ANTIMICROBIAL STEWARDSHIP JOINT COMMISSION REQUIREMENTS AN OPPORTUNITY FOR

ANTIMICROBIAL STEWARDSHIP & JOINT COMMISSION REQUIREMENTS: AN OPPORTUNITY FOR PHARMACY LEADERSHIP Holly Maples, Pharm. D. Associate Professor, Dept of Pharmacy Practiced Jeff & Kathy Lewis Sanders Endowed Chair in Pediatrics UAMS College of Pharmacy Director, Antimicrobial Stewardship Director, Pediatric ID and Antimicrobial Stewardship Fellowship Arkansas Children’s Hospital

Conflict of Interest • Dr. Maples has no conflict of interest to report pertaining to this talk. • This talk is NOT

Objectives • Describe the eight elements of performance in the New Antimicrobial Stewardship Standard • Identify specific antimicrobial stewardship strategies utilizing clinical pharmacists within your institution • Discuss educational opportunities to enhance pharmacists skills in antimicrobial management • Describe antimicrobial usage measurements • Identify quality improvement opportunities within your institution and how to get it accomplished

Antibiotic overuse • Leads to avoidable costs and toxicities • Disruption of the host microbiome • Is the most important contributor to antibiotic resistance • The White House has called for hospitals and healthcare systems to implement stewardship programs by 2020. • Reduce inappropriate abx use by 50% in OP settings • Reduce inappropriate abx use by 20% in IP settings

CDC 2013 Report: Antibiotic Resistance Threats in the United States.

New Antimicrobial Stewardship Standard • Effective January 1, 2017 • Hospitals have an antimicrobial stewardship program based on current scientific literature.

Elements of Performance (1) 1. Leaders establish antimicrobial stewardship as an organizational priority • Accountability documents • Budget plans • Infection prevention plans • Performance improvement plans • Strategic plans • Using the EMR to collect antimicrobial stewardship data

Elements of Performance (2) 2. The hospital educates staff and licensed independent practitioners involved in antimicrobial ordering, dispensing, administration, and monitoring about antimicrobial resistance and antimicrobial stewardship practices. Education occurs upon hire or granting of initial privileges and periodically thereafter, based on organizational need.

Elements of Performance (3) 3. The hospital educates patients, and their families as needed, regarding the appropriate use of antimicrobial medications, including antibiotics. • Education tool that can be used • CDC’s Get Smart document, “Viruses or Bacteria-What’s got you sick? ” at http: //www. cdc. gov/getsmart/community/downloads/getsmartchart. pdf.

Elements of Performance (4) 4. The hospital has an ASP multidisciplinary team that includes the following members, when available in the setting: • ID physician • Infection preventionist • Pharmacist(s) • Practioner Note 1: Part-time or consultant staff are acceptable as members of the ASP multidisciplinary team Note 2: Telehealth staff are acceptable as members of the ASP multidisciplinary team

Elements of Performance (5) 5. The hospital’s ASP includes the following core elements (documentation required) • 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 responsible for working to improve antibiotic use Action: Implementing recommended actions, such as systemic evaluation of ongoing treatment need, after a set period of initial treatment. (example, antibiotic time out after 48 hours) Tracking: Monitoring the antimicrobial stewardship program, which may include information on antibiotic prescribing and resistance patterns. Reporting: Regularly reporting information on the antimicrobial stewardship program, which may include information on abx use and resistance, to doctors, nurses, and relevant staff Education: Educating practitioners, staff, and patients on the ASP, which may include information about resistance and optimal prescribing.

Elements of Performance (5) • Core elements were cited from the CDC’s Core Elements of Hospital Antimicrobial Stewardship Programs (http: //www. cdc. gov/getsmart/healthcare/pdfs/coreelements. pdf) • Joint Commission recommends that organizations use this document when designing their antimicrobial stewardship program.

Elements of Performance (6) 6. The hospital’s ASP uses organization-approved multidisciplinary protocols (example, policies and procedures) (documentation required) • Antimicrobial Formulary Restrictions • Assessment of Appropriateness of Abx for CAP • Assessment of Appropriateness of Abx for SSTI’s • Assessment of Appropriateness of Abx for UTI’s • Care of the Patient with C. diff • Guidelines for Antimicrobial Use in Adults • Guidelines for Antimicrobial Use in Pediatrics • Plan for IV to PO conversion • Preauthorization requirement for specific antimicrobials • Use of prophylactic antibiotics

Elements of Performance (7) 7. The hospital collects, analyzes, and reports data on its ASP. (documentation required) Note: Examples of topics to collect and analyze data on may include evaluation of the ASP, antimicrobial prescribing patterns, and antimicrobial resistance patterns

Elements of Performance (8) 8. The hospital takes action on improvement opportunities identified in its antimicrobial stewardship program. (documentation required)

New Stewardship Guidelines Barlam TF et al. CID 2016 April 13 (Epub ahead of print)

Key Points. Guideline Interventions • Combination of preauthorization and prospective review of antibiotics have shown to be most effective. Barlam TF et al. CID 2016 April 13 (Epub ahead of print)

ACH Example: Pre-authorization of Meropenem Abx Days/1000 Pt Days 55. 00 Antibiotic Days per 1000 Patient Days 50. 00 45. 00 40. 00 35. 00 30. 00 25. 00 20. 00 15. 00 10. 00 5. 00 0. 00 FY 08 FY 09 FY 10 FY 11 FY 12 FY 13 FY 14 FY 15

ACH Cefepime Usage Cefepime Abx Days/1000 Pt Days 60. 00 55. 00 Antibiotic Days per 1000 Patient Days 50. 00 45. 00 40. 00 35. 00 30. 00 25. 00 20. 00 15. 00 10. 00 5. 00 0. 00 FY 08 FY 09 FY 10 FY 11 FY 12 FY 13 FY 14 FY 15

Key Points. Guideline Interventions • Combination of preauthorization and prospective review of antibiotics have shown to be most effective. • Stewardship programs should be led by physicians and pharmacists on equal levels. Barlam TF et al. CID 2016 April 13 (Epub ahead of print)

Key to Success: Multidisciplinary Involvement Hospital Epidemiologist Hospital Administrator Infection Control Program Coordinators Infectious Disease Division • ID physician Medical Information Systems Microbiology Lab • ID Pharm. D. Clinical Pharmacy Specialists Decentralized Pharmacy Specialists P&T Committee Adapted from: Fishman NO. In: Principles and Practice of Infectious Diseases. 4 th ed. 1995: 539 -46.

Education Opportunities for Pharmacists • ID Fellowships • ID Residency • Board Certification in ID • Certificates • MAD-ID (Making a Difference in Infectious Diseases) • SIDP (Society of Infectious Diseases Pharmacists) • Workshops • IDSA (Infectious Diseases Society of America) • SHEA (Society of Healthcare Epidemiology of America)

Key Points. Guideline Interventions • Combination of preauthorization and prospective review of antibiotics have shown to be most effective. • Stewardship programs should be led by physicians and pharmacists on equal levels. • Interventions should be focused at institution level. Barlam TF et al. CID 2016 April 13 (Epub ahead of print)

ACH Top 20 Antibiotics

Key Points. Guideline Interventions • Combination of preauthorization and prospective review of antibiotics have shown to be most effective. • Stewardship programs should be led by physicians and pharmacists on equal levels. • Interventions should be focused at institution level. • Direct input from stewardship team will improve prescriber led review of appropriateness of Antibiotic regimens. Barlam TF et al. CID 2016 April 13 (Epub ahead of print)

5 D’s of Antimicrobial Stewardship Diagnosis Drug Dose Duration Discharge

5 D’s of Antimicrobial Stewardship • Ensuring a diagnosis or Diagnosis indication is established to direct antibiotic therapy • Consistency amongst prescribers in diagnosis • Rapid Diagnostics

VARIATION IN ANTIBIOTIC PRESCRIBING ACROSS A PEDIATRIC PRIMARY CARE NETWORK Jeffrey Gerber, Priya Prasad, Russell Localio et al. J Ped Infect Dis 2015; 4(4): 297 -304 • Abx are the most common Rx drug given to children • Outpatient ARTI’s account for the majority of these Rx’s • Inappropriate Abx prescribing for viral infections has decreased over time while broad spectrum Abx usage has increased. • AAP supports treatment of most ARTI’s with narrow spectrum antibiotics • Current studies lack detailed, patient specific clinical data, including: comorbid conditions, drug allergies, and prior abx use along with the ability to compare prescribing across practitioners and practice groups.

