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Consequences of Inappropriate Antibiotic
Use: Time for Action
Marilee D. Obritsch, Pharm.D., BCPS
Regional Health Antimicrobial Stewardship Program
Clinical Pharmacist
Title Text Title Text Title Text
Objectives
• Review antimicrobial resistance
• Review antibiotic usage in humans and animals
• Describe antimicrobial stewardship (AMS) definitions
• Discuss rationale for AMS activities
• Identify examples of AMS strategies
• List opportunities for training
Alexander Fleming
“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.”
Sir Alexander Fleming – Nobel Lecture. NobelPrize.org. Nobel Media AB 2019. Tue. 12 Feb 2019. <https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture/>
Title Text Title Text Title Text
https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
Mechanisms of Antimicrobials and Resistance
http://www.clinicaleducation.org/wp-content/uploads/Antibiotics-resistance-and-effects.jpg Munita. Microbiol Spectr. 2016;4:1-37.
Antibiotic Resistance
https://www.cdc.gov/narms/faq.html
Spread of Resistance
https://www.cdc.gov/narms/faq.html
Carbapenemase-Resistant Enterobacteriaceae
https://www.cdc.gov/hai/organisms/cre/trackingcre.html
http://civileats.com/2016/12/15/26075/
Antibiotic Expenditures
https://www.train.org/cdctrain/course/1076972/
Outpatient Antibiotic Use
https://www.train.org/cdctrain/course/1076972/
Outpatient Antibiotic Use
https://www.train.org/cdctrain/course/1076972/
Outpatient Antibiotic Use
https://www.cdc.gov/antibiotic-use/community/images/materials/Outpatient-Map-2016.jpg
Inpatient Antibiotic Use
2006-2012
Baggs. JAMA Intern Med. 2016;176:1639-48.
Animal Antibiotic Use 2013-2016
107 countries reporting
http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/docs/pdf/AMR/Annual_Report_AMR_2.pdf
Animal Antibiotic Use 2013-2016
34 countries reporting
http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/docs/pdf/AMR/Annual_Report_AMR_2.pdf
CDDEP document
https://cddep.org/wp-content/uploads/2017/06/india_abx_report-2.pdf
Antimicrobial resistance
IDSA/SHEA/PIDS Consensus Statement:
Antimicrobial Stewardship Definition
“Coordinated interventions designed to improve and measure the appropriate use of antibiotic agents by promoting the selection of the optimal antibiotic drug regimen including dosing, duration of therapy, and route of administration”
SHEA, IDSA, PIDS. Infect Control Hosp Epidemiol. 2012:33:322-7.
AVMA Antimicrobial Stewardship Definition
https://www.avma.org/KB/Policies/Pages/Antimicrobial-Stewardship-Definition-and-Core-Principles.aspx
“Actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision-making while safeguarding animal, public, and environmental health.”
AMS Objectives
• Protect the patient’s natural microbiome
• Improve antibiotic use
• Improve patient safety
• Clostridium difficile
• Adverse events due to inappropriate use of antibiotics
• Reduce antimicrobial resistance
• Reduce cost
Rashid M et al. Clin Infect Dis 2015;60:S77-84. Zaura E et al. mBio 2015;6:e01693-15. Shehab N et al. Clin Infect Dis 2008;6:735-43. Nanwa N, et al. Am J Gastroenterol 2015;110:511-9.
Microbiome
• Unhealthy microbiome • Autoimmune
disorders
• Allergy and atopic disorders
• Obesity
• Infections
Lynch S, et al. N Engl J Med. 2016;375:2369-79. Vangay. Cell host & microbe. 2015;17:553-64.
