THE STATE OF THE STATE: ANTIBIOTIC RESISTANCE AND STEWARDSHIP

THE STATE OF THE STATE: ANTIBIOTIC RESISTANCE AND STEWARDSHIP Naveen Patil, MD, MHSA, MA, FIDSA Medical Kelley Director Garner, MPH, MLS(ASCP) Healthcare-Associated and Antibiotic Resistant Infections Program Program Coordinator/Epidemiology Supervisor Arkansas Department of Health PhD Student Kelley Garner, MPH, MLS(ASCP) CM Program Coordinator/Epidemiology Supervisor Healthcare-Associated and Antibiotic Resistant Infections Program Arkansas Department of Health

HAI Program Timeline 1999 Institute of Medicine s To Err is Human published 2010 Dedicated Funding from Health and Human Services 2014-2015 Ebola Response Received Additional Funding 2007 1st Arkansas HAI Law passed: Voluntary reporting Advisory Committee 2 FTEs 2011 2nd Arkansas HAI Law passed: Mandatory reporting 2016 Dedicated Funding for Antibiotic Resistance and Stewardship 8+ FTEs

Antibiotic Resistance CDC. Antibiotic Resistance Threats in the United States (2013). http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf [Accessed on 4/1/2016]. Graphic located at http://www.cdc.gov/getsmart/community/images/materials/ar-deaths.jpg.

Definitions Antimicrobial all agents that act (kill or prevent further growth) against all types of microorganisms Antibiotic act against bacteria Antiviral act against viruses Antifungal act against fungi Resistance the ability of a microorganism to stop an antimicrobial from working against it Stewardship the careful and responsible management of something entrusted to one s care

How do bacteria become resistant? CDC. What is antibiotic-resistant bacteria?. [Accessed on 9/1/2018]. Graphic located at https://www.cdc.gov/antibioticuse/community/pdfs/aaw/au_what-is-antibiotic-resistant-infographic_8_5x5_5_3_508.pdf.

Identifying Resistance http://www.biomerieux-diagnostics.com/etest E-test https://quizlet.com/124213828/micro-ch-10-pt-2- antimicrobial-drugs-flash-cards/ Kirby-Bauer test PCR (Polymerase Chain Reaction) http://www.biocompare.com/nucleic-acid- Electrophoresis/23398-Thermal-Cyclers- Thermocyclers-PCR-Machine/

CDC 2013 Threat Report CDC. Antibiotic Resistance Threats in the United States (2013). http://www.cdc.gov/drugresistance/pdf/arthreats-2013-508.pdf [Accessed on 4/1/2016].

List of Antimicrobial Resistant Pathogens of Interest Based on Level of Concern Urgent Clostridium difficile * Carbapenem-resistant Enterobacteriaceae (CRE) * Drug-resistant Neisseria gonorrhoeae (cephalosporin resistance) Serious Multidrug-Resistant Acinetobacter * Drug-Resistant Campylobacter Fluconazole-Resistant Candida * Extended Spectrum Enterobacteriaceae (ESBL) * Vancomycin-Resistant Enterococcus (VRE) * Multidrug-Resistant Pseudomonas aeruginosa * Drug-Resistant Non-Typhoidal Salmonella* Drug-Resistant Salmonella Serotype Typhi* Drug-Resistant Shigella* Methicillin-Resistant Staphylococcus aureus (MRSA) * Drug-Resistant Streptococcus pneumoniae * Drug-Resistant Tuberculosis* Concerning- Vancomycin-Resistant Staphylococcus aureus (VRSA) Erythromycin-Resistant Group A Streptococcus Clindamycin-Resistant Group B Streptococcus Pathogens listed with a * have been identified in Arkansas from HAI reports CDC. Antibiotic Resistance Threats in the United States (2013). http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf [Accessed on 4/1/2016]. Unpublished Arkansas Event Reports from CDC s National Healthcare Safety Network.

