bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 ( >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

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< 0.01), acidosis (53,22%;p< 0.01), and posthemorrhagic anemia (43,14%;p< 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

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

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< 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 ( >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 >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
1019. Clinical Impact of a Rapid Cerebrospinal Fluid Diagnostic Stewardship Program for Suspected Central Nervous System Infections in Children
Authors: Messacar Kevin , Palmer Claire , Gregoire LiseAnne , Elliott Audrey , Ackley Elizabeth , Tyler Ken , Dominguez Samuel R , Dominguez Samuel R
Published: December 2021

Background

Despite widespread use, the optimal implementation and clinical impact of FilmArray Meningitis Encephalitis Panel (MEP; Table 1) multiplex PCR testing of cerebrospinal fluid (CSF) in children with suspected (CNS) infections is unknown.

Table 1: FilmArray Meningitis Encephalitis Panel Test Characteristics

Methods

A pre-post quasi-experimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children’s Hospital Colorado (CHCO). MEP was implemented with EMR indication selection to guide testing to children meeting approved use criteria: i. infants < 2mo, ii. immunocompromised, iii. encephalitis, iv. > 5 WBCs in CSF. Positive results were communicated with antimicrobial stewardship real-time decision support (Fig 1). All cases with CSF obtained by lumbar puncture (LP) sent to the CHCO microbiology laboratory meeting any of the 4 criteria above were included with pre-implementation controls (2015-2016) compared to post-implementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials (time from LP to 1st dose of antimicrobials targeted to identified pathogen, or cessation when no treatable pathogen identified).

Figure 1: Rapid Cerebrospinal Fluid Diagnostic Stewardship Program Intervention Design

Results

Post-implementation (n=1127) and pre-implementation (n=1124) group characteristics are in Table 2. Following implementation, MEP was sent in 72% of cases, largely replacing pathogen-specific singleplex CSF testing (Table 3). Time-to-optimal antimicrobials decreased by 10 hours (p< 0.0001; Fig 2). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts or length of stay. Time-to-positive CSF results was faster (4.8 vs. 9.6 hrs, p< 0.0001), IV antimicrobial duration was shorter (24 vs 36 hrs, p=0.004) with infectious neurologic diagnoses more frequently identified (15% vs. 10%, p=0.03). Overall, 3% had bacterial and 9% viral CNS infection identified. Enterovirus (n=128) was most common, then HSV (n=28) and parechovirus (n=17) with similar detection rates between groups

Conclusion

Implementation of MEP with a rapid CNS diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing in high-yield cases rapidly detects common viral causes and rules out bacterial targets to enable antimicrobial optimization

Disclosures

Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support; DiaSorin Molecular (Individual(s) Involved: Self): Consultant; Pfizer (Individual(s) Involved: Self): Grant/Research Support
1020. BioFiring on all Cylinders: Validation of BioFire FilmArray Pneumonia Panel and Determination of Optimal Utility
Authors: Strength Rachel , Bennett Jessica , Patel Jay , Bowden Jarred , Eason Jane V , Thomas-Gosain Neena
Published: December 2021

Background

Respiratory cultures can take up to five days to grow, time that can be crucial in treating patients with serious infections. Newer rapid microbiological identification tests are designed to shorten this delay between specimen collection and test result. The BioFire® FilmArray® Pneumonia Panel is a multiplex PCR panel that can identify 8 viral, 18 bacterial, and 7 resistance gene targets in one hour. In this study, we aimed to calculate the predictive value of this test and its utility in the clinical setting.

Methods

This retrospective study compared BioFire® FilmArray® Pneumonia Panel results to respiratory cultures run at our center from 3/1/2020 to 2/28/2021. For every BioFire sample, a respiratory culture was run concurrently. We examined correlations between these two tests using data collected from the microbiology laboratory and the electronic medical record.

Results

190 BioFire samples from 124 patients were submitted for processing. Of these, 148 samples had a concomitant respiratory culture result that grew organisms that BioFire could detect. BioFire and culture results were compared, and sensitivity and specificity were calculated on a per-sample basis. Sensitivity was calculated at 91%, specificity at 67%, positive predictive value at 46%, and negative predictive value at 96%.

