Why Antimicrobial Stewardship?

Antimicrobial Stewardship: Why and How CAPT Arjun Srinivasan, MD Associate Director for Healthcare Associated Infection Prevention Programs Division of Healthcare Quality Promotion Why Antimicrobial Stewardship? Antibiotics are misused in hospitals Antibiotic misuse adversely impacts patients and society Improving antibiotic use is a public health imperative We re running out of antibiotics to treat our patients. Improving antibiotic use improves patient outcomes and saves money Antibiotics are misused in hospitals It has been recognized for several decades that up to 50% of antimicrobial use is inappropriate IDSA/SHEA Guidelines for Antimicrobial Stewardship Programs Up to 20% in a recent pediatric survey Most common problem- failure to stop or change therapy based on culture results ICHE 2012;33:346 Antibiotics are misused in hospitals It has been recognized for several decades that up to 50% of antimicrobial use is inappropriate IDSA/SHEA Guidelines for Antimicrobial Stewardship Programs Up to 20% in a recent pediatric survey Most common problem- failure to stop or change therapy based on culture results ICHE 2012;33:346 Antibiotics Have Side Effects C. difficile Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile associated disease (CDAD). Exposure to antibiotics increases the risk of C diff by at least 3 fold for at least a month. C difficile Incidence and Mortality Are Increasing 00 Discharges # of CDI Cases per 100,00 90 80 70 60 50 40 30 20 10 0 Principal Diagnosis All Diagnoses Mortality 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 25 20 15 10 5 0 Annual Mortality Rate per Mill ion Population Year Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April 2008. Available at: http://www.hcupus.ahrq.gov/reports/statbriefs/sb50.pdf. Accessed March 10, 2010. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419. 1

Declining : New Antimicrobials to the Market in US 16 14 12 10 8 6 4 2 0 1983-1987 1988-1992 1993-1997 1998-2002 2003-2007 Antibiotic misuse adversely impacts patients - resistance Getting an antibiotic increases a patient s chance of becoming colonized or infected with a resistant organism. Spellberg B, et al CID 2004; 38:1279-86 Susceptibility Profile: KPC-Producing K. pneumoniae Antimicrobial Interpretation Antimicrobial Interpretation Amikacin I Chloramphenicol R Amox/clav R Ciprofloxacin R Ampicillin R Ertapenem R Aztreonam R Gentamicin R Cefazolin R Imipenem R Cefpodoxime R Meropenem R Cefotaxime R Pipercillin/Tazo R Cetotetan R Tobramycin R Cefoxitin R Trimeth/Sulfa R Ceftazidime R Polymyxin B MIC >4mg/ml Ceftriaxone R Colistin MIC >4mg/ml Cefepime R Tigecycline S Geographical Distribution of KPC-Producers: 2001 KPC-producing CRE in the United States September 2012 Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis DC AK HI PR Patel, Rasheed, Kitchel. 2009. Clin Micro News Costelloe C et al. BMJ. 2010;340:c2096. 2

1/10/2013 Stewardship Optimizes Patient Safety: Decreased C. difficile Infection Clinical outcomes better with antimicrobial management program Review of broad spectrum agents followed by form on patient s chart with recommendations 7 day automatic stop orders for antibiotics Exclusion of pharmaceutical detailing 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 Restriction of broad spectrum agents Carling P et al. Infect Control Hosp Epidemiol. 2003;24:699 Fowler S et al. J Antimicrob Chemother. 2007;59:990. Antimicrobial Costs after Stewardship Program Ends 2,500,000 Program Start Program Ends 2,000,000 Pharmnet Implementation CPMOE 1,500,000 3 acute care wards for elderly at a English tertiary center C. difficile rate Percent Carney hospital 100 90 80 70 60 50 40 30 20 10 0 1,000,000 Antibacterial Agents with the Greatest Increase in Costs FY08 FY09 Increase % Change Pip/Tazo 877,809 1,339,270 461,460 53% Linezolid Daptomycin 343,725 102,944 499,845 254,294 156,120 151,350 45% 147% C b 405 181 Carbapenems 405,181 Tigecycline 187,305 548 737 548,737 274,554 143 556 143,556 87,248 35% 47% 999,736 52% Total 1,916,964 2,642,146 500,000 Standiford HC et al. ICHE 2012;33:338 0 FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY FY 98 98 98 98 99 99 99 99 00 00 00 00 01 01 01 01 02 02 02 02 03 03 03 03 04 04 04 04 05 05 05 05 06 06 06 06 07 07 07 07 08 08 08 08 09 09 09 09 10 10 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Actual Dollars FY 98 Avg FY 99 Avg FY 00 Avg FY 01 Avg FY 02 Avg FY 03 Avg FY 04 Avg FY 05 Avg FY 06 Avg FY 07 Avg FY 08 Avg FY 09 Avg FY 10 Avg IMPLEMENTING ANTIMICROBIAL STEWARDSHIP PROGRAMS Long Term Financial Impacts Wake Forest compared actual antimicrobial expenditures to inflation adjusted anticipated expenditures (based on expenditures before the program started). Found sustained cost savings over time- 900K to 2 million per year, depending on the inflation model. Savings increased over time- likely due to better use of new expensive new antibiotics How Stewardship? Traditional stewardship efforts have focused on stewardship programs staffed by ID clinicians and pharmacists. Many hospitals don t have ready access to ID clinicians and very few have ID pharmacists. Even when formal programs exist, their reach is limited. ICHE 2012;33:398 3