Inappropriate Antibiotics
• 70% of adults received
antibiotics for acute
uncomplicated bronchitis
• 40% of adults with upper
respiratory tract infections
prescribed antibiotics
• 51% of patients received
antibiotics for viral
pharyngitis
• 45% of patients with
asymptomatic bacteriuria
treated with antibiotics
CDC. Antibiotic Use in the United States, 2017: Progress and Opportunities. Atlanta, GA: US Department of Health and Human Services, CDC; 2017. Barnett. JAMA. 2014;311:2020-22. Fleming-Dutra. JAMA. 2016;315:1864-73. Flokas. Open Forum Infect Dis. 2017:4:4.
Risk versus Benefits of Antibiotics:
Clostridium Difficile
https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
Risk versus Benefits of Antibiotics
• Adverse effects (1 in 5 ED visits) • Anaphylaxis
• Nausea, vomiting, diarrhea, headache
• Candida infections
• Long term disruptions in the microbiome
• ED ADR related to FQ have highest rate of hospitalization (14.5%)
• Drug interactions
• Black box warnings
Shehab. Clin Infect Dis. 2008;15:735-43. Shehab. JAMA 2016;316:2115-25. Vangay. Cell host & microbe. 2015;17:553-64. Zaura. mBio. 2015;6:1-11. McDonald. J Travel Med. 2017;24:S35-38.
Antibiotic Resistance Morbidity and Mortality
http://battlesuperbugs.com/sites/battlesuperbugs.com/files/Public%20Health%20Costs%20of%20AR_0.jpg
AVMA Stewardship Goals
• Maintain animal health and welfare • Evidence based approach in antimicrobial
decision-making • Use antimicrobials judiciously and sparingly • Evaluate outcomes of therapy
https://www.avma.org/KB/Policies/Pages/Antimicrobial-Stewardship-Definition-and-Core-Principles.aspx
CDC Core Elements of Outpatient Stewardship
• Commitment
• Action for policy and practice
• Tracking and reporting
• Education and expertise
https://www.cdc.gov/antibiotic-use/community/pdfs/16_268900-A_CoreElementsOutpatient_508.pdf
CDC Core Elements Hospitals and Long Term
Care Stewardship
• Leadership commitment
• Accountability
• Drug expertise
• Action
• Tracking
• Reporting
• Education
https://www.cdc.gov/antibiotic-use/healthcare/pdfs/core-elements.pdf
AVMA AMS Core Principles
• Commit to stewardship
• Advocate for a system of care to prevent common diseases
• Select and use antimicrobial drugs judiciously
• Evaluate antimicrobial drug use practice
• Educate and build expertise
https://www.avma.org/KB/Policies/Pages/Antimicrobial-Stewardship-Definition-and-Core-Principles.aspx
AMS Strategies
• Vaccination
• Aggressive diagnostics
• No antibiotics for viral infections
• Watch and wait or delayed prescription
• Use of local antibiogram data to select most appropriate agent based on suspected source of infection
• Electronic health record modifications
• De-escalate once susceptibility returns
• Shortest duration therapy
• Multi-disciplinary approach for success
• Reporting and education
MacDougall. Clin Micro Rev. 2005;18:638-56. Owens. Diag Micro Infect Dis. 2008;61:110-28.
Diagnostic Tools
• Respiratory PCR panel • Positive viruses with infiltrate in hospitalized patients ---check
procalcitonin day 1 and day 3
• GI pathogen PCR panel • Meningitis PCR panel • BCID for blood cultures
• MecA positive = Methicillin resistant staphylococci • VanA positive = Vancomycin resistant enterococci
• Nasal MRSA PCR test • High negative predictive value for pneumonia, deescalate
vancomycin
• PBP2a positive = MRSA • Soon to be others (Pneumonia panel)
Antibiogram
• Link posted on all cultures
• Link on intranet under antibiotic stewardship forms
• Search from main page
• Adding button at top of Epic page
• Example antibiogram
Antimicrobial Indication/Time Out
EPIC Changes for Urine Culture and Urinalysis with
Microscopic, Reflex Culture
Antibiotic Selection
• Cellulitis • Diagnosis • Non-purulent
• Penicillin, first generation cephalosporin • Purulent
• Sulfamethoxazole/trimethoprim, doxycycline, vancomycin • Gram negative coverage unnecessary in a majority of cases
• Diabetic foot infections, water exposure, immunocompromised, bites, surgical site infections
• Uncomplicated UTI • Treat only if signs/symptoms present • Nitrofurantoin, fosfomycin • Fluoroquinolones should not be used first-line • Avoid empiric sulfamethoxazole/trimethoprim when resistance
>20%
Jenkins. Clin Infect Dis 2018;67:1550-8. Gordon. NEJM 2006;353:1945-54.
