756. Clostridioides difficile Burden of Disease: A Prospective Population-Based Surveillance Study of Hospitalized Adults in Louisville, Kentucky

Abstract Background Clostridioides difficile (C. difficile) is an important cause of morbidity and mortality. C. difficile infection (CDI) may be frequently under-diagnosed because laboratory confirmation requires collection of a stool specimen from a patient with diarrhea and appropriate laboratory testing. Methods A prospective population-based CDI surveillance study was launched in 8 adult hospitals in Louisville, Kentucky on September 16, 2019. Surveillance officers in each hospital identified all cases of new-onset diarrhea (≥3 loose stools in the past but not preceding 24 hours) in Louisville residents ≥50 years of age. After informed consent, stool samples were collected and tested at the University of Louisville reference laboratory for 1) glutamate dehydrogenase (GDH) and 2) Clostridioides difficile toxins A and B using C. DIFF QUIK CHEK COMPLETE®, Techlab. We defined CDI as GDH positive and toxin positive. The study was paused on April 3, 2020, due to COVID-19 restrictions. Results There were 85,719 eligible patient-days during the study period. A total of 1541 patients had new-onset diarrhea corresponding to 1.8 cases of new-onset diarrhea per 100 eligible patient-days. We enrolled 84% (1291/1541) of patients with new-onset diarrhea and tested stool samples for C. difficile from 82% (1055/1291) for a testing density of 123 per 10,000 patient-days. Of the 1055 tested stool specimens, 73 (7%) were GDH positive and toxin positive (Figure 1) yielding a hospital-based CDI incidence of 8.5 CDI cases per 10,000 patient-days. Figure 1. Patient Ascertainment Flow Chart Conclusion New-onset diarrhea was common among hospitalized adults ≥50 years of age. CDI was frequently identified through stool specimens collected from eligible inpatients with new-onset diarrhea. Further analysis of these data and additional laboratory testing will contribute to a better understanding of the frequency of CDI underdiagnosis and the burden of CDI in the United States. Disclosures Ruth Carrico, PhD, DNP, APR, CIC, Pfizer (Consultant, Research Grant or Support, Speaker's Bureau)Sanofi Pasteur (Consultant, Grant/Research Support, Speaker's Bureau) Fredrick J. Angulo, DVM, PhD, Pfizer, Inc. (Employee) Joann Zamparo, MPH, Pfizer, Inc. (Employee) Elisa Gonzalez, MS, Pfizer, Inc. (Employee) Kimbal D. Ford, PharmD, Pfizer, Inc. (Employee) Julio Ramirez, M.D., FACP, Pfizer, Inc. (Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)

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Antimicrobial susceptibility of Clostridioides difficile isolated from diarrhoeal stool specimens of Canadian patients: summary of results from the Canadian Clostridioides difficile (CAN-DIFF) surveillance study from 2013 to 2017

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa118 ◽

2020 ◽

Vol 75 (7) ◽

pp. 1824-1832

Author(s):

James A Karlowsky ◽

Heather J Adam ◽

Melanie R Baxter ◽

Christopher W Dutka ◽

Kim A Nichol ◽

...

Keyword(s):

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Surveillance Study ◽

Dilution Method ◽

Agar Dilution Method ◽

In Vitro Susceptibility ◽

Ribotype 027 ◽

Clostridioides Difficile ◽

Vancomycin Mics ◽

Stool Specimens

Abstract Objectives To summarize data generated by the Canadian Clostridioides difficile (CAN-DIFF) surveillance study from 2013 to 2017. Methods Isolates of C. difficile (n = 2158) were cultured from toxin-positive diarrhoeal stool specimens submitted by eight hospital laboratories to a coordinating laboratory. Antimicrobial susceptibility testing was performed according to the CLSI agar dilution method (M11, 2018). Isolate ribotypes were determined using an international, standardized, high-resolution capillary gel-based electrophoresis protocol. Results Of the 2158 isolates of C. difficile, 2133 (98.8%) had vancomycin MICs ≤2 mg/L [i.e. were vancomycin susceptible (EUCAST breakpoint tables, v 9.0, 2019) or WT (CLSI M100, 29th edition, 2019)]. Fidaxomicin MICs were lower than those of all other agents tested (MIC90, 0.5 mg/L); however, one isolate with a fidaxomicin MIC of >8 mg/L was identified. Metronidazole MICs ranged from 0.12 to 4 mg/L; all isolates were metronidazole susceptible by the CLSI breakpoint (≤8 mg/L) compared with 96.8% susceptible by the EUCAST breakpoint (≤2 mg/L). In total, 182 different ribotypes were identified from 2013 to 2017. The most common ribotypes identified were 027 (19.3% of isolates) and 106 (8.2%). Ribotype 027 isolates were frequently moxifloxacin resistant (87.3% of isolates) and MDR (48.6%), associated with vancomycin (10/25, 40.0%) and metronidazole (58/69, 84.1%) resistance and from patients aged ≥80 years. The prevalence of ribotype 027 decreased significantly (P < 0.0001) from 2013 (27.5%) to 2017 (9.0%) and was replaced by increases in ribotype 106 (P = 0.0003) and multiple less common ribotypes. Conclusions Periodic surveillance is required to monitor clinical isolates of C. difficile for changes to in vitro susceptibility testing profiles and ribotype evolution.

