Antimicrobial Stewardship: Response to a Global Crisis Carla Walraven, PharmD, BCPS-AQ ID University of New Mexico Hospital Antimicrobial Stewardship Program
Pharmacist Objectives Explain the implications of antimicrobial resistance Prepare for the new regulatory standards for Antimicrobial Stewardship Programs (ASPs) Outline strategies employed by ASPs to improve outcomes Identify opportunities to apply Antimicrobial Stewardship concepts
Pharmacy Technician Objectives Identify ways in which antibiotics are misused Explain the implications of antimicrobial resistance Recognize the core elements of Antimicrobial Stewardship Programs
Audience Poll A 19 YOM is brought to your ED after an accident cleaning his homemade shotgun, resulting in a penetrating eye socket injury with a metal pipe. How many would recommend antibiotics? Which antibiotics would you use? (What pathogens are you concerned about?)
The Curious Case of Phineas Gage (July 9, 1823 May 21, 1860) In 1848, Phineas Gage was struck by a tamping iron while working on the railroad He survived the accident, but was not the same afterwards Died at the age of 36, after a series of seizures http://www.smithsonianmag.com/history/phineas-gage-neurosciences-most-famous-patient-11390067/?no-ist
Fast Forward to 2016 61 YOM newly diagnosed AML Antibiotic exposure: Cetriaxone, clindamycin x 14 days (shin injury) Vancomycin (cellulitis) Augmentin and ciprofloxain (prophylaxis) Febrile neutropenia 16 days after admission Blood cultures grew an Extended spectrum β- lactamase (ESBL) E. coli ESBL E. coli MIC Amikacin 16 Susceptible Aztreonam > 16 Resistant Ciprofloxacin > 2 Resistant Ceftriaxone > 32 Resistant Cefazolin > 16 Resistant Ertapenem > 1 Resistant Gentamicin > 8 Resistant Meropenem 4 Resistant Ampicillin/sulbac > 16/8 Resistant Piperacillin/tazo > 64/4 Resistant Sulfameth/trimeth > 2/38 Resistant
Going Back to a Pre-Antibiotic Era? Antibiotic resistance has been called one of the world s most pressing public health concerns Antibiotic resistance is associated with increased lengths of hospital stay, increased costs, and increased mortality https://www.cdc.gov/drugresistance/about.html
30-50% of antimicrobial use is either unnecessary or inappropriate. % of Patients with Unnecessary DOT 35% 30% 25% 20% 15% 10% 5% 0% Most Common Reasons for Unnecessary Therapy Noninfectious Syndrome Tx of Colonization or Contamination Duration of tx Longer than Necessary N = 576 DOT Redundant Abx Coverage Reimann HA, D Ambola J. JAMA. 1968;205(7):537. Hecker MT, et al. Arch Intern Med. 2003;163:972-78.
Antibiotic Misuse Antibiotics are given when they are not needed Antibiotics are continued longer than necessary Antibiotics are given at the wrong dose Broad spectrum antibiotics are used to treat highly susceptible bacteria The wrong antibiotic is used to treat an infection http://www.cdc.gov/getsmart/healthcare/evidence.html
Antibiotic Prescribing Trends in US Hospitals, 2006-2012 2006-2012 Baggs J, et al. JAMA Intern Med. doi:10.1001/jamainternmed.2016.5651
Piperacillin/tazobactam Resistant Pseudomonas aeruginosa http://gis.cdc.gov/grasp/psa/mapview.html, Accessed Aug 2016.
National Action Plan for Combating Antibiotic-Resistant Bacteria 5 Goals Slow the emergence and spread of resistant bacteria Includes the implementation of antimicrobial stewardship programs Strengthen national surveillance efforts of resistant bacteria Advance development and use of rapid diagnostic tests Accelerate research and development of new antibiotics, therapeutics, and vaccines Improve international collaborations regarding antimicrobial use and misuse https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf, Accessed Aug 2016.
