Kirthana R. Beaulac, PharmD BCPS

Antimicrobial Stewardship In Acute CarePicking the Low Hanging Fruit and Reaching Beyond

Objectives

• Review the principals and objectives of an antimicrobial stewardship program

• Outline the regulatory requirements surrounding Antimicrobial Stewardship in Hospitals

• Identify the barriers to implementing a successful stewardship program in academic and community hospitals

• Integrate evidence-based practices and resources to improve antimicrobial usage

The bugs are becoming harder to treat…

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…and the antibiotic pipeline is drying up

4Ventola CL. PT. 2015; 40(4):277-283.

ANTIMICROBIAL STEWARDSHIP

• IDSA defines Antimicrobial Stewardship as “an activity that includes appropriate selection, dosing, route, and duration of antimicrobial therapy”

• Goals of Stewardship• Attenuate or reverse antimicrobial resistance• Prevent antimicrobial-related toxicity• Reduce the costs of inappropriate antimicrobials• Decrease health care associated infections

Dellit T, et al. CID. 2007; 44: 159-177.

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In Reality

Pollack LA, van Santen KL, Weiner LM, et al. Clin Inf Dis. 2016; 63(4):443-449..

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Pollack LA, van Santen KL, Weiner LM, et al. Clin Inf Dis. 2016; 63(4):443-449..

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Massachusetts Results

0%10%20%30%40%50%60%70%80%90%

100%

201420152016

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Pollack LA, van Santen KL, Weiner LM, et al. Clin Inf Dis. 2016; 63(4):443-449..

The Easy Stuff

• IV to PO• Implement protocols

and guidelines• Formulary restriction• PK dose optimization

Parenteral To Oral Conversion

• Several antibiotics have good oral bioavailability• Fluoroquinolones• Linezolid• Metronidazole• Clindamycin• SMX/TMP• Fluconazole

• Associated with Decreased:• Length of stay• Cost of care• Risk for line-related

infections• Additional Benefits

• Fluid / sodium restriction• Enterohepatic cycling• Patient Satisfaction

Jones M, et al. Infect Control Hosp Epidemiol. 2012; 33(4): 362-367.

Guidelines and Protocols

Make the Right Choice the Easy Choice

Impact of Protocol

Lancaster JW, et al. Pharmacotherapy. 2008;28(7):852–862.

Restricting Antimicrobials

• Highly effective, but need specialized personnel to be effective• Authorizations done by chief resident compared to no

authorization needed• No difference in antibiotic use

• Authorizations done by ID attending and ID pharmacist compared to ID fellow• Improved antimicrobial appropriateness• Increased clinical cure• Trend towards improved economic outcome

DeVito JM, et al. Arch Intern Med. 1985; 145:1053–6.Gross R, et al. Clin Infect Dis. 2001; 33:289–95.

Dose Optimization

• Patient Characteristics• Age, renal function, weight

• Causative Organism• Site of Infection• Pharmacokinetics

• Extended or continuous infusion of β lactams• High-dose once daily aminoglycoside

Nicasio AM, et al. Journal of Critical Care. 2010; 25: 69-77.Falagas ME, et al. Clin Infect Dis. 2013 Jan;56(2):272-82

Higher Level Interventions

• Bolstering non-specialists

• Complex antibiograms• Antibiotic Time Out• Application of rapid

diagnostics

• Culture change

Non-ID Trained Pharmacists

• Non-specialized clinicians can be effective in stewardship activities with guidance from ID-trained pharmacists or ID Physicians

DiazGranados CA. AJHP. 2011; 68(18): 1691-1692.Laible BR et al. Journal of Pharmacy Practice. 2010; 23: 531-534.

Vancomycin Per Pharmacy

Development of Kidney Dysfunction

Recovery of KidneyFunction

Use of Concomitant Nephrotoxins

Vanco PerPharm (VPP)

48 / 640 (7.5%)

17 / 48 (35.4%)

40 / 48 (83%)

First 4 months without VPP

72 / 684 (10.5%)

p=0.05

39 / 72 (54.12%)

72 / 72 (100%)

1 year after VPP

61 / 767 (7.6%) p>0.05

35 / 61 (57.4%)

55 / 61 (61%)

Syndromic Antibiogram

Wick J, Beaulac KR, Doron S. Inf Ctrl Hosp Epi. 2016; 37)9):1101-1104.

Combination Antibiogram

Wick J, Beaulac KR, Doron S. Inf Ctrl Hosp Epi. 2016; 37)9):1101-1104.

