Implementation of an Antimicrobial Stewardshippg Program ...s3.proce.com/res/pdf/handouts/HermsenHandout.pdf · SIDP – Antimicrobial Stewar dship Certificate Program Implementation

SIDP – Antimicrobial Stewardship Certificate Program Implementation of an Antimicrobial Stewardship Program: Justification, Cost, and Challenges

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Implementation of an Antimicrobial Stewardship Program: p g

Justification, Cost, and Challenges

Elizabeth D. Hermsen, Pharm.D., M.B.A., BCPS-IDDirector, Global Antimicrobial StewardshipDirector, Global Antimicrobial Stewardship

Merck [email protected]

The content presented here does not necessarily reflect the views of Merck.

Objectives

• List the resources necessary to initiate an ti i bi l t d hi (ASP)antimicrobial stewardship program (ASP).

• Identify potential financial and institutional barriers to implementation of an ASP.

• Justify the benefits of an ASP to administrative and clinical leadershipadministrative and clinical leadership.


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Outline

• BackgroundA ti i bi l t d hi• Antimicrobial stewardship– Introduction– Guidelines/strategy summary– Implementation– Subsequent justification– Best practices/Barriers

• Summary

Resistance AmongGram-Positive Organisms

Methicillin-resistant Staphylococcus aureus (MRSA)Vancomycin-Resistant Enterococci (VRE)Vancomycin-Resistant Enterococci (VRE)

60

50

40

30

20

Inci

denc

e (%

)

http://www.idsociety.org/uploadedFiles/IDSA/Policy_and_Advocacy/Current_Topics_and_Issues/Advancing_Product_Research_and_Development/Bad_Bugs_No_Drugs/Statements/AsAntibioticDiscoveryStagnatesAPublicHealthCrisisBrews.pdf. Accessed April 2013.

10

0

1980 1985 1990 1995 2000


3

30

P/T TAZ IMP TOB CIP

Resistance AmongGram-Negative Organisms

4050607080

05

1015202530

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

K pneumoniae

010203040

1999 2000 2001 2002 2003 2004 2005 2007 2008

A baumannii*

*A baumannii not tested in 2006.Rhomberg PR, et al. Diagn Microbiol Infect Dis 2009;65:414-426.

Impact of Antibiotic Resistance

Joo (2011)

Micek (2012)

Rello (1997)

Kollef (1999)

Ruiz (2000)

Ibrahim (2000)

Dupont (2001)

Valles (2003)

Kumar (2009)

( )

Inappropriate initial therapy

Appropriate initial therapy

0 20 40 60 80 100

Luna (1997)

R e llo (1997)

Mortality (% )

Micek S, et al. BMC Infect Dis 2012;12:56. Joo EJ, et al. Infection 2011;39:309-318. Kumar A, et al. Chest 2009;136:1237-1248. Valles J, et al. Chest 2003;123:1615-1624. Dupont H, et al. Intensive Care Med 2001;27:355-362. Ibrahim EH, et al. Chest 2000;118:146-155. Ruiz M, et al. Am J Respir Crit Care Med 2000;162:119-125. Kollef MH, et al. Chest 1999;115:462-474. Rello J, et al. Am J Respir Crit Care Med1997;156:196-200. Luna CM, et al. Chest 1997;111:676-685.


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New Antibacterial Agents

United States, 1983-2012Ap

prov

als

161412108642

Boucher HW, et al. Clin Infect Dis. 2013;56: 1685-94.

01983-1987

1983-1987

1993-1997

1998-2003

2003-2007

2008-2012

• Antimicrobial-resistant organisms are prevalent and are increasingly

Key Points

prevalent and are increasingly encountered.

• Antibiotic resistance is bad for our patients and our healthcare system.

• Novel antimicrobial agents are sparse• Novel antimicrobial agents are sparse.


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Pattern of Antibiotic ResistanceDiscovery

Exuberant Use

Development of Resistance through Mutation and Natural SelectionMutation and Natural Selection

Rapid Dissemination via Clonal Expansion and Horizontal Transmission

Timeline of ResistanceFirst clinical use

Penicillin Ampicillin Cefotaxime

Imipenem(1985)

Fi t i t

Penicillin (1942)

Ampicillin (1962)

Cefotaxime (1979)

1940 2000

14Rice LB. Mayo Clin Proc 2012;87:198-208.