BioFire detected 30 resistance genes total, including mecA/C and MREJ, CTX-M, and KPC. The sensitivity and negative predictive value for BioFire resistance gene detection was 100%. However, specificity was 94-98%, and the positive predictive value ranged between 25-41% when compared to culture.

Conclusion

Despite the promise of faster results and better screening, our data suggests that further study is needed to determine the utility of the BioFire pneumonia panel. The strength of the panel appears to lie in its negative predictive value and sensitivity, but as a positive predictive tool, it is suboptimal.

Disclosures

All Authors: No reported disclosures
1023. Host Gene Expression Biomarkers to Distinguish Between Causes of Acute Respiratory Symptoms in Lung Transplant Recipients
Authors: Steinbrink Julie M , Liu Yiling , Gray Alice , Mohamedaly Omar , Zick Brittany , McClain Micah T
Published: December 2021

Background

Long-term immunosuppression after lung transplantation increases susceptibility to a variety of respiratory infections that are often difficult to diagnose. Host gene expression patterns in circulating leukocytes may provide additional diagnostic information in these settings.

Methods

107 lung transplant recipients (79% with cystic fibrosis) were enrolled at Duke University Medical Center over a 2-year period – 59% with acute respiratory symptoms, the remainder as healthy controls. Whole blood was collected by PAXGene for RNA sequencing. Prior to undergoing biomarker analysis, each case was adjudicated to the appropriate clinical phenotype: bacterial infection, viral infection, allograft rejection, and healthy. Logistic regression models were applied to gene expression data to identify classifiers capable of identifying each etiology.

Results

In lung transplant recipients, 117 genes were upregulated at least 2-fold in the presence of viral infection compared to healthy transplant controls. These genes clustered into expected antiviral pathways, including type I interferon signaling, interferon gamma mediated signaling, and defense response to virus, although the magnitude of gene expression was significantly less than that seen in non-transplant cohorts.

Similar results were seen during bacterial infection (defense response to bacterium, antibacterial humoral response) and rejection (upregulation in defensins DEFA3 and DEFA4). Interestingly, despite the presence of immunosuppression, a previously published gene expression signature of respiratory infection (derived from non-immunosuppressed subjects) was able to differentiate between bacterial and viral infection with 100% accuracy.

Conclusion

Even in the presence of systemic immunosuppression and regardless of presence/absence of cystic fibrosis, core canonical components of the host response to infection and rejection are seen. Gene expression signatures based on these conserved components offer the potential for diagnostic capability in the setting of nonspecific respiratory illness in these vulnerable hosts.

Disclosures

Julie M. Steinbrink, MD, CareDx (Research Grant or Support) Alice Gray, MD, CareDx (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Polarean (Advisor or Review Panel member)
1024. Using DOOR-MAT to Theoretically Compare Three Rapid Diagnostic Tests for Gram-Negative Bloodstream Infections in Immunocompromised Patients
Authors: Groft Lauren , Noval Mandee , Mease James , Kristie Johnson J , Claeys Kimberly C
Published: December 2021

Background

Molecular rapid diagnostic tests (RDTs) for bloodstream infections (BSI) utilize a variety of technologies and differ substantially in organisms and resistance mechanisms detected. RDT platforms decrease time to optimal antibiotics; however, data on RDTs in special populations, such as immunocompromised are extremely limited. This study aimed to compare theoretical changes in antibiotics based on differences in panel identification of organisms and resistance targets among three commercially available RDT panels.

Methods

Retrospective cohort of immunocompromised patients treated for gram-negative BSI at University of Maryland Medical Center from January 2018 to September 2020. Immunocompromised was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) < 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. Verigene BC-GN was performed as standard of care. GenMark ePlex BCID and BioFire FilmArray BCID 2 results were assigned based on respective identifiable organism panels.

