Disclosures. Antimicrobial Stewardship: Who, what, when where, how. Why worry about an-bio-c use? Outline

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1 Antimicrobial Stewardship: Who, what, when where, how Andrew MD George and Esther Gross Presidential Professor University of Utah Disclosures Conflicts: None Funding: CDC 1U181P NIH/NIAID 1 R01 AI Outline What is the problem? Stewardship what is it Approaches in the hospital Approaches in the outpatient setting What next Why worry about an-bio-c use? million an-bio-cs are prescribed annually 45% for outpa-ent use An-bio-c adverse reac-ons are the leading cause of ED visits for drug reac-ons 25-40% of hospitalized pa-ents receive an-bio-cs 30-50% are unnecessary or sub- op-mal 5% of hospitalized pa-ents experience an adverse reac-on >$1.1 billion spent annually on unnecessary adult an-bio-c prescrip-ons for URI 50-80% of outpa-ent an-bio-c use is inappropriate Dellit Clin Infect Dis 2007:44:159 1

2 Extended Sprectrum Beta Lactamase-Producing (ESBL) E. coli Intermountain Hospitals, Utah The rise of carbapenem resistant gram negative rods % ESBL Primary Childrens Medical Center Dixie Regional Medical Center Intermountain Medical Center LDS Hospital McKay-Dee Hospital Center Utah Valley Regional Medical Center Impact of Antibiotic Resistance Annual death rates in the United States for selected infectious diseases. Organism Increased risk of death (OR) Attributable LOS (days) Attributable cost MRSA bacteremia $6,916 MRSA surgical infection $13,901 VRE infection $12,766 Resistant Pseudomonas infection Resistant Enterobacter infection $11, $29,379 Total cost of antimicrobial resistance is estimated to be $30 billion annually. Cosgrove SE. Clin Infect Dis. 2006; 42:S82-9. Boucher H W, and Corey G R Clin Infect Dis. 2008;46:S344-S by the Infectious Diseases Society of America 2

3 Incidence of Clostridium difficile infection per 1000 hospitalizations by age (Healthcare Utilization Project Kids and Inpatient Database, United States, ). Collateral damage Length of stay and Clostridium difficile infection. 50% were community onset Sammons J S et al. Clin Infect Dis. 2013;cid.cit155 Lessa F C et al. Clin Infect Dis. 2012;55:S65-S70 Microbes versus humans. The Pipeline is Dry Only antibiotics are in development Only 8 of these have activity against key Multi-Drug Resistant Gram negative bacteria None have activity against bacteria resistant to all current drugs Spellberg B et al. Clin Infect Dis. 2008;46: Boucher HW et al. Clin Infect Dis 2013; onliine first Spellberg B et al. Clin Infect Dis. 2008;46:

4 2000 B.C. Here, eat this root A.D. That root is heathen. Here, say this prayer A.D. That prayer is superstition. Here, drink this potion A.D. That potion is snake oil. Here, take this penicillin; it s a miracle drug A.D. Penicillin is worthless. Here, take this new antibiotic; it s bigger and better A.D. Those antibiotics don t work any more. Here eat this root. Slide courtesy of CDC/SHEA 13 Variability in Aggregate An8microbial Use, 42 Children s Hospitals, 2011 Antibiotic prescriptions per 1000 persons of all ages according to state, 2010 DOT/1000 pt days Hicks LA et al. N Engl J Med 2013;368:

5 Antibiotic Prescribing in Ambulatory Pediatrics in the United States Condi8on Es8mated visits for condi8on (millions) Respiratory Condi8ons (48%) 16.9 (53%) 1. ARTI where an.bio.cs indicated* (72%) 10.3 (48%) 2. ARTI where an.bio.cs not indicated* (30%) 3.6 (63%) Other condi8ons (8%) 5.1 (42%) Total (20%) 22.0 (50%) Independent Variables No. visits in which No. visi8s with antbio8cs prescribed broad- spectrum (%) an8bio8cs (%) Hersh et al. Pediatrics : 1053 Includes OM, sinusitis, pharyngitis, pneumonia **includes URI, nasopharyngitis, bronchitis, viral pneumonia, influenza Diagnos8c Condi8ons ARTI - an8bio8cs are indicated ARTI - an8bio8cs not indicated Other respiratory condi8ons Skin/cutaneous/mucosal All other condi8ons Age US Census Region Northeast Midwest South West % Receiving P Value Broad- Spectrum Agents Adjusted OR for Broad- Spectrum Prescribing (95% CI) % 63% 64% 38% 45% ref 1.80 ( ) 1.93 ( ) 0.69 ( ) 0.93 ( ) % 47% 49% 1.27 ( ) ref 1.16 ( ) % 48% 55% 42% 1.23 ( ) 1.30 ( ) 1.82 ( ) ref Compared those under 6 months of age treated with antibiotics to those who were not treated Showed increased weight gain by a year of age 22 percent more likely to be overweight at age 3 5

6 Strikingly Similar? Percentage of high school students who were obese* Youth Risk Behavior Survey, 2011 Antibiotic exposure and inflammatory bowel disease Retrospective cohort study from 464 UK ambulatory practices 1,072,426 subjects contributed 6.6 million personyears of follow-up 748 developed IBD Exposure to antibiotics with anaerobic activity associated with IBD (HR 1.87) Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% CI;: ) Kronman et al. Pediatrics 2012; 130:e794 e803 Cases per 100,000 population The Good News The Introduction of a pneumococcal vaccine in 2000 resulted in decreased cases of resistant invasive pneumococcal disease among children Not susceptible to 1 or more antibiotics Not susceptible to 3 or more antibiotics Drivers of Inappropriate Use Inpatients Patient concerns:? Physician concerns: Fear of inadequate coverage drives excessively broad or duplicative coverage Not wanting to rock the boat leads to failure to narrow or reassess need for therapy Lack of knowledge of antibiotic spectrum or infectious disease process Inadequate diagnostic data Pharmaceutical detailing Outpatients Patient concerns: Think it will help them get better faster Previous experience Physician concerns: Perception that patients expect antibiotics Perception it takes too long to explain Fear of wrong diagnosis Pharmaceutical detailing 6

7 What is Antimicrobial Stewardship? Merriam Webster Stewardship: the careful and responsible management of something entrusted to one's care Social Network analysis to market to doctors Antimicrobial Stewardship: Objectives Achieve optimal clinical outcomes Minimize toxicity and other adverse events Minimize development of antimicrobial resistance May reduce excessive costs attributable to: Inappropriate/unnecessary therapy Poor outcomes Adverse events Antimicrobial resistance PCMC Program Overview Identify areas of high variation in antimicrobial prescribing Prospective audit of antimicrobial use feedback Daily report of all antimicrobials reviewed and feedback given at 48 hours Daily cultures reviewed for bug/drug mismatch Review patient records for restart/addition of antibiotics within 48 hours of our intervention Create clinical pathways using best evidence Provide education Benchmark antimicrobial use Approve all order sets that include antimicrobials Monitor cost impact 7

8 700.0 Overall Days of Therapy/1000 Patient-Days (Top 17 agents) Overall Decrease by 75 DOT/1000 Pt-days 90.0 Antimicrobial Days/1000 Patient Days- Top 5 Gram Positive Agents Vancomycin Days of Therapy/ 1000 Patient-Days Clindamycin Cefazolin Nafcillin Linezolid Trends in ASP Recommendations Gentamicin -38 Pip/Tazo +8 Ceftriaxone +8 Meropenem +1 Cefotaxime -20 Ceftazidime Year 2 Recommendation Year 1 % Total (partial) % Total Narrow therapy Extend spectrum Duplicate therapy Stop Therapy Optimize dose IV to po Decrease Duration ID consult Optimize Cost Miscellaneous Total

9 Total Pharmacy Antimicrobial Acquisition Including Palivizumab $2,000,000 $1,800,000 $1,714,393 $1,600,000 $1,527,466 $1,400,000 $1,200,000 $1,000,000 $800,000 $600,000 $400,000 ASP Initiation $1,224,674 Savings in compared to ASP YEAR 2 ASP YEAR 1 Savings from Antimicrobial Stewardship Cost Reduced Cost Reduced Palivizumab -27,000-38,700 IV ABX Change -235,500-48,400 IV ABX Waste Cost -58,900-12,000 IV Dosing Admin Cost -56,600-29,100 Oral ABX change -28,900-14,500 Oral Admin Cost -12,700-6,400 $200,000 $ Total Savings $419,600 $149,100 Doses Avoided 11,300 5,800 Quality Improvement: Palivizumab Palivizumab Utilization: GOAL: 100% of Palivizumab usage has insurance approval and 95% of Palivizumab use is in accordance with AAP guidelines Administration based on local RSV epidemiology (may call season early) Year Patients receiving Palivizumab/ 1000 ptdays $240, $275, $265, $195,000 Total Palivizumab Cost! 9

10 Quality Improvement: Uncomplicated Appendici-s Compliance with clinical pathway for non perforated appendectomy 1 Target >55%, stretch goal > 60% 94% 94% % 73% 69% % % 11% 0.1 0% Rate Target Stretch Run chart for appropriate first-line antibiotic prescribing for CAP in the ED. Outpatient stewardship-the final frontier? Educational efforts in the media and through AAP have led to 24% reduction in overall use. Studies of education alone lead to small improvements Overuse of broad spectrum antibiotics and guideline adherence have not improved Can we adopt stewardship principles to outpatient practice? Ambroggio L et al. Pediatrics 2013;131:e1623-e

11 Effect of an Outpatient Antimicrobial Stewardship Intervention on Broad-Spectrum Antibiotic Prescribing by Primary Care Pediatricians: A Randomized Trial Cluster randomized trial 25 practices pediatric primary care practices in Pennsylvania and New Jersey One on-site clinician education session (June 2010) followed by one year of personalized, quarterly audit and feedback of prescribing for bacterial and viral ARTIs. One on-site clinician education session for controls Results Broad-spectrum antibiotic prescribing decreased from 26.8% to 14.3% (12.5%) among intervention practices versus 28.4% to 22.6% (5.8%) in controls; (DOD = 6.7% p=0.01) Off guideline treatment of pneumonia decreased from 15.7% to 4.2% vs 17.1% to 16.3% in controls (DOD = 10.7%; p < 0.001) Acute sinusitis decreased from 38.9% to 18.8% vs 40.0% to 33.9% in controls (DOD = 14.0%; p = 0.12) Gerber J et al JAMA 2013 In press Gerber J et al JAMA 2013 In press Results Broad-spectrum antibiotic prescribing for pharyngitis Decreased 4.4% to 3.4% vs 5.6% to 3.5%; (DOD = -1.1%; p = 0.82) Prescribing antibiotics for viral infections decreased from 7.9% to 7.7% vs 6.4% to 4.5%;( DOD = -1.7%; p = 0.93) Both of these were low at baseline, suggesting these practices were already above average Conclusions Optimizing antimicrobial use is a key patient safety activity It can improve outcomes, decrease adverse events, reduce costs and hopefully, slow the emergence of resistance. Effective interventions are team efforts, based on evidence-based best practices, reducing unnecessary variation, providing education and feedback Vast amounts of work remains to be done Gerber J et al JAMA 2013 In press 11

12 Research priorities Multicenter studies, improved methodology Identify the best process and outcome measures Identify best formats for intervention Education Restriction Audit with feedback Identify most important targets Develop methods for outpatient, small hospital and health care system wide stewardship Resources: CDC Get Smart: Nebraska ASP: Johns Hopkins antibiotic guidelines: SHEA educational offerings: SHEA Antimicrobial Stewardship Resource page: FeaturedTopicsinHAIPrevention/ AntimicrobialStewardship.aspx University of Utah Emily Thorell Adam Hersh Pediatric Infectious Diseases Division Ed Clark Research Enterprise Kent Korgenski Translational and Comparative Effectiveness Scholars Program Division of Pediatric Surgery Acknowledgements Primary Children s Medical Center Jared Olson-ASP Katy Welkie Systems Improvement team Doug Wolfe Seth Andrews Howard Parker Infection Prevention team Pharmacy support staff Microbiology staff CDC Lauri Hicks Arjun Srinavasan University of Pennsylvania Jeff Gerber Neil Fishman 12