First resistanceOsteomyelitis

due to penicillinase-producing S aureus

(1949)

Description of TEM penicillinase

(1966) First clinical ESBL (SHV-2)

(1985)

Description of CTX-M(1990)

Carbapenemase from

Enterobacteriaceae(1993)


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0)Erythromycin resistance Erythromycin consumption

Controlling Erythromycin Resistance in Group A Streptococci, Finland

1.52

2.53

3.54

15

20

25

30

con

sum

ptio

n (D

DD

/100

0

ycin

resi

stan

ce (

%)

87 88 89 90 91 92 93 94 95 960

0.51

5

10

Year

Eryt

hrom

ycin

Eryt

hrom

y

97 98

Seppala,NEJM. 1997;337:441Post-study data courtesy of Ron Rolk, Pharm.D.

• Antimicrobial use is the key driver of antimicrobial resistance.

Key Points

antimicrobial resistance.

• More prudent use of antimicrobial agents can slow or reverse the development of resistance.


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Antimicrobial Stewardship

• A rational, systematic approach to the use of antimicrobial agents in order to achieve optimalantimicrobial agents in order to achieve optimal outcomes. Focus = patient and public health.

Correct agent

Right dose

Cure/prevent infection

Minimize toxicityRight dose

Appropriate duration

Minimize toxicity

Prevent emergence of resistance

Guidelines Summary• Acute care setting• Multidisciplinary involvement

A ltidi i li ASP t h ld i l d i f ti di (ID)– A multidisciplinary ASP team should include an infectious diseases (ID) physician and pharmacist and other key stakeholders as determined by the institution

– Policy statement ‒ physician-directed or supervised multidisciplinary ASP team with ≥ 1 member trained in antimicrobial stewardship

• Core strategies:– Prospective audit with intervention and feedback– Formulary restriction and authorization

• Supplemental strategies:

Dellit TH, et al. Clin Infect Dis 2007;44:159-177.

IDSA/SHEA/PIDS. Infect Control Hosp Epidemiol 2012;33:322-327.

– Education– Guidelines/

clinical pathways– Order forms

– De-escalation– Dose optimization– IV-to-oral conversion


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Prospective Audit with Intervention & Feedback

• Prescribing/dispensing occurs as usual• Targets established for potential intervention

– Examples:• Drug-bug mismatch• Redundant therapy• Poly-antibacterial therapy

• Retrospective review & intervention if needed• Retrospective review & intervention if needed– Start/stop/change therapy– De-escalation– Dosing optimization


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Prospective Audit & Feedback

• Advantages– Maintain prescriber

• Disadvantages– Compliance voluntary– Maintain prescriber

autonomy

– Educational opportunity

– Review patient information before interaction

– May decrease inappropriate antimicrobial use

– Compliance voluntary

– Identification of patients may require computer support

– Reluctance to change therapy if the patient is doing well

– Permits some inappropriate antimicrobial use (withantimicrobial use (with retrospective audit)

– May be difficult to identify decision-making team

Formulary Restriction & Preauthorization

• Restricted antimicrobial formulary developed with fcriteria to define appropriate use

– Example: micafungin• Invasive aspergillosis in a patient failing/intolerant of

therapy with voriconazole.

• Empiric treatment of moderate-severe invasive candidiasis or those with recent azole exposure.

• Candidal infections refractory to azoles.

• Invasive candidiasis due to non-albicans species.

• Authorization prior to dispensing

• Selective susceptibility reporting


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Formulary Restriction & Preauthorization

• Advantages • Disadvantages– Direct control over

antimicrobial use

– Effective control of antimicrobial use during outbreaks

– Decreased inappropriate f ti i bi l

– Personnel needs

– Antagonistic relationship (loss of autonomy)

– Therapy may be delayed

– Manipulation of the system

use of antimicrobials – ID physicians often exempt

– “Squeezing the balloon”

Education

• Essential foundation of every ASP

• Large group/general vs. one-on-one/patient-specific

• Attempt to change behavior throughAttempt to change behavior through acquisition of new knowledge or reminder of existing knowledge


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Bacterial resistance • Extent, causes, and spread

• Mechanism of action, toxicity, and costs

Core Principles for Education

Mechanism of action, toxicity, and costs (collateral damage)

• Infection, isolation and identification of bacteria,susceptibility to antibiotics

Antibiotics

Diagnosis of infection

Treatment of infection

Infection prevention

• Indication for antimicrobials

• Antibiotic prophylaxis

Medical records

Antibiotic prescribing

• Recording and documentation of antimicrobial choice, duration, and timing

• Empiric therapy, communication with microbiology laboratory, following guidelines in clinical practice

Communication skills • Discussion technique

Pulcini C, Gyssens IC. Virulence 2013;4:192-202.

