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Antibiotic Stewardship in Hospitals: CDC Update Wednesday, January 25, 2017 12:00 PM ET In Case of Technical Difficulties If you hear an echo: Make sure you are only logged in once on your computer Select one form of audio only (either computer speakers or telephone connection) If the audio is choppy: Press pause in the top left corner of your screen Wait 10 seconds and then click play Dial 800-843-9166 at any time for live assistance 1

Agenda Agenda Welcome and Introductions William Schaffner, MD NFID Medical Director and Professor of Preventive Medicine and Infectious Diseases, Vanderbilt University School of Medicine Antibiotic Stewardship: Why We Must, How We Can CAPT Arjun Srinivasan, MD Associate Director for Healthcare Associated Infection Prevention Programs Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Questions and Answers This webinar is supported by an unrestricted educational grant from Merck & Co., Inc. NFID policies restrict funders from controlling program content. General Information Please note that today s webinar is being recorded All phone lines will be placed on mute throughout the program To hear audio: Computer: Follow directions Phone: 303-248-0285; Access Code 6560003 After the presentations, there will be a Question and Answer period Use the Chat box on the lower left side of your screen to type your question At the end of the webinar, an online evaluation link will be sent to participants via email 2

CME Credit & Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM To receive credit, you must complete the online evaluation and pass the posttest with a score of 80% or higher Online evaluation and post-test will be available following the webinar at: http://bit.ly/amrstewardship-125 Certificate will be available for print or download following successful completion of online evaluation and post-test Disclosures Marla Dalton (NFID staff, content reviewer) owns stock, stock options, or bonds from Merck & Co., Inc. William Schaffner (NFID medical director, presenter) served as an advisor or consultant for Dynavax, Merck & Co., Inc., Novavax, Inc., Pfizer Inc., and Sanofi Pasteur; and served as a speaker for Genentech All other speakers, activity planners/reviewers, and staff for this activity have no relevant financial relationships to disclose 3

Learning Objectives At the conclusion of this webinar, participants will be able to: Describe current trends in hospital antibiotic use Describe the CDC standardized antimicrobial administration ratio List key improvement opportunities About NFID Non-profit 501(c)(3) organization dedicated to educating the public and healthcare professionals about causes, treatment, and prevention of infectious diseases across the lifespan Reaches consumers, health professionals, and media through: Coalition-building activities Public and professional educational program Scientific meetings, research, and training Longstanding partnerships to facilitate rapid program initiation and increase programming impact Flexible and nimble organization 4

Antibiotic Stewardship Why We Must How We Can Wednesday, October 5, 2016 12:00 PM ET CAPT Arjun Srinivasan, MD Associate Director for Healthcare Associated Infection Prevention Programs Division of Healthcare Quality Promotion Centers for Disease Control and Prevention beu8@cdc.gov Disclosures No financial disclosures My talk today will focus on antibiotic use in hospital settings and a bit on outpatient clinics There are equally important needs to improve antibiotic use in nursing homes and in agricultural settings There is ongoing work at CDC on these areas as well 5

Improving Antibiotic Use for Patient Safety For too long many have thought of antibiotic stewardship as being about societal good What s more important is that antibiotic stewardship is important to improve the individual outcomes of the patients in the beds in front of us, today Fewer adverse reactions Improved outcomes Antibiotics Are Different From All Other Drugs Antibiotics lose their effectiveness over time- even if we use them perfectly Every specialty (almost) uses them on a regular basis They are a shared resource-the use of antibiotics in one patient can compromise how they work for someone else 6

Receipt of antibiotics in prior patients was significantly associated with incident Clostridium difficile infection (CDI) in subsequent patients (logrank P <.01) This relationship remained unchanged after adjusting for other factors known to influence risk for CDI (receipt of antibiotics by the subsequent patient, prior patient developed CDI) JAMA Intern Med. Published online October 10, 2016. Antibiotics Are Different From All Other Drugs We depend on antibiotics to deliver complex and advanced medical care Many routine procedures increase risks for infections What happens to joint replacements, chemotherapy, transplants if we can t treat infections? Already some patients get denied organs because they have resistant bacteria 7

