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Antimicrobial Stewardship in the ED: 2019 Hot Topics and Literature Updates

Antimicrobial Stewardship in the ED: 2019 Hot Topics and Literature Updates. Bobby Redwood MD, MPH, FACEP Association for Professionals in Infection Control and Epidemiology Spring Educational Meeting (Madison DOC) Tuesday March 12 th , 2019. Aims and Outline.

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Antimicrobial Stewardship in the ED: 2019 Hot Topics and Literature Updates

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  1. Antimicrobial Stewardship in the ED:2019 Hot Topics and Literature Updates Bobby Redwood MD, MPH, FACEP Association for Professionals in Infection Control and Epidemiology Spring Educational Meeting (Madison DOC) Tuesday March 12th, 2019

  2. Aims and Outline • Review core topics in ED Antimicrobial Stewardship • 5 ways to use fewer antibiotics in the ED • 3 ways to improve ED antibiotic choices • Review top 5 articles on ED AMS in 2018-2019 • Open forum for questions • Deep dive on AMS in Sepsis if we have time

  3. Core Principles of AMS • Antimicrobials exert selective pressure on pathogens • Top 3: Meat industry, vets, human medicine • Worldwide: 700,000 annual deaths attributable to nosocomial-resistant organisms • US: 2,049,442 illnesses and 23,000 deaths / yr • Sequelae of AMR costs the US $21-$34 billion with 8 million additional patient-days in the hospital • Right dx, right drug, right dose, right duration

  4. Oh…and there’s this • 1980’s: 16 new abx • 1990’s: 10 new abx • 2000’s: 5 new abx • 2008-2012: 1 new abx • Only 5 of 572 pharmaceutical companies have active antibacterial discovery programs http://www.who.int/bulletin/volumes/89/2/11-030211/en/

  5. Oh…and then there’s this Superbug resistant to every antibiotic available in US kills Nevada woman January 13, 2017 “It was tested against everything that’s available in the United States… and was not effective” Dr Alexander Kallen, a medical officer with the CDC who first reported the discovery of the superbug http://www.pbs.org/newshour/rundown/superbug-resistant-every-available-antibiotic-u-s-kills-nevada-woman/

  6. What is antibiotic overuse? • Abx when a viral pathogen is known/suspected (except critical care) • Abx that is unlikely to be effective against the suspected pathogen • An overly broad spectrum abx for the suspected pathogen • Double-coverage abx when single-coverage is recommended • Abx for longer/higher dose than the literature reccs • Abx for infection prophylaxis without sufficient evidence Shallcross LJ, Davies DSC. Antibiotic overuse: a key driver of antimicrobial resistance. The British Journal of General Practice. 2014;64(629):604-605.

  7. ED Antimicrobial StewardshipCore Curriculum 5 key opportunities to not use antibiotic in the first place

  8. Acute Bacterial Rhinosynovitis • 99% Viral • Treat with abx if: • 10 days of cough w/o improvement • Severe facial pain and fever for 3-4 days • URI with congestion then “doubling” of symptoms • 80% are hemophilus or Strep Pamox BID 10d (7d?) Boisselle C, Rowland K. Rethinking antibiotics for sinusitis—again. Mounsey A, ed. The Journal of Family Practice. 2012;61(10):610-612.

  9. Acute Otitis Media • 60% of true AOMs resolve in 24h w/o tx • Know the high yield symptoms • Parental dx (low spec) • Erythematous TM (low spec) • Pain (low spec) • Bulging TM • Purulence • Air fluid levels • Opaque TM • Loss of light reflex • Loss of bony landmarks • Immobility on pneumatic otoscopy Lieberthal, Allan S., et al. "The diagnosis and management of acute otitis media." Pediatrics 131.3 (2013): e964-e999.

  10. Asymptomatic Bacteriuria • an isolation of bacteria in an appropriately collected urine sample from an individual without signs or symptoms referable to a urinary infection • 80% discordance between recommended practices and actual practices • Hall pass • Once in first trimester • Pre urologic procedure • Post renal transplant Nicolle LE et al. Clin Infect Dis.2005;40(5):643-654.

  11. Pulpal, periapical, & gingival pain • Waste-basket diagnoses like “Dental infection” or “Dental abscess” are misleading and push providers towards unnecessary abx. • Patient expectations are high • When to treat with abx: • drainage is not possible AND there is evidence of spreading infection (PCN) Cope A, et al. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database Syst Rev. 2014; 6.

  12. Group A Strep Pharyngitis • Non-invasive bacterial infection of the pharyngeal epithelial cells (usually S Pyogenes) • Improves w/o treatment in 3-4 days, abx reduce length of symptoms by 16 hours • 0.03% get a PTA • 0.00045% get Rheum fever • Modified CENTOR criteria Aalbers J, et al. Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score. BMC Med. 2011;9:67.

