1. Vikas KesarwaniVikas Kesarwani MD FICM FCCPMD FICM FCCP
Asstt. Professor & In-charge,Asstt. Professor & In-charge,
Department of Critical care medicineDepartment of Critical care medicine
ANTIMICROBIAL STEWARDSHIP:ANTIMICROBIAL STEWARDSHIP:
A CONCERN FOR ALL PRACTITIONERSA CONCERN FOR ALL PRACTITIONERS

2. Guideline ResourcesGuideline Resources
• IDSA and SHEAIDSA and SHEA
– Guidelines for Developing an Institutional ProgramGuidelines for Developing an Institutional Program
to Enhance Antimicrobial Stewardshipto Enhance Antimicrobial Stewardship
• ASMASM
– Antimicrobial Resistance Prevention Initiative—AnAntimicrobial Resistance Prevention Initiative—An
UpdateUpdate
IDSA: Infectious Disease Society of AmericaIDSA: Infectious Disease Society of America
SHEA: Society of Heathcare Epidemiology of AmericaSHEA: Society of Heathcare Epidemiology of America
ASM: American Society of MicrobiologyASM: American Society of Microbiology

3. Appropriate initial antibioticAppropriate initial antibiotic
(usually empirical)(usually empirical) whilewhile
improvingimproving patientpatient
outcomesoutcomes andand heathcareheathcare
Appropriate initial antibioticAppropriate initial antibiotic
(usually empirical)(usually empirical) whilewhile
improvingimproving patientpatient
outcomesoutcomes andand heathcareheathcare
UnnecessaryUnnecessary
AntibioticsAntibiotics (broad(broad
spectrum) and increasedspectrum) and increased
resistanceresistance andand costcost
UnnecessaryUnnecessary
AntibioticsAntibiotics (broad(broad
spectrum) and increasedspectrum) and increased
resistanceresistance andand costcost
Antimicrobial Therapy :Antimicrobial Therapy :
Anti-Anti-
MicrobialMicrobial
StewardshipStewardship
A Balancing ActA Balancing Act

4. Why Stewardship is Needed
– Up toUp to 50% antimicrobial50% antimicrobial prescribingprescribing inappropriateinappropriate**
– Causal relationshipCausal relationship betweenbetween antimicrobial useantimicrobial use andand
emergence ofemergence of resistanceresistance
– IDSA’s:IDSA’s: Bad Bugs, No Drugs task forceBad Bugs, No Drugs task force to call forto call for
a global commitment from stakeholders to supporta global commitment from stakeholders to support
thethe development of 10 new drugs indevelopment of 10 new drugs in novelnovel classesclasses
by the year 2020by the year 2020:: 10 × 20 initiative10 × 20 initiative
*Dellit TH et al. IDSA and SHEA guidelines. Clin inf dis 2007;44(2):159-177.
IDSA: Infectious Diseases Society of America

5. Those of us not developing new drugsThose of us not developing new drugs
have another job:have another job:
Conserve the antibiotics byConserve the antibiotics by
Antibiotic stewardshipAntibiotic stewardship

6. What is Antimicrobial Stewardship?What is Antimicrobial Stewardship?
• ““The optimalThe optimal selectionselection,, dosagedosage, and, and
durationduration ofof antimicrobial treatmentantimicrobial treatment thatthat
results in theresults in the best clinical outcome”best clinical outcome” oror
““TreatmentTreatment andand prevention of infectionprevention of infection,,
withwith minimal toxicityminimal toxicity to the patient andto the patient and
minimal impactminimal impact on subsequenton subsequent
resistanceresistance.”.”
Dellit TH, et al. CID 2007;44:159-77,Dellit TH, et al. CID 2007;44:159-77,
Hand K, et al. Hospital Pharmacist 2004;11:459-64Hand K, et al. Hospital Pharmacist 2004;11:459-64
Paskovaty A, et al IJAA 2005;25:1-10Paskovaty A, et al IJAA 2005;25:1-10

