ab, Abbott NC IgG, and Abbott Spike IgG II) per vendor instructions.

Results
312 MVP participants consented to the pilot (52%) of which 136 (43.6%) were sent Mitra and 176 (56.4%) were sent Tasso-SST (Table 1). Participants rated the Mitra Tasso-SST equally on average as 4.4 on a 0-5 usability scale. The Abbott IgG II assay had the highest sensitivity across both devices (87% Mitra and 98% Tasso-SST) for detecting known COVID infection and/or vaccination. The InBios IgG assay with the Tasso-SST had the best sensitivity (97%) and specificity (80%) for detecting known COVID-19 infection and/or vaccination (Table 2).
Table 1. COVID-19 At-Home Capillary Blood Specimen Collection Pilot Outcomes

Conclusion
Veterans successfully collected their own specimens and had no strong preference for either device. The Tasso-SST combined with the InBios Spike IgG assay provided the highest combination of sensitivity and specificity. Limitations included one collection device per subject, varied timing of testing, unknown infection or vaccination status among some, and Tasso collection volume and Mitra whole blood dilution may have affected comparison across assays or performance.

Disclosures
All Authors: No reported disclosures
1007. Hypermutability in Clinical Strains of Klebsiella pneumoniae: Role of the V76G Mutation in MutH
Authors: Cheng Shaoji , Liu Guojun , Hao Binghua , Newbrough Anthony , Clancy Cornelius J , Nguyen Minh-Hong 
Published: December 2021

Abstract

Background
Hypermutator (HM) bacteria exhibit high spontaneous mutation rates due to DNA mismatch repair (MMR) gene mutations, which may facilitate antibiotic resistance. HM is best described for chronic infections or colonization, in particular with P. aeruginosa. HM K. pneumoniae (KP) and carbapenem resistant Enterobacterales (CRE) are rarely studied.

Methods
Longitudinal isolates from 5 patients (pts) with long-term ST258 CRKP infections (median: 1.4 yr, 0.5-4.1 yr) underwent Illumina HiSeq whole genome sequencing. Strains from 1 pt were tested for HM and resistance. Mutant strains were created by complementation and CRISPR.

Results
In each pt, initial and recurrent isolates were genetically related (≤7 core genome (cg) SNP). In 1 pt, infection recurred 3.3 yrs after initial infection; baseline and recurrent (T0) isolates differed by 7-10 cgSNP. 4 ceftazidime-avibactam (CAZ) resistant isolates (T1-T4) were recovered ≥2 wks after treatment of T0 infection. Strains T1-T4 differed from T0 and each other by 109-214 and 58-137 cgSNP (Fig.1), respectively, and carried mutations in MMR genes (mutS -149∆C (∆pmutS); mutH V76G) and blaKPC3 (D179Y). T1-T4 mutations were enriched for genes involved in metabolism (adjusted p=1.46e-10), ABC transport (p=4.1e-7), 2-component systems (p=9.2e-5), signal transduction (p=6e-4), and transcription regulation (p=2.1e-4). mutS and mutH expression was 46-49% lower in T1-T4 than in T0. T1-T4 demonstrated rifampin mutational frequency &gt;10-6.4, compared to &lt; 10-7.3 for earlier strains. Upon passage in meropenem-vaborbactam (MV), colistin and gentamicin, T1-T4 developed resistance faster and higher MICs than T0 (Fig 2). MV resistance was associated with IS5 ompk36 promoter insertions or point, deletion or STOP mutations in ompK36 coding region. Complementation of T1-T4 with wild-type (WT) mutH restored phenotypes. Introduction of V76G to WT mutH in T0 established HM and in vitro passage resistance phenotypes.
SNP matrix of 11 clinical isolates from a single patient with recurrent KPC-Kp infections

The first 6 isolates were recovered within 6 months of transplant (Tinitial). The later 5 isolates were recovered ~40 months after intial GI colonization. Number of SNPs for each pariwise comparision on isolates are shown. Gray highlighted boxes shown SNP defferences between the 5 later strains.
Serial passages of 4 clinical isolates.

