ANTIBIOTICS IN THE ER:

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ANTIBIOTICS IN THE ER: EXPLORING THE ROLE OF ANTIMICROBIAL STEWARDSHIP IN THE EMERGENCY DEPARTMENT ANGELINA DAVIS, PHARMD, MS, BCPS (AQ-ID) LIAISON CLINICAL PHARMACIST DUKE ANTIMICROBIAL STEWARDSHIP OUTREACH NETWORK dason.medicine.duke.edu

Financial Disclosures There are no financial disclosures

Objectives Review trends in antimicrobial prescribing in the emergency department (ED) and consider the opportunity for optimization of patient care through antimicrobial stewardship Discuss challenges to implementation of antimicrobial stewardship efforts in the ED Identify key strategies for antimicrobial stewardship in the ED to optimize patient care, reduce the risk for antibiotic resistance and decrease healthcare costs Explore the potential role of rapid diagnostics in the ED for optimization of antimicrobial prescribing

Antibiotic resistance costs an estimated $20 billion annually to the U.S. healthcare system and increases patient hospital stays by more than eight million days. -Infectious Diseases Society of America

Antibiotic Resistance Threats in the United States, 2013 http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf#page=11

Four Core Actions to Prevent Antibiotic Resistance 1. Preventing infections, preventing the spread of resistance 2. Tracking 3. Improving antibiotic prescribing/stewardship 4. Developing new dugs and diagnostic tests http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf#page=11

Clinical Outcomes: ASP versus Usual Practice Fishman N. Antimicrobial stewardship. Am J Med 2006;119(6) Suppl 1:S53 S61 7

Infection Rates Pre- and Post- Implementation of an ASP C. DIFFICILE RESISTANT ENTEROBACTERIACEAE Carling P et al. Infect Control Hosp Epidemiol. 2003;24(9):699-706.

Expanding ASPs Beyond the Inpatient Setting To date, ASPs have primarily targeted the inpatient acute care setting ~136 million ED visits occur annually in the U.S. ~16.2 million visits result in hospital admission An interface between the inpatient and community settings The ED represents a critical setting for initiating interventions that can reduce inappropriate antibiotic prescribing www.cdc.gov/nchs/fastats/emergency-department.htm May L, et al. Annals of Emergency Medicine 2013; 62 (1): 69-77

The ED as a Target for ASPs ED practitioners are optimally positioned to determine appropriate empiric antimicrobial therapy Initial prescribing in the ED has the ability to impact the care continuum (i.e. admission, observation, discharge) Antimicrobial overprescribing in the ED can cause collateral damage downstream Adverse drug events (ADEs) Hypersensitivity/allergy Side effects Clostridium difficile infection Antimicrobial resistance Increased health-care costs

Antimicrobial Prescribing in the ED Leading infection related primary diagnosis groups: Acute upper respiratory infections (URIs), excluding pharyngitis Cellulitis and abscess Urinary tract infection (UTI), site not specified Otitis media and eustachian tube disorders ED trends in antibiotic overprescribing ~48% of patients with antibiotic inappropriate URI received antibiotics >40% of visits for UTI included broad-spectrum fluoroquinolones Unnecessary use of antibiotics with broad gram-negative and/or anaerobic coverage frequency observed for cellulitis or abscess 2011 National Hospital Ambulatory Medical Care Survey (NHAMCS), https://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2011_ed_web_tables.pdf Donnelly JP, et al. Antimicrob Agents Chemther. 2014; 58 (3): 1451 1457 May L, et al. Acad Emerg Med. 2014; 21 (1): 17 24 Jenkins TC, et al. Clin Infect Dis. 2010; 51 (8): 895-903

Antimicrobial Prescribing in the ED

ED Visits for Antibiotic ADEs Over 142,000 visits annually in the US for antibiotic-related ADEs Antibiotics implicated in 19% of all ED visits for drug-related ADEs Allergic reaction was the most common antibiotic-related ADE (79%) Shehab N, et al. CID 2008; 47: 735-743

