LUNCH AND LEARN Overview of Antimicrobial Stewardship January 13, 2017 Featured Speaker: Jamie Kisgen, PharmD, BCPS (AQ ID) Pharmacotherapy Specialist Infectious Diseases Antimicrobial Stewardship Program PGY1 Pharmacy Practice Residency Coordinator Sarasota Memorial Health Care System CE Activity Information & Accreditation (Pharmacist and Tech CE) 1.0 contact hour Funding: This activity is self funded through PharMEDium. It is the policy of to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Kisgen has served as an Advisory Board Member for Astellas Pharma. 2 www.proce.com 1
Online Evaluation, Self-Assessment and CE Credit Submission of an online self assessment and evaluation is the only way to obtain CE credit for this webinar Go to www.proce.com/pharmediumrx Print your CE Statement online Live CE Deadline: February 10, 2017 CPE Monitor CE information automatically uploaded to NABP/CPE Monitor upon completion of the self assessment and evaluation (user must complete the claim credit step) Attendance Code Code will be provided at the end of today s activity Attendance Code not needed for On Demand 3 Ask a Question Submit your questions to your site manager. Questions will be answered at the end of the presentation. Your question...? 4 www.proce.com 2
Resources Visit www.proce.com/pharmediumrx to access: Handouts Activity information Upcoming live webinar dates Links to receive CE credit 5 Overview of Antimicrobial Stewardship Jamie Kisgen, PharmD, BCPS (AQ-ID) Pharmacotherapy Specialist Infectious Diseases Sarasota Memorial Health Care System 6 www.proce.com 3
Disclosure I have a relevant financial relationship with the following company: Served on advisory board for Astellas Pharma US, Inc I will be discussing content involving unlabeled use of a commercial product 7 Objectives Summarize the epidemiology and economic impact of antibiotic resistant infections Describe the goals of antimicrobial stewardship Discuss the role of pharmacists in developing and sustaining antimicrobial stewardship programs Compare and contrast the common stewardship strategies utilized by health systems to improve antimicrobial prescribing and patient outcomes Discuss how premixed intravenous antibiotics can be used to improve quality metrics for antimicrobial stewardship 8 www.proce.com 4
Interesting Quotes The time has come to close the book on infectious diseases. We have basically wiped out infection in the United States. Surgeon General William Stewart, 1967 One can think of the middle of the 20 th century as the end of the most important social revolutions in history, the virtual elimination of the infectious diseases as a significant factor in social life Sir Franklin McFarland Burnet, Nobel Laureate, 1962 9 Fast forward to Today Our medicine cabinet is nearly empty of antibiotics to treat some infections Tom Frieden, MD, MPH Director of the Centers for Disease Control and Prevention The threat of untreatable infections is real. Although previously unthinkable, the day when antibiotics don t work is upon us. We are already seeing germs that are stronger than any antibiotics we have to treat them. Arjun Srinivasan, MD Associate Director for Healthcare Associated Infection Prevention Programs at CDC 10 www.proce.com 5
11 Antibiotic Resistance is Now a Global Concern 11 A Few Numbers At least 2 million people acquire resistant bacterial infections every year in the U.S. 23,000 die as a result of the infection Many more die from other conditions that were complicated by the infection Resistant pathogens lead to higher health care costs because they often require more expensive drugs and extended hospital stays Total cost to U.S. society ~ $20 billion annually CDC Antibiotic resistance threats in the United States, 2013 CDC Antibiotic resistance threats in the United States, 2013 12 www.proce.com 6
How did we get here? Antibiotics can be prescribed by any provider They are the only drug that can impact other people if used inappropriately They have become devalued by the public You can even get some for free!! Big Pharma doesn t see a return on investment Physician fear What if I make the wrong diagnosis? What if I get sued? What if the patient decides to leave my practice? Darwinism vs a dwindling antibiotic pipeline 13 Number of New Antibacterial Agents Approved by the FDA has Been Declining 16 14 12 10 8 6 4 2 0 1983 1987 1988 1992 1993 1997 1998 2002 2003 2007 2008 2013 2014 2016 Adapted from Boucher HW, et al. Clin Infect Dis. (2009) 48(1): 1 12 14 14 www.proce.com 7