What is Antimicrobial Stewardship? Coordinated program that promotes the appropriate use of antimicrobials, improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multi-drug resistant organisms. Barlam TF, et al. Clin Infect Dis. 2016; e1-e27. http://www.apic.org/professional-practice/practice-resources/antimicrobial-stewardship
CDC s Core Elements for ASPs Obtain leadership commitment Includes dedicating necessary human, financial and information technology resources Appoint a single leader responsible for program outcomes Appoint a single pharmacist leader responsible for working to improve antibiotic use Obtain support from key stakeholder Infection control and prevention Information technology Quality improvement Clinicians http://www.ahaphysicianforum.org/resources/appropriate-use/antimicrobial/content%20files%20pdf/cdc%20checklist.pdf
CDC s Core Elements for ASPs (cont.) Implement policies and interventions to improve antibiotic use Evaluate ongoing treatment need after an initial treatment period E.g. Antibiotic timeout after 48 hours Monitor antibiotic prescribing and resistance patterns Regularly report information on antibiotic use and resistance to doctors, nurses, and relevant staff Educate clinicians about resistance and optimal prescribing
CMS 482.42(b): Antibiotic Stewardship Program Organization and Policies Effective January 1, 2017 Demonstrate coordination among all components of the hospital responsible for antibiotic use and factors that lead to antimicrobial resistance Document the evidence-based use of antibiotics in all departments and services of the hospital Demonstrate improvements, including sustained improvements in proper antibiotic use https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-13925.pdf
TJC s New Antimicrobial Stewardship Standard Effective January 1, 2017 Download available at: https://www.jointcommission.org /standards_information/prepublic ation_standards.aspx
Antimicrobial Stewardship Team Hospital Admin Infection Control Microbiology ASP Physician Pharmacist Infectious Diseases Informatics Pharmacy
ASP Interventions ASP Activities Patient Centered Prospective audit and review Formulary management Identify patients who may benefit from ID consult Impact of Interventions Goal: Decrease or slow antimicrobial resistance National Institutional Antibiograms Clinical pathways Dose optimization Institution Patient Global
ASP Core Strategies Core Strategies Prospective audit with direct intervention and feedback Advantages Formulary restriction and preauthorization requirements Disadvantages May reduce inappropriate antimicrobial use Educate to modify future prescribing Allows prescribers to maintain autonomy Difficulty identifying patients with inappropriate therapy and communicating with prescribers May result in immediate and substantial reduction in antimicrobial use and costs May increase staffing requirements May delay order implementation with potential adverse patient outcomes May increase use of and resistance to alternative antimicrobial agents Perceived loss of prescriber autonomy Dellit et al. Clin Infect Dis. 2007;44:159-77. Drew et al. Pharmacotherapy. 2009;29:593-607.
ASP Supplemental Strategies Supplemental Elements Advantages Disadvantages Education May influence prescribing behavior Marginally effective when used without active intervention Evidence based guidelines and clinical pathways May improve antimicrobial use and practice variations Poor adherence Streamlining or de-escalation therapy Reduces antimicrobial exposure, selection of resistant pathogens, and health care costs Prescriber reluctance to deescalate when cultures are negative and clinical improvement observed Dose optimization Tailors therapy to patient characteristics, pathogen, and PK/PD of antimicrobial Nursing concerns regarding incompatibilities and administration IV to PO conversion May decrease length of hospital stay and costs May reduce complications associated with IV access Difficulty identifying patients in whom conversion is appropriate Dellit et al. Clin Infect Dis. 2007;44:159-77. Drew et al. Pharmacotherapy. 2009;29:593-607.
Implementing Antimicrobial Stewardship PATIENT CASE
Healthcare-Associated Pneumonia 49 YOF with history of severe COPD is admitted from a skilled nursing facility for respiratory distress and acute disorientation (per family) Increased cough with sputum production over the past 24h No fevers or chills Diagnosis: Acute hypoxic respiratory failure due to healthcare-associated pneumonia (HCAP)/aspiration with sepsis
HCAP Physical Exam General: Obese female, respiratory distress, alert/responsive ENT: no nasal discharge Respiratory: Bilateral rhonchi, crackles in right upper & middle lobes, intermittent expiratory wheeze Vitals & Labs T 37.6 C, HR 123, BP 151/73, RR 21, O2 91% WBC 24.4 Lactate 1.8 No medication allergies Patient is started empirically on vancomycin and piperacillin/tazobactam
Antimicrobial Timeout As soon as possible, or within 48 hours: 1. Does the patient have an infection that will respond to antibiotics? 2. If so, is the patient on the right antibiotic(s), dose, and route of administration? 3. Can a more targeted antibiotic be used to treat the infection (de-escalate)? 4. How long should the patient receive the antibiotic(s)? http://pqc-usa.org/timeout/
Incorporating Culture Results True Bacteremias N TTP at 24 h TTP at 48 h TTP at 72 h Gram positives MRSA MSSA S. pneumonia E. faecalis E. faecium 52 41 6 30 19 85% 93% 100% 87% 89% 98% 98% 100% 97% 100% 98% 100% 100% 100% 100% Gram negatives E. coli Klebsiella spp. Pseudomonas spp. Acinetobacter spp. 161 62 30 22 8 88% 97% 97% 82% 100% 98% 100% 100% 100% 100% 99% 100% 100% 100% 100% Anaerobic 23 39% 74% 91% All Contaminants 210 48% 85% 92% TTP = Time to Positivity Pardo J, et al. Ann Pharmacother. 2014; 48(1):33-40.