An infectious diseases clinician blinded to final antimicrobial susceptibility testing (AST) results used RDT results to assign antibiotic treatments for each platform. Decisions were referenced against a priori DOOR-MAT matrices. A partial credit scoring system (0 to 100) was applied to each decision based on final AST results. The mean and standard deviation (SD) were compared across panels using One-Way Repeated Measures ANOVA with modified Bonferroni for multiple comparisons.

Results

A total of 146 patients met inclusion. Baseline characteristics are summarized in Table 1. The mean (SD) DOOR-MAT scores for the three RDT panels were: 86.1 (24.4) Verigene BC-GN vs. 88.5 (22.2) GenMark BCID vs. 87.2 (24.4) BioFire BCID 2. There was no statistically significant difference between the panels for DOOR-MAT score (P=0.6).

Table 1. Baseline Patient Characteristics and Organism Identification

Conclusion

Within an immunocompromised patient population, differences in organism identification between three commercially available RDT panels did not impact theoretical antibiotic prescribing.

Disclosures

J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)
1025. Prediction of Intravenous Immunoglobulin Resistance and Coronary Artery Dilatation in Kawasaki Disease: a Multicenter Study from Oman
Authors: Al Mwaiti Fatma , Alhinai Zaid , AlAbrawi Safiya , mamari Asmhan A L , Abdwani Reem , Senidi Khalfan Al
Published: December 2021

Background

Prediction of intravenous immunoglobulin (IVIG) resistance and coronary artery dilatation continues to be a challenge in the management of Kawasaki disease. Significant differences exist among different populations.

Methods

Children < 13 years of age who presented to the two main tertiary care hospitals in Oman (Royal Hospital and Sultan Qaboos University Hospital) between 2008 and 2019 with a diagnosis of Kawasaki disease were included. Diagnosis was confirmed and clinical, laboratory and echocardiography data was systematically collected and checked for accuracy. The primary outcome was the presence of IVIG resistance or coronary artery dilatation at the 6-week follow-up. Bivariate analysis was used to identify significant predictors of the primary outcome, followed by multivariable logistic regression to determine independent predictors. The Muscat Index of Kawasaki disease Severity (MIKS) score was created based on the results.

Results

156 children with Kawasaki disease were included. Median age was 2.1 years (IQR 0.9-3.8), and 64% were males. All patients received IVIG, 26 (17%) received steroids, and one received infliximab. Coronary dilatation was identified in 41 (26%) patients on initial echocardiogram, and 26 (18%) at the 6-week follow-up visit. Variables significantly associated with the primary outcome were age ≤15 months (P=0.031), hemoglobin (P=0.009), WBC count (P=0.002), absolute neutrophil count (P=0.006), and CRP ≥150 mg/L (P=0.015). These variables in addition male gender (P=0.058), ALT >80 IU/L (P=0.10) and serum sodium (P=0.10), were entered into multivariable logistic regression. A predictive model based on CRP ≥150 mg/L (LR=2.2, P=0.049), male gender (LR=2.1, P=0.095) and WBC (LR=1.1, P=0.017) resulted, and it was used as basis for the MIKS score (Table 1). The MIKS score performed favorably to the Kobayashi score in its sensitivity to predict the primary outcome and its separate components (Table 2). Combining the MIKS score with other high-risk criteria had a sensitivity of 95% in predicting the primary outcome and a specificity of 56%.

Table 1. Calculation of the Muscat Index of Kawasaki disease Severity (MIKS) score

Table 2. Sensitivity, specificity and P value for the Kobayashi, MIKS, and combined high risk criteria in predicting IVIG resistance, coronary dilatation at 6 weeks, separately or in combination, among patients with Kawasaki disease. MIKS: Muscat Index of Kawasaki disease Severity. *High risk: presence of coronary artery dilatation on initial echocardiogram or age <1>

Conclusion

The MIKS score predicts IVIG resistance and coronary artery dilatation in Kawasaki disease in our setting, with favorable performance compared to the Kobayashi score.