Challenges to AS in the ED High patient turnover High physician turnover Diagnostic uncertainty Rapid decision-making Automated dispensing National health care quality benchmarks (i.e. CMS Core Measures) Lack of patient follow up

ASP Implementation in the ED Successful implementation highly dependent on involvement of ED and administrative leadership Requires a collective and multi-disciplinary effort AS Physician Champion AS Pharmacy Champion and/or ED Pharmacist (EPh) ED Antibiotic Stewardship Champion Microbiology Information Technology Antimicrobial stewardship interventions must be applied to commonly encountered ED scenarios

AS Interventions in the ED Education Post-prescription review Streamlining/De-escalation Dose optimization Shortening duration of therapy ED antibiogram development Guidelines and clinical pathways Focused order sets Clinical decision support Rapid diagnostic testing

Pharmacist-Managed ASP for Patients Discharged from the ED Study Design: A retrospective case-control study of 212 patients >18 years old who were discharged from the ED with subsequent positive cultures Pre-implementation (November 2007 - January 2008) vs. post-implementation of an EPh-managed program (November 2008 - January 2009) Conducted at a university teaching hospital with over 97,000 ED visits per year Intervention: EPh involvement included education regarding appropriate empiric antibiotic selection and assistance with follow up Education involved didactic lectures and preparation of clinical resources for use when EPh unavailable Outcomes: Primary: time to positive culture review and time to patient or PCP notification Secondary: appropriateness of antimicrobial therapy Baker SN, et al. Journal of Pharmacy Practice; 25: 190-194

Post-Implementation Culture and Susceptibility Follow Up Process Step #1: Night-shift MLP separates positive and negative culture results Step #2: Night-shift MLP obtains patient charts for those with positive culture results Step #3: Positive culture results and charts assessed by the EPh between 1100 and 1500 Step #4:Antimicorbial changes based on EPh assessment are relayed to patient, PCP, or patient s pharmacy (issues are discussed with the dayshift MLP as needed) Weekend culture review was performed by the midlevel provider (MLP) as the EPh does not provide clinical services during this time. Baker SN, et al. Journal of Pharmacy Practice; 25: 190-194

Results Note: Discontinuation of unnecessary antimicrobials or optimization of therapy when broad-spectrum agents were not necessary was not addressed

The Impact of AS Intervention on UTI Treatment in the ED Study Design: A quasi-experimental study comparing two separate periods before and after intervention 439-bed tertiary-care teaching center with > 57,000 ED visits annually Patients aged 12 to 70 years old, discharged home from the ED with an uncomplicated UTI, and received an antibiotic prescription Interventions: ED-specific antibiogram Institution-specific recommendations for empiric treatment of uncomplicated UTIs Education of resident physicians and ED providers Outcomes: Primary: Adherence to recommendations for the treatment of uncomplicated UTIs based on local resistance rates Secondary: Agreement between empiric antibiotics prescribed and isolated pathogen susceptibilities Reevaluation in the ED or hospital admission for a UTI within 30 days Percival KM, et al. American Journal of Emergency Medicine. 2015; 33: 1129-1133

Empiric Treatment for UTI Percival KM, et al. American Journal of Emergency Medicine. 2015; 33: 1129-1133

Results of Adherence Recommendations Percival KM, et al. American Journal of Emergency Medicine. 2015; 33: 1129-1133

Secondary Outcomes and Antibiotics Prescribed at Discharge Secondary Outcomes: Prescribed antibiotic was susceptible to the isolated pathogen more often in cystitis after education (74% vs 89%, P = 0.05) but not in pyelonephritis patients (90% vs 76%, P = 0.23) Rate of patients seeking follow-up care for a UTI at the institution within 30 days was unchanged at 4.6% compared with 7.4% (P = 0.27) Percival KM, et al. American Journal of Emergency Medicine. 2015; 33: 1129-1133

