1. 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

2. 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 Miller BA, et al. Infect Control Hosp Epidemiol 2011

3. 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

4. CDAD Epidemiology - Texas
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

5. 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 Huang SS, et al. Clin Infect Dis 2006
Robicsek A, et al. Ann Intern Med 2008

6. 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

7. 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

8. 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

9. 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 ( ): 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

10. 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

11. 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

12. 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

13. 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

14. 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

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

16. 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

17. 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)

18. 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 HA-CDAD rates

19. 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

20. 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)

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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)

28. 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

29. 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

30. 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

31. 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