  13. ED Antimicrobial StewardshipCore Curriculum 3 key opportunities to make better antibiotic choices

  14. Azithromycin for CAP in the Midwest? Outdated Practice Best Practice (1st) Doxy 100mg BID (2nd) Levofloxacin 750mg Q24 or Moxifloxacin 400mg Q24 (3rd) Amox 1g Q8 + Z-pack Azithromycin pack alone only if resistance rates are <25% (i.e. nowhere in the US) • Azithromycin pack alone for CAP • Azithromycin pack for COPD exacerbation w/o evidence of PNA or positive PCT • Azithromycin pack for bronchitis Treatment of community-acquired pneumonia in adults in the outpatient setting - UpToDate. https://www.uptodate.com/contents/treatment-of-community-acquired-pneumonia-in-adults-in-the-outpatient-setting?source=see_link#H4. Accessed March 27, 2017.

  15. Words of Wisdom From the Dental Literature • “The dental pulp tissue after succumbing to liquefaction necrosis is no longer vascularized, and orally distributed drugs are unable to reach the site of infection” • “No difference in clinical outcomes between penicillin VK, amoxicillin, or amoxicillin and clavulanate” • “Penicillin is still the gold standard in treating dental infections” Dar-Odeh, NajlaSaeed, et al. "Antibiotic prescribing practices by dentists: a review." Therapeutics and clinical risk management 6 (2010): 301.

  16. My ED Dentalgia Practice • First step: Determine if abx can be justified at all • Low concern no abx • Moderate concern PCN VK 500mg QID 3-5d • High concern PCN VK 500mg QID 5-7d • Allergy to PCNs Clinda 300mg QID 5-7d • Amox or FlagylOnly if treatment failure • Courses > 7d Never Cope A, et al. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database Syst Rev. 2014; 6.

  17. Say No to Quinolones:“You should always ask for a safer alternative if fluoroquinolones are prescribed to you” • Fluoroquinolones are a major driver of Clostridium difficileoutbreaks. • E. Coli resistance to ciprofloxacin averaging eighty-two percent in the Midwest. • Tendonopathy, neuropathy, QT prolongation, multisystem toxicity syndrome Tennyson, Lauren E., and Timothy D. Averch. "An Update on Fluoroquinolones: The Emergence of a Multisystem Toxicity Syndrome." Urology Practice 4.5 (2017): 383-387..

  18. ED Antimicrobial Stewardship2019 Literature Update 5 Most High Yield Articles Published Last Year

  19. Article #1 (04.13.2018, May et al): MITIGATE Toolkit, an ED AMS Implementation Guide • CDC initiative • First ED specific toolkit for AMS QI projects • First iteration focuses on avoiding abx for viral URIs • Framework: Nudges • Provider Education • Patient education • Provider commitment • Program champion • Departmental feedback • Personalized feedback http://shea-online.org/images/priority-topics/MITIGATE_TOOLKIT_final.pdf

  20. Article #2 (06.02.2018, Wirz et al.):Procalcitonin Meta-analysis • Patient-level meta-analysis based on 11 RCTs (2252 pts) • Primary endpoint: mortality within 30 days • Secondary endpoints: duration of abx & LOS • Statistically lower mortality rates in PCT group vs controls (21.1% vs 23.7%) • PCT group also had fewer abx days (9.3 vs 10.4) • Bottom line: Procalcitonin reduces antibiotic use with no negative outcomes Wirz, Yannick, et al. "Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials." Critical care 22.1 (2018): 191.

  21. Article #3 (08.03.18, Bidell et al):Cefazolin vs. anti-staphylococcal PCNs for MSSA • Meta-analysis, 7 studies, 1589 CF ptsvs 2802 PCN pts • Primary endpoint: All-cause 90 day mortality • OR = 0.63 (lower mortality with Cefazolin) • Secondary endpoint: Odds of discontinuation d/t ADEs • OR = 0.25 (much lower ADEs with Cefazolin) • No differences is treatment failure rates • Bottom-line: Anticipate an RCT to put this issue to rest, err on the side of Cefazolin unless biogram disagrees Bidell, Monique R., Nimish Patel, and J. Nicholas O’Donnell. "Optimal treatment of MSSA bacteraemias: a meta-analysis of cefazolin versus antistaphylococcalpenicillins." Journal of Antimicrobial Chemotherapy 73.10 (2018): 2643-2651.

  22. Article #4(08.23.18, Lovegrove et al):Abx-related pediatric adverse drug events • National ADE Surveillance project and retail pharmacy dispensing data (2011–2015) • 6542 peds surveillance cases, 69,464 ED visits • 40.7% of ED visits for antibiotic ADEs involved a child aged ≤2 years • 86.1% involved an allergic reaction • Amoxicillin was the most commonly implicated antibiotic among children aged ≤9 years Lovegrove, Maribeth C., et al. "US emergency department visits for adverse drug events from antibiotics in children, 2011–2015." Journal of the Pediatric Infectious Diseases Society (2018).