CDC Call to Action CDC Antibiotic resistance threats in the United States, 2013 15 CDC Threat Report CDC Antibiotic resistance threats in the United States, 2013 16 www.proce.com 8
Core Actions to Prevent Resistance 1) Preventing infections, preventing the spread of resistance 2) Tracking 3) Improving antibiotic prescribing/ stewardship Perhaps the single most important action needed to greatly slow down the development and spread of antibiotic resistant infections is to change the way antibiotics are used. 4) Developing new drugs and diagnostic tests CDC Antibiotic resistance threats in the United States, 2013 17 What is Antibiotic Stewardship? 18 A coordinated effort to promote thejudicious and effective use of antibiotics. In other words The right antibiotic, at the right dose, for the right duration of therapy! 18 www.proce.com 9
Stewardship Guidelines Barlam et al. Clinical Infectious Diseases 2016;62:1 27 19 Goals of Stewardship Optimize patient clinical outcomes Reduce morbidity and mortality Improve patient safety by minimizing unintended consequences of antimicrobial use e.g. Clostridium difficile infection Minimize the emergence of antibiotic resistant organisms VRE, MRSA, ESBLs, KPCs Reduce healthcare costs without adversely impacting quality of care Decrease length of stay, decrease adverse drug events Dellit et al. Clin Infect Dis 2007; 44:159 77 20 www.proce.com 10
Stewardship Team Core Members: Infectious Diseases physician and a clinical pharmacist with ID training 21 Infection Prevention and Control Develop hospital policies for IPC Monitor for outbreaks of nosocomial infections Coordinate employee screening and vaccination program Provide education 22 22 www.proce.com 11
Microbiology Develop and publish hospital Antibiogram Determine list of antibiotics for susceptibility testing Help identify new technologies to aid stewardship (e.g., Rapid MRSA PCR) 23 23 Stewardship Strategies Core Strategies Prospective audit and feedback Preauthorization/formulary restriction Additional strategies Education, guidelines, clinical pathways Dose optimization of antimicrobial agents (vancomycin, aminoglycosides) Implement interventions to reduce the use of antibiotics associated with a high risk of CDI Encourage prescriber led review of appropriateness of antibiotic regimens (e.g., antibiotic time out) Incorporate computerized clinical decision support at order entry IV to PO conversion Barlam et al. Clinical Infectious Diseases 2016;62:1 27 24 www.proce.com 12
Daily Activities for Antimicrobial Stewardship Prospective Audit and Feedback: each patient s antibiotics should be reviewed daily Optimize antibiotic doses:renaldose, IV to PO, indication, cultures, etc Antibiotic Time Out at 72 hours: Review cultures and contact provider to encourage de escalation of broad spectrum therapy Decrease days of therapy: assist with setting stop days based on diagnosis and clinical response 25 Core Strategy: Prospective Audit and Feedback 26 www.proce.com 13
Checklist for Evaluating Antimicrobial Therapy Indication documented and appropriate? Dose appropriate for site of infection and renal function? Any Drug Drug or Drug Disease interactions? Review microbiology data Is the identified organism a contaminant or colonizer? Were appropriate tests for the indication ordered and collected? Able to deescalate or switch patient from IV to PO? Does order have a stop date or has prescriber documented duration in the progress note? Is patient experiencing any side effects from the antibiotics? 27 Core Strategy: Formulary Restriction 28 www.proce.com 14