Community Antibiotic Prescribing Rates per 1000 Population United States, 2014 WA MT ND ME Lowest state: 501 per 1000 OR NV CA ID UT AZ WY CO NM SD NE KS OK MN WI IA IL MO AR NY MI PA OH IN WV VA KY NC TN SC VT NH MA RI CT NJ DE MD DC Highest state: 1,285 per 1000 MS AL GA AK HI TX LA FL prescriptions_per_k 501-648 692-744 768-852 853-925 927-1,000 1,021-1,285 Data: IMS Health Xponent http://www.cdc.gov/getsmart/community/programs-measurement/measuring-antibiotic-prescribing.html JAMA IM published on-line 9/19/16 55.1 % of all patients got at least 1 dose of an antibiotic Overall use was 755 DOT/1000 patient days No change from 2006-12 Use did not vary by bed size Non-teaching hospitals had higher use than teaching hospitals 8

National Estimate of US Hospital Antibiotic Use Use varied between ICU and non-icu locations 1092 DOT/1000 PD vs 720 DOT/1000 PD Use of some classes went down: Quinolones (20%), 1 st generation cephalosporins (7%) Use of many classes went up: Vancomycin (32%), beta-lactam/inhibitor (26%), 3 rd /4 th generation cephalosporins (12%) Biggest increase in Carbapenem use: 37% JAMA IM published online 9/19/16 Consequences of Any Antibiotic Exposure Selective pressure for antibiotic resistance Increased risk of candidemia Increased risk for C. difficile infection 7-10 fold increased risk for up to 3 months Adverse drug reactions About 140,000 visits to emergency departments every year for adverse reactions to antibiotics Disruption of normal gut bacteria 9

Days of Therapy 1/25/2017 Increased Risk of Sepsis After Antibiotic Exposure Disruption of the gut microbiome increases the risk of sepsis in animal models Retrospective study of ~9 million patients discharged without sepsis in 473 US hospitals 0.6% were readmitted with sepsis in 90 days Exposure to broad spectrum antibiotics during hospitalization was independently associated with risk of sepsis: OR=1.50 95% CI:1.47-1.53 Baggs, J. et al. IDWeek 2016 250 Most Common Reasons for Unnecessary Days of Therapy 576 (30%) of 1941 days of antimicrobial therapy deemed unnecessary 200 192 187 150 100 94 50 0 Duration of Therapy Longer than Necessary Noninfectious or Nonbacterial Syndrome Treatment of Colonization or Contamination Hecker MT et al. Arch Intern Med. 2003;163:972-978. HAI Regional Training HAI Training Requirements is sponsored by SHEA and CDC 20 10

Defined daily doses in hospital inpatients Number of all (HA+CA) CDI cases in >65 years old 1/25/2017 47 million unnecessary antibiotic prescriptions per year Impact of Reductions in Antibiotic Prescribing on C. difficile in England 7,000,000 Cephalosporin doses Fluoroquinolone doses C. difficile in > 65 y.o. 60000 6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 70% reduction in C. difficile infections over 7 years 50000 40000 30000 20000 10000 0 2004 2005 2006 2007 2008 2009 2010 2011 Year 0 Ashiru-Oredope et al. J Antimicrob Chemother 2012; 67 Suppl 1: i51 i63 Wilcox MH et al. Clinical Infectious Diseases 2012;55(8):1056 63 http://www.hpa.org.uk/web/hpaweb&page&hpawebautolistname/page/1179745282388 11

Percent 1/25/2017 Antibiotic Stewardship and Decreased Risk of Resistant Infections Cipro Standard Antibiotic duration 3 days 10 days LOS ICU 9 days 15 days Antibiotic resistance/ superinfection 14% 38% Study terminated early because attending physicians began to treat standard care group with 3 days of therapy Singh N et al. Am J Respir Crit Care Med. 2000;162:505-11. Clinical Outcomes Better with Antimicrobial Stewardship Program 100 90 80 70 60 50 40 30 20 10 0 AMP UP Appropriate Cure Failure RR 2.8 (2.1-3.8) RR 1.7 (1.3-2.1) RR 0.2 (0.1-0.4) Fishman N. Am J Med. 2006;119:S53. AMP = Antibiotic Management Program UP = Usual Practice 12

