Antimicrobial Stewardship: When to Study, and When to Act Addressing ABX Resistance Curtailing ABX Resistance Antimicrobial Use Interventions Agricultural Animals Humans Infection Control Interventions Inpatient Development of New Agents Outpatient Rob Owens, PharmD Co-director, Antimicrobial Stewardship Program Maine Medical Center, Portland, Maine Clinical Assistant Professor University of Vermont, College of Medicine Burlington, Vermont Antimicrobial Stewardship Program ASP Vaccines Surveillance / Diagnostics Ignore / Blame Others Nursing Home Emergency Dept. Is there a need for antimicrobial stewardship? IF NOT, why even bother developing new antibiotics If so, what is the magnitude of the problem? >5,000 Hospitals in U.S. ~40 Accredited ID Pharmacy residency training programs No official antimicrobial stewardship program (ASP) guidelines for much of the antibiotic era Individuals acting independently (anyone from podiatrists, optometrists, to ID physicians can prescribe antibiotics) but, why get an Rx? I can get them all OTC just across our own border and bring them home with me Interventions from multiple studies demonstrate an impact in reducing unnecessary use, leading to outcome benefits (less C. difficile) Which Approach Is Best? Restrictive Use (Front end method) Prospective Audit with Feedback (back end method) (Blend of both probably best) Chief concern, accountability IDSA-SHEA ASP Guidelines Introduced 2007 Support at the Local Level Depends on Administrator buy in Era of Rapidly changing regulatory environment/ reform Culture of Patient safety Reduce medication errors Duplication of therapy unnecessary use excessive durations Still, diagnostic uncertainty remains much of the time Pay for performance introduced In 2010, CEO types starting to understand resistance (MRSA, ESBL, KPC ) is more than an acronym, being financially penalized Pressure funneled down to the hospital pharmacy/id division to create ASPs Expertise of those intervening needs to be addressed ID Fellowship training opportunities ID Pharmacist training opportunities Certification Programs Outcome metrics How Best can we measure outcomes? Process measures Outcome measures Opportunity for harmonization
Sometimes the link between use and outcomes can be direct Yet Sometimes, it can be more elusive Ann Intern Med 2001; 134:298 Increased morbidity/mortality 60-80,000 deaths Increased hospitalization Transmission to others Influences antibiotic choices Direct/indirect costs 2 million pts suffer nosocomial infections/yr; 50-60% involve resistant pathogens Cost = ~$30 billion/yr at $24K per case Shehab N, et al. Clin Infect Dis 2009;47:735-43. Case (Laboratory work courtesy of Dr. John Quinn and Karen Lolans; Jim Johnson) 48 y.o. female (Pt. A) with recurrent UTIs (E. coli) requiring near continuous antimicrobial treatment (years) Ceph B-R Cephalosporin B Ceph A-R Amoxicillin Amoxicillin-R?s Cephalosporin A Pt. A Cares for her sister (Pt. B) Pt. B admitted to hospital with urosepsis (never received antibiotics, did not suffer from UTIs): Died 4 days later Pt. B acquired organism from Pt. A, resulting in infection and mortality (same organism, both MDR E. coli due to CTX-M- 15 ST131 ESBL) Success Enhanced IF: Lay ground work (Aided by Regulatory Agencies) Administrative buy in (remuneration) Clinician Champions Pick Strategy that will work locally, PERSISTANCE... Start small, pick 3 interventions and do them well, document through Surrogate markers Benchmarking Externally of great value End goal, extend the useful lifetime of the current antimicrobials we have in our quiver (Todd Webber) Inpatient Stewardship Strategies: 10,000 ft View Antimicrobial Stewardship Program: Action Plan Intervention Database Benchmarking Reports Restriction expert advice CPOE CDSS expert systems (guidance given when little is known, educated guess based on expertise) Rapid Diagnostics in progress Traditional Culture in progress Microbiological Data Trickling in (Gram Stain), Imaging studies, etc Audit/Feedback De-escalation IV-Oral STOP abx Active Interventional Program (Daily Rounding Adult Patients) Antibiotic Consumption Measurement Initiative (DDD data) Formulary Guide Publication Report Tracking (CPI) Formulary Guide I.V. to P.O. Initiative Ongoing initiative Vancomycin Monitoring Initiative Reports from NorDx Periodic Initiative Funded project Correlate Abx Use/Resistance DDD data/antibiogram Tracking mechanism Optimizing abx testing results Optimizing abx testing results Top 10 $$$ Antibiotic Review Abelcet; Pip/Tazo Best Contract Pricing Initiative Therapeutic Interchange: ASP Gatifloxacin to Moxiflox. Formulary Management Strategies Restrictions: Voriconazole launched Prospective evaluation: reports sent MUE: Moxifloxacin MRSA LOS Initiative In Progress FP Rounds March 03
Where we have evidence, ACT! (oh how common this is ) Too many Chefs in the Kitchen Intervention, stop redundant therapy Approaches Guided by Technology Computerized Decision Support Led to More Patients Capable of Being Intervened Upon By the ASP
Total number of patients admits and number of patients given antibiotics, 2005-2007 at one university affiliated hospital DO THE MATH, How Many People are We Underdosing. Choosing the Wrong Drug, Wrong Duration? Front End Interventions (Example) Garey et al. J Hosp Infect 2008 Front End Interventions (Example) Front End Interventions (Example) ID Pharmacist, ID Physician, ID Fellow, Pharmacy Resident: Hand Holding Ginn E, et al. ICAAC/IDSA, Washington, DC, 2008 124 abx days days less! 33% increase
ASP Prospective Audit With Feedback: Ginn E, et al. ICAAC/IDSA, Washington, DC, 2008 Results (Antibiotic Duration Reduction in HAP, VAP) Ginn E, et al. ICAAC/IDSA, Washington, DC, 2008 # Antibiotic Da ays Antibiotic Days & CPIS Score Day 1 and 3 25 20 P=0.005 15 10 5 0 0 5 10 15 20 25 CPIS Sco ore PRE-intervention Intervention group Optimizing Dose Better Ways to Give Older Drugs Why is this not Done as a Standard in ICUs? From Benchtop to Bedside Extended Infusions Associated with Reduced Mortality in Patients with Higher Apache II Scores Pip-Tazo & P. aeruginosa Bacteremia: Mortality by MICs within Susceptible Range mortality rate P =.67 P =.004 30-day Lodise et al. Clin Infect Dis 2007;44:357-63. Tam VH et al. Clinical Infectious Diseases 46(6):862 867.
Metrics (Science needed) Dosed adequately (>10mg/kg): Underweight patients: 100% Normal weight patients: 93.9% Overweight patients: 27.7% And only 3.3% of patients receiving <10mg/kg had disturbingly, their dose changed within first 24 hours ASP Surrogates Process measures: # patients reviewed/day # phone calls received for approval/d # interventions/day Type of intervention made Outcome Measures RESISTANCE rates C. difficile infections (not + toxin tests) Antimicrobial use Traditional: DDD/1000 pt days Proposed: DOT/Optimal Denominator % Outcome Measures: Antibiotic Use Reduction(over 7 years) Parenteral antibiotic use, cost per 1,000 patient-days, and Medicare Case Mix Index (MCCMI) NHSN: (http://www.cdc.gov/nhsn/psc_ma.h tml) - Courtesy of Melinda Neuhauser Length of stay Others Carling P, et al. Infect Control Hosp Epidemiol2003;24:699-706. Reduction in CDAD (p=0.002) Outcome Measures: Antimicrobial Stewardship Program Combined With Infection Control Interventions on Epidemic CDI Antibiotic Intervention Period Usefulness of Internal Benchmarking Fluconazole Consumption By Unit Time it took to identify: 5 minutes ICUs Oncology Unit Use of Targeted Abx 200 180 160 140 120 100 80 60 200 180 160 140 120 100 80 60 40 20 Mean DDD / 1,000 PD 40 20 Mean DDD / 1,000 PD 0 0 Qtr1 Qtr2 Qtr3 Qtr4 Qtr1 Qtr2 Qtr3 Qtr1 Qtr2 Qtr3 Qtr4 Qtr1 Qtr2 Qtr3 2003 2004 2003 2004 Bars represent CDI Order sets: ampho b to fluconazole Valiquette et al. Clin Infect Dis 2007;45:S112-21.
Antimicrobial Stewardship is Sporadically Practiced Data Support ASPs Reduce Unnecessary Use We are Losing Antibiotics Need for training in ID/Education Antibiotic consumption measurement harmonization for benchmarking, better detect use-resistance trends We herd sheep, we drive cattle, we lead people. Lead me, follow me, or get out of my way. -George S. Patton