Impact of Prior Antibiotics on Cultures Positive by 48 hours Positive by 72 hours Off Antibiotics On Antibiotics P-value Off Antibiotics On Antibiotics P-value Gram positives (n = 232) 183 / 186 (98%) 44 / 46 (96%) 0.258 183 / 186 (98%) 46 / 46 (100%) >0.99 Gram negatives (n = 161) 137 / 139 (99%) 20 / 22 (91%) 0.09 138 / 139 (99%) 21 / 22 (95%) 0.255 Anaerobes (n = 23) 15 / 19 (79%) 2/4 (50%) 0.270 18 / 19 (95%) 3/4 (75%) 0.324 All episodes (n = 416) 335 / 344 (97%) 66 / 72 (92%) 0.03 339 / 344 (99%) 70 / 72 (97%) 0.348 Pardo J, et al. Ann Pharmacother. 2014; 48(1):33-40.
Using Surveillance Cultures Association between MRSA nasal swab results and the presence of MRSA pneumonia Nasal colonization is a risk factor for infection Results within a few hours MRSA PCR assay N = 435 Sensitivity 88% Specificity 90.1% Positive predictive value 35.4% Negative predictive value 99.2% Dangerfield B, et al. Antimicrob Agents Chemother. 2014; 58(2):859-64.
Utility of Negative Culture Results Early antibiotic discontinuation with negative cultures Early Discontinuation (n = 40) Late Discontinuation (n = 49) P-value 10 (25%) 15 (30.6%) 0.642 4 4 0.523 Signs/symptoms Abnormal temp Abnormal WBC Sputum purulence 15 (48.4%) 20 (69%) 24 (66.7%) 21 (61.8%) 23 (65.7%) 34 (80.9%) 0.324 1.00 0.196 Superinfection Bacteremia Respiratory infection MDR Superinfection 9 (22.5%) 1 (2.5%) 4 (10%) 3 (7.5%) 18 (42.9%) 3 (7.1%) 12 (28.6%) 15 (35.7%) 0.008 0.616 0.036 0.003 Hospital mortality Clinical Pulmonary Infection Score, median Raman K, et al. Crit Care Med. 2013; 41(7): 1656-63.
How Long to Treat? Comparison of 8 vs. 15 Days Antibiotic duration for VAP Primary outcome: death, 28 days after VAP onset Prospective, randomized double-blind, clinical trial 51 French ICUs May 1999 to June 2002 Adults meeting clinical criteria for VAP Chastre J, et al. JAMA. 2003; 290(19):2588-2598. 60-Day VAP Mortality
Stewardship Recommendations Clinical Status & Culture Results T 36.7 C, RR 18, HR 98, BP 128/62, O2 95% on 3L NC WBC 18.7 MRSA nares negative Urine S. pneumoniae antigen negative Blood cultures x 2 sets: no growth Now What? MRSA nares has > 99% negative predictive value Discontinue vancomycin Do we need Pseudomonal coverage? Consider de-escalating piperacillin/tazobactam IV to PO if possible Duration: 7 days
DO YOU REALLY NEED DEDICATED STEWARDSHIP PERSONNEL?
Lessons Learned from one ASP University of Maryland Medical Center (UMMC) 725 bed medical facility in Baltimore, MD 175 ICU beds Active cancer, transplant, and trauma centers Stewardship program started in 2001 to help contain increasing drug costs Goal: To save 10-20% the cost of antibiotics over a 3-year period Standiford HC, et al. Infect Control Hosp Epidemiol. 2012: 33(4):338-45.
