Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems

Transcription

1 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems A podcast educational activity based on a live program conducted December 8-10, 2008 in Orlando, Florida

2 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems INSTRUCTIONS FOR TAKING POST-TESTS AND RECEIVING YOUR CE STATEMENTS ONLINE FOR PODCAST ACTIVITIES The online ASHP Learning Center allows participants to obtain their CE statements conveniently and immediately using any computer with an Internet connection. To take the post-test and obtain your CE statement for this ASHP Advantage Podcast activity, please follow these steps: Type in your internet browser. Log in to the ASHP Learning Center using your address and password. If you have not logged in to the new ASHP Learning Center (launched August 2008) and are not a member of ASHP, you will need to set up an account by clicking on Become a user and following the instructions. Once logged in to the site, click on Take a Test. After logging in, you will see the list of activities for which CE is available. To process CE for one of the activities in the list, click on the Start button next to the title of the activity. Click on the radio button next to the correct answer for each question. Once you are satisfied with your selections, click Finish CE to process your test and complete the remaining steps to complete the program evaluation and print your CE statement. If you have any problems processing your CE, contact ASHP Advantage at support@ashpadvantage.com.

3 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems D I S C L O S U R E S T A T E M E N T In accordance with the Accreditation Council for Continuing Medical Education s Standards for Commercial Support, ASHP Advantage requires that all individuals involved in the development of program content disclose their relevant financial relationships. A person has a relevant financial relationship if the individual or his or her spouse/partner has a financial relationship (e.g., employee, consultant, research grant recipient, speakers bureau, or stockholder) in any amount occurring in the last 12 months with a commercial interest whose products or services may be discussed in the CME activity content over which the individual has control. The existence of these relationships is provided for the information of participants and should not be assumed to have an adverse impact on presentations. All faculty and planners for ASHP Advantage education activities are qualified and selected by ASHP Advantage and required to disclose any relevant financial relationships with commercial interests. ASHP Advantage identifies and resolves conflicts of interest prior to an individual s participation in development of content for an educational activity. The faculty and planners report the following relationships: Debra A. Goff, Pharm.D., FCCP Dr. Goff reports that she has served as a speaker for Merck and has been the recipient of a grant from Merck and Wyeth. Susan R. Dombrowski, M.S., R.Ph. Ms. Dombrowski reports no relationships pertinent to this activity. Cathy C. Bowles, R.Ph. Ms. Bowles reports no relationships pertinent to this activity.

4 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems P R O G R A M O V E R V I E W Antimicrobial resistance is a major public health crisis because it leads to increased morbidity, mortality, hospital lengths of stay, and healthcare costs. The emergence of antimicrobialresistant pathogens has been attributed in part to improper antimicrobial use. Resistance can be stemmed by an effective antimicrobial stewardship program in conjunction with a comprehensive infection control program. Antimicrobial stewardship programs promote appropriate antimicrobial drug product selection, dosing, administration, and duration of therapy. The primary goal of antimicrobial stewardship programs is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms, and the emergence of resistance. Reducing healthcare costs without adversely impacting the quality of care is a secondary goal. Implementing an antimicrobial stewardship program in health systems can present a challenge. A multidisciplinary team approach to antimicrobial stewardship is recommended in guidelines for developing an institutional program published in 2007 by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clinical pharmacists with infectious diseases training play key roles in this multidisciplinary effort. On October 1, 2008, the Centers for Medicare and Medicaid Services (CMS) limited reimbursement for certain hospital-acquired conditions ( never events ) that the agency considers preventable in an effort to protect patients from serious harm and death. Some of these no pay conditions vascular-catheter associated infection, catheter-associated urinary tract infection, and certain surgical site infections (after certain orthopedic surgeries and bariatric surgery for obesity) have implications for antimicrobial use. The specific infectious conditions proposed for 2009 include ventilator-associated pneumonia, Clostridium difficile-associated disease, Legionnaire s Disease, Staphylococcus aureus septicemia, and surgical site infections following elective surgeries. Pharmacists need to understand the implications of CMS reimbursement policies for antimicrobial stewardship in health systems, and use evidencebased strategies to prevent never events and antimicrobial resistance. This program will describe the relationships between inappropriate antimicrobial use, antimicrobial resistance, and increased morbidity, mortality, hospital length of stay, and healthcare costs. The potential impact of antimicrobial stewardship programs on the emergence and transmission of antimicrobial-resistant microorganisms also will be discussed. Challenges associated with antimicrobial stewardship program implementation and examples of successful multidisciplinary approaches to antimicrobial stewardship will be provided. The financial impact of CMS reimbursement policies for infectious disease-related never events, the implications for pharmacy practice of the policies, and the role of evidence-based strategies in preventing never events and antimicrobial resistance also will be addressed.