CRE Background Carbapenems Beta lactam class of antibiotics Available for clinical use in the mid-1980s Used as a last drug of resort for multidrug-resistant infections Enterobacteriaceae Large family of gram-negative bacteria Pathogens include: E coli, Klebsiella, Enterobacter, Salmonella, Shigella, Proteus, Serratia, Citrobacter, etc. Capable of sharing genetic material through plasmids

Enhanced capacity for resistance State Public Health Lab has capacity to confirm and/or identify: Species identification Carbapenemase production Carbapenemase genetic mechanism Results are reported back to submitting facility within 2 business days of findings HAI Program is coordinating submission of isolates through online form and tracking results to investigate and implement thorough infection control recommendations

11 Testing in 50 States and Six Large Jurisdictions Suspected CRE/CRPA isolates are forwarded to State PHLs Isolates with suspected novel resistance * REGIONAL PHL Testing at the State/Jurisdictional PHL may include: Species confirmation Antimicrobial susceptibility testing confirmation Phenotypic screening for carbapenemase production Molecular detection of mechanism * Positive for carbapenemase production by phenotypic methods and negative by PCR; Alert sent to state HAI coordinator and CDC within 1 day

AR Lab Network Regional Labs and TB Center 12

Multi-Drug Resistance Isolate Pre-Submission Form Developed to streamline the process of obtaining necessary information regarding isolates that require approval to be sent to the ADH laboratory. Reduces lag time for isolate submission approval Aids in finding appropriate healthcare facility/personnel to contact Collects information and allows document upload related to: Patient and facility demographics Medical history Initial laboratory results Including susceptibility results Found at: https://adhredcap.arkansas.gov/redcap/surveys/?s=wmwxdwehmp

Multi-Drug Resistance Isolate Pre-Submission Form https://adhredcap.arkansas.gov/redcap/surveys/?s=wmwxdwehmp

https://adhredcap.arkansas.gov/redcap/surveys/?s=wmwxdwehmp

New* reportable conditions Carbapenem-resistant Enterobacteriaceae Any Enterobacteriaceae species that is found to be resistant to at least one carbapenem antibiotic from any source (not screening cultures) Ideally, please include a copy of the susceptibility report Candida auris Any report of Candida auris or Candida haemulonii from any source Submit isolate to state public health laboratory *Pending approval and finalization

Summary of Arkansas Healthcare-Associated Infections (HAI) and Standardized Infection Ratios (SIR) for 2017 HAI Metric Number of observed infections Interpretation as compared to national baseline Number of Infections needed to be prevented to meet national goals* Percentage Difference from 2016 Central line-associated bloodstream infections (CLABSI) Catheter-associated urinary tract infections (CAUTI) Surgical Site Infections (SSI) after colon surgeries 235 17% 134 10% 271 18% 98 11% 97 10% 31 30% Surgical Site Infections (SSI) after abdominal hysterectomies 17 41% Surpassed Prevention Goal 1% Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections 94 16% 53 5% Clostridium difficile infections (CDI) 734 22% 78 1% These data were collected and analyzed using the Centers for Disease Control and Prevention s National Healthcare Safety Network. *National prevention goals have been set by the US Department of Health and Human Services in the 2020 National Action Plan to Prevent Health Care-Associated Infections: Road Map to Elimination. These goals represent a decrease beyond the national baseline (SIR =1.0). The SIR goals are 0.5 for CLABSI, 0.75 for CAUTI and both SSI, 0.50 for MRSA bloodstream infections, and 0.70 for CDI.

CDC. Deadly diarrhea: C. difficile causes immense suffering, death. Table 3 from Lessa FC, Mu Yi, Bamberg WM et al. N Engl J Med 2015;372:825-34. DOI: 10.1056/NEJMoa1408913. Available at: https://www.cdc.gov/hai/pdfs/cdiff/cdiff-one-pager.pdf

Clostridium Difficile CDC. Deadly diarrhea: C. difficile causes immense suffering, death. Table 3 from Lessa FC, Mu Yi, Bamberg WM et al. N Engl J Med 2015;372:825-34. DOI: 10.1056/NEJMoa1408913. Available at: https://www.cdc.gov/hai/pdfs/cdiff/cdiff-one-pager.pdf

Four Core Actions to Prevent Resistance Preventing infections Tracking Improving antimicrobial prescribing/stewardship Developing new drugs and diagnostic tests CDC. Antibiotic Resistance Threats in the United States (2013). http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf [Accessed on 4/1/2016].