Purpose • Compare management of common pediatric infections across practices to generate • benchmarking data and • help to define high-impact targets for intervention • Time/Place: • Jan 1 -Dec 31 2009 • pediatric healthcare network that included 29 primary care pediatric practice sites staffed by 222 pediatric practitioners who share a comprehensive EHR. • Outcome Measures • Abx prescriptions • Broad-spectrum prescriptions • Encounter diagnosis based on ICD-9 code

Data Analysis • Total of 102, 102 prescriptions evaluated • 59, 259 narrow spectrum • 42, 843 broad spectrum • 9597 had an abx allergy • 3611 prior abx • 29, 635 broad spectrum prescriptions evaluated • Between the 29 clinics a significant difference was found between the clinics for abx usage for sick visits: • • • All Abx (Range of 18 -36%; P<. 001) Broad spectrum Abx (Range of 15 -57%; P<. 001) All Abx for otitis media (Range 8 -20%; P<. 001) Broad spectrum Abx for otitis media (Range 18 -60%; P<. 001) Others (sinusitis, streptococcal pharyngitis, pneumonia) • Just not UTI…. why?

Conclusions • Wide variation in diagnosis and management behaviors, despite adjustment through exclusion and regression for patient clinical and demographic factors. • Stewardship interventions can now target specific practices, providers, and conditions

5 D’s of Antimicrobial Stewardship • Empiric choice • Antibiogram Diagnosis Drug • De-escalate • Narrowest spectrum • Allergies • Are they real? • Duplicate therapy • Know MOA • Know coverage

Predictors of Increased Mortality with Bloodstream Infections • Lodise TP et al. found for patients with Pseudomonas bloodstream infections they had an ↑ 30 day mortality if therapy delayed for > 52 hours by 44%. • Tumbarello M et al. found for patients with an ESBL producing Enterobacteriacea a 3 -fold increase in mortality compared to an initial adequately treated group. • 21 Day mortality rate of 59. 5% compared to 18. 5% Lodise TP et al. Antimicrob Agents Chemother 2007; 51: 3510 -15 Tumbarello M et al. Antimicrob Agents Chemother 2007; 51: 1987 -94

CVICU Gram Negative Antibiogram 2014 -2015

NICU Gram Negative Antibiogram 2013 -2014 Percentage of Susceptible Isolates

Total Antibiotic NICU Data

Broad Spectrum Cefepime Ciprofloxacin Daptomycin Levofloxacin Linezolid Meropenem Pip/Tazo Ticar/Clav Vancomycin Hospital Census FY 08 FY 09 FY 10 FY 11 FY 12 FY 13 FY 14 FY 15 32. 35 28. 75 28. 83 36. 17 44. 21 42. 93 50. 91 52. 96 2. 12 2. 83 2. 57 2. 01 2. 48 2. 55 2. 81 1. 28 1. 36 0. 71 0. 28 0. 87 1. 36 1. 64 1. 31 1. 65 7. 35 11. 86 6. 16 4. 87 2. 78 3. 03 2. 37 2. 17 8. 38 1. 97 3. 86 1. 89 2. 10 0. 60 1. 58 0. 52 51. 09 47. 61 44. 90 47. 51 31. 83 20. 66 13. 02 7. 02 28. 88 27. 96 27. 52 30. 11 27. 50 30. 16 41. 96 31. 71 15. 24 12. 73 14. 90 3. 50 0. 83 0. 20 2. 84 2. 06 141. 48 140. 48 133. 47 101. 14 96. 73 76. 28 88. 72 70. 51 86, 0 83, 6 87, 0 80, 4 79, 4 81, 1 79, 6 83, 4 01 62 53 74 55 05 54 52

ACH NICU Antibiotic Usage Broad Spectrum includes: Vanc, Dapto, Linezolid, Mero, Cefepime, Pip/tazo, Ticar/clav, Levo, Cipro

De-escalation • Once culture results are finalized, unnecessary antibiotics are discontinued and or narrowed to a smaller spectrum so as to minimize selective pressure.

Impact of Incorrect Antibiotic Allergy • Penicillin is the most common allergy, reported in 5 -10% of all patients • Only 2 -15% of patients with reported penicillin allergies actually have a positive reaction to penicillin skin testing • Non-immunologically mediated adverse drug reactions make up more than 80% of all adverse drug reactions • The rate of positive skin testing in patients with reported penicillin allergy have been decreasing over the past 20 years Trubiano J, Phillips E. Curr Opin Infect Dis 2013. Rimawi RH, Cook PP, Gooch M, et al. J Hosp Med 2013. Macy E, Schatz M, Lin C, Poon K-Y. Perm J 2009. Macy E, Ngor E. J Allergy Clin Immunol Practice 2013. Charneski L, Deshpande G, Smith SW. Pharmacotherapy 2011. Unger NR, Gauthier TP, Cheung LW. Pharmacotherapy 2013. Lee CE, Zembower TR, Fotis MA, et al. Arch Intern Med 2000.

Implications of Antibiotic Allergies • When treated for infections, patients with reported penicillin allergies often receive broader spectrum (fluoroquinolone, 3 rd/4 th-generation cephalosporin, clindamycin, aminoglycloside), suboptimal, and even more toxic agents than patients without reported penicillin allergies. • Reported penicillin allergy has been associated with increased antibiotic resistance, cost, length of hospital stay, and mortality Lee CE, Zembower TR, Fotis MA, et al. Ann Intern Med 2000. Unger NR, Gauthier TP, Cheung LW. Pharmacotherapy 2013.

CONSEQUENCES OF AVOIDING Β-LACTAMS IN PATIENTS WITH Β-LACTAM ALLERGIES Meghan Jeffres, Prasanna Narayanan, Jerrica Shuster et al. J Allergy Clin Immunol 2016; 137: 1148 -53.

Cross-sensitivity Adapted from: Trubiano J, Phillips E. Curr Opin Infect Dis 2013; 26: 526 -537.

Antimicrobial Combinations: • Synergy: Gram Positive (MRSA) • Vancomycin plus • Gentamicin • Rifampin • Treatment: Gram Negative (Pseudomonas) • Utilization of 2 gram negative antibiotics that work by different MOA • 3 main MOA • Cell wall break down (beta lactams) • Inhibition of protein synthesis (Aminoglycosides) • Inhibition of DNA gyrase (fluoroquinolones) • To Prevent the Emergence of Resistance Liu C et al. Clin Infect Dis 2011; 52: 1 -38. Kanj SS et al. Mayo Clin Proc 2011; 86: 250 -9.

EFFECT OF BEHAVIORAL INTERVENTIONS ON INAPPROPRIATE ANTIBIOTIC PRESCRIBING AMONG PRIMARY CARE PRACTICES: A RANDOMIZED CLINICAL TRIAL Daniella Meeker, Jeffrey Linder, Craig Fox et al. JAMA 2016; 315: 562 -70. • Despite published clinical guidelines and decades of efforts to change prescribing patterns…antibiotic overuse still persists. • Interventions that have been tried but with minimal reductions in prescription rates for ARTI’s include education, computerized clinical decision support, and financial incentives

Purpose • To apply behavioral science to design 3 interventions to reduce the rate of unnecessary antibiotic prescribing for ARTI’s • Interventions: • Suggested alternatives • Accountable justification – “abx justification note” • Peer comparison – email to peers

Results (no evidence of diagnosis shifting) Antibiotic Prescribing • Control: (educational module or observation alone) • Mean abx prescribing rates decreased from 24. 1% at intervention start to 13. 1% at month 18. • Suggested alternatives: • Mean abx prescribing rates decreased from 22. 1% at intervention start to 6. 1% at month 18. (P=0. 66) • Accountable justification: • Mean abx prescribing rates decreased from 23. 2% at intervention start to 5. 2% at month 18. (P <. 001 • Peer Comparison: • Mean abx prescribing rates decreased from 19. 9% at intervention start to 3. 7% at month 18. (P <. 001)

Results Safety • The rate of return visits for possible bacterial infections within 30 days following visit for ARTI where abxs were NOT prescribed (both abx inappropriate and potentially appropriate) among the control group was 0. 43%. • Only one intervention group had a statistically significantly higher rate of return visits and that was in the accountable justification plus peer comparison group was 1. 41%. • 33 Cases were reviewed • 12 - abx unlikely to have been helpful if prescribed at index visit (cold symptoms with clear chest and no fever at return visit • 8 - uncertainty (pt returned with diagnosis of pneumonia, but no chest radiograph was obtained at the index or return visit • 13 - abxs might have been helpful

5 D’s of Antimicrobial Stewardship • Location • MIC • Age/renal function Diagnosis Drug Dose • Weight (obesity) • Other Disease states • Drug Interactions • Fluids • Pressors

Meaning of a Number: MIC

5 D’s of Antimicrobial Stewardship • Positive cx vs negative • What research is current Duration LOT based on?

DECREASING DURATION OF ANTIBIOTIC PRESCRIBING FOR UNCOMPLICATED SKIN AND SOFT TISSUE INFECTIONS Christine Schuler, Joshua Courter, Shannon Conneely et al. Pediatrics 2016; 137(2): e 20151223 • SSTI’s accounts for the 8 th most common cause of hospitalization at children’s hospitals. • Increasing incidence due to MRSA • IDSA guidelines for management of SSTIs suggest 5 days of abx therapy is effective in cases of nonpurulent cellulitis

Purpose/Methods • To decrease duration of abxs prescribed in children hospitalized for u. SSTIs • Cincinnati Children’s Hospital Medical Center • Fiscal year 2013 • 4 Interventions • Physician awareness of IDSA guidelines • 2 - 15 min didactic sessions to resident and attending • Access to best practices • Lanyard cards • Modification of Electronic Order Sets • Default moved from 14 days to 7 day • ID and review of abx plans before discharge

Results • 641 admissions (90% hospital medicine, 10% community pediatrics) • Increase from 23% to 74% of patients discharged with short courses • Most common abx • Clinda- 88% • TMP/SMX- 8% • Cephalexin- 4% • Readmissions (no sig differences from prior to study) • 26 (4%) were readmitted • 11 for recurrence • 16 for treatment failure

Short vs Prolonged Courses of Antibiotic Therapy for Children with Uncomplicated Gram-negative bacteraemia Park SH et al. J Antimicrob Chemother 2014; 69: 779 -85. Objectives: • Compare clinical outcomes of patients with uncomplicated GN bacteremia receiving short (710 days) versus prolonged (>10 days) duration of antibiotic therapy. • Method: Retrospective cohort study between 2002 and 2012. Estimated bacteremic relapse among children who received short vs prolonged antibiotic therapy.

Results • 170 matched pairs • Duration of therapy in short and prolonged were 10 days and 14 days, respectively • 30 day mortality was similar • Prolonged therapy did not reduce the relapse risk • Possible association with an increased risk found for candidemia in prolonged treatment.

5 D’s of Antimicrobial Stewardship • IV to PO • GAP in current Discharge stewardship research/intervention between hospital and community for PO Rx’s. • Ensuring consistency with what was prescribed inpatient.

Summary • ASP standard goes into effect per the Joint Commission in January…. Are you ready? • Leaders must be identified. . . are you the one? • If you are the one. . empower those around you to help with the cause. . . this is a huge undertaking. • If you are not the one. . there are many things you can do to help. • This is a TEAM effort. . . all healthcare providers are needed. . and pharmacy can take the initiative. . . we have the drug expertise!!!

What prevents the intravenous to oral antibiotic switch? A qualitative study of hospital doctor’s accounts of what influences their clinical practice. • Broom J et al. J Antimicrob Chemother 2016; 71: 2295 -99.

Question • Which of the following is the narrowest spectrum antibiotic? Linezolid B. Levofloxacin C. Cefepime D. Nafcillin A.

Questions