  23. Article #5 (01.08.2019, Mistry et al):A Framework for Pediatric EM AMS • Identifies a critical need for pediatric–focused AMS in general and community ED settings • Academic/community partnerships • ED/ID/ASP collaboration and engagement • Dissemination of best practices • Use of effort-independent mechanisms • Automated clinical decision support built into EHR • Emphasis on behavior economics principles Mistry, Rakesh D., Larissa S. May, and Michael S. Pulia. "Improving Antimicrobial Stewardship in Pediatric Emergency Care: A Pathway Forward." Pediatrics 143.2 (2019)

  24. Honorable Mentions & Non-Academic Work: • 11.04.18 (Pulia et al): EM Book chapter dedicated to AMS • 11.18.18: AAEM AMS Pledge • 01.09.19: ACEP, AAEM, SCCM reject the Sepsis 1-hour bundle in its present form • Promising Pre-Post QI Studies • 05.02.18 (Jorgensen et al): Successful ED UTI Project (swapping Cipro for Nitrofurantoin) • 11.29.18(Cantels et al): POCT for flu decreased pedsabxtx for flu by 70.1% (16.9% to 5.1%) • 09.14.18 (Dona et al): Clinical AMS peds ED pathway results in fewer abx for AOM & GAS

  25. Resources • Discussion Board • Printed clinical resources • AMS Toolkits • Best practice summaries • Archived AMS Webinars • #1: When to Test and When to Treat…A Deep Dive on Asymptomatic Bacteriuria • #2:Evidence-based Strategies to Avoid Prescribing Unnecessary Antibiotics • #3:Evidence-based Strategies to Prescribe Antibiotics More Effectively • #4:Pre-op Urinalysis Before Orthopedic Surgery…What is the Current Evidence? • New 2019 AMS Webinars! WHA Quality Center

  26. Contacts

  27. Questions • Be sure to check out WHA’s quick AMS references for your hospital’s ED! • Top Ten Ways for Emergency Physicians to Avoid Prescribing Unnecessary Antibiotics • Top Ten Ways for Emergency Physicians to Improve Antibiotic Choices • Pulia, M; Redwood, Robert; May, L. Antimicrobial Stewardship in the Emergency Department.Emergency Medicine Clinicsof North America. Volume 36, Issue 4, pp853-872. October 2018.

  28. Antimicrobial Stewardship in Sepsis

  29. Antimicrobial Stewardship in Sepsis: Overview • Right drug, right dose, right duration (and right diagnosis) • Sepsis is unique • a life-threatening, complex clinical syndrome without a gold standard diagnostic test • Recent literature will likely improve AMS in sepsis care • Importance of time to antibiotics has been called into question • qSOFA score and emphasis on end organ damage may reduce the extensive use of broad spectrum antibiotics Pulia, Michael S., Robert Redwood, and Brian Sharp. "Antimicrobial stewardship in the management of sepsis." Emergency Medicine Clinics 35.1 (2017): 199-217.

  30. Antimicrobial Stewardship in Sepsis: Best Practices • Blood cultures! • Craft policy to limit use of restricted drugs (i.e. fluoroquinolones) • Stop vancomycin as soon as organism is ID’d as non-Gram+ • Identify organism as soon as possible • Narrow antibiotics as soon as possible • Pending improvement, adjust regimen to smallest effective dose and duration • Transition from IV to oral • Confirm that team has a ‘stop plan’ for antibiotics Pulia, Michael S., Robert Redwood, and Brian Sharp. "Antimicrobial stewardship in the management of sepsis." Emergency Medicine Clinics 35.1 (2017): 199-217.

  31. Procalcitonin Biomarker in Sepsis

  32. Highlight on the Procalcitonin in Sepsis • PCT is a biomarker that exhibits greater specificity than other proinflammatory markers (eg, cytokines) in identifying patients with sepsis • PCT's primary uses • (1) to distinguish bacterial infections from viral infections (FDA approved). • (2) to predict which patient are high risk for progression to septic shock. •  0.5 ng/mL-2.0 ng/mL = moderate risk for progression to septic shock. •  2.0 ng/mL-10.0 ng/mL = high risk for progression to septic shock.  • >10.0 ng/mL = 99.5% likelihood of progression to septic shock. • (3) to gauge whether or not a septic shock resuscitation is trending towards improvement or worsening shock. • Expense: $56 - $175+ (Fair price = $70) Bouadma L, et al. "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units". The Lancet. 2010. 375(9713):463-74.

  33. Highlight on the Procalcitonin in Sepsis • In critically ill ICU patients with suspected bacterial infections, what is the benefit of a procalcitonin-guided strategy on mortality and antibiotic-free days? (PRORATA Trial) • more antibiotic-free days than those in the control group (14.3 days vs 11.6 days, P<0.0001) • Mortality was non-inferior at day 28 and at day 60, using 10% as the margin of non-inferiority (inferior if 5% had been used) • Surviving Sepsis Campaign PCT recommendations • measure PCT to shorten duration of antimicrobial therapy in patients with sepsis (weak recommendation, low quality of evidence) • use PCT to discontinue empiric antibiotics in patients who initially seemed to have sepsis but subsequently had limited evidence of an infection (weak recommendation, low quality of evidence) Bouadma L, et al. "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units". The Lancet. 2010. 375(9713):463-74.

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