Arkansas Activities Preventing infections Conducting Infection Control Assessment and Readiness (ICAR) visits ~90 on-site visits to healthcare facilities in 2 years Promoting vaccinations Targeting outreach to facilities with higher numbers of healthcareassociated infections Tracking Implementing standard surveillance for antibiotic resistant pathogens, especially for the urgent category Identifying important resistant mechanisms at the state public health laboratory Improving antimicrobial prescribing/stewardship Providing education to prescribers Analyzing antimicrobial prescribing patterns across the state by working with key partners

Cumulative Infection Control Assessment and Readiness (ICAR) Visits Conducted in Arkansas 2016-17, by Facility Type 100 90 80 70 Number of Visits 60 50 40 30 20 10 0 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Dec-16 Jan-17 Feb-17 Ma r-17 Apr-17 Ma y-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Jan-18 Feb-18 Ma r-18 Apr-18 Ma y-18 Jun-18 Jul-18 Aug-18 Sep-18 Oct-18 Acute Care Hospital Critical Access Long-Term Care Acute Care Critical Access Nursing Homes Total n 37 14 36 87 Unpublished aggregate data

CDC s Tiered Strategies for Containment CDC has issued guidance for highly drug resistant organisms that defines three different categories (Tiers 1-3) and the recommended approach to control each. General definitions of each Tier are included in the next slide. Classification of an organisms tier is dependent on the regional and state epidemiology for that resistance mechanism. CDC. Interim Guidance for a Public Health Response to Contain Novel or Targeted Multidrug-resistant Organisms (MDROs). Available at: https://www.cdc.gov/hai/outbreaks/docs/health-response-contain-mdro.pdf. Accessed on 08/31/2018.

Tiered Containment Response Tier 1: Resistance mechanisms novel to the United States (i.e., never previously or only very rarely identified in the United States). Organisms for which no current treatment options exist (pan-resistant) and that have the potential to spread more widely within a region. Tier 2: Organisms found in healthcare settings but not believed to be found regularly in the region. Includes organisms that might have been found more commonly in other areas in the United States. For Arkansas, this includes resistance mechanisms for carbapenemresistant Enterobacteriaceae that are not found to be the Klebsiella pneumoniae carbapenemase (KPC) type. Tier 3: Organisms that are already established in the United States and have been identified before in the region but are not thought to be endemic.

Response Element Comparison Infection Control Assessment Element Tier 1 Tier 2 Tier 3 Prospective Surveillance Lab Lookback Screening of Healthcare Roommates Broader Screening of Healthcare Contacts Household Contact Screening Environmental Sampling Healthcare Personnel Screening Yes No Sometime s Adapted from CDC KPC, Containment, and ARLN presentation on January 17, 2018.

Areas Identified as Key Support Activities from practicing Infection Preventionists N= 56 respondents Data collected as part of 2016 Infection Prevention Needs Assessment

ADH utilized a joint venture with the University of Arkansas for Medical Sciences Center for Distance Learning to develop a webinar series dedicated to infection control This program offers 20+ continuing education hours for physicians, nurses, pharmacists, and Watch the webinars others online for free at https://learnondemand.org/registration.as px Credits will be available Continuing education for five credits years and can available for physicians, be accessed nurses, pharmacists, health afterwards educators, for free etc.

Oral Outpatient Antibiotic Prescriptions Dispensed in U.S. Community Pharmacies Per 1000 Population, All Antibiotic Classes, 2015 1,154 (antibiotic RX per 1,000 pop) Arkansas ranks 46 th in number of antibiotic RXs dispensed CDC. Patient Safety Atlas using 2011-2015 Xponent database from QuintilesIMS. Available at: https://gis.cdc.gov/grasp/psa/aumapview.html.

