If your name starts with a C, we are looking for you!!

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Active surveillance for C. diff, CRE, (and Candida auris) in Houston If your name starts with a C, we are looking for you!! Kevin W. Garey, PharmD, MS, FASHP Professor and Chair Dept of Pharmacy Practice and Translational Research

Update on progress of city-wide surveillance projects We are leading the nation in active surveillance of MDRO pathogens CRE: characterize resistance mechanisms of CRE from at least 10 hospitals in the Houston area Initial hospitals recruited (St. Luke s and Memorial Hermann) If anyone wants to participate (aka, send samples), let me know! C difficile infection (CDI): Active, state-wide surveillance system to detect emerging epidemics of CDI Houston-wide outbreak investigations of CDI Lots of data to present! Still looking for more sites, let me know! Candida auris: Newest surveillance effort supported by TMC Public Policy Institute Surveillance to start at 10 hospitals (guess which ones) Will have the capability to expand XDRO protocol: Future work to mimic work done in Illinois (Bob Weinstein) Reporting network to alert patients admitted with a past history of select MDRO organisms Will present protocol, some results, and brainstorm on potentials

Components of an active surveillance system: C difficile Clinical data BUG Biobank / longterm storage Regrowth QA Ribotyping C. diff growth and confirmation MLVA/WGS DNA extraction Long-term storage Cytotoxicity testing Clinical or environmental sample Microbiome Stool DNA extraction 16S RNA analysis Immune response Long-term storage DNA Blood Serum

TMC C. diff surveillance network Methodist Hospital (Pat Cernoch) 200 cases/yr UT Memorial Hermann (Cesar Arias) 50 cases/yr Ben Taub Hospital (Robert Atmar) 50 cases/yr VA Medical Center (Dan Musher) C diff alley Baylor St. Luke s (main group) 200 cases/yr Texas Children s hospitals (Tor Savidge) 100 cases/yr MD Anderson (Javier Adachi) 200 cases/yr UH COP (us) UT SPH (Herbert DuPont)

Thanks to the systemization of health-systems, HCA, and some buddies, we have an active surveillance system that covers Houston

Active surveillance of C. diff in Houston 50 Ribotypes 45 40 35 30 25 20 15 10 5 0 F014-020 F027 F106 F002 F001 Other (n=48) Ribotypes

PCR ribotyping is commonly used worldwide Ribotype Houston Australia Belgium Europe 014/020 15% 26% 20% 12% 002 11% 11% 8% 3% 106 12% NR 6% 2.5% 027 14% 1.6% 4.2% 12% 001 4% NR NR 9% Congratulations, Houston! We have our own unique C. difficile ribotype!! Collins et al. Pathology 2017:309-13 Neely et al. J Hosp Infect 2017; 394-9 Freeman et al. Clin Microbiol Infect 2015:248e9-e16

Ribotype distribution looks pretty similar within our health systems 50 45 40 35 30 25 20 15 10 5 0 F014-020 F027 F106 F002 F001 Other (n=48) Health system 1 Health system 2

Where we live may be more important than what health-system we go to! 50 45 40 35 30 25 20 15 10 5 0 F014-020 F027 F106 F002 F001 Other (n=48) TMC Sugarland Woodlands

One Health meets C. diff Fig. 1: Isolation of Clostridium difficile from park tree leaves Fig. 2: Ribotypes of Clostridium difficile from park tree leaves

Going a little deeper: We can start to see how our C diff compares to the rest of the world Ribotype 027 FQR1 FQR2

We can also use these tool to impact patient care In 2016, we were consulted on an increased number of CDI cases at a nursing home (n=4). One patients was originally symptomatic with three subsequent cases developing over the next month. This was the first case of CDI occurring at this nursing home ever! ALL STOOL SAMPLES WERE POSITIVE FOR RIBOTYPE 027 Environmental samples also positive to ribotype 027 Based on these results, the nursing home underwent an institution-wide terminal clean We then performed a follow-up environmental sampling study

Proportion of positive environmental samples before and after facility-wide terminal clean with 10% bleach solution P<0.001 50% P=0.17 Proportion of samples positive for C. difficile 45% 40% 35% 30% 25% 43% 20% 15% 30% 10% 5% 0% Before terminal clean (n=50 samples) Patient care rooms (30 swabs from each sampling period) P=0.76 5% 3% After terminal clean (n=50 samples) Non-patient care room (20 swabs from each sampling period)

Components of an active surveillance system: CRE Clinical data Biobank / longterm storage Regrowth QA Clinical or environmental sample CRE growth and confirmation carbr assay WGS DNA extraction Long-term storage

City of Houston Health Dept has validated the Cepheid Xpert carba-r assay in their labs Targets for carba-r assay KPC USA IMP Europe, Latin America VIM Greece, Italy, Turkey, Spain NDM India emerging globally OXA-48 Europe, Latin America

Houston: We have an active CRE surveillance system!! Approximately, 50 samples have been sent to the health department for testing Clinical and microbiology data available for the first 11 All 11 samples positive for blakpc! Age (range) 35-73 Gender Race 6 male; 5 female 6 Caucasian; 3 Black; 2 not reportednr Source Blood: 3; Urine: 3; Respiratory: 3; Abdominal: 1; Other: 1 Antibiotics at day 7: Ceftaz-avi: 5; Meropenem: 1; Polymixin B: 1; Aminoglycoside: 1

Candida auris

December 15, 2017: case count updated to 203

We have experience looking at clonality of Candida

Components of an active surveillance system: C. auris Clinical data Clinical or environmental sample Candida growth and confirmation Biobank / longterm storage DNA extraction Regrowth QA WGS Long-term storage

Candida auris surveillance Details 1-2 year evaluation of Candida bloodstream isolates from 2 health systems WGS for clonal relatedness and identification of C. auris (if it is present in Houston) Outreach to the Houston medical community for evaluation of Candida outbreaks or difficult to identify isolates

Future: XDRO registry CDC Vital Signs, August 2015 www.cdc.gov/vitalsigns/stop-spread

XDRO registry: Texas style! Automated admission feed CRE registry ELR feed XDRO notification

Summary of Houston-based surveillance systems Surveillance Strength Weakness / growth C diff Largest (and only) active, culture-based surveillance system in the country Needs to expand statewide and nationally CRE Clinical data capture with WGS capabilities Needs to grow C. auris Only active, culture-based system in the country Needs to start XDRO registry Conversations have already started at the Houston and state level Needs $$

My questions for you: kgarey@uh.edu What other organisms should we target for active surveillance, why? What other clinical uses would you like us to do with these surveillance mechanisms? Provide suggestions on what is needed to get the XDRO registry established Anything else profound you want to add!

Acknowledgements Funding: NIH (NIAID 1UO1 AI24290-01) & Houston Dept of Health and Human Services Merck & Co, Summit PLC