5 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems P R O G R A M O B J E C T I V E S At the conclusion of this educational activity, participants should be able to Explain the effects of inappropriate antimicrobial use on antimicrobial resistance, morbidity, mortality, hospital length of stay, and healthcare costs. Describe the potential impact of antimicrobial stewardship programs on the emergence and transmission of antimicrobial-resistant microorganisms. Identify a potential challenge in implementing an antimicrobial stewardship program and an advantage of using a multidisciplinary approach in an institutional setting. Name two infectious disease-related hospital-acquired conditions ( never events ) that the Centers for Medicare and Medicaid Services (CMS) considers preventable and for which reimbursement is limited, and describe the CMS reimbursement policies for these never events and the pharmacy practice implications of these policies. Discuss the role of evidence-based strategies for prevention of never events and antimicrobial resistance. P R O G R A M F A C U L T Y Debra A. Goff, Pharm.D., FCCP Clinical Associate Professor The Ohio State University College of Pharmacy Infectious Diseases Specialist The Ohio State University Medical Center Columbus, Ohio C O N T I N U I N G E D U C A T I O N A C C R E D I T A T I O N The American Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This program provides 1 hour (0.1 CEU) of continuing education credit (program number H01P). F O R M A T A N D M E T H O D S This is an online activity consisting of audio with slides, a post-test, and an activity evaluation tool. Participants must listen to the entire presentation, take the activity post-test, and complete the course evaluation to receive continuing education credit. A minimum score of 70% is required on the test for credit to be awarded, and participants may print their official statements of continuing education credit immediately. The estimated time to complete this activity is one hour. This activity is provided free of charge.

6 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems Debra A. Goff, Pharm.D., FCCP Clinical Associate Professor The Ohio State University College of Pharmacy Infectious Diseases Specialist The Ohio State University Medical Center Columbus, Ohio Debra A. Goff, Pharm.D., FCCP, is Infectious Diseases Specialist and Antibiotic Utilization Review Coordinator at The Ohio State University Medical Center (OSUMC) in Columbus, Ohio. Dr. Goff is also Clinical Associate Professor at OSU College of Pharmacy. Dr. Goff serves as a preceptor in the infectious diseases residency program at OSUMC and she is Chairperson for the OSUMC Robert J. Fass Memorial Infectious Diseases Fund. She received her Bachelor of Science and Doctor of Pharmacy degrees and completed a pharmacy residency at the University of Illinois at Chicago. Dr. Goff serves as an abstract reviewer for the American College of Clinical Pharmacy. She was honored by the OSUMC Leadership Council for Clinical Value Enhancement for developing clinical practice guidelines entitled Community-Acquired Pneumonia in Immunocompetent Adult Patients. She has received over 100 research grants and presented over 200 lectures nationally and internationally. Dr. Goff has published in several scientific journals, including Pharmacotherapy, Current Opinion in Infectious Diseases, Archives of Internal Medicine, and Clinical Infectious Diseases. Dr. Goff is a fellow of the American College of Clinical Pharmacy and a member of the Infectious Diseases Society of America, the American Society for Microbiology, and the Society of Infectious Diseases Pharmacists. Dr. Goff s research interests include antimicrobial resistance, clinical outcomes research, and antifungal agents.