Antimicrobial Stewardship Core Elements Leadership Commitment Dedicating necessary human, financial, and IT resources Accountability Appointing a single leader responsible for program outcomes Drug Expertise Appointing a single pharmacist leader to improve antibiotic use Action Implementing at least one recommended action Tracking Monitoring antibiotic prescribing and resistance patterns Reporting Regular reporting information on antibiotic use and resistance to staff Education Educating staff about resistance and providers on optimal prescribing CDC. Core Elements of Hospital Antibiotic Stewardship Programs. Atlanta, GA: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html

Unpublished Arkansas aggregate data from CDC s National Healthcare Safety Network N = 2014-55 2015-57 2016-54

Pharmacist Stewardship Survey Background - Arkansas Department of Health (ADH) Healthcare-Associated Infections and Antimicrobial Stewardship sub-committee idea - Establish basic demographics and brief summary of antimicrobial stewardship actions at hospitals across the state. - Questions aligned with the CDC s 7 Core Elements of Antimicrobial Stewardship - Survey targeted pharmacists - Previous collaboration with the Arkansas Association of Health- System Pharmacists

Location Distribution of Survey Results Emailed on 9/6/2017 and closed on 10/6/2017 75 pharmacists contacted 34 total responses 45% response rate 11 from Central AR 9 from NW AR 9 from NE AR 3 from SE AR 2 from SW AR

Q32. What areas do you envision ADH helping with your institution s ASP? Area of Interest # of Respondents N=35 Connection to resources 31 (91%) Education and training 30 (88%) Antimicrobial monitoring processes 22 (65%) Data feedback to clinicians 20 (59%) Patient and community engagement 19 (56%) Data feedback to administration 17 (50%) Implementing evidenced-based guidelines 15 (44%) Data Interpretation 14 (41%) Leadership buy-in 11 (32%) Evaluation of diagnostic testing methods 9 (26%)

Q36. Other comments/ideas on how ADH can help with your ASP Increase/promote awareness when ID guidelines are updated or published Quick link on ADH website Email List Serve ID Physician peer education Retail/Community Pharmacy ASP Opportunity Ideas State-wide education initiative targeting specific ID syndromes Help with Administration/Physician Buy-in Help share data within Arkansas hospitals

Overall Discrepancies between 2017 Pharmacist Survey and NHSN Data 9 8 7 Number of NHSN and Pharmacist Survey Discrepancies between Survey Respondents 8 7 Number of Respondents 6 5 4 3 2 1 3 6 2 2 1 0 0 0 1 2 3 4 5 6 7 Number of Discrepancies per Facility n=35

Statewide Antimicrobial Stewardship Initiative (SASI) - Structured after Infection Control Assessment and Response (ICAR) visits - Created 7 page tool for facilities to complete - Schedule onsite visit to meet with a facility s Antimicrobial Stewardship Program - After the visit, each facility receives an updated SASI tool, and formal visit summary letter, and a list of antimicrobial stewardship recourses

SASI Visits to Date - 18 Hospitals since Dec. 2017-5 Critical Access Hospitals - 13 General Acute Care Hospitals Goal of 32 hospitals

Going forward Establishing a surveillance and response program to provide data back to stakeholders on antibiotic prescribing and resistance Using data to target outlier facilities to drive prevention progress Exploring novel data sources to evaluate antibiotic resistance in the state Identifying new partners to collaborate and share experiences

Making Health Care Safer: Stop Spread of Antibiotic Resistance. Vital Signs. CDC, August 2015. http://www.cdc.gov/vitalsigns/stop-spread/index.html [Accessed on 04/01/2016].

Containment Public Health Efforts Potential Effect on Resistance An estimated 619,000 infections and 37,000 deaths could be potentially averted. Slayton, Rachel B., et al. "Vital Signs: Estimated Effects of a Coordinated Approach for Action to Reduce Antibiotic-Resistant Infections in Health Care Facilities United States." MMWR. Morbidity and Mortality Weekly Report 64.30 (2015): 826-31

Program Staff Naveen Patil, MD, MHS Gary Wheeler, MD, MPS Dirk Haselow, MD, PhD, MS Sandra Chai, MD Margaret Holaway, RN, BSN Corey Lance, PharmD Rohan Chakravorty, MPH Trent Gulley, MPH Rachel Mahurin, BS Melissa Jenson, BS Kelley Garner, MPH, MLS(ASCP) Kelley.Garner@arkansas.gov (501) 661-2296 ADH.HAI@arkansas.gov Questions?