Solution Title: Antibiotic Stewardship: A Journey Toward the Triple Aim

Solution Title: Antibiotic Stewardship: A Journey Toward the Triple Aim Program/Project Description, including Goals What was the problem to be solved? How was it identified? What baseline data existed? What were the goals how would you know if you were successful? In today s healthcare environment, healthcare organizations are challenged to meet the Institute for Healthcare Improvement s Triple Aim. The Triple Aim emphasizes improving the care experience, health of populations and reducing healthcare costs [1]. Upper Chesapeake health has taken many steps in this journey toward the Triple Aim, but none compares to the efforts put forth in our Antibiotic Stewardship Program. In 2008 our Infectious Disease physician was called in to see an 80-year-old male who had bilateral Pneumonia and Clostridium difficile (C.difficile) colitis. The patient initially presented with shortness of breath and a chest X-Ray suggestive of pneumonia. After receiving antibiotics for a week, he developed diarrhea and tested positive for C. difficile colitis. The team was between a rock and a hard place: continuing the antibiotics would have worsened the C. difficile colitis while stopping them would increase his risk of a worsening lung infection. After a detailed review of the chart, the Infectious Disease physician determined that the patient did not have pneumonia to begin with. Broad spectrum antibiotics were stopped, C. difficile was treated aggressively, and after another week the patient was discharged. Our experience with this patient who received inappropriate antibiotics, causing more harm than good was in line with National trends. The Centers for Disease Control and Prevention (CDC) estimates that 20-50% of antibiotics are either prescribed inappropriately or unnecessarily [2]. Antibiotic misuse can lead to adverse drug reactions, C.difficile infections, and increased antibiotic resistance. Emerging antibiotic resistance is currently a major threat to public health warranting the development of antibiotic stewardship programs. Antibiotic stewardship programs have been associated with decreases in C. difficile infections and antibiotic resistance while decreasing associated healthcare costs [2]. Cases like these prompted us to take a deeper dive. We realized that our institution s nosocomial C. difficile rates during the years 2004-2008 were averaging around 1/1000 patient days. Rates of Vancomycin resistance enterococci were over 40% and community acquired MRSA infections were an emerging threat. Anecdotal evidence pointed to occasional inappropriate antibiotic use at our two hospitals. That's when we decided to establish an antibiotic stewardship program with the ultimate goal of promoting appropriate use of antimicrobial therapy, minimizing the emergence of antimicrobial-resistant bacteria, and preventing hospital acquired C. difficile infections, while reducing healthcare costs in alignment with the Triple Aim. 1

While 8 out of 10 US hospitals belong to the non-teaching community hospitals (NTCH) category, most published studies describe antibiotic stewardship programs (ASP) established at large academic centers [2]. We present our 4-year experience (2011-2015) of implementing a clinically and cost-effective ASP at two NTCH in Maryland. University of Maryland Upper Chesapeake Health (UM UCH) comprises of two NTCHs: Upper Chesapeake Medical Center (UCMC, 203 beds) and Harford Memorial Hospital (HMH, 103 beds). Process & Solution What methodology or process was used to develop the solution? What Solution was developed? How was it implemented? IMPRV (Identify, Measure, Process, Re-Think and Validate) is a best-in-class methodology founded upon the key tenets of Lean, Six Sigma, project management, and change management theories. IMPRV provides a structured way for UM UCH teams to identify opportunities for improvement, analyze the situation, and develop a solution to solve the problem at hand. In late 2011, UM UCH formed a multidisciplinary team to create a robust Antibiotic Stewardship Program (ASP). Led by a Clinical Pharmacist and an Infectious Disease (ID) physician, the team applied the IMPRV Methodology to meet their goal as follows. Identify: The key objective of the Identify Phase is to clearly define the problem, identify the current state, and develop a solid business justification for executive and organizational sponsorship. Trending Nosocomial infection rates and patient outcomes served as a compelling value proposition for an ASP. The multidisciplinary team consisting of members from Pharmacy, Infection Prevention, Medicine, Nursing, and Microbiology assembled to outline the problem, scope, and goals of the project. Once the team felt they had a keen understanding of the problem to be solved, they moved on to Measure Phase. Measure: In the Measure Phase the team worked to further understand the current state of the process and collect sound data on process performance. The team reviewed pathogen resistance data, examined current state antibiotic prescribing practices, and evaluated UM UCH Pharmacy workflow. Process: During the Process Phase, the team used the process and performance information from the Measure Phase to assess and analyze process data, perform root cause analysis for potential issues, and identify waste and inefficiency. The team recognized multiple opportunities for improvement. The team noted that level 1 antibiotics such as Vancomycin and Zosyn were the most widely misused anti-infectives. Orders for Level 1 and 2 antibiotics remained prescribed for patients despite being negated by culture and sensitivity results. In cases where level 1 and 2 antibiotics were warranted, patient specific dosing considerations were needed. Additionally, clinical pathways and order sets existed but were underutilized. Re-Think: The main objective of Re-Think is to design a safer and more efficient process. During this phase we outlined a full-scale implementation plan of our improvement solutions. 2