Errors in Duration of Therapy
• Shorten number of days of antibiotic therapy to minimum effective duration
• Cellulitis • 5 days as effective as 10 days
• CAP • 3-5 days as effective as 7-10 days
• HAP/VAP • 7 days as effective as 8-15 days
• Pyelonephritis • 5-7 days as effective as 10-14 days
Hepburn. Arch Intern Med. 2004;164:1669-74 . Spellberg. JAMA IM. 2016;176:1541255. Kalil. Clin Infect Dis. 2016;63:E61-111. Liu. Clin Infect Dis. 2011;52:e18-55.
Errors in Duration of Therapy
• Include the days of therapy received in the hospital when calculating the outpatient duration of therapy
• Minimum effective duration in certain infections • Complicated Staphylococcus aureus bacteremia requires
longer durations of IV therapy (ID consult highly recommended)
• Duration may start from date of first negative
blood culture or last procedure
Olans RN et al. Clin Inf Dis 2016;62:84-9.
Multi-disciplinary Involvement
Standardized Antimicrobial Administration Ratio
(SAAR)
• Days of therapy (DOT) submitted to NHSN to calculate SAAR
• Goal SAAR rate is 1.0 • If above 1.0, evaluate what changed that month
Antibiotic Stewardship Posters
https://www.cdc.gov/antibiotic-use/week/toolkit.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fantibiotic-use%2Fweek%2Fpromotional-materials%2Fgraphics.html
PROTECT ME
• BSAVA website • P – Prescribe only when necessary
• R – Reduce prophylaxis
• O – Offer other options
• T – Treat effectively
• E – Employ narrow spectrum
• C – Culture appropriately
• T – Tailor your practice
• M – Monitor
• E – Educate others
https://www.bsavalibrary.com/content/chapter/10.22233/9781910443644.chap6_1#supplementary_dataGuadrabass L. Vet Clin Small Anim. 2015;45:361-76.
Antibiotic Stewardship Posters
http://www.health.state.mn.us/divs/idepc/dtopics/antibioticresistance/animal/index.html
Hospital AMS Progress
https://www.cdc.gov/antibiotic-use/community/images/materials/2017-Core-Elements-Percentages.jpg
Change in Inpatient Antibiotic Use
2006 to 2012
Baggs. JAMA Intern Med. 2016;176:1639-48.
Change in Animal Antibiotic Use - UK
Veterinary Medicines Directorate (2019). UK One Health Report - Joint report on antibiotic use and antibiotic resistance, 2013–2017. New Haw, Addlestone: Veterinary Medicines Directorate.
Barriers to AMS
• Common • Lack of time and resources
• Lack of access to education and training
• Veterinary • Client expectations and competition between practices
• Costs of microbiological testing
• Lack of AMS governance structures
• Lack of independent guidelines for antimicrobial use
• Lack of perceived benefit
• Lack of susceptibility testing/antibiograms
Hardefeldt L. J Vet Intern Med. 2018; 32:1092-9. Guadrabass L. Vet Clin Small Anim. 2015;45:361-76.
CDC Antimicrobial Stewardship Training
https://www.train.org/cdctrain/course
USDA Antimicrobial Training
https://nvap.aphis.usda.gov/ABX/index.htm
Thank you!