UMMC ASP Program ASP Duties ID Physician, 0.5 FTE ID Pharmacist, 0.8 FTE Data Analyst, 0.05 FTE Disbanded in 2008 Use resources to increase the number of ID physicians Standiford HC, et al., Infect Control Hosp Epidemiol. 2012, 33(4):338-45. Duties - Identify ineffective or excessive antibiotic coverage - Ensure adherence to hospital policies and guidelines - Identify opportunities for IV to PO conversions - Suggest ID consult in complex cases - Review restricted antibiotics - Review patients not serviced by the ID physicians (e.g. the trauma center)
Before, During and After UMMC ASP Antimicrobial Costs by Quarter, FY 98 FY 10
Post-ASP Conclusions Despite unchanged quality markers, antimicrobial costs continued to increase (by 41.2%) in the 2 years after the ASP ended suggesting that more and more costly antibiotics were being used without an increase in benefit. Average Cost Savings: $500K per year (2001 2008) Average Cost Increase: $1 million per year (2009 2010)
Differing ASP Models Evaluation of two Department of Veterans Affairs Hospitals Similar range of services available ID consultation available at all times Inpatient rehabilitation facilities Antimicrobial stewardship efforts at both with active ID physician participation Dedicated ASP Model 312 beds Average daily census: 230 ID pharmacist rounds daily with the ID team 2011 to 2012 Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483. Geographic ASP Model 137 beds Average daily census: 103 4 ward PharmDs round daily with their respective teams 2010 to 2011
Primary Endpoint Composite of compliance with the all of the following: Therapy modification within 24 hours of laboratory data Discontinuation of therapy when determined to be non-bacterial Intravenous to oral (IV to PO) conversion when appropriate Policies and guidelines based on the Department of Veterans Affairs (VA) National Formulary and VA Pharmacy Benefits Management group Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.
Antimicrobial Stewardship Activities Dedicated ASP Geographic ASP P-value 37/48 (77.1%) 11/33 (33.3%) 0.0002 Therapy modification based on laboratory data 143/190 (75.2%) 51/100 (51%) < 0.0001 Therapy modification within 24 hours of laboratory data 124/143 (86.7%) 37/51 (72.6%) 0.029 IV to PO conversion when appropriate 97/120 (80.8%) 41/67 (61.2%) 0.0052 All of the above streamlining activities 165/182 (90.7%) 47/95 (49.5%) < 0.0001 Discontinuation of therapy when not bacterial Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.
Conclusions An ASP with a dedicated pharmacist was associated with better adherence to stewardship activities There was a higher rate of adherence to stewardship activities even when ID was consulted Benefit of having both ID consult and an ASP with dedicated personnel Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.
HOW CAN ONE PHARMACIST OVERSEE ALL ANTIMICROBIAL USE?
Using Clinical Pathways Concise summary of national guidelines Includes local susceptibility recommendations Contains key educational points Goal is to capture 80% of patients with a particular disease state
the strength of the Pack is the Wolf, and the strength of the Wolf is the Pack. Mean ± SD Expenditure Cost Savings Baseline Intervention Daily Yearly Ceftazidime $115 ± $47 $80 ± $27 $35 $12,775 Imipenem $299 ± $84 $232 ± $112 $67 $24,455 Levofloxacin $497 ± $35 $448 ± $31 $49 $17,885 Piperacillin/tazo $2,110 ± $134 $2,037 ± $11 $73 $26,645 Vancomycin $1,221 ± $79 $1,008 ± $9 $213 $77,745 Extrapolated savings based on cost data during intervention period Grady Memorial Hospital in Atlanta, GA Prospective audit with intervention and feedback of non-icu patients Mortality, LOS, and re-admissions were similar for both periods Emergence of resistance decreased from 9.5% to 5% (P = 0.06) DiazGranados CA, et al. Am J Health-Syst Pharm. 2011;68:1691-2.
WE DON T HAVE ANY INFECTIOUS DISEASE TRAINED SPECIALISTS
Stewardship Training Programs Making a Difference in Infectious Diseases (MAD-ID) Society of Infectious Disease Pharmacists (SIDP) Basic program Advanced program 19 contact hours (1.9 CEUs) each http://madid.org/antimicrobialstewardship-programs/ Partnered with ProCE info@proce.com Offers up to 43 contact hours (4.3 CEUs) http://www.sidp.org/stewa rdship-program
Additional Resources STEWARDSHIP-EDUCATION.org Collaborative project between SHEA, IDSA, PIDS, NFID, MAD-ID, SIDP, and ASHP APIC s Stewardship Toolkit http://www.apic.org/professional-practice/practiceresources/antimicrobial-stewardship CDC s Get Smart Campaign http://www.cdc.gov/getsmart/ Checklist for Core Elements of Hospital Antibiotic Stewardship Programs
Summary Antibiotics are a communal but scarce resource Reducing unnecessary antibiotic use can decrease antibiotic resistance Starting in 2017, TJC and CMS will mandate all hospitals have ASPs Successful ASPs impact the patient, the institution, and hopefully beyond
Questions? Contact Info: Carla Walraven, PharmD, BCPS-AQ ID University of New Mexico Hospital 2211 Lomas Blvd NE Pharmacy Department, 4ACC North Albuquerque, NM 87106 (505) 272-4669 cwalraven@salud.unm.edu