T1 and T4 harbored ΔpmutS. Ti=Tinitial (baseline) isolates

Conclusion
MMR mutations emerged in longitudinal CRKP, which conferred HM phenotypes and were associated with CAZ and other anti-CRE antibiotic resistance. mutH V76 is crucial in MMR. Long-term colonization or recurrent infections in face of antibiotic exposure might predispose CRKP strains to HM.

Disclosures
Cornelius J. Clancy, MD, Merck (Grant/Research Support)
1011. Geospatial Analysis of Antibiotic Susceptibility in Wisconsin
Authors: Legenza Laurel , McNair Kyle , Lacy James P , Gao Song , Rose Warren 
Published: December 2021

Abstract

Background
The global threat of antimicrobial resistance (AMR) varies regionally. Regional differences may be related to socio-economic factors such as the Area Deprivation Index (ADI) score. Our hypothesis is that AMR spatial distribution is not random.

Methods
Patient level antibiotic susceptibility data was collected from three regionally distinct Wisconsin health systems (UW Health, Fort HealthCare, Marshfield Clinic Health System [MCHS]). Patient addresses were geocoded to coordinates and joined with US Census Block Groups. For each culture source, we included the initial E. coli isolate per patient per year with a patient address in Wisconsin. Percent susceptibility was calculated by block group. Spatial autocorrelation was determined by Global Moran’s I, which quantifies the attribute being analyzed as spatially dispersed, randomly distributed, or clustered by a range of −1 to +1. Linear regression correlated ADI to susceptibility. Hot spot analysis identified blocks with statistically significant higher and lower susceptibility (Figure 1).
Figure 1. Geographic example of hot spot analysis and interpretation.

Results
The UW Health results included more urban areas, more block groups and greater isolate geographic density (n = 44,629 E. coli, 2009-2018), compared to Fort HealthCare (n = 6,065 isolates, 2012-2018) and MCHS (50,405 isolates, 2009-2018). A positive spatially clustered pattern was identified from the UW Health data for ciprofloxacin (Moran’s I = 0.096, p = 0.005) and trimethoprim/sulfamethoxazole (TMP/SMX) susceptibility (Moran’s I = 0.180, p &lt; 0.001; Figures 2-3). Fort HealthCare and MCHS distribution was likely random for TMP/SMX and ciprofloxacin by Moran’s I. Linear regression of ADI (scale 1-10, least to most disadvantaged) and susceptibility did not find significance, but susceptibility was lower in more disadvantaged block groups. At the local level, we identified hot and cold spots with 90%, 95%, and 99% confidence, with more hot spots in rural regions.
Figure 2. Results from Moran’s Index analysis identifying geographically clustered ciprofloxacin susceptibility results.

Figure 3. Results from Moran’s Index analysis identifying geographically clustered sulfamethoxazole/trimethoprim susceptibility results.

Conclusion
Overall, Moran’s I analysis is more able to identify a clustered pattern in urban versus rural areas. Yet, the local hot spot results indicate that variations in antibiotic susceptibility may be more common in rural areas. The results are limited to data from patients with access to the health systems included.

Disclosures
Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support, Advisor or Review Panel member)
1014. Effect of Levofloxaclin and Trimethoprim-sulfamethoxazole on Planktonic and Biofilm Cells of Stenotrophomonas maltophilia Isolates Obtained from Blood and Respiratory Samples
Authors: Del Río-Chacón José Mauricio , Rojas-Larios Fabian , Villarreal-Salazar Verónica , Ibarías Paola Bocanegra , Newton-Sanchez Oscar Alberto , Camacho-Ortiz Adrian , Flores-Treviño Samantha 
Published: December 2021

Abstract

Background
Stenotrophomonas maltophilia is a non-fermenting Gram-negative pathogen, which causes healthcare-associated infections and exhibits increasing drug resistance rates. In this study, we compared the effect of levofloxacin and trimethoprim-sulfamethoxazole on planktonic and biofilm cells of S. maltophilia isolates obtained from blood and respiratory samples.

Methods
S. maltophilia isolates were recollected from patients older than 18 years from 2018-2020 from Hospital Universitario Dr. Jose Eleuterio Gonzalez, a tertiary care hospital from Nuevo Leon, Mexico. Bacteria were dentified by MALDI-TOF MS. Biofilm formation was determined using the crystal violet staining method.Antimicrobial susceptibility in planktonic cells and biofilm cells were determined by the broth microdilution and the Calgary device, respectively.

Results
During the 3-year study period, 44 S. maltophilia isolates were identified, 28.8% of which were biofilm producers. Of those, 69.2% were obtained from blood cultures. Isolates were obtained from several wards: 25% infectious diseases ward, 18% nephrology, 18% intensive care units, 14% geriatric ward, 7% plastic surgery, and 18% from other wards. The majority of the studied subjects were men (34.6%), and the mean age was 41 years. The majority of the isolates were susceptible to levofloxacin (94.1%) and to trimethoprim-sulfamethoxazole (76.4%) in planktonic assays. All the isolates were resistant to both antibiotics when analyzing biofilm cells. Levofloxacin resistance was at least four-fold higher in biofilm cells compared to planktonic cells. Trimethoprim-sulfamethoxazole resistance was at least ten-fold higher in biofilm cells compared to planktonic cells.

Conclusion
The majority of S. maltophilia clinical isolates causing blood infections in a hospital in Mexico were able to produce biofilm. The production of biofilm in S. maltophilia strains enhanced resistance to levofloxacin and trimethoprim-sulfamethoxazole.

Disclosures
All Authors: No reported disclosures
1015. Hemophagocytic Lymphohistiocytosis: A Contemporary Single Center Case Series
Authors: Jabr Ra’ed , Ryan Miriam , Mohyuddin Ghulam Rehman , Hammoud Kassem , Male Heather , El Atrouni Wissam 
Published: December 2021

Abstract

Background
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation due lack of normal downregulation of activated macrophages and lymphocytes. We describe clinical and laboratory features, underlying conditions, prognostic factors and outcomes of a contemporary cohort of adults with HLH.

Methods
We performed a retrospective case series of adults diagnosed and treated for HLH at the University of Kansas Medical Center from January 1, 2006 through September 30, 2017. Patients were identified by ICD9/10 search of our HERON database, followed by manual review of electronic medical records using the HLH-04 criteria for inclusion. Patients were followed until February 20, 2018. Descriptive statistics and Cox survival model for mortality were used for data analyses.

Results
Among 76 patients reviewed, 39 met the HLH-04 criteria and were included in the cohort. Median age was 46 years , 26 (66.7%) were male, 26 (66.7%) were white, 5 (12.8%) were Asian, and 5 (12.8%) were African American. Twenty-one patients (53.8%) had HLH associated with an infection and 11 patients (28.2%) had HLH associated with malignancy. Median follow up time was 180 days (range 1 – 4002 days). Twenty patients died with case fatality rate of 51.3%, and among those who died, median survival was 17 days (range 1 –180 days). On univariate analysis, variables associated with mortality were: male gender (hazard ratio (HR) 5.32, 95% confidence interval (CI) 1.51-18.78, p=0.004), age ≥ 65 years (HR 2.51, 95% CI 0.99-6.39, p-value 0.005) and bilirubin ≥ 5 mg/dL at diagnosis (HR 3.27, 95% CI 1.34-8.00, p=0.006). These remained significantly associated with mortality on multivariate analysis: male gender (HR 12.34, 95% CI 1.87-29.73, p=0.020) and age ≥ 65 years (HR 7.45, 95% CI 1.87-29.73, p=0.008) and bilirubin ≥ 5 mg/dL (HR 4.75, 95% CI 1.09-20.72, p=0.002).

Conclusion
In this retrospective case series of adults with HLH, mortality at a median follow up of 180 days remained high (53%) and is associated with older age age ( &gt;65 years), male gender, and elevated bilirubin ≥ 5mg/dL at diagnosis. Better therapeutic options for this syndrome are needed.

Disclosures
All Authors: No reported disclosures
121. Mucormycosis and COVID-19 in the United States: a Real-World Evidence Analysis of Risk Factors and Survival Among Patients with Mucormycosis, with and without COVID-19 Preceding the Infection
Authors: Brzozowski Kaylen 
Published: December 2021

Abstract

Background
Mucormycosis has been associated with COVID-19 infections, notably in India, and known risk factors for mucormycosis such as diabetes mellitus have been studied in this context. This analysis aims to characterize patients in the US with mucormycosis, with and without COVID-19, by risk factor and mortality.

Methods
Data from the TriNetX Research Network representing over 66M de-identified patient-lives in the US was used to examine characteristics and outcomes among mucormycosis patients with and without preceding COVID-19 infection. Patients must have had a mucormycosis diagnosis recorded from 1/1/2020 to 6/8/2020. Patients were then identified as having either a COVID-19 diagnosis or positive SARS-CoV-2 RNA laboratory result (M+COV) or no COVID-19 diagnosis or positive RNA result (MnCOV) any time prior to through one day after the mucormycosis diagnosis. These cohorts were evaluated across characteristics recorded in the EMR within 1 year prior to and including the date of mucormycosis record. Mortality was evaluated with Kaplan-Meier statistics as survival until recorded death on or after mucormycosis diagnosis.

Results
Of 302 patients with mucormycosis from 1/1/2020-6/8/2021, 30 patients (10%) had M+COV, and 272 (90%) had MnCOV. Among the M+COV cohort, 22 patients (73%) had mucormycosis recorded within 2 weeks of COVID-19 infection. The M+COV and MnCOV cohorts had majority male sex (60,59%;p=0.93) and a similar prevalence of transplanted organs (40,28%;p=0.16), long-term drug therapy (60,54%;p=0.56), chronic kidney disease (43,31%;p=0.16), and glucocorticoid treatment (67,64%;p=0.76). The M+COV cohort had a greater prevalence of type II diabetes mellitus (67,35%;p&lt; 0.01), acidosis (53,22%;p&lt; 0.01), and posthemorrhagic anemia (43,14%;p&lt; 0.01) than the MnCOV cohort. M+COV patients seem to progress to mortality more quickly than MnCOV patients (p=0.01, see Figure 1).
Figure 1. Survival until all-cause mortality after mucormycosis diagnosis, 0-180 days, among patients with (M+COV) and without (MnCOV) COVID-19 preceding the infection.

Conclusion
This study found that patients in the US with mucormycosis and current or previous COVID-19 infection have a greater prevalence of underlying conditions, including diabetes, and more rapid progression to mortality than those without COVID-19. The nature of the potential relationship between comorbidities, mucormycosis, and COVID-19 should be explored further.

Disclosures
All Authors: No reported disclosures
1016. Long-term Follow-up after Fecal Microbiota Transplantation via Colonoscopy or Freeze-Dried Capsules for Recurrent Clostridioides difficile infection
Authors: Donskey Curtis , Hecker Michelle , Rosero Christian 
Published: December 2021

Abstract

Background
Background: Fecal microbiota transplantation (FMT) is effective for treatment of recurrent Clostridioides difficile infection (CDI). However, limited data are available on the durability of FMT, especially after FMT via capsules and with more than 1 year of follow-up.
Figure. Outcomes after FMT in 162 patients with recurrent CDI

Methods
Methods: A retrospective cohort study was conducted for all patients undergoing FMT from April 2013–November 2020 in a tertiary care hospital. Initial management was considered successful if 1 to 3 FMTs resulted in improved symptoms with no diagnosis of recurrent CDI at 3 months after the initial FMT. Medical record review and telephone interviews were conducted to determine the frequency of recurrent CDI after initial successful management.