Our solutions include antibiotic restrictions, de-escalation, pharmacokinetic and renal dosing, IV to oral antibiotic conversion, pharmacy rounding, and clinical pathways. Solution 1: Antibiotic Restrictions We started by imposing restrictions on level 1 and level 2 antibiotics. Empiric use of Level 1 ABX (piperacillin-tazobactam and Vancomycin) is restricted for 72 hours, after which either a positive culture or an ID consult is required to continue the ABX further. Empiric use of Level 2 ABX (carbapenems, echinocandins, tigecycline, daptomycin, linezolid, ganciclovir, voriconazole, lipid amphotericin and non-formulary antibiotics) requires an ID consult within 24 hours. Pharmacy reviews culture data of patients receiving these restricted ABX daily and informs prescribers of stop date by placing a sticker, notifying prescribers of ABX that will expire, in the chart. Solution 2: De-escalation Pharmacy reviews a daily Microbiology report and suggests de-escalation of antibiotics based on culture results. Solution 3: Pharmacokinetic and Renal Dosing The pharmacy performs all pharmacokinetic dosing for patients on vancomycin and aminoglycosides per guidelines and monitors for toxicities. Pharmacy is authorized to order drug levels, BUN/creatinine and adjust dosages for these antibiotics. The pharmacy is additionally authorized to adjust dosages for all antibiotics according to renal function per hospital guidelines. Solution 4: IV to Oral Antibiotic Conversion We also implemented extended infusion dosing of piperacillin-tazobactam. During the daily review of patients receiving ABX there is evaluation for eligibility to convert to oral therapy. Pharmacy is authorized to automatically switch some ABX from IV to PO when criteria are met per hospital guidelines. Solution 5: Pharmacy Rounding Clinical pharmacists make rounds in the ICU and some nursing units daily. The rounds provide means to review every single ABX to make sure they are used for the appropriate indications, duration and with the optimal dosing and routes of administration. Pharmacy also enforces the use of all restricted ABX during these clinical rounds. Solution 6: Clinical Pathways Order sets and clinical pathways guide providers regarding the choices of ABX based on clinical indications. Incorporated in our order sets and clinical pathways for sepsis, COPD, cellulitis, meningitis, and pneumonia are evidence-based guidelines and review of our annual antibiograms. We limited the duration of ABX in surgical prophylaxis order sets to 24 hours, and in some surgical procedures, 1 dose pre-op only. Validate: The key objective of the final phase of IMPRV is to complete solution implementation, ensure process accuracy, and provide comprehensive training on the solutions to ensure sustainment. Ownership is transferred from the project facilitator to the process owners and team members who will implement the solutions put in place, in this case our Antibiotic 3