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Clostridioides difficile Strains in the Gut by Next-Generation Shotgun Sequencing: Innocent Bystander or Villain?

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1142 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s467-s468

Author(s):

Sabine Hazan ◽

Andreas Papoutsis ◽

Jordan Daniels

Keyword(s):

Representative Sample ◽

The United States ◽

Protective Role ◽

Next Generation ◽

Bioinformatics Pipeline ◽

Dna And Rna ◽

Clostridioides Difficile ◽

Stool Samples ◽

Asymptomatic Adult ◽

Study Participants

Background: Pathogenic Clostridioides difficile is the most common cause of nosocomial infections in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. Objective: In this study, we sought to determine the presence and nature of various strains of Clostridioides difficile colonizing a representative sample of 121 asymptomatic adult volunteers from around the globe, consisting of 110 healthy and 11 stable Crohn’s patients. Methods: Next-generation sequencing was performed on fecal samples from 121 study participants. Stool samples were collected by patients utilizing a Zymo collection kit, which preserves bacterial DNA and RNA. Following collection, DNA was extracted, quantitated, and then normalized for downstream library fabrication utilizing shotgun methodology. Prepared and indexed libraries were subsequently pooled and sequenced on the Illumina NextSeq 550 System. Results: All 121 of 121 subjects (100%) were found to possess the bacterium Clostridioides difficile as identified by the NGS bioinformatics metagenomic pipeline. To visualize comparative abundances of Clostridioides difficile present in study participants, normalized read counts were highlighted (Fig. 1). Conclusions: NGS provides a unique opportunity to increase the resolution and identification of Clostridioides difficile compared to traditional categorizations, such as PCR ribotypes (ie, RT027), restriction endonuclease groups (BI), and North American pulsotypes (ie, NAP1). This is accomplished by its ability to differentiate species based on a nucleotides, while targeting entire bacterial genomes. Our approach for this study was to utilize a bioinformatics pipeline that would provide Clostridioides difficile strain-specific resolution when aligning to genomes in the NCBI (National Center for Biotechnology Information) database. In our representative sample of 121 volunteers, all (100%) possessed at least 1 Clostridioides difficile strain in their gut. Although it is recognized that some Clostridioides difficile strains are pathogenic, our findings suggest that nonpathogenic Clostridioides difficile strains make up an important component of the commensal gut microbiome and may perhaps play a protective role. Although symptomatic toxigenic CDI is a clear indication for therapy, Clostridioides difficile colonization with nontoxigenic strains is not believed to be a direct precursor for CDI. These findings demonstrate the need to be aware of the existence of numerous strains of Clostridioides difficile, and the relevance of sequencing prior to hospitalization or antibiotic treatment to help predict those at risk of CDI, and after treatment to be aware of any loss of what appear to be protective components of our microbiome.Funding: NoneDisclosures: Dr. Sabine Hazan reports that she is the founder and CEO of Ventura Clinical Trials and that she and her spouse receive salaries from the company. She also receives a salary from ProgenaBiome.

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Epidemiologic Trends in Clostridium difficile Isolate Ribotypes in United States from 2010 to 2014

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.973 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S391-S391 ◽

Cited By ~ 4

Author(s):

David R Snydman ◽

Laura A McDermott ◽

Stephen G Jenkins ◽

Ellie J C Goldstein ◽

Robin Patel ◽

...

Keyword(s):

United States ◽

Medical Center ◽

The United States ◽

Surveillance Study ◽

Surveillance Program ◽

Phase 2 Trial ◽

The Us ◽

Grant Recipient ◽

Over Time ◽

Research Grant

Abstract Background Trends in the distribution of ribotypes for C. difficile associated diarrheal isolates obtained over time in the United States are lacking. As part of surveillance program for C. difficile susceptibility, we analyzed stool isolates for ribotype distribution from a phase 2 trial of surotomycin (2010–2011) (North America sites) as well as a national surveillance study from 2011–2014. Isolates for the surveillance study were referred from 6 geographically distinct medical centers. Methods C. difficile isolates or C. difficile toxin + stools from patients with C. difficile associated diarrhea (CDAD) were submitted for testing to Tufts Medical Center. Following isolation and confirmation as C. difficile, a random sample of isolates were ribotyped by PCR capillary gel electrophoresis. Results 673 isolates over the 5 years of the analysis have been ribotyped to date. There were 49 unique ribotype designations, and 16 ribotypes had more than 10 isolates. The ribotype distribution by year is shown in the table. Conclusion There has been a change in the frequency of ribotypes over time in the US. Of the most common ribotypes seen, 027 has decreased by over 50% while there has been an increase of 014-020, 002, and 106. 014-020 is now the most common ribotype seen in the US. These data suggest that there is a changing epidemiology of C. difficile in the US and continuous monitoring of the ribotype distributions and clinical implications is warranted. Disclosures D. R. Snydman, Merck: Consultant and Grant Investigator, Consulting fee and Research grant; Shire: Consultant, Consulting fee; Summit PLC: Consultant and Grant Investigator, Consulting fee and Research grant; BioK+: Consultant, Consulting fee; Actelion: Grant Investigator, Research grant; S. G. Jenkins, Cormedix: Consultant, Consulting fee; Bayer: Consultant, Consulting fee; Merck: Grant Investigator and Scientific Advisor, Research grant; E. J. C. Goldstein, Merck: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Grant recipient; Cubist: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee; Actelion: Grant Investigator, Grant recipient; Summit PLC: Grant Investigator and Scientific Advisor, Grant recipient; R. Patel, Curetis: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee and Research grant; Pocared: Grant Investigator, Research grant; nanoMR: Grant Investigator, Research grant; BioFire: Grant Investigator, Research grant; Check-Points: Grant Investigator, Research grant; 3M: Grant Investigator, Research grant; Cubist: Grant Investigator, Research grant; Merck: Grant Investigator, Research grant; S. Johnson, Bio-K+: Consultant, Consulting fee; D. N. Gerding, Merck, Shire, Cubist, Rebiotix, sanofi pasteur, Summit, DaVoltera, Actelion: Consultant, Consulting fee; CDC, US Dept of Veterans Affairs Research Service: Grant Investigator, Research grant

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Frequency of Testing for Clostridioides difficile in Long-Term Care Facilities in Louisville, Kentucky

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1114 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s445-s445

Author(s):

Frederick Angulo ◽

Senen Pena ◽

Ruth Carrico ◽

Furmanek Stephen ◽

Zamparo Joann ◽

...

Keyword(s):

Long Term Care ◽

Stool Specimen ◽

Diagnostic Testing ◽

Term Care ◽

Clostridioides Difficile ◽

Specimen Collection ◽

Care Facilities ◽

Stool Specimens ◽

New Onset

Background:Clostridioides difficile infection (CDI), caused by toxigenic C. difficile and predominately manifested by moderate-to-severe diarrhea, is an important cause of morbidity and mortality in long-term care facilities (LTCFs). However, for CDI to be diagnosed in an LTCF resident, an LTCF resident with diarrhea must have a stool specimen collected for CDI diagnostic testing. The objective of this study was to define the frequency of stool specimen collection and testing for CDI in adult LTCF residents with diarrhea in Louisville, Kentucky. Methods: A cross-sectional study was conducted in 14 (31%) of the 45 LTCFs in Louisville (adults aged ≥18 years; population, 599,276) to identify LTCF residents with diarrhea and to observe the frequency of stool specimen collection for CDI diagnosis. For 14 consecutive days in February 2019, each LTCF was visited to identify new onset diarrhea (≥3 loose stools in 24 hours) by interviews of nursing staff. For residents with diarrhea, staff reviewed electronic medical records to determine whether a stool specimen was collected for CDI diagnosis and interviewed nurses about potential noninfectious causes of diarrhea. Results: The 14 participating LTCFs have 1,208 beds (median, 86 beds and 43 occupied beds per participating LTCF). Among 743 LTCF residents (with 10,402 patient days of surveillance), new-onset diarrhea was identified in 63 residents (21% male; median age 75 years); 0.6 diarrhea cases per 100 patient days (diarrhea attack rate, 0.6% per day). Nurses indicated that 16 (25%) of the 63 residents with diarrhea had a potential noninfectious cause of diarrhea (11 laxatives, 3 feeding tube, 1 colostomy, and 1 gastric surgery). Stool specimens were collected for CDI testing from 20 of 63 of residents (32%) with diarrhea; none with potential noninfectious cause of diarrhea and from 20 of 47 other residents (42%) with diarrhea. Of 20 stool specimens tested, 9 (47%) yielded toxigenic C. difficile (8.6 CDI cases per 10,000 patient days). During this survey, none of the 63 LTCF residents with diarrhea were transferred to a hospital or other healthcare facility. Conclusions: Diarrhea was common among LTCF residents, and toxigenic C. difficile was frequently identified in stool specimens collected from LTCF residents with diarrhea. The majority of non–laxative-receiving LTCF residents with diarrhea did not have a stool specimen collected for CDI diagnosis. The low frequency of CDI diagnostic testing of LTCF residents with diarrhea indicates that CDI may be underdiagnosed in these LTCFs and suggests that the CDI disease burden may be larger than currently appreciated.Funding: Pfizer Vaccines provided support for this study.Disclosures: Frederick Angulo, Kimbal D. Ford, Joann Zamparo, Elisa Gonzalez, Sharon Gray, David Swerdlow, and Catia Ferreira all report salary from Pfizer.

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741. Antifungal Resistant Candida glabrata Are Most Commonly Colonized in Clostridioides difficile Infection (CDI) Patient Guts in Texas

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.931 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S419-S419

Author(s):

Khurshida Begum ◽

Farnoosh Haghighi ◽

M Jahanbgir Alam ◽

Kevin W Garey ◽

Kevin W Garey

Keyword(s):

Invasive Candidiasis ◽

Candida Glabrata ◽

Brain Heart Infusion ◽

The United States ◽

Candida Spp ◽

Predominant Species ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Stool Samples ◽

Culture Positive

Abstract Background Candida glabrata is the second most common cause of invasive candidiasis in the United States. The echinocandin class of antifungals, including caspofungin has become the preferred therapy for invasive candidiasis due to C. glabrata and other species demonstrating decreased azole susceptibility. Caspofungin resistance has been uncommon, but reports suggest that the incidence is increasing, particularly among C. glabrata isolates. The dysbiosis associated with Clostridium difficile allows for overgrowth of Candida spp. However, the prevalence of C. glabrata in stool of C. difficile infection (CDI) patients is not well studied. Therefore, our objectives were to investigate the incidence of potentially pathogenic species of C. glabrata in stool samples of CDI patients. Methods We collected 1,241 Clostridioides difficile infection (CDI) patient stool samples from two large hospitals in Houston, Texas and enrich the samples in brain heart infusion (BHI) broth at 37C for 48-72 hours and then sub-cultured onto selective HardyChrom Candida agar and incubated at 37C for 48 to 72 hours. Characteristic Candida colonies were stocked in cryovials and kept at -80C for further analyses. Isolates were then identified by multiplex PCR. C. glabrata isolates were screened for caspofungin resistance on Muller-Hinton agar (with 8.0 ug/ml). Results Overall, 14.8% (184/1241) samples were culture positive for Candida spp. The predominant species was C. glabrata (9.2 %) followed by C. albicans (2.3%), C. tropicalis (1.6%), C. parapsilosis (1.2%), C. krusei (0.6%) or not speciated (6.9%). The majority of C. glabrata isolates (70.2%; 80/114) were caspofungin resistant. Conclusion The results of this study showed that colonization of C. glabrata is common in patients with CDI and could be a source of antifungal-resistant pathogens. Disclosures All Authors: No reported disclosures

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Frequency of Testing for Clostridioides difficile in Adults Hospitalized with Diarrhea in Louisville, Kentucky

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1113 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s444-s444

Author(s):

Frederick Angulo ◽

Senen Pena ◽

Ruth Carrico ◽

Furmanek Stephen ◽

Zamparo Joann ◽

...

Keyword(s):

Disease Burden ◽

Stool Specimen ◽

Diagnostic Testing ◽

Hospitalized Patients ◽

Research Staff ◽

Patient Interviews ◽

Clostridioides Difficile ◽

Specimen Collection ◽

Stool Specimens ◽

New Onset

Background: Although Clostridioides difficile infections (CDIs) are associated with significant morbidity and mortality, CDI disease burden may be underestimated if a high proportion of inpatients with diarrhea do not have stool specimens collected for CDI diagnostic testing. The objective of this study was to define the frequency of stool specimen collection and testing for CDI in adult hospitalized patients with diarrhea. Methods: A cross-sectional study was conducted in all 9 adult hospitals (total, 3,532 beds) in Louisville (adult aged ≥18 years; population 599,276) to identify patients with diarrhea and to observe the frequency of stool specimen collection for CDI diagnosis. For 7 consecutive days in December 2018, each ward was visited to identify new onset diarrhea (>3 loose stools in 24 hours) among Louisville adults: first via electronic medical record (EMR) review, then by nurse interviews, and finally by interviewing patients. For patients with diarrhea, research staff reviewed EMRs to determine whether a stool specimen was collected for CDI diagnosis, and they interviewed nurses about potential noninfectious causes of diarrhea. Results: Among 2,565 hospitalized adults (with 14,042 patient days), research staff identified 167 patients (47% men; median age, 64 years) with new onset diarrhea, 1.2 diarrhea cases per 100 patient days. Patients with diarrhea were initially ascertained by EMR review (50%), nurse interviews (42%) or patient interviews (8%); all cases identified by patient interviews were identified by nurses the following day (but many cases identified by nurses were never identified by EMR review). Nurses indicated that 67 cases had a potential noninfectious cause of diarrhea (eg, laxatives, feeding tube, colostomy, liquid diet, etc). Stool specimens were collected by hospital staff for CDI testing from 53 of 167 patients (32%) with diarrhea; 10 of 67 patients (15%) with diarrhea for whom nurses reported potential noninfectious causes of diarrhea (laxative use, enteric feeding, or gastric survey) in the past 24 hours; and 43 of 100 patients (43%) with diarrhea with no reported potential noninfectious causes of diarrhea. Stool collection frequency was similar on weekdays and weekends. Conclusions: The low frequency of CDI diagnostic testing of hospitalized patients with diarrhea indicates that CDI may be underdiagnosed in these hospitals and suggests, given that only 32% of patients with diarrhea had a stool specimen collected, that the CDI disease burden may be 3 times larger than currently appreciated. New-onset diarrhea occurred in >1% of patients each day; the most effective method for identifying patients with diarrhea was via nurse interviews.Funding: Pfizer Vaccines supported this study.Disclosures: Frederick Angulo, Kimbal D. Ford, Joann Zamparo, Elisa Gonzalez, Sharon Gray, David Swerdlow, and Catia Ferreira all report salary from Pfizer.

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Divergence in the epidemiological estimates of traumatic brain injury in the United States: comparison of two national databases

Journal of Neurosurgery ◽

10.3171/2020.7.jns201896 ◽

2020 ◽

pp. 1-10

Author(s):

Brittany M. Stopa ◽

Maya Harary ◽

Ray Jhun ◽

Arun Job ◽

Saef Izzy ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Emergency Department ◽

Brain Injury ◽

Data Bank ◽

The United States ◽

National Sample ◽

Population Based ◽

Weighted Estimates ◽

True Incidence ◽

Ed Visits

OBJECTIVETraumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US, but the true incidence of TBI is unknown.METHODSThe National Trauma Data Bank National Sample Program (NTDB NSP) was queried for 2007 and 2013, and population-based weighted estimates of TBI-related emergency department (ED) visits, hospitalizations, and deaths were calculated. These data were compared to the 2017 Centers for Disease Control and Prevention (CDC) report on TBI, which used the Healthcare Cost and Utilization Project’s National (“Nationwide” before 2012) Inpatient Sample and National Emergency Department Sample.RESULTSIn the NTDB NSP the incidence of TBI-related ED visits was 59/100,000 in 2007 and 62/100,000 in 2013. However, in the CDC report there were 534/100,000 in 2007 and 787/100,000 in 2013. The CDC estimate for ED visits was 805% higher in 2007 and 1169% higher in 2013. In the NTDB NSP, the incidence of TBI-related deaths was 5/100,000 in 2007 and 4/100,000 in 2013. In the CDC report, the incidence was 18/100,000 in both years. The CDC estimate for deaths was 260% higher in 2007 and 325% higher in 2013.CONCLUSIONSThe databases disagreed widely in their weighted estimates of TBI incidence: CDC estimates were consistently higher than NTDB NSP estimates, by an average of 448%. Although such a discrepancy may be intuitive, this is the first study to quantify the magnitude of disagreement between these databases. Given that research, funding, and policy decisions are made based on these estimates, there is a need for a more accurate estimate of the true national incidence of TBI.

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