Prevention of Clostridium difficile Associated Disease (CDAD) with an Active Surveillance and Contact Isolation Program for Asymptomatic C. difficile Patients Hoonmo Koo, MD, MPH Clinical Associate Professor Baylor College Of Medicine

Public Impact of Clostridium difficile Associated Disease (CDAD) Most common healthcare-associated infection Exceeds Staphylococcus aureus Most common cause of hospital-acquired diarrhea Approximately 453,000 infections in US each year Lessa FC, et al. N Engl J Med. 2015 Miller BA, et al. Infect Control Hosp Epidemiol 2011

Clostridium difficile Associated Disease in US Leads to ~29,300 deaths annually >80% of deaths among individuals >65 years 1 of 11 pts >65 years with a healthcare-associated CDAD died <30 days of diagnosis 83,000 pts experienced >1 recurrence; half of which have repeated recurrences Lessa FC, et al. N Engl J Med. 2015

CDAD Epidemiology - Texas 2000-2009 Texas hospital discharge rate for CDAD: 3.1 to 6.8 per 1,000 discharges Responsible for 0.52% of total Texas discharge diagnoses 2009: CDAD discharges were 0.64% of total discharges 2009 the last year of data examined Texas DSHS data

Reduction of HAI by Active Surveillance Significant reductions in MRSA and VRE infection rates Active Surveillance Contact Precautions for Colonized Patients Muto CA, et al. Infect Control Hosp Epidemiol 2003 Huang SS, et al. Clin Infect Dis 2006 Robicsek A, et al. Ann Intern Med 2008

Asymptomatic C. difficile (CD) Carriers as a Source for CDAD Transmission First study to epidemiologically evaluate CD isolates by whole genome sequencing Only 35% of CD diarrhea isolates genetically related to CD from other symptomatic CDAD hospital patients Patients asymptomatically colonized with CD may serve as an important reservoir for CDAD transmission In this study, they concluded that genetically similar isolates would only differ by 2 or less nucleotides The remaining 65% of the Cdiff isolates from diarrhea pts were distinct from previous Cdiff isolates from CDAD patients SNVs = single nucleotide variants DW Eyre, et al. NEJM 2013

Reduction in CDAD Incidence by Screening for CD in ED Before Admission and Isolation of CD Carriers Quebec Heart and Lung Institute (QHLI): 354- bed tertiary hospital in Quebec City, Quebec, Canada HA-CDAD rates frequently exceeded government-imposed target (9.0 per 10,000 patient-days) CD screening and isolation program initiated in November 2013 Longtin Y, et al. JAMA Int Med 2016

Reduction in CDAD Incidence by Screening and Isolation of CD Excretors Patients admitted through ED screened for CD Rectal swab tested by PCR for tcdB (BD GeneOhm) Asymptomatic CD carriers placed in contact isolation: Gloves, dedicated equipment (thermometer, sphygomomanometer) Handwashing with soap and water Dedicated toilet Patient cohorting Daily environmental disinfection (chlorine-based product) Contact isolation until hospital discharge Gowns were not required once daily, 7days aweek.Theresultswere availablewithin 24 hours and documented in the patients’ medical records. Longtin Y, et al. JAMA Int Med 2016

Reduction in CDAD Incidence by Screening and Isolation of CD Carriers 7599 patients were screened from Nov 2013 – March 2015 368 (4.8%) identified as C difficile excretors 56% reduction in HA-CDAD rate (P < .001) Pre-intervention control period (2007-2013): 6.9 per 10,000 patient-days (416 HA-CDAD pts) Intervention period: 3.0 per 10,000 patient-days (38 HA-CDAD pts) Intervention estimated to have prevented 62% of expected cases Epidemic period (Aug 22, 2004 – July 21, 2007) Post-epidemic period (July 22, 2007-November 18, 2013 Longtin Y, et al. JAMA Int Med 2016

Screening and Isolation of CD Carriers 56% reduction in HA-CDAD rate in hospital in Canada Using forecast modeling, the intervention estimated to have prevented 63 of the 101 (62.4%) expected cases Of HA-CDI. Oct 2009: switch from cell cytotoxicity assay to PCR for tcdB gene Longtin Y, et al. JAMA Int Med 2016

Other Quebec City or Quebec Province Hospitals No significant decrease in HA-CDAD rates from pre- to post-Intervention periods Segmented regression analysis Longtin Y, et al. JAMA Int Med 2016

Funded by the Texas Department of State Health Services Evaluating the Effectiveness of Reducing CDAD Rates with an Active Surveillance Program for C. difficile and Contact Isolation of all Patients Identified with C. difficile Ben Taub Hospital and Baylor St. Luke’s Medical Center PI: Hoonmo Koo, MD Funded by the Texas Department of State Health Services

Study Aims 1) To define the role of asymptomatic C. difficile carriers in CDAD transmission at Ben Taub Hospital (BTH) with active surveillance 2) To evaluate the effectiveness of an active surveillance and contact isolation program (for asymptomatic and symptomatic CDAD pts) in reducing CDAD incidence at BTH

Ben Taub Hospital 486-bed hospital Level I trauma center Largest county hospital in the Harris Health System Teaching hospital for Baylor College of Medicine

Study Design 1) Active surveillance alone: Months 1-6 2) Active surveillance and contact precautions for asymptomatic and symptomatic CDAD pts: Months 7-12