Disclosures

All Authors: No reported disclosures
1026. Following the Hoof Prints: Detecting Coxiella and Brucella infections with A Plasma-based Microbial Cell-Free DNA Next-generation Sequencing Test
Authors: Degner Nicholas R , Castillo-Galvan Ricardo , Alexander Jose , Arun Aparna , de Vries Christiaan R , Macintyre Ann , Perkins Bradley , Ahmed Asim A , Smollin Matthew
Published: December 2021

Background

Coxiella burnetii and Brucella spp. are zoonotic bacterial pathogens responsible for Q fever and Brucellosis, respectively. Both pathogens have a global distribution and Brucellosis is the most common zoonosis in the world. However, the CDC reports only 80-120 cases of human brucellosis and ~150 cases of acute Q fever annually. The diagnosis of these infections can be limited by: (1) their difficulty to culture; (2) the insensitivity and nonspecificity of serology; (3) the clinical overlap with other infections; and (4) the unreliability of epidemiological exposure history for these zoonoses. Unbiased microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations.

Methods

The Karius TestTM (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Coxiella and Brucella were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting.

Results

KT detected 8 cases of Coxiella burnetii (1735 MPM +/- 3000) and 5 cases of Brucella melitensis (avg 296 MPM +/- 223) (Table 1), representing approximately 1-2% of all detections in the US during this period. All of the Coxiella detections were in adults (100% male) with 5 cases of fever of unknown origin, 2 cases of culture-negative endocarditis and one case of endovascular graft infection. Brucella detections occurred in 3 adults and 2 children (60% male), 3 with exposure to unpasteurized dairy and included 3 cases of spine infection (2 vertebral osteomyelitis, 1 epidural abscess).

Conclusion

Open-ended, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical manifestations of zoonotic infections such as Q fever and Brucellosis against competing broad differential diagnoses. Furthermore, these cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with cryptic clinical presentations.

Disclosures

Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)
1028. Performance and Patient Acceptability Evaluation of the Chembio DPP® HIV-Syphilis Assay in an Emergency Department
Authors: Maliszewski Kendall N , Hsieh Yu-Hsiang , Myer Deanna , Perez Danielle A , Gaydos Charlotte A , Manabe Yukari C , Ricketts Erin , Rothman Richard E
Published: December 2021

Background

Emergency departments (EDs) serve as sentinel settings for diagnosing sexually transmitted infections (STIs), including HIV and syphilis. We aimed to assess performance and patient acceptability of a point-of-care (POC) test, the Chembio Dual Path Platform (DPP®) HIV-Syphilis Assay, in an urban ED in Baltimore.

Methods

170 patients were enrolled via convenience sampling from Oct 2019 – March 2020 and Jan 2021 – June 2021. Patients eligible were < 70 yrs, men who have sex with men, pregnant without care, had STI concerns, or history of drug use. Subjects received standard of care (SOC) HIV and syphilis testing under institutional laboratory algorithms. Subjects were then tested with the finger-stick POC test and completed a survey, both before and after the POC test to assess subjects’ attitudes about the POC test.

Results

Comparing the SOC and POC results, 165/170 (97.1%) were test concordant. 3 syphilis POC results were false negative, but reported successful treatment over 10 years prior to enrollment (treponemal antibody remains after treatment). 1 HIV result was false negative and 1 was false positive. Overall the sensitivity and specificity of the HIV POC test were 96.8% (95%CI: 83.3%, 99.9%) and 99.3% (95% CI: 96.1%, 100%), and for syphilis were 85.7% (95%Cl: 63.7%, 97.0%) or 100% (95%CI: 81.5%, 100%), if excluding 3 persons having been successfully treated, and 100% (95% CI: 97.6%, 100%) respectively.

The pre-test survey found 67% and 77% of participants were comfortable with a finger-stick test and agreed the POC test result would be as good as the SOC test result, which increased to 96% and 86% in the post-test, respectively, (p< 0.05). At post-test, 86% reported they would feel confident to perform this test at home and 81% would use it at least once per year if it were available. 97% reported they were more likely to seek treatment if receiving a positive result during their ED visit and 91% reported it would reduce their stress/anxiety if receiving a negative test result in the ED.

Conclusion

Our findings demonstrated satisfactory performance and high patient acceptability of the Chembio DPP® HIV-Syphilis Assay. Given the test is FDA approved, implementation studies are needed to determine whether adoption of this POC test will benefit patients and be consistent with ED workflows.

Disclosures

Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support)
1029. Torus Synestia Nucleic Acid Analysis Platform for Fast, High Multiplex Analysis of Nucleic Acids With Single-Nucleotide Discrimination Level
Authors: Rockwood Tyler , Sullivan Andrew , Gandhi Jahnavi , Gruszka Sarah , Turczyk Brian , Khodakov Dmitriy
Published: December 2021

Background

Nucleic acid amplification testing (NAAT) is an essential tool both for biomedical research and for clinical molecular diagnostics. Currently, there are multiple NAAT platforms available, each offering certain performance and utility advantages and disadvantages as compared to each other. Next generation NAAT platforms aim to deliver increased target detection sensitivity and specificity, low limits of target detection, quantitative high multiplex target capacity, rapid time to results, and simple sample-to-answer workflow.

Methods

Here we describe the Torus Synestia System, a NAAT platform capable of rapid, highly multiplexed amplification and detection of both DNA and RNA targets. The platform comprises a small, portable (~ 2kg) amplification and detection device and a disposable single-use cartridge housing a PCR amplification chamber with an integrated label-free microarray for real-time data acquisition and interpretation. The platform offers a 30-min turnaround time with a detection limit of 10 DNA/RNA molecules per assay and single nucleotide discrimination.

Results

We demonstrate the Synestia System performance and utility with three distinct molecular applications: 1) detection of 20 genetic loci and 30 single nucleotide polymorphisms in human genomic DNA; 2) detection and genotyping of 43 unique bacterial species associated with human urinary tract infections; and 3) detection and profiling human respiratory viral pathogens including SARS-CoV-1/2, seasonal coronaviruses, Influenza A/B, and human respiratory syncytial viruses. In addition, the single-nucleotide specificity of our label-free microarray probes allowed for robust identification and discrimination of newly emerging SARS-CoV-2 lineages, such as B.1.1.7 (a.k.a. UK), B.1.351 (a.k.a. South African), P.1 (a.k.a. Brazilian), and B.1.617 (a.k.a. Indian).

Conclusion

The Torus Synestia System has broad applicability in both clinical and research environments. We are confident that the Torus Synestia System will revolutionize syndromic diagnostics at the point of care (PoC) and lead to improved response times during future epidemic and pandemic pathogen outbreaks.

Disclosures

All Authors: No reported disclosures
1031. Utility of Broad-Range Polymerase Chain Reaction Sequencing for Infectious Diseases Clinical Decision Making: A Pediatric Center Experience
Authors: Li Caitlin Naureckas , Nakamura Mari M
Published: December 2021

Background

Broad-range polymerase chain reaction (PCR) sequencing is a promising tool for diagnosis of infectious conditions when traditional microbiologic strategies fail to identify a pathogen. Data on the optimal clinical scenarios in which to use this tool are limited.

Methods

We assessed the rate of organism identification from broad-range PCR testing sent from our quaternary care children’s hospital between March 2017 and June 2020. We completed a retrospective chart review to evaluate patients’ baseline demographic and clinical features as well as clinical significance of results (defined as influencing antimicrobial management) by specimen type.

Results

Among 184 total samples, 111 (60%) were obtained from immunocompromised patients. The median age of patients at the time of sample collection was 11.4 years (IQR 6.5-16.0). 128/181 (71%) samples were from patients known to be on ≥ 1 antimicrobial, including prophylaxis, in the 24 hours prior to sample collection. 52/184 (28%) patients ultimately had an infectious disease diagnosed by another testing modality. The most common PCR sample types were bronchoalveolar lavage (BAL) fluid (35), lung tissue (20), and bone (14). An organism was identified from 41 (22%) samples, but positive results for only 8 samples (4%) led to a change in antimicrobial management: addition of agents in 4 cases, cessation of agents in 2, and transition from one agent to another in 2. Negative results for 3 (2%) samples led to discontinuation of antimicrobials. Organisms were identified from 11 (31%) BAL samples, of which only 2 (6%) were judged to be clinically significant. No results from lung tissue, CSF (11), skin biopsies (6), or joint fluid (4) affected antimicrobial management.

Conclusion

We found that only 6% of broad-range PCR results influenced antimicrobial management in a diverse pediatric cohort. Our findings suggest that many positive results, especially in BAL fluid, do not lead to changes in antimicrobial management. Additional work is necessary to characterize the ideal clinical scenarios in which broad-range PCR should be used as over a quarter of patients had a causative infectious disease identified by another modality.

Disclosures

All Authors: No reported disclosures
1032. Evaluation of a Multiplex Rapid Diagnostic Panel in Respiratory Specimens from Critically Ill Patients with Hospital-Acquired Pneumonia
Authors: Erich Bradley J , Kilic Abdullah , Palavecino Elizabeth , Williamson John , Johnson James , Ohl Chris , Luther Vera , Luther Vera , Beardsley James
Published: December 2021

Background

Rapid diagnostic tests can be a valuable aide in clinical decision-making but often cost more than traditional cultures. Prior to its implementation at our institution, we sought to evaluate the potential clinical and financial impact of using the FilmArray® Pneumonia Panel® (FP panel) in patients with hospital-acquired pneumonia (HAP).

Methods

This was a retrospective, observational, comparative study conducted at an 885-bed academic medical center. Respiratory samples obtained by bronchoalveolar lavage or tracheal aspiration from adult intensive care unit (ICU) patients with a diagnosis of HAP from Nov 2019 – Feb 2020 were tested by the FP panel in addition to routine cultures. Medical records were reviewed to determine potential changes in antimicrobial therapy if FP panel results were known by the treatment team in real time. A cost analysis was also performed incorporating the cost of the FP panel and the savings associated with the potential avoidance of antibiotics and other rapid diagnostic tests normalized per patient.

Results

56 patients met study criteria. FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with a mean reduction in time to optimized therapy of approximately 51 hours. The panel identified 3 cases where the causative pathogen was not treated by empiric therapy and 34 opportunities for antibiotic de-escalation, the most common being the discontinuation of empiric vancomycin. 36 patients had been tested with a Respiratory Virus Panel, which could have been avoided if the FP panel was used. The potential therapy impact based on specific ICU and respiratory culture results is summarized in Table 1. The cost analysis calculated an additional cost of &10 per patient associated with using the FP panel.

Table 1. Potential Changes in Therapy Based on Patient Location and Culture Result

Conclusion

The FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include quicker time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.

Disclosures

James Johnson, PharmD, FLGT (Shareholder) Vera Luther, MD, Nothing to disclose
1033. Skin Surface Thermal Imaging to Differentiate Cellulitis and Pseudocellulitis in the Emergency Department
Authors: Pulia Michael , Schwei Rebecca , Harwick Edward , Haleem Ambar , Hess Jamie , Glinert Robert , Keenan Thomas , McBride Joseph , Redwood Robert
Published: December 2021

Background

Cellulitis is misdiagnosed in up to 30% of cases, resulting in overuse of antibiotics. This represents a threat to patient safety and public health. Surface thermal imaging has been proposed as a tool to reduce errors in diagnosing cellulitis. The study objective was to compare skin surface temperature measurements between patients with cellulitis and pseudocellulitis.

Methods

We prospectively enrolled patients presenting to the emergency department (ED) with dermatologic lower extremity complaints that involved visible erythema. Using a thermal imaging camera, the maximum temperature value (Tmax) for the affected area of skin and corresponding area on an unaffected limb were captured. The Tmax gradient between the affected and unaffected limb was calculated. Gold standard diagnosis (cellulitis versus pseudocellulitis) was determined by consensus of a blinded, multidisciplinary physician review panel (two infectious disease, two dermatologists and two emergency medicine). Differences in temperature variables (Tmax and Tmax gradient) between cellulitis and pseudocellulitis were compared using t-tests.

Results

The sample included 204 participants, 59% male with an average age of 57 years. Based on expert panel consensus diagnosis, 92 (45%) of the participants had cellulitis. The cellulitis group had an average Tmax of 33.2°C and 30.2°C for affected and unaffected skin respectively, which was a significant difference of 2.9°C (CI: 2.5 to 3.6; p< 0.001). The difference in the Tmax gradients between patients with cellulitis and pseudocellulitis was 2.08°C (CI: 1.46-2.70; p< 0.001).

Conclusion

This represents the largest validation study of skin surface temperature differences between cellulitis and pseudocellulitis. Significant difference in temperature gradients between cases of cellulitis and pseudocellulitis suggests thermal imaging could be a useful diagnostic adjunct that can help differentiate these conditions. Such a modality could be particularly helpful in the ED setting where providers must balance diagnostic uncertainty with antimicrobial stewardship principles. Future work will identify the best performing temperature variables and determine optimal cutoff values for use in diagnostic algorithms.

Disclosures

All Authors: No reported disclosures
1039. Rapid Restoration of Bile Acid Compositions After Treatment with RBX2660 for Recurrent Clostridioides difficile Infection—Results from the PUNCH CD3 Phase 3 Trial
Authors: Papazyan Romeo , Fuchs Bryan , Blount Ken , Gonzalez Carlos , Shannon Bill
Published: December 2021

Background

Microbiota-based treatments are increasingly evaluated as a strategy to reduce recurrence of Clostridioides difficile infection (rCDI), and their proposed mechanisms include restoration of the microbiota and microbiota-mediated functions, including bile acid metabolism. RBX2660—a broad-consortium investigational live biotherapeutic—has been evaluated in >600 participants in 6 clinical trials, with consistent reduction of rCDI recurrence. Here we report that fecal bile acid compositions were significantly restored in treatment-responsive participants in PUNCH CD3—a Phase 3 randomized, double-blinded, placebo-controlled trial of RBX2660.

Methods

PUNCH CD3 participants received a single dose of RBX2660 or placebo between 24 to 72 hours after completing rCDI antibiotic treatment. Clinical response was the absence of CDI recurrence at eight weeks after treatment. Participants voluntarily submitted stool samples prior to blinded study treatment (baseline), 1, 4 and 8 weeks, 3 and 6 months after receiving study treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 33 bile acids from all participant fecal samples received up to the 8-week time point. Mean bile acid compositions were fit to a Dirichlet multinomial distribution and compared across time points and between RBX2660- and placebo-treated participants.

Results

Clinically, RBX2660 demonstrated superior efficacy versus placebo (70.4% versus 58.1%). RBX2660-treated clinical responders’ bile acid compositions shifted significantly from before to after treatment. Specifically, primary bile acids predominated before treatment, whereas secondary bile acids predominated after treatment (Figure 1A). These changes trended higher among RBX2660 responders compared to placebo responders. Importantly, median levels of lithocholic acid (LCA) and deoxycholic acid (DCA) showed large, significant increases after treatment (Figure 1B).

A. Bile acid compositions before (BL) and up to 8 weeks after RBX2660 treatment among treatment responders. Compositions are shown as the fraction of total bile acids classified as primary or secondary conjugated or deconjugated bile acids. B. Concentrations of lithocholic acid (LCA) and deoxycholic acid (DCA) among RBX2660 treatment responders, shown with individual samples and time point group median with interquartile ranges.

Conclusion

Among PUNCH CD3 clinical responders, RBX2660 significantly restored bile acids from less to more healthy compositions. These clinically correlated bile acid shifts are highly consistent with results from a prior trial of RBX2660.

Disclosures

Romeo Papazyan, PhD, Ferring Research Institute (Employee) Bryan Fuchs, PhD, Ferring Pharmaceuticals (Employee) Ken Blount, PhD, Rebiotix Inc., a Ferring Company (Employee)
1040. Knee Explant Analysis (KnEA) Using PLG0206 in Periprosthetic Joint Infection (KnEA Study)
Authors: Huang David , Parker Dana , Pachuda Nicholas , Dobbins Despina , Steckbeck Jonathan , Urish Kenneth
Published: December 2021

Background

PLG0206 is a novel engineered cationic antimicrobial peptide being evaluated for treatment of prosthetic joint infections (PJI). This study evaluated the rapid bactericidal activity of PLG0206 to decrease biofilm and planktonic bacteria on ex vivo infected prosthesis following removal from patients with chronic PJI.