7 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems Debra A. Goff, Pharm.D., FCCP Clinical Associate Professor Infectious Diseases Specialist The Ohio State University Medical Center Columbus, Ohio Outline Impact of antimicrobial resistance Role of antimicrobial stewardship programs Media influence (consumer advocacy groups, newspapers) Examples of antimicrobial stewardship Centers for Medicare & Medicaid Services (CMS) Surgical Care Improvement Project (SCIP) Impact of Antibacterial Resistance In 2004, ~2 million hospital-acquired infections in U.S. hospitals >90,000 deaths 1,2 In-hospital costs of nosocomial infection caused by 6 common resistant bacteria: at least $1.3 billion 3 On October 1, 2008, CMS limited reimbursement for hospital-acquired conditions deemed preventable catheter-associated urinary infections vascular catheter-associated infections mediastinitis after coronary artery bypass graft (CABG) surgery surgical site infections 1. Weinstein RA. Emerg Infect Dis. 1998; 4: Centers for Disease Control and Prevention U.S. Congress, Office of Technology Assessment. Impacts of Antibiotic-Resistant Bacteria. September OTA-H-629.

8 6 Top Resistant Pathogens Infectious Diseases Society of America Hit List Gram-negative pathogens Pseudomonas aeruginosa Extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae Acinetobacter species Gram-positive pathogens Community-associated methicillin-resistant Staphylococcus aureus (MRSA) Penicillin-resistant Streptococcus pneumoniae (also resistant to macrolides) Vancomycin-resistant enterococci (VRE) Infectious Diseases Society of America. Talbot GH et al. Clin Infect Dis. 2006; 42: Hospital Infections: Preventable and Unacceptable $2.5 million awarded by a jury in a medical malpractice suit against a heart surgeon. The patient had a pacemaker surgically implanted and developed MRSA. It was so severe that he had 15 operations, spent 84 days in the hospital, and lost his right leg, part of his left foot, a kidney, and most of his hearing. The medical community can t afford to be complacent. We have the knowledge to prevent infections. What is lacking is the will. McCaughey B. The Wall Street Journal. August 14,

9 New Drugs for Superbugs Oprah O Magazine Oct 2008 Consumer Advocates safecarecampaign.org In 1 year 3 family members in 3 different states in 3 different hospitals had health careacquired (HCA) infections 1 is recovering 1 is well 1 is dead Consumer Advocates Web Site What information is available on your hospital s web site?

10 Why have Antimicrobial Stewardship? Antibiotics are unlike any other drugs in that use of the agent in one patient can compromise its efficacy in another. Anyone can prescribe antibiotics despite a lack of specialized training. Unlike an antihypertensive agent, which benefits only the patient for whom it is prescribed, antimicrobials can impact countless others. Resistant microorganisms can be spread to patients who have never received an antibiotic. You can t catch cancer from the patient next to you. You CAN catch MRSA or many other drug-resistant microorganisms! True/False Question Antimicrobial stewardship programs should include an infectious disease (ID) physician and an ID-trained Pharm.D. OSU Antimicrobial Management Program

11 What if your team looks like this? Infectious Disease Pharm.D. Selling Your Program to Hospital Administration Delineate your BATNA * Use your own hospital data to build your case Prepare for negotiation Talk to the medical staff Remember they must know and trust the steward * Best alternative to negotiating an agreement McQuillen DP et al. Clin Infect Dis. 2008; 47: Ury W. Getting past no:negotiating your way past confrontation to cooperation. New York, NY: Bantam Books; True/False Question The most effective antimicrobial stewardship programs are in large medical centers because resources are more plentiful than in smaller hospitals.