Even More Important We need better use of antibiotics to become part of the daily work flow of clinicians. Not just relegated to the task of a stewardship program. Stewardship is something each practitioner should do, not something that should be done for them or to them. Key Questions? How do we structure specific interventions that can be implemented in any care setting? How do we build interventions that fit well into clinical work flow? How do we structure interventions so that they are viewed as value added and not just one more thing people have to do? Some Ideas We need to think about stewardship interventions, not just programs. We need to engage front line clinicians to lead stewardship- hospitalists. We need to focus our efforts on some high yield areas. Stewardship- How Some recent publications point to important opportunities to improve antibiotic use. Infection Control and Healthcare Epidemiology special edition on stewardship published in April 2012. Many Patients Diagnosed with CAP Don t Have CAP 106 patients met criteria for CAP per ED CAP pathway Antibiotics Are Not Tailored to Culture Results 16 (23.5%) patients had micro data that would have supported use of a narrower-spectrum agent Only 3/16 had antibiotics appropriately narrowed 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 4

CAP is Treated for Too Long Median length of stay: 5 days (range 2-31) Total median antibiotic duration = 11 days, median of 4 days as inpatient and 6 days as an outpatient > 7 days in 88% of patients > 10 days in 53% of patients > 14 days in 15% of patients Immunocompetent patients had similar duration of therapy to those who were immunocompromised (median of 10.5 days vs. 11 days) Durations Improve With Feedback Prospective intervention for patients being treated for CAP. Treatment duration reduced from 10 d to 7 d (p<0.001) 001) with 148 fewer antibiotic days. Antibiotics more frequently narrowed based on culture results (67% v. 19%). Fewer patients got duplicate therapy (10% vs 45%). CID 2012;54:1581-7 There Is Still Low Hanging Fruit Analysis of IV to PO conversion at 128 VA hospitals. Looked at IV quinolone use among patients getting gat least 1 oral med. Among all patients, 91% of all IV quinolone days were in patients getting at least 1 oral medication. Was still 46% when excluding ICU patients and the 1 st 2 days of treatment. ICHE 2012;33:362 But Is It Stewardship? Some debate about IV to PO as true stewardship. Dose not reduce use Might improve safety- reduced IV access. But stewardship programs often remain under pressure to show cost savings (at least initially) and IV to PO conversion can be a good way to do this. More Low Hanging Fruit Antimicrobial Stewardship at Hospital Discharge. Cleveland Clinic implemented mandatory ID consult for planned IV antibiotics at discharge. Post discharge antibiotics were avoided in 28% of cases. No re-admits or ED visits among patients who did not get antibiotics. Stewardship at Discharge Another important patient safety benefit of stewardship. Potential to reduce C. difficile, IV catheter complications, other adverse drug events. Another key area for ID clinicians in stewardship. 5

Stewardship in Patients With C difficile Treatment recommendation for C. diff urge providers to stop all unnecessary antibiotics when patients are diagnosed with C. diff. Antibiotic therapy in patients with C. diff can worsen outcomes. Antibiotics in Patients with C. diff Study in MN VA looked at 246 patients with new onset C. diff. 141 received non C. diff antibiotics within 30 days of completion of C. diff therapy. Receipt of non C. diff antibiotics increased the risk of recurrent disease, even after adjusting for other factors. American Journal of Medicine 2011;124:1081 Antibiotics in Patients with C. diff Another study showed that receipt of non-c. diff antibiotics during or soon after C. diff therapy was associated with: Lower cure rates Prolonged diarrhea Recurrent C. diff Clin Infect Dis 2011;53:440 Stewardship in Patients with C. Difficile New diagnoses of C. diff present a critical moment for stewardship interventions. Providers might be even more receptive to stewardship since Their patient is experiencing an adverse event from antibiotics. Stopping unnecessary antibiotics will improve their patients outcome. There s Some Good Stuff Higher Up Too 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. Implications The ICU is always considered one of the most difficult places to do stewardship. This study shows that stewardship can be done in this setting and that it has important benefits to patient care (not just costs). Interventions at specific points in time can be high yield. This is clearly an area where ID clinicians need to be involved. ICHE 2012;33:354 6