Education

• AdvantagesI f

• DisadvantagesP i– Increase awareness of

guidelines, susceptibility patterns

– May influence prescribing behavior

– Promotes acceptance

– Passive

– Time consuming

– Attendance often mandatory

– Dilution

of ASP


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Guidelines/Clinical Pathways

• Create protocols to guide antimicrobial use f i i f tifor a given infection– Specific to institutional formulary, patient

populations, and resistance patterns

• Evidence-based

Guidelines/Clinical Pathways

• AdvantagesD i i

• DisadvantagesAdh i ll– Decrease inappropriate

antimicrobial use

– Form of education

– Adherence is usually voluntary

– “Cookbook medicine”

– Maintenance

– Awareness


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Antimicrobial Order Forms

• Paper vs. integrated into electronic health drecord

– Optional vs. mandatory

• Potential Uses:– Support guidelines/pathways

– Communicate/enforce ASP recommendations– Communicate/enforce ASP recommendations

– Enhance documentation & thought process

Example: Surgical Prophylaxis• Features of Form

– Antibiotic recommendations with alternatives for allergiesallergies

– Dosing automatically adjusted by pharmacists for weight and renal function

– Automatic antibiotic discontinuation at 24 hours– Flexibility for “off-protocol” prescribing

– Pre-/post-intervention study (n=406; n=396, respectively)espec e y)– Significantly increased appropriate antibiotic choice

(62% vs. 85%, p<0.001), dose (62% vs. 90%, p<0.001), and duration (78% vs. 89%, p<0.001) and decreased cost ($46 vs. $40, p=0.02)

Hermsen ED, et al. Infect Control Hosp Epidemiol. 2008;29:457-61.


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Order Forms

• Advantages • DisadvantagesA il bili– Increase compliance

with guidelines/ pathways

– Form of education

– Enhance documentation

– Availability

– “Cookbook medicine”

– Maintenance

– Potential for therapy to be inadvertently stoppeddocumentation

– Decrease inappropriate use

pp

De-Escalation

• Narrow spectrum of activity as appropriate in response to culture/susceptibility results andresponse to culture/susceptibility results and clinical response


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De-escalation Case

• EB, a 61 y.o. female, was admitted to the hospital on 12/26 with abdominal pain, brown p p ,vomit, fever, and chills.– Started on piperacillin/tazobactam and metronidazole

• Underwent appendectomy and abscess drainage on 12/30– Culture Bacteroides spp.

I d O i t th t t• Increased O2 requirements over the next two days. Chest X-ray – LLL consolidation– Added ciprofloxacin and vancomycin– Sputum culture – K. pneumoniae and C. albicans– Added fluconazole

De-escalation Case

ASP ASP

Date 26 27 28 29 30 31 1 2 3 4 5 6 7

PTZ

MTZ

CIP

VA

FLUC


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De-escalation• Advantages

– Balance need for initial

• Disadvantages– Reluctance to change

fuse of broad-spectrum therapy to “get it right up front” with need to target the organism

– May influence future prescribing behavior

therapy if patient is doing well

– May narrow therapy inappropriately

– Decrease inappropriate use

Dose Optimization

• Use pharmacokinetic (PK)/pharmacodynamic(PD) principles to choose dose that will most(PD) principles to choose dose that will most likely eradicate the organism, minimize toxicity, and prevent resistance

• Affected by minimum inhibitory concentration (MIC)

• Examples:– Once-daily dosing of aminoglycosides

– Extended infusion β-lactams


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Impact of MIC value on PD TargetsBeta-lactam via standard 30-minute infusion

Breakpoint for susceptibility = 4 mg/L.

cent

ratio

n (m

g/L)

~30% T>MIC

Isolate #2MIC 2 mg/L

~50% T>MIC

Both isolates are susceptible, but isolate #2 has a higher MIC & therefore less T>MIC when administered the same dose.

2

Time (hrs)

Con

c

1 2 3 4 5

MIC 2 mg/L

Isolate #1MIC 1 mg/L

6

1

Slide adapted from presentation by Daryl DePestel, Pharm.D., BCPS-ID.

Piperacillin/tazobactam Target Attainment vs. P. aeruginosa

3.375g q8h over 4h achieves over 90% probability of target attainment up to an MIC of 16 mg/L versus an MIC of 1 mg/L for standard dose of 3.375g q6h over 30min

Lodise TP, et al. Clin Infect Dis. 2007;44:357-363.


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Dose Optimization

• AdvantagesI lik lih d f

• DisadvantagesL i i– Increase likelihood of

achieving PD target

– May decrease resistance

– May decrease drug costs

– Logistics

– Lack of MIC data

– May increase pharmacy/nursing time

– Potential for error

– May allow use of drug for organisms with increased MICs

How to Start


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Steps Toward Building an ASP

Identify Key StakeholdersStakeholders

Build Buy-In

How do you gain support?

FQ-resistant E. coli MDR P. aeruginosa50

25

e

05

101520253035404550

Per

cent

Res

ista

nce

0

5

10

15

20

Per

cent

Res

ista

nce

NHSN 2007-2008

NHSN 2009-2010

Your hospital 2007-2008

Your hospital 2009-2010

Sievert DM, et al. Infect Control Hosp Epidemiol. 2013;34:1-14.

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National Hot Topic

• CDC NHSN AUR ModuleCDC 7 C El t f H it l A ti i bi l• CDC: 7 Core Elements of Hospital Antimicrobial Stewardship Programs

• PCAST Report, National Strategy, Executive Order, & National Action Plan to Combat Antibiotic-resistant BacteriaCMS Proposed Rule(s)• CMS Proposed Rule(s)

http://www.cdc.gov/nhsn/PDFs/pscManual/11pscAURcurrent.pdf. Accessed August 2014.

http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf. Accessed August 2014.

Pollack LA et al. Clin Infect Dis. 2014;59(S3):S97–100.

http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/pcast_carb_report_sept2014.pdf. Accessed November 17, 2014.

http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf. Accessed November 17, 2014.

http://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic-resistant-bacteria. Accessed November 17, 2014.

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf

https://s3.amazonaws.com/public-inspection.federalregister.gov/2015-17207.pdf

Steps Toward Building an ASPIdentify Key

Stakeholders

Build Buy-In

Identify Core/Supplemental

Strategies

Delineate Goals & Outcome Measures


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Outcome Measures

Patientoutcomes

Collateraldamage

Drug consumption/

Processmeasuresoutcomes

• Clinical cure• LOS/ICU LOS• Readmission• Patient mortality

damage

• Selection of pathogenic organisms (e.g., CDI)

• Resistance• Toxicity

consumption/ costs

• Defined daily doses, days of therapy, length of therapy

• Predefined costs, prices, or charges

measures

• Appropriateness of therapy

• Adherence to guidelines

• Time to appropriate therapy

McGowan JE. Infect Control Hosp Epidemiol 2012;33:331-337. Goldmann DA, et al. JAMA 1996;275:234-240.

Steps Toward Building an ASPIdentify Key

Stakeholders

Build Buy-In

Identify Core/Supplemental

Strategies

Delineate Goals & Outcome Measures

Draft Formal Proposal


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Formal Proposal

• Background– Impact of resistanceImpact of resistance

– ASP literature

– Legislative/policy proposals/changes

• Proposed Program– Goals

– Required core personnel & compensation

– Core/supplemental strategies

• Benefits & Outcome Measures– Focus on more appropriate patient care… then reduced costs

– Period of review

• Future plans & Areas of Growth

• Financial Justification

Initial Cost Justification

• Personnel

• Cost savings vs. Cost avoidance

• Length of stay


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ASP is approved! Now what?