Formulary Restriction Broad spectrum coverage High cost High risk for toxicity Limited indications Potential for collateral damage Restriction Options: Limit use to specific indications/criteria for use Require ID physician or ASP approval 29 Restriction Examples Ceftaroline restricted due to broad spectrum of activity and high cost Tigecycline restricted due to broad spectrum of activity, high cost, and safety concerns Telavancin restricted due to limited indications, high cost, and safety concerns Fidaxomicin restricted to specific providers but also available if patient meets criteria for use 30 www.proce.com 15
Dose Optimization 31 Dose Optimization (PK/PD) Activity Antibiotics Parameter Goal Concentrationdependent, Prolonged PAE Aminoglycosides Metronidazole Daptomycin Peak/MIC High peak concentration Time dependent, Minimal PAE Penicillins Cephalosporins Carbapenems Time>MIC Maintain concentration above the MIC Time dependent, Moderate to prolonged PAE Fluoroquinolones Tetracyclines Macrolides Tigecycline Vancomycin AUC/MIC Increase total drug exposure PAE: Post antibiotic effect 32 www.proce.com 16
Beta lactams Craig WA. Clin Infect Dis 1998;26:1 10. 33 Can We Use Different Infusion Rates to Improve Outcomes? Intermittent infusion: Administered over 30 to 60 minutes Extended infusion: Administered over 3 to 4 hours Continuous infusion Administered over a 24 hour period at a constant rate 34 www.proce.com 17
Extended Infusion Strategy 35 Piperacillin/tazobactam Dosing Time dependent bactericidal killing Max effect seen when free conc is > MIC for at least 50% of the dosing interval Normal adult dose: 3.375 grams IV q6hr over 30 min Pseudomonas: 4.5 grams IV q6hr over 30 min Extended infusion: 3.375 grams IV every 8hr infused over 4 hours 36 www.proce.com 18
Probability of Free Drug Concentration Above the MIC at Least 50% of the Time (ft>mic) Poor empiric coverage below red line Lodise TP, et al. Pharmacotherapy. 2006;26(9):1320 32 37 Extended Infusion Summary Pros Improved target attainment (time>mic) May improve outcomes, decrease resistance Less total drug needed in some cases, lower pharmacy costs Cons Risk for errors by pharmacy and nursing Could lead to under dosing if given over 30 minutes Off label dosing, sometimes difficult to get MD buy in Compatibility concerns with other drugs since it ties up a line for an extended period of time 38 www.proce.com 19
Education, Guidelines, and Clinical Pathways 39 Education, Guidelines, Pathways Continuing education Live grand rounds, webinar, or on demand Hospital/Department Newsletters Stewardship website Direct detailing to providers Disease specific order sets Pneumonia, Sepsis, Surgical Prophylaxis, UTI 40 www.proce.com 20
Guideline Example 41 IV to PO Conversion 42 42 www.proce.com 21
IV to PO Switch Many new antimicrobial agents have near 100% oral bioavailability. Intravenous formulations are useful in situations where the patient may have compromised GI function. However, in patients who are clinically stable with a functioning GI tract, oral therapy is a viable and preferred option. Studies have documented pharmacoeconomic benefit of a pharmacist managed automatic IV to PO conversion program. 43 43 Advantages of Early Switching Reduction in pharmacy drug preparation, mixing, and dispensing times Shorter hospital length of stays Reduction in nosocomial infections, especially bacteremia secondary to line sepsis Decreased compatibility issues Lower drug acquisition costs Reduction in nursing time caring for patients not connected to drug delivery system Easier to transport patients for diagnostic studies 44 44 www.proce.com 22
De escalation/streamlining Reduces antimicrobial exposure Reduces selection of resistant pathogens Reduces drug costs Difficult to do when cultures are negative or unavailable and patient is improving 45 45 De escalation/streamlining 46 46 www.proce.com 23
National Quality Metrics 47 Stewardship is a National Priority New Condition of Participation for Antibiotic Stewardship in Hospitals and Nursing Homes New Antimicrobial Stewardship Standard 48 www.proce.com 24
Joint Commission and Stewardship 49 CDC Core Elements for Antibiotic Stewardship Obtain leadership commitment Promote physician accountability Utilize pharmacy as drug experts Make policy and practice changes to improve antibiotic use Track antibiotic prescribing and resistance patterns Report information on antibiotic use and resistance to doctors, nurses and relevant staff Educate health care professionals 50 www.proce.com 25