What is Antibiotic Stewardship Ensuring that every patient gets: An antibiotic only when one is needed The right agent At the right dose For the right duration Goals of Stewardship The primary goal of antibiotic stewardship is better patient care Reducing antibiotic use and saving money are NOT the primary goals of antibiotic stewardship Optimized and fast empiric therapy for sepsis is an important part of antibiotic stewardship They simply happen to be desirable side effects 13

How Can We Improve Antibiotic Use? Lessons learned from preventing central line associated blood stream infections Well-defined programs and interventions with education on implementing them A strong, national measurement system A national emphasis on solving the problemincluding national goals New policies to spur action Research A First Step: Defining Expectations It is hard to measure implementation of antibiotic stewardship programs without a clear definition of what they entail Previous definitions worked very well in large, academic hospitals, but were difficult or even impossible in smaller hospitals We needed to define what every hospital should do 14

Core Elements for Antibiotic Stewardship Programs Based on experience from successful stewardship programs in many types of hospitals Attempts to define the what and leave flexibility on the who Now available for nursing homes and outpatient settings as well http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html Core Elements for Antibiotic Stewardship Programs: Hospitals and Nursing Homes Leadership commitment from administration Single leader responsible for outcomes Single pharmacy leader Antibiotic use tracking Regular reporting on antibiotic use and resistance Educating providers on use and resistance Specific improvement interventions 15

Findings on Antibiotic Stewardship in US Hospitals: NHSN Annual Facility Survey In 2014, 41% of US hospitals reporting having a stewardship program that meets all 7 CDC Core Elements Factors associated with meeting all Core Elements Bed size Teaching Status Leadership support (written > salary) Clinical Infectious Diseases 2016;63(4):443 9 48% Percentage of Facilities in Each State Meeting all 7 Core Elements, 2015 Overall: 48% 30% 12% 51% 37% 54% 33% 24% 47% 59% 7 % 27% 59% 33% 48% 77% 70% 49% 31% 28% 26% 36% 45% 51% 48% 54% 47% 41% 54% 60% 67% 47% 58% 38% 60% 50% 63% 40% 35% 43% 47% 56% 67% 24% 45% 48% 41% 33% 40% 60% 64% 24% Percentage Meeting All 7 elements 7-33 34-45 47-54 56-77 4569 hospitals responded in 2015 (4184 in 2014) 16

Percentage of US Acute Care Hospitals (n=4,569) responding to the 2015 National Healthcare Safety Network Annual Survey that meet all 7 of CDC s Core Elements for Hospital Antibiotic Stewardship Programs 100% 90% 80% 70% 66.1% 63.4% 60% 50% 49.6% 53.2% 53.1% 45.4% 42.4% 40% 30% 31.1% 26.3% 20% 10% 0% 0-50 beds 51-200 beds >200 beds Children's hospital General acute care hospital Surgical hospital Critical access hospital Major teaching Non-teaching Bed Size Facility Type Teaching Status Measuring For Improvement- Antibiotic Use Broad (ideally national) assessments of aggregate use Facility, practice and provider specific assessments of antibiotic administration data Assessments of appropriate antibiotic use 17

National Healthcare Safety Network Antibiotic Use Option Captures electronic data on antibiotics administered, along with admission/discharge/ transfer data Calculates rates of administration for use: By facilities to monitor interventions on single units or facility wide To collect aggregate information on antibiotic use at regional and national level Eventually, to create antibiotic use benchmarks Challenges With Benchmarking Antibiotic Use Will require good risk adjustment to help facilities know if they are outliers The goal is not 100% or zero Being an outlier does not necessarily mean there is a problem Always have to be alert for unintended consequences 18

Standardized Antibiotic Administration Ratio (SAAR) CDC s 1st attempt at developing a risk-adjusted benchmarking measure for hospital antibiotic use SAAR expresses observed antibiotic use compared to predicted use CDC working with many partners to develop the SAAR measure to try and make it most useful for stewardship Standardized Antibiotic Administration Ratio (SAAR) Experts in stewardship suggested that a variety of different SAARs would be useful SAARs for different patient populations (adult, peds, ICU, non-icu) SAARs for different groups of antibiotics: Agents mainly for healthcare associated pathogens Agents mainly for community pathogens Agents active against MRSA Agents frequently use for surgical prophylaxis All agents 19

Key Points About the SAAR The SAAR is risk adjusted based only on facility characteristics (e.g., presence of ICUs, hospital size) The SAAR does not indicate if antibiotic use is good or bad, only higher or lower than expected The SAAR helps direct stewardship programs to places where use should be reviewed Some Questions About the SAAR Does the SAAR help point to locations and/or agents where there are meaningful opportunities to improve antibiotic use? How would additional data for risk-adjustment impact the SAAR? Will the SAAR values change if antibiotic use is improved? Should the SAAR be used for hospital quality reporting and/or payment programs? 20

Measuring Appropriate Use We all agree that the ultimate goal of stewardship is to improve appropriate use of antibiotics It will be hard to measure progress towards that goal if we don t have measures of appropriate use National data from outpatient clinics with diagnoses and medications prescribed 12.6% of all outpatient visits resulted in an antibiotic prescription About 30% of all visits that resulted in an antibiotic prescription had no diagnosis that would justify an antibiotic Viral upper respiratory tract infections prescribed antibiotics in 26% of cases JAMA. 2016;315(17):1864-1873 21

Assessing Appropriate Use in Hospitals Is trickier Simply looking at discharge diagnosis does not usually help assess if antibiotic use was appropriate Most inappropriate use in hospitals occurs in patients who are either misdiagnosed with an infection or who have an infection, but are treated incorrectly That is labor intensive to assess and has not been done nationally Assessment of Vancomycin Use in 36 Hospitals Patients treated with intravenous Vancomycin 185 No diagnostic culture obtained around antibiotic initiation, although standard practice with most infections 17 (9.2) Diagnostic culture showed no Gram-positive bacterial growth, but patient still treated for long duration (>3 days) (excludes presumed SSTI, which often can be culture negative) Diagnostic culture grew only oxacillin-susceptible Staphylococcus aureus, but patient still treated for long duration (>3 days) (likely missed opportunity to switch antibiotic based on culture result) 40 (21.6) 9 (4.9) No. of patients with potential for improvement in prescribing 66 (35.7) MMWR March 7, 2014 / 63(09);194-200 22

Advancing Assessments of Appropriate Use in Hospitals Exploring ways to use electronic health information to assess appropriate antibiotic use Vancomycin assessment could probably be automated pretty easily Could we do this for others agents or infections? Improving Antibiotic is a National Priority 23

Priorities Get Funding The US is making new investments to improve antibiotic use Funding for state health departments to begin stewardship efforts Funding for expanded public awareness efforts Funding for research to improve implementation of existing stewardship practices and to find new ones Priorities Get Requirements CMS issued requirement that all nursing homes have antibiotic stewardship programs CMS has proposed the same requirement for hospitals The Joint Commission issued an accreditation standard to require all accredited facilities (starting with hospitals) have stewardship programs by January 1, 2017 24

But Programs and Core Elements Won t Solve the Problem Ultimately, improving antibiotic use comes down to implementing interventions that will improve prescribing The goal of a stewardship program is to create an environment where improvement interventions will be most successful Stewardship After Day Three Audit and Feedback to Reduce Broad Spectrum Antibiotic Use in an ICU Gave providers feedback on antibiotics on days 3 and 10 of antibiotics Mean monthly antibiotic use decreased from 644 DOT/1000 pt days to 503 (P<0.001) C. difficile decreased (11 cases to 4) Meropenem susceptibility increased ICHE 2012;33:354 25

Targeting Specific Infections In a 2011 survey in ~180 hospitals, CDC and state collaborators reviewed charts of patients who got antibiotics to determine the reason for use: Lower respiratory tract infections: 34.6% Urinary tract infections: 22.3% JAMA. 2014;312(14):1438-1446 Many Patients Diagnosed with Community Acquired Pneumonia (CAP) Don t Have It 106 patients met criteria for CAP per ED CAP pathway 103 patients had CAP diagnosis by ED physician 76 patients had CAP diagnosis by treating team 68 patients had CAP diagnosis by external adjudication Sara Cosgrove, Johns Hopkins Hospital 26

Duration of Therapy for CAP Guidelines recommend that most patients should get 5-7 days of antibiotics for CAP Average duration of treatment is 10 days No difference between immune competent and suppressed patients Simple, prospective intervention for patients being treated for CAP Treatment duration reduced from 10 d to 7 d (p<0.001) with 148 fewer antibiotic days CID 2012;54:1581-7 Asymptomatic Bacteriuria (ASB) Too Often Treated Like Infection Study Patient Population Lack of Adherence to Guidelines Dalen, 2005 Gandhi, 2009 Cope, 2009 Ottawa Hospital 29 patients with catheter associated ASB U Michigan 49 patients with UTI diagnosed Houston VA 164 episodes of catheter associated ASB 52% prescribed antimicrobials inappropriately 32.6% did not meet criteria for UTI (most due to lack of symptoms) 32% prescribed antimicrobials inappropriately Dalen DM et al. Can J Infect Dis Med Microbiol. 2005;16:166. Gandhi T et al. Infect Control Hosp Epidemiol. 2009;30:193. Cope M et al. Clin Infect Dis. 2009;48:1182. 27

Kicking CAUTI Developed a simple algorithm to guide sending of urine cultures Overtreatment of ASB during intervention fell: From 1.6 to 0.6 per 1000 bed-days; (IRR, 0.35; 95% CI, 0.22-0.55) Reductions persisted during the maintenance period: 0.4 per 1000 bed-days; (IRR, 0.24; 95% CI, 0.13-0.42) P <.001 for both JAMA Intern Med. 2015 Jul;175(7):1120-7. Public Commitment Posters: Inappropriate Prescribing for Acute Respiratory Infections Adjusted absolute reduction: -20% compared to controls, p=0.02 Meeker. JAMA Intern Med. 2014;174(3):425-31. 28

Behavioral Clinical Decision Support: Accountable Justification Antibiotic justification note in medical record Triggered by diagnosis for which antibiotics are not indicated and antibiotic prescription Free text field If no text entered: No justification given appeared in medical record Note disappeared if antibiotic prescription deleted Idea: Clinicians want to preserve their reputation Reduced inappropriate antibiotic prescribing from 23.2% to 5.2% pre and post-intervention (-7.0% difference in differences, p<0.001) Meeker, Linder, et al. JAMA 2016;315(6): 562-570. Peer Comparison to Top Performers You are a Top Performer: You are in the top 10% of clinicians. You wrote 0 prescriptions out of 21 acute respiratory infection cases that did not warrant antibiotics. You are not a Top Performer: Your inappropriate antibiotic prescribing rate is 15%. Top performers' rate is 0%. You wrote 3 prescriptions out of 20 acute respiratory infection cases that did not warrant antibiotics. Mean antibiotic prescribing for antibiotic-inappropriate diagnoses decreased from 19.9% to 3.7% (-16.3%) Statistically significant versus controls Meeker, Linder, et al. JAMA 2016;315(6): 562-570. Slide courtesy of Jeff Linder 29

Conclusions Improving antibiotic use is critically important to the safety of our patients and the future of medicine Antibiotic stewardship has always been a good idea Now it s a good idea that s required We have to do it, but we have to do it right I would love to hear your thoughts on what CDC can do to help make this happen Questions & Answers 30

CME Credit & Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM To receive credit, you must complete the online evaluation and pass the posttest with a score of 80% or higher Online evaluation and post-test will be available following the webinar at: http://bit.ly/amrstewardship-125 Certificate will be available for print or download following successful completion of online evaluation and post-test Join Us For Upcoming NFID Webinars Interview with Stanley Plotkin, MD: Greatest Vaccinology Discoveries of the Last Decade and Future Predictions Wednesday, February 15, 2017 at 12:00 PM ET Updates from February 2017 ACIP Meeting Wednesday, March 1, 2017 at 12:00 PM ET Registration: www.nfid.org/webinars Subscribe to NFID email updates: www.nfid.org/subscribe 31