1. Promoting a Public Health Approach to Detecting and Containing Novel and Emergent Antibiotic Resistant Organisms
Maroya Walters, PhD, ScM
Division of Healthcare Quality Promotion
Centers for Disease Control and Prevention
Topic:  Some forms of emerging antibiotic resistance make bacteria resistant to most or all available antibiotics and have the potential for epidemic spread.  Spread of these forms of resistance could severely limit the utility of antibiotics for treatment of healthcare associated infections. In 2017, the Centers for Disease Control and Prevention (CDC) launched the Containment Strategy with the goal of slowing the spread of emerging antibiotic resistance through rapid and robust public health response. Key elements of the Containment Strategy include early detection of resistance, infection control assessments, and screening for asymptomatic carriage. This presentation will describe emerging antibiotic resistant threats such as carbapenem resistant Enterobacteriaceae, discuss approaches to preventing the spread of resistant organisms, and describe the CDC Containment Strategy.
Learning Objectives:
1.   Discuss emerging antibiotic threats and describe why they are a public health concern.
Describe the CDC Containment Strategy and how it is applied in healthcare settings.                 
                                                                                                                                                                                                                 
Provide examples of successful containment of antibiotic resistance.                  
September 24, 2018
No Disclosures

2. Outline Emerging antibiotic resistant threats
CDC Containment Strategy: a new approach to controlling emerging resistant organisms

3. Antibiotic Resistance
Antibiotic resistant (AR) germs avoid the effects of the drugs designed to kill them
AR evolves faster than new antibiotics are created
AR is not stoppable but its spread can be slowed
Easiest to control when problem is small/emerging
Resistant germs can be anywhere and can affect every aspect of human life
Travel
Environment
Healthcare
Sex
Food
AR pathogens emerge and spread in healthcare settings
Antibiotics select for resistant organisms
Ill persons more likely to acquire these organisms
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential

4. Without Early Intervention Antibiotic Resistance Spreads Like Wildfire
DC*
2008
DC*
2017
DC*
2012
DC*
2005
DC*
2001
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential
States with Klebsiella pneumoniae carbapenemase (KPC)-producing Carbapenem-resistant Enterobacteriaceae (CRE) confirmed by CDC
Simulation of Transmissions Per Day Following Importation of Antibiotic Resistant Bacteria

5. Resulting in Staggering Increases in Percent Resistant in Short Time
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential
Friedman N, et. al. (2017). doi: /ice

6. Emerging Antibiotic Resistant Threats

7. Carbapenem-resistant Enterobacteriaceae (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
Cause invasive infections associated with high morbidity and mortality
Resistant to most or all antibiotics
Older adults with underlying medical conditions at highest risk
Carbapenemase-producing strains have potential for epidemic spread
Carbapenemases: KPC, NDM, VIM, IMP, OXA-48
Large outbreaks
Person to person transmission: post-acute care, longer length of stay ACH units
Devices, sink drains: short stay ACH
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential

8. Candida auris
Fungus that causes invasive infections with high mortality (60%)
Discovered in Japan in 2009 and rapidly spread worldwide
High level resistance
Incredible capacity for spread
Persistently contaminates the healthcare environment
Transmission in SSACH
Challenging outbreaks in long-term care

9. Common Attributes of Emerging Antibiotic Resistant Threats
Cause serious infections
Associated with large outbreaks
Potential for epidemic spread
Can be transmitted silently (asymptomatic carriers)
Spread rapidly
Among bacterial strains
Within healthcare facilities
Between healthcare facilities
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential

10. Colonization (Asymptomatic Carriage)
Colonization: individuals carry a bug but don’t have symptoms of illness
Most individuals with a resistant organism
Only a fraction detected by clinical cultures
Asymptomatically colonized individuals can
Transmit to others
Develop infections themselves
Be detected by screening tests
Body sites colonized depend on organism
Skin, nares, digestive tract
INFECTIONS
ASYMPTOMATIC CARRIAGE

11. Spread by Sharing Resistance Between Strains
Some resistance can move between strains of bacteria
In a patient
In the environment
Antibiotic-resistant cell

12. Spread by Sharing Resistance Between Strains
Some resistance can move between strains of bacteria
In a patient
In the environment
Antibiotic-resistant cell
Antibiotic-resistant cell
Some types of CRE and CRPA have this type of resistance
Carbapenemase-producing strains
For infection control, important to know what mechanism makes organism resistant
Most clinical laboratories are not able to detect carbapenemases

13. Transmission in Facilities
Hands and clothes of healthcare workers
Patient environment
Improperly cleaned medical devices
Transmission can be prevented through
Hand hygiene
Use of gown and gloves
Environmental cleaning
Device reprocessing
But only if performed consistently and correctly!
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential

14. Amplification in High Acuity Post-acute Care
Mathematical modeling, supported by real world experience, shows that long lengths of stay and high acuity care are the primary drivers of transmission. As a result, high acuity post acute care settings like LTACHs and the ventilator units of skilled nursing facilities can serve as amplifiers of novel resistance. These are the settings where we most commonly observe transmission, and outbreaks in these settings can be particularly hard to control. In particular, containment responses in ventilator units have shown that these settings may have very high prevalence of multiple MDROs. These types of facilities are distinct from residential facilities in terms of the acuity of residents, but one of the challenges for controlling MDROs in them is that these units developed from more residential skilled nursing facilities, and the built environment and staffing levels are more similar to SNFs than to LTACHs or short stay ACH. For example, retrofitting residential facilities to vent units can result in infection control challenges, like caring for ventilated patients in the triple and quad rooms shown here.
Long lengths of stay + high acuity = increased risk of transmission
Multiple high concern AR pathogens may be present

15. Outbreaks Often Not Contained to a Single Facility
Spread accelerated by
Undetected transmission
Poor communication of AR pathogen status during patient transfer between facilities
Spread occurs not just within single facilities but also through transfer of patients through a region. This figure shows the KPC-CRE outbreak in Chicago. The colored circles are different healthcare facilities. The red dot is an LTACH that was the primary amplifier of the outbreak. Some nursing homes – the green dots - also served as amplifiers. Therefore emerging resistance can quickly become a regional issue, due to long term care facilities serving as reservoirs and amplifiers of resistance and disseminate to the larger hospital network.
KPC-CRE outbreak in Chicago, 2008
Won et al. Clin Infect Dis 2011; 53:

16. Attributes That Accelerate Spread of Resistance
Spread among patients in a facility through infection control lapses
Spread among healthcare facilities through patient sharing
Imagine if every urinary tract infection or pneumonia had to be treated with IV antibiotics. That is the potential
Spread among bacterial strains

17. Containing a Facility Outbreak
CRE patients cohorted
Biweekly outbreak calls
Daily audits, invasive device stewardship
Point prevalence surveys
Audits of hand hygiene and PPE
Dedicated nurses on ICU, Dedicated equipment for CRE patients
Chitnis AS, et al. Infect Control Hosp Epidemiol 2012; 33:

18. Containing a National Outbreak: Israel KPC-CRE
Central authority
ACH: Mandatory reporting, contact precautions, cohort patients and nursing staff
Inclusion of LTCF
Active surveillance
National intervention following sudden emergence of KPC-CRE.
Acute care hospitals
Intervention coordinated by national health authority
Mandatory CRE reporting
Acute care contact isolation and cohorting of nursing staff
79% reduction
Schwaber et al, CID 2011; 52:

19. Application of Interventions in a National Setting Israel KPC-CRE Outbreak
-Infection Control education
-Active surveillance
-Gowns and gloves
-Resident cohorting
Ben-David et al, CID 2018; in press.

20. Summary of Emerging Antibiotic Resistant Threats
Pathogens that cause serious infections and are resistant to first line therapies
Associated with high morbidity and mortality
Spread easily
Movement of resistance mechanism across strains
Transmission within facilities due to infection control gaps and unrecognized asymptomatically colonized individuals
Cause regional outbreaks through patient sharing
Adherence to basic infection control measures can slow transmission
Success in controlling spread in individual facility outbreaks and through experiences of other countries can guide the U.S. strategy

21. “Containment” – A New Strategy to Prevent Spread of Emerging Resistance

22. Why was a new strategy needed?
Combination of lack of availability, high cost, absence of guidance limited
Detection of target organisms/mechanisms
Horizontal and vertical infection control measures
Screening for asymptomatic colonization
Coordination across a region
Needs
Detailed guidance
Laboratory support
Infection control support

23. The Containment Strategy
Goal: identify new resistance and control transmission
Rapid detection and response
Single case of emerging resistance
Infection control assessments
Led by public health using standardized tools
Colonization screenings
Available through public health laboratories
Coordination between healthcare facilities
Continued vigilance until spread is controlled

24. Containment Responses
Guidance applies to all healthcare facilities (post-acute care, acute care)
Containment responses occur in facilities
Where patient or resident with targeted resistance is currently present
Where patient or resident with targeted resistance is not currently present but had stay within prior ~30 days
That frequently shares patients or residents with a healthcare facility that has ongoing transmission of targeted resistance
Where response occurs is not necessarily where resistant organism was acquired

25. Detection: Antibiotic Resistance Laboratory Network
Tiered network established in 2016 to support nationwide lab capacity to rapidly detect and respond to antibiotic resistance
Tests performed include
Carbapenemase testing for CRE and CRPA
C. auris identification
Colonization screening for carbapenemase-producing organisms and C. auris
Hundreds of cases of unusual resistance identified since inception
This has tested tens of thousands of isolates in <2 years since inception and performed thousands of colonization screening tests.