Results
Results: One-hundred sixty-two patients received 228 FMT procedures (range, 1 to 5), including 78 (34%) via colonoscopy, 144 (63%) via freeze-dried oral capsules, and 6 (3%) via nasogastric/duodenal/PEG tube. The median follow-up time after initial FMT was 61 months (range, 10 to 99 months). Initial management was successful in 132 (81%) patients after 1 FMT and in 24 (14%) patients with 1-2 additional FMTs (Figure). During long-term follow-up, 29 recurrences occurred in 22 of 159 (14%) patients evaluated. Ten (34%) of the recurrences occurred greater than 12 months after the initial FMT. Of the 22 patients with recurrence after 3 months, 16 (73%) were successfully managed with CDI therapy or additional FMT.

Conclusion
Conclusion: In our center, FMT via colonoscopy or freeze-dried capsules was very successful in initial management of recurrent CDI and 85% had a durable response with no further recurrences. However, more than 1 FMT procedure was often required to achieve initial success and to manage late recurrences.

Disclosures
All Authors: No reported disclosures
1017. Gut Microbiota Diversity and Beneficial Metabolite Production is Reduced in Liver Transplant Recipients and Associated with Post Operative Infection
Authors: Lehmann Christopher J , Keskey Robert , Odenwald Matthew , Nayak Ravi , Khalid Maryam , Littmann Eric , Pamer Eric G , Pamer Eric G , Baker Talia 
Published: December 2021

Abstract

Background
Liver transplant (LT) recipients have abnormal microbiota before and after transplantation. (1,2) Associations between fecal microbiota, microbial metabolites, and clinical outcomes in liver transplantation are not well established. We correlated fecal microbiota composition and metabolite concentrations with early LT outcomes, including infection.

Methods
In a prospective observational study, we collected peri-transplant fecal samples and determined microbiota composition by 16S ribosomal RNA gene sequencing in LT recipients. Fecal short chain fatty acid (SCFA) and bile acid concentrations were measured by targeted GC- and LC-MS analyses, respectively. Inverse Simpson index was used to determine microbiota alpha-diversity in subjects and healthy controls. Clinical outcomes including length of stay, ICU admission, liver function, antibiotic use, immunosuppressive requirement and post-operative infection were correlated with microbiota composition.

Results
69 patients were enrolled, 70 liver transplants were performed and 307 peri-transplant fecal samples were collected and analyzed. Compared to healthy controls, the fecal microbiota of LT recipients had reduced alpha-diversity (p&lt; 0.001). [Fig1] Bacteroidetes, Ruminococcaceae, and Lachnospiraceae, three taxa associated with a health-promoting microbiota, and their metabolites, SCFA and secondary bile acids, were markedly diminished 55% of LT patients.(3) Intestinal domination ( &gt;30% frequency) by Enterococcus or Proteobacteria species was common and occurred in 36% of LT recipients. 76 post-operative infections occurred in 40 LT recipients, with Enterococci causing 52% and Proteobacteria 41% of bacterial infections. In subjects with fecal samples collected within 5 days of infection, 9/17 infections were caused by the organism dominating the microbiota. [Fig2]
Microbiota Composition and Metabolite Production

16s gene sequencing color coded by taxonomy. Each bar represents one stool sample nearest to LT compared to healthy controls. Alpha diversity measured by inverse simpson index. Absolute values of microbial metabolites and ratio of primary to secondary bile acids.
Comparison of Microbiota Composition and Post Operative Infection

All bacterial infections captured with a microbiota sample within 5 days of infection.

Conclusion
Microbiota diversity and microbially derived metabolites are markedly reduced in &gt;50% of LT recipients. Intestinal domination and post-operative infections caused by antibiotic-resistant Enterococcus and Proteobacteria correlate with loss of Bacteroidetes, Ruminococcaceae, and Lachnospiraceae species, suggesting a potential role for microbiota reconstitution therapy in LT patients.

Disclosures
Eric G. Pamer, MD;FIDSA, Nothing to disclose