7. 3 Goals of Antimicrobial Stewardship3 Goals of Antimicrobial Stewardship
• 11stst
Goal:Goal: each patient receive the mosteach patient receive the most
appropriateappropriate antimicrobialantimicrobial
• 2nd Goal:2nd Goal: preventprevent antimicrobialantimicrobial
overuse, misuse, and abuse.overuse, misuse, and abuse.
• 3rd Goal :3rd Goal : minimizeminimize the development ofthe development of
resistance.resistance.
• Secondary goalSecondary goal
ReduceReduce healthcarehealthcare costscosts without adversely impactingwithout adversely impacting
quality of carequality of care

8. Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship
11stst
Goal:Goal: each patient receive the mosteach patient receive the most
appropriate antimicrobialappropriate antimicrobial
““4 D’s4 D’s of optimal antimicrobial therapy”:of optimal antimicrobial therapy”:
-- RightRight DrugDrug,,
--RightRight DoseDose,,
-- De-escalationDe-escalation to pathogen-directed therapy,to pathogen-directed therapy,
-- RightRight DurationDuration of therapy.of therapy.

9. Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship
• 22ndnd
Goal: prevent antimicrobialGoal: prevent antimicrobial
overuse, misuse, and abuse.overuse, misuse, and abuse.
Overuse:Overuse:
Antibiotics toAntibiotics to patients withpatients with viral infectionsviral infections,,
noninfectious processes (noninfectious processes (pancreatitispancreatitis), infections), infections
that do not require antibiotics (that do not require antibiotics (small skin abscessessmall skin abscesses
that willthat will resolve with I & Dresolve with I & D), and), and
bacterial colonizationbacterial colonization (positive urine culture result in(positive urine culture result in
catheterized patient.).catheterized patient.).

10. Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship
• 22ndnd
Goal: prevent antimicrobialGoal: prevent antimicrobial
overuse, misuse, and abuse.overuse, misuse, and abuse.
• Misuse:Misuse: use ofuse of broad-spectrum antibioticsbroad-spectrum antibiotics that coverthat cover
MDR organisms in a patient withMDR organisms in a patient with community acquiredcommunity acquired
infectioninfection or theor the failure to adjust antibiotics accordingfailure to adjust antibiotics according
to culture.to culture.
• Abuse:Abuse: use of oneuse of one particular antibiotic preferentiallyparticular antibiotic preferentially
over othersover others as a result ofas a result of aggressive detailing byaggressive detailing by
pharmaceutical representativepharmaceutical representative or worse becauseor worse because ofof
financial interest.financial interest.

11. Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship
• 33rdrd
Goal :Goal : minimizeminimize the development ofthe development of resistance.resistance.
Antimicrobial resistance is associated withAntimicrobial resistance is associated with
increased morbidity and mortalityincreased morbidity and mortality

12. Building the Stewardship teamBuilding the Stewardship team
Infectious DiseasesInfectious Diseases
SpecialistsSpecialists
AntimicrobialAntimicrobial
ControlControl
Infection ControlInfection ControlAdministrationAdministration
ClinicalClinical
PharmacistsPharmacists
ID trainedID trained
NursingNursing
Surgical InfectionSurgical Infection
Experts/SurgeonsExperts/Surgeons
OT PersonnelOT Personnel
MicrobiologistMicrobiologist
IntensivistIntensivist

13. The stewardship team does notThe stewardship team does not
have to fit a particular mold.have to fit a particular mold.