Key Moments for Antibiotic Stewardship We should take a page from the WHO Hand Hygiene Campaign. It s great to tell people to clean their hands. It s way better to tell them exactly when they need to do it. Same is true for stewardship. Key Moments for Antibiotic Stewardship There are certain moments when interventions are likely to be both well received by providers and helpful in improving patient outcomes. We should identify and take advantage of them. Key Moments for Antibiotic Stewardship Patients being given IV antibiotics at discharge Patients with positive blood cultures Patients being treated for CAP Patients being treated for UTI Patients with C. difficile Patients who have gotten 3 or 10 days of therapy. Monitoring Antibiotic Use Remains an important, but challenging issue. We are making progress. CDC National Healthcare Safety Network Antibiotic i Use Module is now available. Module allows facilities to monitor antibiotic use for administered antibiotics in DOT/1000 pt days at risk (to get antibiotics). NHSN Antibiotic Use Module Data are sent directly from the hospital s pharmacy vendor system to NHSN and are then available in real time to the facility. Data also available to CDC for potential antibiotic use benchmarking. NHSN Antibiotic Use Module- Where are We Now A few companies have built the AU module into their recent software releases and are ready to connect facilities. Working on a pilot with four states to try and enroll ~60 facilities by the end of the year. 7

NHSN AU Module- Considerations Requires that your pharmacy vendor be participating and that you have e-mar or bar code administration data. We are hearing that companies are charging to connect facilities. NHSN AU Module Has the potential to transform use measurement since it provides data both to inform facility interventions and national benchmarking in one system. Still a lot to be done, both in enrollment and in determining best ways to benchmark use. Quality Measures for Antibiotic Use The Centers for Medicare and Medicaid Services included a few antibiotic use quality measures in the pilot version of the Acute Care Infection Control Worksheet. Piloting of the worksheet is on-going. Quality Measures 1. C.2.a Facility has a multidisciplinary process in place to review antimicrobial utilization, local susceptibility patterns, and antimicrobial agents in the formulary and there is evidence that the process is followed. 1. C.2.b Systems are in place to prompt clinicians to use appropriate antimicrobial agents (e.g., computerized physician order entry, comments in microbiology susceptibility reports, notifications from clinical pharmacist, formulary restrictions, evidenced based guidelines and Quality Measures 1. C.2.c Antibiotic orders include an indication for use. 1. C.2.d There is a mechanism in place to prompt clinicians to review antibiotic courses of therapy after 72 hours of treatment. 1. C.2.e The facility has a system in place to identify patients currently receiving intravenous antibiotics who might be eligible to receive oral antibiotic treatment. Quality Measures There is also interest among IDSA leadership in thinking about quality measures for stewardship that could be submitted to the National Quality Forum. 8

Quality Measures Should we be thinking about a broad measure like the one in California: California Senate Bill 739 mandated that, by January 1, 2008, CDPH require general acute care hospitals to monitor and evaluate the utilization of antibiotics and charge a quality improvement committee with the responsibility for oversight of the judicious use of these medications Quality Measure Challenges Pros and cons to both general and specific measures Broad- Might create better systems Harder to assess compliance Narrow- Might lead to implementation of specific improvements Improvements might be very narrow My Opinion Not whether, but how. I think our experience with health care associated infections, and CA s experience suggest that quality measures can be helpful in driving improvement. They have to be written well and then monitored for unintended consequences. Beyond Use The goal of stewardship programs is to promote the optimal use of antibiotics. We can t really measure optimal use. So how do we know we re accomplishing our goal? Measuring Appropriate Use Has been done in some individual studies. Usually done by an expert panel of ID clinicians. Very labor intensive i Results not comparable from one study to another Can we develop some methods to assess good use that are easier and more standardized? Measuring Appropriate Use CDC working with partners to develop some antibiotic use assessment tools. Forms for both specific conditions or agents and one for general assessment of antibiotic use. UTI CAP Anti-MRSA agents 9

Measuring Appropriate Use CDC planning to pilot these tools in several Emerging Infections Program sites that participated in the HAI/Antibiotic Use prevalence survey. CDC also hosting experts meetings to bring together experts in various specialties to discuss ways to better measure appropriate antibiotic use in out-patient, acute care and long term care settings. Conclusion There is growing momentum for improving antibiotic use in healthcare facilities. There has never been a more important time to do. Please let us know what you learn from your experiences and how we can help you. 10