Stewardship Program. We tract the success of our ASP via DDD/1000 patient days for the restricted ABX. We report ABX pharmacy purchases, percentage of inpatient pharmacy ABX purchased over total pharmacy budget, and cost per patient day. We also tract and report the rates of C. difficile, ESBL, VRE, MRSA and other resistant pathogens. We develop annual antibiograms for both hospitals and distribute them to all house staff. Initial and annual education by ID physician provides education for hospitalists and pharmacists throughout the organization. Measurable Outcomes What are the results of implementing the Solution? Provide qualitative and/or quantitative results to data. (Please include graphs, charts, or tools.) Since establishing of our ASP, our rates of C. difficile infections have stayed in the range of 0.2-0.3/1000 patient days. This rate reduction has been sustained over the past five years without any other intervention which could have decreased C. difficile rates (Figure 1). Infection Rate per 1,000 Patient Days 1.4 1.2 1 0.8 0.6 0.4 0.2 UM UCH Trend of C. difficile Infections 0 2002 2004 2006 2008 2010 2012 2014 2016 Figure 1: UM UCH Trend of C. difficile Infections We also tracked the percentage of Vancomycin resistant Enterococci (VRE) in our clinical specimens. Over the past four years, the rates of VRE have declined significantly at both of our hospitals (Figure 2). 4

VRE Rates 43 41 39 37 35 33 31 29 27 25 2012 2013 2014 2015 Figure 2: UM UCH VRE Rates Overall antibiotic utilization also went down significantly. Two specific antibiotics, Vancomycin and Zosyn, which were restricted to a three-day empiric use saw the greatest decline over the past four years (Figure 3 and Figure 4). Figure 3: Zosyn Utilization Trends 5

Figure 4: Vancomycin Utilization Trends Cumulative savings of ABX purchases of approximately $1,000,000 were calculated over a four year period (Figure 5). Our percentage of ABX purchases over total pharmacy purchases decreased from 15% to 9% (Figure 6), and our cost per patient day decreased from $16 to $8 (Figure 7). Figure 5: Anti-infectives Expenditure Total Dollars Purchase 6

$ ABX COST PER PATIENT DAY 20 15 10 5 0 ANTI-INFECTIVES EXPENDITURE: ABX Cost per Patient Day 2011 2012 2013 2014 2015 UCMC HMH Figure 6: Anti-infectives Expenditure ABX Cost per Patient Day % OF INPATIENT BUDGET 20 15 10 5 0 ANTI-INFECTIVES EXPENDITURE: Percent of Inpatient Budget 2011 2012 2013 2014 2015 UCMC % HMH % Figure 7: Anti-infectives Expenditure Percent of Inpatient Budget In terms of the solutions implemented, the outcomes of the clinical pharmacist s review and interventions continue to occur daily (Figure 8). Pharmacy Antibiotic Stewardship Program Interventions 2012 2013 2014 2015 Cultures reviewed 24152 23618 25488 23131 Antibiotic orders reviewed 10024 10251 11134 9446 Stickers placed in chart 694 796 812 757 Calls made to MD 203 265 273 273 Restricted Antibiotic streamlined 303 217 163 214 Figure 8: Clinical Pharmacist Interventions 7

As part of the Clinical Pathway solutions, our team s use of antibiotic prescribing guidelines continues to increase each year, as evidenced in the use of order sets detailing said guidelines such as the Pneumonia order sets (Figure 9). Number of Pneumonia Order Sets Used Hospital CY2013 CY2014 CY2015 CY2016 (Jan Oct) HMH 240 245 251 262 UCMC 603 651 727 749 Figure 9: Antibiotic Prescribing Guidelines in Pneumonia Order Set Use Sustainability What measures are being taken to ensure that results can be sustained and spread? A solid business justification for executive and organizational sponsorship remains related to the Antibiotic Stewardship Program at UM UCH. Day-to-day operations support the interventions developed to drive success. Prescribing trends are monitored to identify super-prescribers doctors who are outliers in terms of their prescribing habits. One on one follow-up with such physicians serve to coach and reinforce our local bacterial resistance patterns and improvement strategies. Educational sessions are also held by the Infectious Disease physician champion with the pharmacy staff and hospitalists. Leaders of our Antibiotic Stewardship program provide both quarterly and annual updates to relevant oversight committees. Quarterly feedback and updates are presented at the Pharmacy and Therapeutics Committee and the Infection Prevention Committee. Annual updates are provided to the Medical Executive Committee and the Board of Directors. Role of Collaboration and Leadership What role did teamwork and collaboration play in the Solution? What partners and participants were involved? Was the organization s leadership engaged and did they share the vision for success? How was leadership support demonstrated? Our ASP runs under the leadership of our Chief of Infectious Diseases, who is responsible and accountable for the performance outcomes of our ASP. Our Chief of ID works closely with pharmacy to provide guidance and support for our ASP activities. Pharmacists are educated and provided with well-defined guidelines / procedures, and are empowered to implement all clinical ASP activities. We collaborate with the microbiology lab to not only generate an annual antibiogram but also speed up tests results so unnecessary antibiotics can be stopped. This year we have invested in a molecular technology that is expected to further reduce the turnaround times for our cultures. The Information Technology (IT) department continuously works to find ways to generate 8

