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

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

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

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

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:10.1017/ice.2017.42

Emerging Antibiotic Resistant Threats

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

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 https://www.cdc.gov/fungal/diseases/candidiasis/tracking-c-auris.html

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

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

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

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

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

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

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; 53:532-540

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

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; 33:984-992

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: 848-55

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.

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

Potential Impact of Containment Courtesy of Prabasaj Paul and Rachel Slayton

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

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

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 https://www.cdc.gov/hai/outbreaks/mdro/index.html