Effect of an Electronic Order Set on Guideline Adherence in UTI Study Design: Before and after study at an academic urban level 1 trauma center with >90,000 visits annually Women age 18 65 with UTI and no structural or functional abnormalities of the urinary system seen in the ED during twelve specified months over a 3 year time period (2010 2012) Interventions: Electronic order set (period 1) Audit and feedback (period 2) Additional interventions: Educational lecture and pre-existing policy providing small financial incentive based on compliance with quality indicators Outcomes: Primary Overall adherence to guidelines (medication choice and duration of therapy) Secondary Total and unnecessary days of antibiotic therapy for UTI Use of fluoroquinolones for uncomplicated cystitis Treatment failure Adverse events Diagnostic accuracy http://dx.doi.org/10.1371/journal.pone.0087899

Electronic UTI Order Set http://dx.doi.org/10.1371/journal.pone.0087899

Audit and Feedback Pharmacist reviewed cases daily and discussed them with an ID physician ~1.5 3 hours of pharmacist time ~30 minutes of ID physician time Feedback given to providers via staff messages in the EMR within 5 7 days of the ED visit for the following: Recommended UTI medication choice or duration of therapy not used Urine cultures not sent in cases of suspected pyelonephritis UTI diagnosis determined unlikely or rejected

Results Overall Adherence http://dx.doi.org/10.1371/journal.pone.0087899

Results Secondary Outcomes http://dx.doi.org/10.1371/journal.pone.0087899

Percentage of Cases Deemed Unlikely or Rejected http://dx.doi.org/10.1371/journal.pone.0087899

Clinical Decision Support in the ED Use of health information technology to deliver information to the clinician at the point of care Effective in reducing antibiotic use in other clinical settings (i.e. ICU, outpatient) Limitations: Lack of information technology infrastructure Need for streamlined clinical decision support Cost

The Role of Rapid Diagnostics Standard techniques for identification of organisms are based on phenotypic methods (48 72 hrs) Rapid diagnostics are considered game changers Provide organism identification within hours of growth Speed up the diagnostic process Guide antimicrobial selection and treatment duration Rapid molecular methods commercially available Polymerase chain reaction (PCR) Multiplex PCR Nanoparticle probe technology (Nucleic acid extraction and PCR amplification) Peptide nucleic acid fluorescent in situ hybridization (PNA FISH) Matrix-assisted laser desorption/ionization time-of-flight mass spectometry (MALDI-TOF MS) Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Rapid Molecular Testing for S. aureus vs. Standard of Care for Patients with Cutaneous Abscesses in the ED Study Design: Prospective, randomized controlled trial comparing multiplex PCR with standard of care culture-based testing Patients 18 years years old presenting with a chief complaint of abscess, cellulitis, or insect bite and receiving incision and drainage Enrolled 252 patients presenting to two urban, academic EDs from April 1, 2011 through April 30, 2014 Outcomes: Primary: Antibiotic selection (anti-mrsa, beta-lactam, or no antibiotic therapy) stratified by detection of MRSA or MSSA Secondary: Clinical outcomes (1 week, 1 month and 3 months) Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Clinical Actions Based on Rapid Test Results Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Results No decrease in overall antibiotic use observed No significant differences found in 1-week or 3- month outcomes Mean turnaround time for molecular testing was 82 minutes Availability of rapid molecular test results was associated with more-targeted antibiotic selection Bauer KA, et al. CID 2014; 59 (S3): S134 S145

Summary Expansion of AS efforts to the ED has the ability to impact the care continuum Although potential barriers to implementation exist, successful implementation can be achieved with multidisciplinary involvement including ED and administrative leadership Several general AS strategies can be effectively applied to the ED setting to improve antimicrobial use Rapid diagnostics offer timely identification which can further optimize antimicrobial prescribing

Questions? Email: angelina.davis@duke.edu

Question 1 The emergency department (ED) presents an opportunity for creative antimicrobial stewardship interventions to affect change across the care continuum. a) True b) False 39

Question #2 Rapid diagnostics that can be utilized to guide antimicrobial prescribing in the ED include which of the following? a) BioFire FilmArray b) BD Phoenix c) Cepheid Xpert d) a and b e) a and c f) all of the above 40

Question #3 Potential barriers for successful implementation of antimicrobial stewardship in the ED include which of the following? a) High patient turnover b) High physician turnover c) Rapid decision making d) a and b e) a and c f) all of the above 41