12 Impact of Antibiotic Stewardship Programs Hospital Size Team Members 250 beds MD, Pharm.D., microbiologist, data analyst 120 beds MD, pharmacists, infection control specialist, microbiologist Antimicrobial Cost Outcomes Cost-savings over 18 months $913,236 Antibiotic cost/pt-day decreased $18.21 to $ Saved $177, beds MD, pharmacists Cost/pt-day decreased $18.00 to $14.40 Drug Resistance & Infectious Outcomes Increased cefepime use & decreased 3 rd generation cephalosporin use correlated with decreased resistance Not reported Reduced resistance for several bug-drug pairs 1200 beds 4 ID MDs Saved $322,000 Decreased resistance rates 900 beds MD, Pharm.D., microbiologist Saved $1,841,203 over 3 years Decreased resistance rates McQuillen DP et al. Clin Infect Dis. 2008; 47: Tools to Get Started Practice Guidelines IDSA & Society for Healthcare Epidemiology of America publication Dellit TH et al. Clin Infect Dis. 2007; 44: Owens RC Jr. Diagn Microbiol Infect Dis. 2008; 61: Knowledge of Medicare reimbursement as it relates to antimicrobial stewardship Centers for Medicare & Medicaid Services Surgical Care Improvement Project As of October 2008, Medicare no longer reimburses for hospitalacquired conditions deemed preventable Meet the other team members in your hospital Learn what they do and how they do it Explore existing computer software programs Theradoc, Sentri7, QC Pathfinder What Can the Microbiologist Do? Antibiograms unit-specific and house-wide combination antibiograms Example: P. aeruginosa resistant to cefepime 20% amikacin 100% aztreonam 83% ciprofloxacin 39% tobramycin so cefepime + amikacin best combination Diagnostic tests to help you make better antibiotic decisions -vancomycin MIC for MRSA -rapid (2 hours) Gene Ohm MRSA blood testing -Hodge test to detect carbapenemases Daily culture results from sterile sites Text message multi-drug resistant (MDR) organisms Clonal characterization of resistant strains can help focus appropriate intervention Dellit TH et al. Clin Infect Dis. 2007; 44:

13 What Do Epidemiology and Infection Control Practitioners Do? IC receive daily culture results and list of MDR organisms to identify which patients must be in isolation Both monitor post-op infection rates and benchmark rates against national data Both monitor compliance with surgical prophylaxis guidelines Both track patients with Clostridium difficile infections (CDI) and identify rates of CDI/10,000 patient-days Evidence-Based Strategies for CDI Bundled approach antimicrobial use, infection control, and proper environmental cleaning Curtail use of 3 rd generation cephalosporins In an effort to ensure that antibiotics were given within 4 hours to meet CMS core measures, many patients received antimicrobials unnecessarily Consequently, 50% of patients who received antibiotics for community-acquired pneumonia (CAP) who developed CDI were later found not to have had CAP 1/3 died from their CDI antibiotic Infection control housekeeping Owens RC Jr et al. Clin Infect Dis. 2006; 42(Suppl 4):S Polgreen PM et al. Infect Control Hosp Epidemiol. 2007; 28: Hospitals with Antimicrobial Management Programs: Published Impact on Resistance Rates VRE colonization rates decreased from 47% to 15% Quale J et al. Clin Infect Dis. 1996; 23: ESBL-producing Klebsiella infections 44% hospital-wide decrease Rahal JJ et al. JAMA. 1998; 280: Antibiotic-induced C. difficile infections 50% increase in antibiotics associated with outbreak Muto CA et al. Infect Control Hosp Epidemiol. 2005; 26:

14 Impact of Antibiotic Resistance Infection and Causative Organism Increased Risk of Death (OR) Attributable Length of Stay (days) Attributable Cost ($) MRSA bacteremia ,916 MRSA surgical infection ,901 VRE infection ,766 Resistant Pseudomonas ,981 infection Resistant Enterobacter infection ,379 Total cost of antimicrobial resistance is estimated to be $30 billion annually. Cosgrove SE. Clin Infect Dis. 2006; 42(Suppl 2):S82-9. True/False Question The most challenging gramnegative MDR organisms include P. aeruginosa, Acinetobacter baumanni, K. pneumoniae, & E. coli (ESBLproducing) Extreme Drug Resistance (XDR) gram-negative bacilli XDR ESBL-producing K. pneumoniae mortality rate is 45% to 67% Outbreaks reported in Chicago, Pittsburg, New York City Pathogens in outbreaks are resistant to carbapenems and tigecycline ESBL-producing K. pneumoniae coming from the community has increased at OSUMC OSUMC has 1 effective antibiotic class (carbapenems) % ESBL K. pneumoniae Antibiogram % ESBL-producing Paterson DL et al. Clin Infect Dis. 2007; 45: % ESBL- producing

15 Extreme Drug Resistance (XDR) Acinetobacter baumanni Extensive drug resistance in M. tuberculosis was CNN breaking news XDR Acinetobacter baumanni is documented in several U.S. hospitals Paterson DL et al. Clin Infect Dis. 2007; 45: Antibiotic Imipenem Ampicillin/ sulbactam Piperacillin/ tazobactam Cefepime Ciprofloxacin Amikacin Tigecycline Colistin XDR Colistin Resistance 265 isolates of Acinetobacter from 2 Korean hospitals Forty-eight isolates (18.1%) and 74 isolates (27.9%) were resistant to polymyxin B and colistin, respectively. Ko KS et al. J Antimicrob Chemother. 2007; 60: Surrogate for Serious Infections Caused by MDR Gram-Negative Bacilli Colistin Use at OSUMC Year Cost $2, $23,309 Colistin is only prescribed for MDR organisms when there are no other options.

16 How does an antimicrobial management team actually work together? OSUMC Example 4. ID is consulted, and we discuss options with the surgeon 1. SICU PharmD calls to say he has an XDR Acinetobacter 3. I ask microbiology to set up an Etest to tigecycline Infectious Disease MD Infectious Disease PharmD Microbiologist Infection Control Epidemiologist Information system specialist 2. I call the infection control practitioner 5. Hospital epidemiology tracks the patient s care in our hospital. Schafer JJ et al. Pharmacotherapy. 2007; 27: OSUMC Example 3.Presents declining E.coli susceptibilities to antibiotic subcommittee 4.Presents recommended change to empiric antibiotics for ciai to surgical division 1. Publishes the antibiogram Infectious Disease MD Infectious Disease Pharm.D. Microbiologist Infection Control Epidemiologist Information system specialist 5. Monitors hand hygiene compliance in SICU 2. Presents surgical infection data by surgeon at infection control meeting ciai = complicated intra-abdominal infection

17 Complicated Intra-Abdominal Infections Common Pathogens Facultative & Aerobic Gram-Negatives Escherichia coli Klebsiella spp Pseudomonas aeruginosa Proteus spp Enterobacter spp Other gram-negatives Gram-Positive Organisms Streptococcus spp Enterococcus faecalis Enterococcus faecium Enterococcus spp Staphylococcus aureus 71.3% 14.3% 14.1% 5.2% 5.1% 12.3% 38.0% 11.6% 3.4% 7.8% 3.5% Anaerobic Organisms Bacteroides fragilis Other Bacteroides Clostridium spp Prevotella spp Peptostreptococcus spp Fusobacterium spp Eubacterium spp Others 34.5% 71.0% 29.2% 12.0% 16.7% 8.6% 16.5% 19.4% Incidence of various bacteria in 702 patients with intra-abdominal infections Solomkin J et al. Intra-abdominal infections. In: Schwartz SI et al. Principles of Surgery, 7 th ed. New York, NY: McGraw-Hill; OSUMC SICU and Hospital Antibiogram 2007 Organism Ampicillin/ sulbactam Ertapenem SICU hospital SICU hospital E. coli 42% 45% 100% E. coli 0% 0% 100% ESBL-producing K. pneumoniae 75% 78% 100% K. pneumoniae ESBL-producing 0% 0% 100% Anaerobes Enterococcus Neither ampicillin-sulbactam nor ertapenem covers P. aeruginosa Evidence-Based Surgical Use of Ertapenem Ertapenem is FDA-approved for: Complicated intra-abdominal infections (ciai) Ertapenem 1 g daily vs. piperacillin/tazobactam g every 6 hr 665 patients with perforated/abscessed appendicitis, colonic, small intestine, or biliary infections, and generalized peritonitis Success rates: ertapenem 83.6% vs. 80.4% pip/tazo * Patients with enterococcus treated with ertapenem had outcomes similar and numerically superior to pip/tazo, regardless of susceptibility Solomkin JS et al. Ann Surg. 2003; 237: Prophylaxis for colorectal procedures Ertapenem 1 g vs. cefotetan 2 g Itani K et al. N Engl J Med. 2006; 355:

18 E. coli is the most frequently cultured organism in ciai Review of 2007 OSUMC antibiogram Ertapenem was selected as a therapeutic substitution for ampicillin/sulbactam for surgical patients with community-acquired ciai Background Plan of Action Ampicillin/sulbactam is not an effective empiric option at OSUMC for community-acquired ciai Results presented to the surgical division In collaboration with our surgeons and others, we are developing CPOE antibiotic ordering screens by disease state Each team member contributed different data CPOE screen template The Team Approach to Improving Patient Care Presented rationale for change to the surgeons Provided the new antibiogram data Monitored surgical infection rate by procedure Presented surgical infection rates to committee Developed CPOE screens

19 Pharmacodynamic Dose Optimization Extended infusion pip/tazo, cefepime, meropenem, doripenem Purpose: optimize current antimicrobials Maximize dosing to treat resistant or high MIC organisms Efficacy of pip/tazo extended infusion reduced mortality compared with intermittent infusion in patients with P. aeruginosa infection and APACHE II scores 17 APACHE II = Acute Physiological and Chronic Health Evaluation-II Lodise TP Jr et al. Clin Infect Dis. 2007; 44: Extended-Infusion Dosing Strategy Must get nursing buy-in Lodise TP Jr et al. Clin Infect Dis. 2007; 44: Antimicrobial Stewardship and CMS What s Our Role? Core measures are submitted and available for public viewing on JCAHO and CMS websites JCAHO: CMS: Consumers should be given the opportunity to make informed decisions regarding their health care Hospitals should improve the quality of care they provide

20 New CMS Never Events Catheter-associated urinary infections Mediastinitis after CABG Surgical site infections Air embolism Blood incompatibility Falls Vascular catheter-associated infections Deep vein thrombosis or pulmonary embolism after knee or hip replacement Foreign object retained after surgery Pressure ulcers Complications from poor glucose control What does this mean for the pharmacist? Opportunity! Publicly Reported Core Measures Acute myocardial infarction Heart failure Community-acquired pneumonia Surgical Care Improvement Project (SCIP) Community-Acquired Pneumonia OSUMC

21 SCIP 30 million operations performed annually in the U.S. Surgical site infections (SSI) are among the most common complications: ~500,000 annually Each SSI increases length of stay by ~7 days Patients who develop SSI are 60% more likely to spend time in the ICU are 5 times more likely to be readmitted have twice the mortality Other complications: cardiovascular, respiratory, & thromboembolic Nichols RL. Emerg Infect Dis. 2001; 7: Agency for Healthcare Research and Quality. SCIP Measures CABG & other cardiac surgeries, hip/knee arthroplasties, hysterectomies, colorectal and vascular surgery Prophylactic antibiotics received within 1 hour prior to surgical incision Prophylactic antibiotic selection for surgical patients Prophylactic antibiotics discontinued within 24 hours after surgery end time (48 hours for CABG/cardiac surgery) Surgical Prophylaxis Grid OSUMC