Active Surveillance Program: Months 1-6 Screen and consent BTH pts within 72 hrs of admission to a Medicine floor After consent is obtained: Complete one-page questionnaire (Clinical and demographic data for CDAD risk factors) Collect fecal swabs Test stool for CD by real-time PCR Enrollment: 1,200 pts

C. difficile Contact Precautions Education Program for Intervention Wards During Month 6, an education program provided to all Intervention floors: Target the nurses, medical assistants, residents, medical students Review study objectives, design, and methods Training for hand hygiene and contact precautions compliance (CDC and WHO guidelines)

Active Surveillance and Contact Precautions Program: Months 7-12 1,000 patients will be enrolled: - 10 Medicine units - 5 Control units (n=500) - 5 Isolation units (n=500) Assignment of Control vs Isolation units by systematically matching the units from 2015 HA-CDAD rates

Active Surveillance and Contact Precautions Program Control Units: 5 Hospital Units Place symptomatic pts with CDAD in contact isolation Gloves and isolation gowns for diarrhea pts Dedicated medical equipment (e.g. stethoscopes) Hand hygiene only with soap and water Isolation Units: 5 Hospital Units Both asymptomatic and diarrhea pts with CDAD will require contact isolation: Assign diarrhea pts a private room Cohort asymptomatic pts with CDAD together Both asymptomatic and diarrhea pts with CDAD will require: Gloves and isolation gowns

Primary Endpoints 1) Compare CDAD incidence rates during the surveillance and intervention periods for control and isolation units 2) Compare genetic similarity of CD isolates from asymptomatic and symptomatic pts by Whole Genome Sequencing (WGS)

Data Analysis Comparison of HA-CDAD incidence density rates between surveillance and intervention periods by Poisson regression analysis: Overall hospital 5 Control and Isolation study floors Polytomous logistic regression with CD absence as reference categories, including group indicator (control, intervention), period (first, second), group by period interaction and CDAD risk factors and predictors To account for potential confounders

Genetic Analysis of CD Isolates Whole genome sequencing of CD isolates will be performed and analyzed by the Texas Children's Microbiome Center Compare genetic similarity of CD isolates from asymptomatic CD excretors and symptomatic patients with CDAD

C. difficile Surveillance January 11 – July 4, 2016 Screened 2,148 patients Enrolled 1044 (49%) subjects who consented Fecal swabs collected from all 1,044 patients 53 (5%) of the 1,044 stool samples positive for C. difficile by real-time PCR

Hand Hygiene and Contact Precautions Training 268 medical staff on the Intervention units attended training sessions Presentations well-received: Evaluation survey (1, lowest, to 5, highest): Average scores for the training session components: (1) Content of the Information Session: 4.8 (2) Presenter: 4.9 (3) Overall Presentation: 4.8

Active Surveillance and Contact Precautions for Asymptomatic CD Excretors July 5, 2016 – present Enrolled 427 (58%) subjects who have provided informed consent: Control wards: 183 patients: 2 (1%) positive Isolation wards: 244 patients: 6 (2%) positive

Hand Hygiene and PPE Compliance Surveillance Research coordinators trained by BTH Infection Control for auditing hand hygiene and personal protective equipment (PPE) compliance for contact precautions Coordinators monitoring hand hygiene and PPE compliance of medical staff on Intervention units Hand hygiene and PPE compliance rates will be compared between: Intervention and Control units Surveillance and Interventions periods

Genetic Analysis of CD Isolates 33 PCR-positive stool specimens from enrolled pts anaerobically cultured 125 stools from CDAD pts identified by the BTH Microbiology Laboratory cultured CD isolates transferred to the Texas Children's Microbiome Center Preparing the C. difficile isolates for Whole Genome sequencing (WGS)

Baylor St. Luke’s Medical Center (BSLMC) Roderick D. MacDonald Research Fund Grant Increase power of this study 500-bed tertiary care hospital Healthcare-associated C. difficile-associated disease prevalence is higher at BSLMC 2013 point prevalence study: frequency of asymptomatic CD carriers at BSLMC (13%) Longer average length of hospitalization: BSLMC (7 days) vs BTH (3 days) Greater impact with contact isolation

Conclusions Asymptomatic CD excretors may serve as an important source for CDAD transmission Contact isolation of asymptomatic CD excretors represents a novel infection control strategy for decreasing CDAD transmission The benefit of this intervention may be greater among healthcare institutions with high rates of CD colonization (e.g., Long-term acute care facilities with up to 50% of patients colonized) Future study needed to determine essential components for contact isolation

Acknowledgements Harris Health System and Baylor College of Medicine Payel Acharya Robert Atmar Ericka Brown Herbert DuPont Jennifer Kramer Julio Cesar Rojas-Quintero Samantha Salcedo Charles Stager John Van University of Houston College of Pharmacy Kevin Garey Texas Children’s Microbiome Center Aiswarya Ramanujam Tor Savidge Texas Department of State Health Services David Bastis Marilyn Felkner

C. difficile Gulf Coast Collaborative Formed in 2012 to foster research and best practices among scientists and clinicians with an interest in CDAD Partnership between the Texas Medical Center, surrounding communities, and Gulf Coast states Work with national C. difficile and fecal transplant foundations to promote community awareness