meaningful reports. Our Infection Prevention department works hand in hand with Nursing and other stakeholders to monitor trends in resistant pathogens and appropriate placement of patients who have a communicable disease. Leadership support is critical to the success of our ASP. Hospital leadership has been committed to support our ASP and is moving toward dedicating the necessary human, financial and IT resources to ensure sustained success of our ASP. A formal Letter of Support was signed by the Chief Medical Officer and a Board member of the UM-Upper Chesapeake Health. Innovation What makes this Solution innovative? What are its unique attributes? Antibiotic Stewardship Programs are essential to combatting emerging antibiotic resistance. While most published studies describe antibiotic stewardship programs in large academic hospitals, ASP can be successfully implemented in resource-limited, non-teaching community hospitals. Successful implementation begins with executive sponsorship and requires commitment of the care team. The Pharmacy team is committed to the daily Microbiology report reviews and de-escalate antibiotics based on culture results. For patients meeting criteria for use of vancomycin and aminoglycosides, pharmacy performs all pharmacokinetic dosing per guidelines. The Pharmacy additionally monitors for toxicities to prevent adverse drug reactions. Pharmacists order drug levels, BUN/creatinine and adjust dosages according to renal function per hospital guidelines for these antibiotics. Daily rounds in the units are innovative and provide means to review every single ABX to make sure they are used for the appropriate indications, duration and with the optimal dosing and routes of administration. This serves as another opportunity for the Pharmacist to enforce the use of all restricted ABX during these clinical rounds. The use of order sets and clinical pathways guide providers regarding the choices of ABX based on clinical indications. This drives consistency with the antibiotic restriction guidelines established for the organization. Guidelines are incorporated in order sets and clinical pathways across the organization. Culture of Safety What impact did the solution have on the culture of safety within the organization? UM UCH recognizes the risks to the patients who receive inappropriate antibiotics and the impact on public health. The organization is committed to promoting a culture of safety. This is evidenced by the initial and ongoing sponsorship to provide the resources needed to address the safety concerns around antibiotic misuse. Collaboration is encouraged and fostered through our IMPRV methodology to seek sustainable solutions for these concerns. Over the years, we have observed a gradual culture change where physicians now take pride in stopping unnecessary 9