Methods

De-identified infected prosthetics were removed from nine patients with PJI, despite chronic suppressive oral antibiotics, during a 2-stage revision procedure. Removed prosthetics were then submersed ex vivo to an expected clinical exposure of PLG0206, 1 mg/mL, for ~15 minutes. Upon completion of the 15-minute exposure, the treated explant was placed into buffer and sonicated. The sonication solution was then plated for bacterial analysis including colony forming unit (CFU) enumeration. Remaining explanted implants from the same patient served as a control and was processed similarly but without exposure to PLG0206.

Results

As shown in the Table, both Gram-positive and Gram-negative bacteria were identified from removed prosthetics during a 2-stage revision procedure of chronic PJI. Eight of ten infected prosthetics treated ex vivo to PLG0206 1 mg/mL were sterilized (No. 1-5, 8-10). Of the two infected prosthetics that were not sterilized (No. 6 and 7), one was polymicrobial (No. 6) and the other was monomicrobial (No. 7). Collectively, infected prosthetics exposed to PLG0206 demonstrated a mean 4log10 reduction (range 2 to 7).

Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206

Table: Summary of culture and CFU log reduction among infected prosthetics exposed and not exposed to PLG0206

Conclusion

Overall, these findings support the ongoing development of PLG0206 as a local irrigation solution at 1 mg/mL concentration in the wound cavity for 15 minutes in patients undergoing treatment of a PJI occurring after total knee arthroplasty.

Disclosures

David Huang, MD, PhD, Peptilogics (Employee) Nicholas Pachuda, DPM, Peptilogics (Employee) Despina Dobbins, BS, Peptilogics (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Kenneth Urish, MD, PhD, Peptilogics (Grant/Research Support)
1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies
Authors: Braun Tricia , Guthmueller Beth , Harvey Adam J
Published: December 2021

Background

Microbiota-based treatments have shown promise to reduce recurrence, morbidity, and mortality for recurrent Clostridioides difficile infections (rCDI), but consistent and reliable safety data are needed to support regulatory approvals and broaden patient access. Here we provide cumulative safety data from 5 prospective clinical studies evaluating RBX2660—a standardized, microbiota-based investigational live biotherapeutic—for reducing rCDI.

Methods

This analysis included three Phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad hoc analysis). Participants were ≥18 years old with documented rCDI who completed standard-of-care oral antibiotic therapy prior to treatment with RBX2660. PUNCH CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). Depending on the trial, assigned study treatment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months.

Results

Among 620 participants who received at least one RBX2660 dose (assigned treatment or after recurrence), 324 (52.3%) received 1, 270 (43.5%) received 2, 14 (2.3%) received 3, and 12 (1.9%) received 4. 83 participants received blinded placebo only. A total of 1980 TEAEs were reported from 432 (69.7%) RBX2660-treated participants, compared to 174 TEAEs in 50 (60.2%) placebo-only treated participants. Most TEAEs were mild or moderate in severity, with diarrhea common in all treatment groups. No potentially life-threatening TEAEs were considered related to RBX2660. Study discontinuation due to TEAEs was minimal (< 1%) with none related to RBX2660. There were no reported infections for which the causative pathogen was traced to RBX2660.

Conclusion

Across five clinical studies with consistent investigational product, RBX2660 was well-tolerated in rCDI participants. In aggregate, this data provides compelling and consistent safety data for RBX2660.

Disclosures

Tricia Braun, PharmD, Rebiotix, a Ferring Company (Employee) Beth Guthmueller, AS, Rebiotix Inc, A Ferring Company (Employee) Adam J. Harvey, PhD, Rebiotix, A Ferring Company (Employee)