Sepsis Core Measure Sepsis is now a Core Measure (started Oct 2015) Consistent with Surviving Sepsis Campaign guidelines Goal is to promote early management bundle in patients with severe sepsis/septic shock Measurement of lactate and blood cultures Administering broad spectrum antibiotics, fluid resuscitation, vasopressors Reassessment of volume status and tissue perfusion, and repeat lactate measurement 51 Impact of Customized Premixed Antibiotics To optimize timing of antibiotics, we use mini bag plus or premix antibiotics whenever possible Vancomycin is not ideal for mini bag plus because of the volume requirements Premixed vancomycin can be obtained from commercial compounding pharmacies Improved stability for prolonged storage Stored easily in ED and ICU refrigerators Easily available for rapid administration 52 www.proce.com 26
Healthcare Associated Infections (HAI) 5 10% of all hospitalized patients develop a hospitalacquired infection (HAI) HAI monitored by CMS for quality and potential reduction in Medicare payments: Central line associated bloodstream infections (CLABSI) Catheter associated urinary tract infections (CAUTI) Methicillin resistant Staphylococcus aureus (MRSA) Bloodstream infections Clostridium difficile infections (CDI) Surgical Site Infections (SSI) https://www.medicare.gov/hospitalcompare/hac reduction program.html 53 Surgical Site Infections (SSI) SSI are the most common cause of HAI About 300,000 SSI occur annually in the U.S. Patients with surgical site infections are 2 to 11 times as likely to die as a result Lead to higher costs, longer lengths of stay and increased risk of hospital readmissions http://www.centerfortransforminghealthcare.org 54 54 www.proce.com 27
Evidenced Based Methods to Improve SSI Appropriate antibiotic selection for surgical patients Prophylactic antibiotic is received within 1 hr prior to surgical incision Prophylactic antibiotics discontinued within 24 hours after surgery end time Goals: Decrease morbidity and mortality associated with postoperative SSI Promote the appropriate selection and timing of prophylactic antimicrobials 55 Impact of Customized Premixed Antibiotics Cefazolin 2 gram prefilled syringe Smaller volume compared to standard IVPB Quicker administration time (IV push) Stores easily in OR refrigerators Cefazolin 3 gram IVPB Meets the needs for our obese patients Improved stability for prolonged storage Stores easily in OR refrigerators 56 www.proce.com 28
Conclusion Antibiotics are a shared resource that need to be protected for future generations Stewardship can help us improve patient outcomes, minimize drug resistance, and decrease healthcare costs Pharmacists are core members of stewardship programs and need to be trained to manage antibiotics effectively New standards by CMS and Joint Commission will impact pharmacists in all settings of patient care Each institution needs to tailor stewardship strategies to meet the needs of their patients 57 References CDC Antibiotic resistance threats in the United States, 2013. https://www.cdc.gov/drugresistance/threat report 2013 [Accessed 12/29/2016] Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1 12. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program:guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62:1 27 Dellit TH, Owens RC, McGowan JE Jr, 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(2):159 77. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998 Jan;26(1):1 10 58 www.proce.com 29
References Lodise TP, Lomaestro BM, Drusano G. Application of antimicrobial pharmacodynamic concepts into clinical practice: focus on beta lactam antibiotics: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2006 Sep;26(9):1320 32. Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended infusion dosing strategy. Clin Infect Dis. 2007 Feb 1;44(3):357 63. https://www.jointcommission.org/assets/1/6/new_antimicrobial_stewardship_ Standard.pdf (Accessed 1/3/2017) The Joint Commission Center for Transforming Health Care. http://www.centerfortransforminghealthcare.org/projects/detail.aspx?project=4 (Accessed 12/29/2016) 59 Questions? 60 www.proce.com 30