antibiotics. If a nosocomial infection occurs, the team huddles together in real time to identify opportunities to improve. Transparency is fostered throughout the organization. Performance updates are shared in multiple forums and varying levels of the organization. We have white boards on our floors showing Days since last nosocomial C. difficile infection which motivates the teams in real time. Patient and Family Integration How did the solution include the patient and family? Our infectious disease group treats nearly 2000 new patients every year. Each patient is educated about the risks and benefits of antibiotics. Meticulous follow up appointments are made with patients to further strengthen the message of safe antibiotic usage in the outpatient setting. A few months ago, our Infectious Disease doctor was asked to see a similar elderly patient who was admitted with bilateral pneumonia and was started on broad spectrum antibiotics by the overnight admitting team. The ASP served as that critical step requiring an Infectious Disease consultation at day 3 of her hospitalization. The patient was distraught over the fact that she wanted to attend her granddaughter s graduation ceremony on the coming weekend but her hospitalization and the resulting broad spectrum intravenous antibiotics were going to prevent her from attending the event. Upon review of the case, the infectious disease physician reached an alternate diagnosis. The patient s antibiotics were stopped, she was discharged home the same day with an out-patient follow up appointment the week after. Not only that she never developed any side effects, she was also able to go home the same day and then enjoy her granddaughter s graduation ceremony. At a one week follow up office visit, she was doing well, and praised our antibiotic stewardship program. Conclusion Theodore Roosevelt, the 26 th President of the United States, was quoted to have said In any moment of decision, the best thing you can do is the right thing, the next best thing is the wrong thing, and the worst thing you can do is nothing. In 2008, a moment of decision served as the catalyst for innovative change at UM Upper Chesapeake Health. Instead of being paralyzed by doing nothing, we endeavored to do things right. However, through our journey toward Antibiotic Stewardship we learned to not only do things right, but to do the right thing the best thing for our patients. Doing the best thing has further positioned us to achieve the Triple Aim of better health, improve patient quality and experience, and cost-efficient healthcare. Although this journey has not been without its huddles, it has become a transformational initiative that has helped to change the culture at UM UCH related to the use of antibiotics. We truly believe that we have been progressive thought leaders and thank you for the opportunity to share our journey with you. 10

HMH antibiogram 2016 (Jan 1 - Dec 31, 2015) % Susceptible Addendums RESISTANCE RATES: MRSA = 46.0% E. FAECALIS VRE = 6.0% E. FAECIUM VRE = 64.0% E COLI ESBL = 9.2% K. PNEUMO ESBL = 9.0% P. MIRABILIS ESBL = 3.6% Overall ESBL (+) = 8.1% GRAM NEGATIVE Escherichia coli - non-urine isolates 36 100 83 44 78 86 83 83 86 64 100 94 61 86 64 Escherichia coli- urine isolates 114 99 82 47 83 91 89 90 85 63 100 97 99 63 88 68 Escherichia coli - ESBL(+) 12 92 42 0 0 0 0 0 42 0 100 78 100 8 25 25 Pseudomonas aeruginosa 26 92 88 85 81 85 92 100 Klebsiella pneumoniae 44 100 91 0 86 91 80 91 93 93 100 57 93 84 93 89 Klebsiella pneumoniae - ESBL(+) 4 100 25 0 0 0 0 0 25 25 100 0 75 50 25 50 Proteus mirabilis 28 100 96 93 96 96 96 96 93 75 100 100 96 89 Proteus mirabilis - ESBL(+) 1 100 0 0 0 0 0 0 0 0 100 100 100 0 Enterobacter cloacae 8 100 63 0 63 75 75 100 50 63 75 75 63 Acinetobacter baumannii (1) 17 88 71 47 82 59 65 41 94 29 Serratia marcescens (1) 21 100 100 0 100 100 95 95 62 5 95 95 GRAM POSITIVE Staphylococcus aureus (MRSA) 44 49 2 93 18 (3) 100 0 0 100 89 100 100 Staphylococcus aureus (MSSA) 51 100 0 100 73 57 100 84 (3) 100 100 18 100 98 100 100 Staphylococcus Coagulase Negative 21 29 0 29 50 33 81 24 (3) 93 29 10 100 71 43 100 Enterococcus faecalis 49 100 19 69 96 100 47 16 94 Enterococcus faecium 11 18 0 18 33 9 9 9 36 Streptococcus pneumoniae (1) 17 100 94 88 100 (2) 94 59 100 88 94 (2) 82 71 100 # isolates tested Amikacin Amoxicillin/Clav. Ampicillin Cefazolin Cefepime Cefuroxime Ceftriaxone Clindamycin Erythromycin Gentamicin Levofloxacin (2) Meropenem Nitrofurantoin-urine Oxacillin Penicillin Piperacillin/Tazo Rifampin Tetracycline Tobramycin Trimethoprim/Sulfa Vancomycin (1) Isolates from both facilities due to low numbers (30 isolates), consider % susceptibility value less statistically valid than isolates > 30 (2) Non-meningitis breakpoint (3) Susceptibilities to Levofloxacin are predictably susceptible to Ciprofloxacin UCMC antibiogram 2016 (Jan 1 - Dec 31, 2015) % Susceptible RESISTANCE RATES: MRSA = 48.0% E. FAECALIS VRE = 7.0% E. FAECIUM VRE = 75.0% E COLI ESBL = 6.8% K. PNEUMO ESBL = 9.2% P. MIRABILIS ESBL = 6.4% Overall ESBL (+) = 7.2% GRAM NEGATIVE Escherichia coli - non-urine isolates 163 100 83 50 87 93 89 92 88 67 100 98 69 87 72 Escherichia coli- urine isolates 616 100 82 48 84 94 88 92 91 68 100 95 97 74 91 75 Escherichia coli - ESBL(+) 53 96 47 0 0 0 0 0 68 11 100 61 87 42 53 40 Pseudomonas aeruginosa 168 95 88 86 81 95 93 96 Klebsiella pneumoniae 239 99 90 0 90 92 86 91 95 92 100 48 95 85 93 88 Klebsiella pneumoniae - ESBL(+) 22 91 14 0 0 0 0 0 50 32 95 44 64 82 18 23 Proteus mirabilis 157 100 97 80 89 95 94 95 93 69 100 99 94 82 Proteus mirabilis - ESBL(+) 10 100 90 0 0 0 0 0 50 20 100 100 70 20 Enterobacter cloacae 47 100 87 72 96 91 100 25 77 85 96 85 Acinetobacter baumannii (1) 17 88 71 47 82 59 65 41 94 29 Serratia marcescens (1) 21 100 100 100 100 95 95 62 5 95 95 GRAM POSITIVE Staphylococcus aureus (MRSA) 186 -- 0 0 -- -- -- 0 50 10 96 13 (3) -- 100 0 0 -- 100 88 95 100 Staphylococcus aureus (MSSA) 199 -- 100 0 -- -- -- 100 76 67 98 80 (3) -- 100 100 25 -- 100 95 100 100 Staphylococcus Coagulase Negative 115 -- 42 0 -- -- -- 42 54 35 85 44 (3) -- 100 42 11 -- 98 88 62 100 Enterococcus faecalis 227 -- -- 100 -- -- -- -- -- 14 -- 60 -- 99 -- 100 -- 56 15 -- 93 Enterococcus faecium 44 -- -- 11 -- -- -- -- -- 7 -- 5 -- 41 -- 11 -- 7 14 -- 25 Streptococcus pneumoniae (1) 17 100 94 88 100 (2) 94 59 100 88 94 (2) 82 71 100 # isolates tested Amikacin Amoxicillin/Clav. Ampicillin Cefazolin Cefepime Cefuroxime Ceftriaxone Clindamycin Erythromycin Gentamicin Levofloxacin (2) Meropenem Nitrofurantoin-urine Oxacillin Penicillin Piperacillin/Tazo Rifampin Tetracycline Tobramycin Trimethoprim/Sulfa Vancomycin (1) Isolates from both facilities due to low numbers (30 isolates), consider % susceptibility value less statistically valid than isolates > 30 (2) Non-meningitis breakpoint (3) Susceptibilities to Levofloxacin are predictably susceptible to Ciprofloxacin Related Tools and Resources [1] The Triple Aim: Care, health, and cost. Berwick DM, Nolan TW, Whittington J. The Triple Aim: Care, health, and cost. Health Affairs. 2008 May/June;27(3):759-769. 11

[2] Centers for Disease Control and Prevention. Core Elements of Hospital Antibiotic Stewardship Programs. 2016; http://www.cdc.gov/getsmart/healthcare/implementation/coreelements.html. Accessed 10/24/2016. [3] 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 the Healthcare Epidemiology of America. Clinical Infectious Diseases. 2016. 12