Recruitment…


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Implementation Plan: Key Considerations

• Low hanging fruit

• Data availability

• Core strategy– “Hours of operation”

– Coverage in the absence of ASP personnel

• Mechanism of communication

• Prescriptive authorityp y

• Intervention documentation/tracking

• Trending/benchmarking

• Reporting structure and frequency

• Integration across multiple institutions

Building Buy-In

• Identify key opinion leadersI di id l ti– Individual meetings

• Marketing– Branding

– Elevator pitch

Ne sletters/”La nch”– Newsletters/”Launch”

• Communication/Education


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Committee Infrastructure

• Antimicrobial Subcommittee

• Pharmacy & Therapeutics Committee

• Medical Executive Committee

• Clinical Microbiology Operations CommitteeCommittee

• Infection Prevention Committee

• Quality/Patient Safety Committee

Subsequent Cost Justification

($)

obia

l Exp

endi

ture

s

ASP

Ant

imic

ro

Time (yrs.)


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Subsequent Cost Justification (cont.)

• Specific projectsED Contaminated Blood Cultures Oct 2006-May 2008

5

6

7

8

9

10

t con

tam

inate

d

lab draw

nurse drawTotal

Trend

0

1

2

3

4

Oct-06

Nov-06

Dec-06

Jan-07

Feb-07

Mar-07

Apr-07

May-07

Jun-07

Jul-07

Aug-07

Sep-07

Oct-07

Nov-07

Dec-07

Jan-08

Feb-08

Mar-08

Apr-08

May-08

Perc

ent

ED = emergency department


• Specific projects

– Blood culture contamination in ED• 7.4% in Oct 06 to 2.1% in May 08

• ~4800 blood cultures/year

• Previous study contaminated culture costs $104.75

• Saved ~$26,500


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• Antimicrobial surgical prophylaxis order f


form

– Pre-/post-intervention study

– Average cost of antimicrobial surgical prophylaxis decreased by $6/patient (p=0.02)

70% compliance with form– 70% compliance with form

– Save ~$30,000/year

Hermsen ED, et al. Infect Control Hosp Epidemiol 2008;29:457-61.

• Clostridium difficile infection (CDI)management


management

– 2001 to 2007 CDI rate increased from 0.99 to 1.46 cases/1000 patient days

– Management algorithm and cleaning procedures implemented July 2007p p y

• ASP, Infection Control, Microbiology, Environmental Services, ID, Gastroenterology, Hem/Onc, Solid Organ Transplantation, and Pediatrics


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Clostridium difficile Infection Rates

2.5


0.94

2

1.62

1.73

1.84

1.36

1.92

1.51

0.990.9

1.04

1.17

1.44

1.281.36

0.95

1.29

1.031

1.5

2

ate

per 1

000

patie

nt d

ays

0.76

0.68

0

0.5

Jan-07

Feb Mar Apr May Jun July Aug Sept Oct Nov Dec Jan-08

Feb Mar Apr May June July Aug

Month

Ra

• Clostridium difficile infection (CDI)management


management

– From Jul 2007-Aug 2008, decreased CDI rate by 1.21 cases/1000 patient days 194 cases/year

– $2 454 attributable costs/CDI episode*$2,454 attributable costs/CDI episode saved ~$475,000

*Dubberke ER, et al. Clin Infect Dis 2008;46:497-504.


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Tips for Success• Round with ID team, study antibiogram trends, and

meet with key stakeholders to survey for ID problemsp

• Network!• Marketing• Information resource (website)• Build relationships across disciplines• Standard operating procedures, policies• Ensure appropriate data and timing• Establish mechanism for evaluation• Establish mechanism for evaluation• Study what you do• Partner with Finance Dept.• Budget for growth• Baby steps

Potential Barriers• Enhancing patient care vs. saving money• Human and financial resources• Information systems• Communication• Inflation/new products• Evaluation• ID staff resistanceID staff resistance• Internal medical staff resistance

– Enforcement

• Competing initiatives


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Summary

• Antimicrobial resistance is increasing negatively affects patients & healthcare g y psystems

• More prudent use of antimicrobial agents can slow or reverse the development of resistance antimicrobial stewardship– Focus is patient outcomes and public health

• Many potential best practices and barriers learn by sharing experiences!

Documents

Implementation of an Antimicrobial Stewardshippg Program ...s3.proce.com/res/pdf/handouts/HermsenHandout.pdf · SIDP – Antimicrobial Stewar dship Certificate Program Implementation