VAP Antibiogram

Randhawa V, Sarwar S, Walker S, et al. Critical Care. 2014; 18: R112.

Age-Stratified Antibiogram

Swami SK, Banerjee R. SpringerPlus. 2013; 2:63.

Antibiotic Time-Out

• Hard Stop vs. Soft Stop• Electronic vs. Manual • Passive Alert vs.

Actionable Item• Resources for next steps

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Graber CJ, Jones MM, Glassman PA, et al. Hosp Pharm. 2015; 50(11):1011-1024.

Rapid Molecular Diagnostics: Most Common Applications

• Blood• Multiplex PCR (polymerase chain reaction)• MALDI-TOF (matrix assisted laser desorption/ionization- time of flight)• PNA-FISH (peptide nucleic acid fluorescence in situ hybridization)

• Respiratory Viruses• RADT (rapid antigen detection test)• NAAT (nucleic acid amplification test)• PCR

• Stool• Immunoassay and PCR for C. diff• PCRs for various common stool bacteria and viruses

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Molecular Rapid Diagnostics

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Timbrook TT, Morton JB, McConeghy KW, et al. Clin Inf Dis. 2017; 64(1):15-23.

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Application of Multiplex PCR for Bacteremia at Tufts

Page Clinician

• Micro lab alerts clinician as Critical Value

Written Guidance

in EMR

• Pathogen-directed treatment guidance designed by Tufts Antimicrobial Management Team

Follow-up from

AMT

• Antimicrobial Management Team checks to ensure appropriate antibiotics are initiated within 1 hr

Positive BiofireResult

• Incorporates previous year’s antibiogram, hospital formulary and policies, and DPH reporting requirements

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Time to Adequate Therapy

Composite Outcome:Hours to adequate

therapy (including d/c abxfor contaminants)

median (IQR)(N= 152)

Pre- Implementation

(N= 82)

23.95 (6.29-58.50)

Post- Implementation

(N= 70)

14.82 (4.07-44.79)

Culture change

• Solicit feedback and give feedback• Provide a helpful (“teaching”) service• Use concepts of behavior change theory• Physician Reluctance

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Beerlage-de Jong N, Wentzel J, Hendrix R, et al. Am J Inf Ctrl. 2017; 45:365-71.

Evaluation of Programmatic Changes to the ASP Program with House Officer Feedback• House officer survey on Tufts Medical Center ASP• 2008 Survey• Programmatic interventiono Enhanced training on ASP procedures at orientationo Changes to the antimicrobial order formo “ASP question of the week”

• 2010 Survey

Hong SY, Epstein LH, Lawrence K, Davidson L, Taur Y, Nadkarni L, Doron S. Journal of Evaluation in Clinical Practice 2012:1365-2753.

Antimicrobial Stewardship Program (ASP) Impact on Patient Care 2008 and 2010

Differences between 2008 and 2010

Hong SY, Epstein LH, Lawrence K, Davidson L, Taur Y, Nadkarni L, Doron S. Journal of Evaluation in Clinical Practice 2012:1365-2753.

Small Nudges

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Hallsworth M, Chadburn T, Salis A, et al. Lancet. 2016; 387; 1743-1752.

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Dealing with Holdout Prescribers

• Cater to their wants and needs• Preferred communication methods

• Tug at their heart strings• Make it personal• Underscore their role in protecting the greater good

• Call in reinforcement if needed• But make sure you have leadership on your side first!

• Steward around them• Micro/Laboratory Stewardship• Nursing support

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Goldstein EJC, Goff D, Reeve W, et al. Clin Inf Dis. 2016; 63(4):532-538.Olans RN, Olans RD, DeMaria A. Clin Inf Dis. 2016; 62(1):84-89.

Let me pull out my violin…

• The CDC estimates 37,000 deaths annually as a consequence of antibiotic overuse (antibiotic resistant infections and C. difficile)• 32,000 deaths annually from motor vehicle accidents• 15,000 deaths annually from homicide• 33,000-38,000 deaths annually from opiate overdose

• How many people have that have died from one of those 3 things at this institution?

• How many people do you think have died as a consequence of antibiotic overuse at this institution?• What percent were your patients?

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A Moment For Reflection

• Based on the strategies discussed here today, are there any feasible strategies that you think you can implement?

• What are the barriers that you face that have not been addressed?

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We’re All In This Together, But It Starts With You

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Antibiotic Resistance