26. Infection Control Assessments: Public Health Resources
Local AR/HAI expertise in 50 states, 6 cities and Puerto Rico
500 CDC-funded positions in state and local health departments
Health departments experienced with standardized onsite infection control assessment through Infection Control Assessment and Response (ICAR) activities
Non-regulatory assessment of infection prevention program and practices using setting specific tools
These tools often used for assessment during containment response

27. Key Infection Control Assessment Elements
Educate healthcare personnel and visitors
Adherence to hand hygiene
Use of gown and gloves
Environmental cleaning
Patient placement
Cohorting patients and staff where feasible
Interfacility notifications when transferring patients

28. Importance of Hand Hygiene, Gown and Gloves
Study of health care provider and environmental contamination when caring for patients with CRE*
14% of interactions resulted in contamination of gloves or gowns
Factors associated with increased contamination: wound care, manipulation of catheter or drain, caring for patient with endotracheal tube or tracheostomy
Compliance often challenging
Limited accessibility of supplies
Healthcare worker knowledge
*Rock, C. et. al, Infect Control Hosp Epidemiol 2014;35(4):426

29. Use of Hand Hygiene, Gown and Gloves
Need to make compliance easy!
Supplies necessary for hand hygiene should be readily accessible
In every patient/resident room
Ideally, ABHR within arms reach of care activities
Setting-specific recommendations for gowns and gloves
Contact Precautions for targeted antibiotic resistance used in most acute care hospitals
For colonized long-term care facility residents
Gown and gloves for high risk activities recommended
No restriction from group activities

30. Environmental Cleaning and Disinfection
The environment can serve as a source for transmission
Many challenges observed during responses
Insufficient staff time to perform cleaning and disinfection
Lack of respect for EVS staff as part of healthcare team
Inadequate communication of cleaning responsibilities
EVS and nursing
Insufficient cleaning and disinfection of mobile equipment
Objective measures of cleaning processes critical for assessing quality

31. Colonization Screening
Multiple point prevalence surveys might be conducted if transmission identified
2022 screening tests for carbapenemase-producing organisms, 2017
11% of screening tests positive
14% positive in post-acute care
Nursing homes, ventilator units of skilled nursing facilities, LTACHs
6% in short stay acute care
Only a fraction of patients colonized with CRE will have positive clinical cultures. Although estimates vary depending on setting and study, it is most commonly estimated that only about 1 of every 10 patients with CRE are detected through clinical cultures.
Colonized patients can transmit to other patients
Surveillance cultures used to detect previously unidentified colonization
Epidemiologically-linked contacts of index case
Active surveillance

32. Colonization Screening Best Practices
Patients/residents asked for verbal consent
Consent scripts and FAQ available
Collection performed by trained healthcare worker
Generally facility nursing staff
Surveyors informed of containment response activities
Results shared with patient/family
Results used to inform infection control
In consultation with public health

33. What Containment Looks Like in a Healthcare Facility
Containment responses might result in
More use of gowns and gloves
More specific signage about PPE on patient/resident rooms
Moving patients/residents in order to cohort
Colonization screening
Containment responses should not result in
Colonized residents restricted to room indefinitely
Exclusion from group activities in post-acute care facilities

34. Example Containment Response #1
CP-CRE identified in patient with history of healthcare in India through AR Laboratory Network
Patient in U.S. acute care hospital for >1 week
Infection control assessment and screening of hospital contacts was completed and results returned within 48 hours of identification of index case
No transmission identified

35. Example Containment Response #2
AR Laboratory Network identified CP-CRE in a nursing home resident with a urinary tract infection
The state health department assessed infection control practices and performed a point prevalence survey that identified five additional colonized residents among 30 surveyed at the nursing home
The health department conducted additional infection control assessments to ensure adherence to recommended practices and two follow-up surveys of the nursing home wing
No additional cases identified

36. Potential Impact of Containment
Courtesy of Prabasaj Paul and Rachel Slayton

37. Containment Summary New approach Responding before problem becomes big
Identifying and controlling transmission
Protects patients/residents across continuum of care
Keys to control
Detection – clinical cases and asymptomatically colonized individuals
Good infection control practices
Hand hygiene, gowns and gloves, environmental cleaning

38. Final Messages
Antibiotic resistance is scary but its spread can be slowed
Containment is a new, more aggressive strategy for control
Best success when facilities, public health, and surveyors to work together
Reach out to public health if questions about containment response

39. Thank you! Contact: MSWalters@cdc.gov Additional Resources
Slide Acknowledgements
CDC Division of Healthcare Quality Promotion
Prevention and Response Branch
Alex Kallen
AR team
Epidemiology Research and Innovations Branch
Rachel Slayton and Prabasaj Paul
Antimicrobial Resistance Laboratory Network
Allison Brown
CDC Mycotic Diseases Branch
Snigdha Vallabhaneni