22 Stop Antibiotics Within 24 Hours Stop Antibiotics Within 24 Hours January 2007 through December 2007 Managing Resistance with Antimicrobial Stewardship Programs No hiding in the basement They must know and trust the steward! AMP Advertise & promote your program You re part of a team A successful program means the patient wins

23 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems S E L E C T E D R E F E R E N C E S Agency for Healthcare Research and Quality. Prophylactic antibiotics given to prevent surgical site infections are more timely if given in the operating room. (accessed 2008 Oct 31). Anderson DJ, Kaye KS, Classen D et al. Strategies to prevent surgical site infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008; 29(Suppl 1):S Calfee DP, Salgado CD, Classen D et al. Strategies to prevent transmission of methicillinresistant Staphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol. 2008; 29(Suppl 1):S Centers for Disease Control and Prevention. Campaign to prevent antimicrobial resistance in healthcare settings. (accessed 2008 Oct 31). Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006; 42(Suppl 2):S82-9. 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: Dubberke ER, Gerding DN, Classen D et al. Strategies to prevent Clostridium difficile infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008; 29(Suppl 1):S Infectious Diseases Society of America. IDSA releases hit list of dangerous bugs. March 1, (accessed 2008 Oct 31). Itani KM, Wilson SE, Awad SS et al. Ertapenem versus cefotetan prophylaxis in elective colorectal surgery. N Engl J Med. 2006; 355: Ko KS, Suh JY, Kwon KT et al. High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea. J Antimicrob Chemother. 2007; 60: Landro L. Curbing antibiotic use in war on superbugs. Accessed September 3, Lo E, Nicolle L, Classen D et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008; 29(Suppl 1):S 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; 44: Marschall J, Mermel LA, Classen D et al. Strategies to prevent central line-associated bloodstream infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008; 29(Suppl 1):S McCaughey B. Hospital infections: preventable and unacceptable. Accessed August 14,

24 Implementation of Evidence-based Strategies for Managing Antimicrobial Resistance in Health Systems McQuillen DP, Petrak RM, Wasserman RB et al. The value of infectious diseases specialists: non-patient care activities. Clin Infect Dis. 2008; 47: Muto CA, Pokrywka M, Shutt K et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005; 26: Nichols RL. Preventing surgical site infections: a surgeon s perspective. Emerg Infect Dis. 2001; 7: Owens RC Jr, Rice L. Hospital-based strategies for combating resistance. Clin Infect Dis. 2006; 42(Suppl 4):S Owens RC Jr. Antimicrobial stewardship: concepts and strategies in the 21st century. Diagn Microbiol Infect Dis. 2008; 61: Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis. 2007; 45: Polgreen PM, Chen YY, Cavanaugh JE et al. An outbreak of severe Clostridium difficileassociated disease possibly related to inappropriate antimicrobial therapy for communityacquired pneumonia. Infect Control Hosp Epidemiol. 2007; 28: Rahal JJ, Urban C, Horn D et al. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA. 1998; 280: Schafer JJ, Goff DA, Stevenson KB et al. Early experience with tigecycline for ventilatorassociated pneumonia and bacteremia caused by multidrug-resistant Acinetobacter baumannii. Pharmacotherapy. 2007; 27: Solomkin J et al. Intra-abdominal infections. In: Schwartz SI, Shires GT, Spencer FC et al, eds. Principles of surgery, 7th ed. New York, NY: McGraw-Hill Book Co., Solomkin JS, Yellin AE, Rotstein OD et al. Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial. Ann Surg. 2003; 237: Talbot GH, Bradley J, Edwards JE Jr et al. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006; 42: Ury W. Getting past no: negotiating your way past confrontation to cooperation. New York, NY: Bantam Books; U.S. Congress, Office of Technology Assessment. Impacts of antibiotic-resistant bacteria. Washington, D.C.:U.S. Government Printing Office; September OTA-H-629. Weinstein RA. Nosocomial infection update. Emerg Infect Dis. 1998; 4: