Disclosures ANTIMICROBIAL STEWARDSHIP. Objectives. What is Antimicrobial Stewardship? Who is talking about it? Why Stewardship 9/28/12

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Disclosures ANTIMICROBIAL STEWARDSHIP Nothing to disclose. I may inadvertently mention proprietary products, but it is not meant as an endorsement. Katherine Lusardi, PharmD Clinical Specialist, Antimicrobial Stewardship UAMS Medical Center Little Rock, AR ktlusardi@uams.edu Objectives Pharmacists Describe the stewardship strategies outlined in the 2007 IDSA/ SHEA guidelines Discuss current literature evaluations of stewardship practices Design practical goals for stewardship programs List tools and resources available to new stewardship programs Technicians Discuss the importance of timely antibiotic administration List the advantages and disadvantages of oral antibiotic administration List some high cost antimicrobials that can be targeted for stewardship What is Antimicrobial Stewardship? The judicious and appropriate use of antibiotics The primary goal of antimicrobial stewardship is to improve patient care by: Optimize selection, dosing and duration of antimicrobials Minimize collateral damage Reduce the emergence of resistance Who is talking about it? Why Stewardship IDSA/SHEA (and SIDP!) ASHP JCAHO California www.idsociety.org 1

IDSA/SHEA/SIDP ASHP and JCAHO Bad Bugs Need Drugs 10 x 20 Campaign Push for 10 new antimicrobials by 2020 Solve the pipeline problem by bringing together global political, scientific, industry, economic, intellectual property, policy, medical and philanthropic leaders to develop creative incentives that will stimulate new antibacterial research and development. ASHP: assembling a Stewardship Task-Force Statement on Pharmacist s role available Joint Commission: Acknowledge the correlation between stewardship and resistance http://www.ashp.org/doclibrary/bestpractices/specificstantimicrob.aspx California Benefits of Stewardship California Senate Bill 739 mandated that, by January 1, 2008, CDPH require general acute care hospitals to monitor and evaluate the utilization of antibiotics In February 2010 the CDPH Hospital Acquired Infections (HAI) program developed the only state wide stewardship initiatives Reduces secondary consequences from broad spectrum therapy Decreases mortality Minimizes the development of antimicrobial resistance Supports institutional infection control processes Minimizes toxicity and/or adverse effects Decreases healthcare expenditures h"p://www.cdph.ca.gov/programs/hai/pages/an6microbialstewardshipprogramini6a6ve.aspx Guidelines Approach to Stewardship IDSA/SHEA released guidelines in 2007 Endorsed by SIDP Outlined Stewardship team Stewardship strategies Target outcomes 2

Stewardship Plan The Team Core Team: - ID Physician - ID Pharmacist Core Strategies: - Prospec1ve Review - Pre- authoriza1on/ restric1ng Core ID Physician ID Pharmacist Other members Microbiologist Infection control Information technologist Hospital epidemiologist Dellit TH, et al. Clin Infect Dis. 2007; 44: 159-177 Post-Prescriptive Review Assess the appropriateness of order and intervene if necessary Combined with a direct intervention and feedback Post-Prescriptive Review: application Sunnybrook Health Services Centre in Toronto, Canada Evaluate the impact on antibiotic use of a formal prospective audit and feedback program in critical care patients 48 ICU beds (including a burn unit) Process Review broad spectrum antibiotics at 3 & 10 days Place note in the chart Give verbal feed back to the team Elligsen M, et al. ICHE. 2012; 33: 354-361 Post-Prescriptive Review: application Primary Outcome Target antibiotics Days of Therapy (DOT) per 1000 patient days (DOT/1000 PD) o Pre-Intervention 2,358 Patients 14,225 PD DOT: 644 Post-Intervention 2,339 Patients 15,431 PD DOT: 503 Recommendation Acceptance Rate: 82% 56% for discontinue 26% to change agent 8% to change dose or route of administration Elligsen M, et al. ICHE. 2012; 33: 354-361 Post-Prescriptive Review: application Secondary outcomes Overall DOT/1000 PD: 1134 985 Antibiotic spend: decreased by $95,000 Susceptibility changes: Meropenem susceptibility 78% 83% C difficile: 16 cases 11 cases (decrease 31%) Non-ICU cases increased 33% in same period Elligsen M, et al. ICHE. 2012; 33: 354-361 3

Restriction/Pre-authorization Requires approval before an antibiotic would be dispensed Based on indications, physician services Limited antibiotics available Potential to sharply decrease antibiotic costs At OSU, 30% of antibiotic spend is on daptomycin, linezolid and piperacillin/tazobactam Goff DA, et al. CID. 2012; 55: 587-592. Restriction/Pre-authorization: application Pitt County Memorial Hospital, Greenville, NC Examine the affect of ciprofloxacin restriction on use patterns, and Gram-negative bacteria 861 Beds; 11 ICUs; no burn unit ASP began in 2001, ciprofloxacin restriction began 2007 Compare 42 months pre/post restriction Procedure: pre-approval required from on-call ID fellow Lewis GJ, et al. ICHE. 2012; 33: 368-373. Restriction/Pre-authorization: application Outcome Drug Usage Change in Defined Daily Doses/1000PD (DDD/ 1000PD) Pre-restriction Post-restriction DDD/1000 PD DDD/1000 PD Ciprofloxacin 87.09 8.04 P=0.0027 Group 2 Carbapenem Cefepime and Pip/tazo 11.96 28.19 P=0.0134 No statistically significant change All Abx Decreased 18.4% P <0.001 Lewis GJ, et al. ICHE. 2012; 33: 368-373. Restriction/Pre-authorization: application Outcome Resistance Pseudomonas aeruginosa: 1,664 non-duplicate isolates Pre-restriction 18+5 isolates/month Post-restriction 22+6 isolates/month Ciprofloxacin-resistant P. aeruginosa Pre-restriction - stable Post-restriction decreased 13.7% (p<0.001) Carbapenem-resistant P. aeruginosa Pre-restriction - stable Post-restriction decreased 13.2% (p=0.0351) No significant changes in resistance observed for Enterobacteriaceae, Acinetobacter, and Stenotrophomonas Lewis GJ, et al. ICHE. 2012; 33: 368-373. Timeliness of Antibiotics Delays in antibiotic therapy have been associated with higher mortality Winters et al found more delays >1 h for antibiotics associated with restriction and pre-approval Education Most effective when combined with intervention Education as a process Raise awareness Utilization of restriction after first dose allows for combination of both core strategies Antibiotic ordered Patient receives first dose without delay Martin CA, et al. AJHP. 2011; 68: 109-110 Review of subsequent doses 4

Guidelines Common Infections and most likely pathogens National guideline recommendations Our Institute specific susceptibilities Order Sets Incorporate: Institution guidelines Automatic stop dates Paper or CPOE Core measure compliance Care bundles Formulary status and cost Order Sets: application Banner Estrella Medical Center, Phoenix, AZ 214 Bed, suburban, non-academic medical center Evaluate the impact of linezolid guidelines for use integration with CPOE on usage Order Sets: application Outcomes usage in DDD/1000PD Process: First intervention: developed guidelines for use, rolled out to medical staff with education led by ID physicians Second intervention: Incorporation of guidelines into CPOE system, integrating alternative antibiotic recommendations Po JL, et al. ICHE. 2012; 33: 434-435. Po JL, et al. ICHE. 2012; 33: 434-435. Order Sets: application Outcome linezolid spend 16 month savings - $638,000 Annualized $479,000 No changes in VRE infection rates were noted Streamlining/De-escalation Most likely organisms and risk factors taken into consideration Narrow based on preliminary culture data Finalize antibiotic choice with final report Po JL, et al. ICHE. 2012; 33: 434-435. 5

Dose-optimization IV to PO Pharmacokinetic and pharmacodynamics Antibiotic dosing protocols Renal dosing protocols Effective antibiotic use Patients on oral therapy: Shorter hospital stay Less cost Reduce risk of infection Owens RC. Diag Micro Infect Dis. 2008; 61: 110-128 IV to PO: application IV to PO: application Considered the lowest of the low hanging fruit Ohio State Medical Center Collaborated with dietary to get list of patients taking PO diet Cost avoidance: $242,713 Johns Hopkins Target: voriconazole, pantoprazole, levetiracetam, chlorothiazide Budget burden of $1,166,769 Acute Care VA hospitals across US Retrospective analysis of IV fluoroquinolone use Ciprofloxacin, levofloxacin, moxifloxacin Assess whether it could have been avoided Results Avoidable FQ usage: 46.8% of all FQ; 90.9% of all IV FQ ICU 65% avoidable; Non-ICU 42.7% avoidable Could have avoided ~$4million in expenses Goff DA, et al. CID. 2012; 55: 587-592. Jones M, et al. ICHE. 2012; 33: 362-367. Outcome tracking Goals of Stewardship Improve patient outcomes Improve patient safety Reduce resistance Reduce cost 6

Antibiotic usage/cost Easiest to measure DDD/1000 PD DOT/1000 PD LOT/1000 PD Abx $/PD Cochrane review (through 2003) showed improved clinical outcomes when the stewardship interventions focused on optimizing treatment, not reducing antibiotic use Wake Forest University, North Carolina Projected Abx$/PD based on two inflation models, looked at savings over 11.5 years Method A - $10,350,787 Method B - $23,224,961 Beardsley JR, et al. ICHE. 2012; 33: 398-400 Patient Safety Inappropriate empiric antibiotics are associated with decreased survival Collateral damage C. difficile infection after a national stewardship iniative in Scotland, the rate of CDI had dropped over 40% among patients over 65 years of age Nathwani D, et al. Int J Antimicrob Agents. 2011; 38: 16-26. Resistance Takes years to notice benefits on resistance Reduction of 3 rd generation cephalosporins leads to reduction of MDR GNR Reduction of fluoroquinolones leads to reduction in MRSA Also decreases resistance to beta-lactams in GNR Hospital acquired infections MDRO infection rate CLABSI rate Culture contamination rate CDI rate Tips for getting started 7

Getting Started Know why stewardship is being undertaken Start small with measurable goals Define how success will be measured up front Establish reporting Identify champions Resources Resources Summary Stewardship Certificate Programs MAD-ID (www.mad-id.org) SIDP (www.sidp.org) Free Online CE ASHP Advantage (http://www.leadstewardship.org/) Industry Sponsored (Pfizer, Cubist, Astellas) Established Programs Nebraska Medical Center http://www.nebraskamed.com/careers/education-programs/asp University of Kentucky http://www.hosp.uky.edu/pharmacy/amt/default.html Stewardship is about optimizing antibiotic usage, in order to deliver the best care to patients Start a program small, with reasonable, measurable goals Recent literature and established programs provide great resources References ANTIMICROBIAL STEWARDSHIP Katherine Lusardi, PharmD Clinical Specialist, Antimicrobial Stewardship UAMS Medical Center Little Rock, AR ktlusardi@uams.edu Dellit TH, et al. Infectious diseases society of America and the society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 44: 159-177. Owens RC. Antimicrobial stewardship: concepts and strategies in the 21 st century. Diag Micro Infect Dis. 2008; 61: 110-128. Tamma PD and Cosgrove SE. Antimicrobial Stewardship. Infect Dis Clin N Am. 2011; 25: 245-260. Martin CA, et al. Moving antimicrobial stewardship from restriction to facilitation. AJHP. 2011; 68: 109-110. Srinivasan A. Engaging hospitalists in antimicrobial stewardship: The CDC perspective. J Hosp Practice. 2011; 6: S31-S33. Goff DA, Bauer KA, Reed EE, et al. Is the low-hanging fruit worth picking for ASP? Clin Infect Dis. 2012; 55: 587-592. Jones M, Huttner B, Madaras-Kelly K, et al. Parenteral to oral conversion of fluoroquinolones: low-hanging fruit for antimicrobial stewardship programs? ICHE. 2012; 33: 362-367. Po JL, Nguyen BQ, Carling P. The impact of an ID specialist-direct CPOE antimicrobial stewardship program targeting linezolid use. ICHE. 2012; 33: 434-435. 8

References McGowan JE. Antimicrobial stewardship the state of the art in 2011: focus on outcomes and methods. ICHE. 2012; 33: 331-336. Lewis GJ, Fang X, Gooch M, Cook PP. Decreased resistance of Pseudomonas aeruginosa with restriction of ciprofloxacin in a large teaching hospital intensive care and intermediate care unit. ICHE. 2012; 33: 368-373. Standiford HC, Chan S, Tripoli M, et al. antimicrobial stewardship at a large tertiary care academic medical center: cost analysis before, during and after a 7-year program. ICHE. 2012; 33: 338-346. Seemungal IA, Bruno CJ. Attitudes of housestaff towards a prior-authorization based antimicrobial stewardship program. ICHE. 2012; 33: 429-431. Elligsen M, Walker SA, Pinto R, et al. Audit and feedback to reduce broad-spectrum antibiotic use among ICU patients: A controlled interrupted time series analysis. ICHE. 2012; 33: 354-361. Beardsley JR, Williamson JC, Johnson JW, et al. Show me the money: long-term financial impact of an antimicrobial stewardship program. ICHE. 2012; 33: 398-400. Shrestha NK, Bhaskaran A, Scalera NM. Antimicrobial stewardship at transition of care from hospital to community. ICHE. 2012; 33: 401-404. 9