14. Building the Stewardship teamBuilding the Stewardship team
Hospitalist interested inHospitalist interested in
infectious diseaseinfectious disease
AntimicrobialAntimicrobial
ControlControl
Infection ControlInfection ControlAdministrationAdministration
NursingNursing
Surgical InfectionSurgical Infection
Experts/SurgeonsExperts/Surgeons
OT PersonnelOT Personnel
MicrobiologistMicrobiologist
IntensivistIntensivist
InfectionInfection
preventionistpreventionist

15. Antimicrobial StewardshipAntimicrobial Stewardship
Core StrategiesCore Strategies

16. IDSA Grading System for RankingIDSA Grading System for Ranking
Recommendations in Clinical GuidelinesRecommendations in Clinical Guidelines
Kish MA et al. CID 2001; 32: 851 - 4Kish MA et al. CID 2001; 32: 851 - 4
Category, GradeCategory, Grade DefinitionDefinition
Strength ofStrength of
recommendationrecommendation
AA Good evidence to supportGood evidence to support
BB Moderate evidence to supportModerate evidence to support
CC Poor evidence to supportPoor evidence to support
Quality of evidenceQuality of evidence
II ≥≥ 1 randomized, controlled trials1 randomized, controlled trials
IIII ≥≥ 1 clinical trial unrandomized, cohort1 clinical trial unrandomized, cohort
or case-controlled studies, dramaticor case-controlled studies, dramatic
results from uncontolled experimentsresults from uncontolled experiments
IIIIII Opinion of experts, clinical experience,Opinion of experts, clinical experience,
descriptive studiesdescriptive studies

17. Antimicrobial Stewardship Core StrategiesAntimicrobial Stewardship Core Strategies
• Front endFront end (pre-prescription approach):(pre-prescription approach):
Formulary restrictionFormulary restriction andand preauthorizationpreauthorization
(expert approval) leading to reductions in(expert approval) leading to reductions in
antimicrobial use and cost .antimicrobial use and cost . (A II)(A II)
• Back endBack end (Post prescription approach):(Post prescription approach):
Interventions after antimicrobials have beenInterventions after antimicrobials have been
prescribedprescribed. (A II). (A II)
• Prospective audit with intervention and feedbackProspective audit with intervention and feedback ofof
antimicrobial use and resistance patternsantimicrobial use and resistance patterns to reduceto reduce
inappropriate antimicrobial useinappropriate antimicrobial use (A I)(A I)
Dellit TH, et al. CID 2007;44:159-77Dellit TH, et al. CID 2007;44:159-77
Hand K, et al Hospital Pharmacist 2004;11:459-64Hand K, et al Hospital Pharmacist 2004;11:459-64
Paskovaty A, et al IJAA 2005;25:1-10Paskovaty A, et al IJAA 2005;25:1-10

18. Core strategy “The Front End”Core strategy “The Front End”
• Restrictive prescriptive authorityRestrictive prescriptive authority::
- Certain- Certain antimicrobialsantimicrobials requirerequire prior authorizationprior authorization
for use by all except a select group of clinicians.for use by all except a select group of clinicians.
- Approved- Approved for a specificfor a specific durationduration, thereby, thereby
prompting reviewprompting review after cultureafter culture data obtained.data obtained.
-- TargetTarget aa specific diseasespecific disease or indication withor indication with
specific antimicrobialsspecific antimicrobials associated withassociated with highhigh ratesrates
ofof resistance and costresistance and cost..
Advantage:Advantage:
--PreventsPrevents overuse, misuseoveruse, misuse andand abuseabuse..
- Significant- Significant reduction in cost.reduction in cost.

19. Core Strategy “The Back end”Core Strategy “The Back end”
• Post prescription restriction: Uses prospective review andPost prescription restriction: Uses prospective review and
feedback.feedback.
• Specific AntimicrobialsSpecific Antimicrobials areare reviewed at specified intervalsreviewed at specified intervals
after initiation. Adviced toafter initiation. Adviced to continue, adjust, change, orcontinue, adjust, change, or
discontinuediscontinue the therapythe therapy based on microbiology resultsbased on microbiology results andand
clinical featuresclinical features of the case.of the case.
AdvantageAdvantage
Focus is onFocus is on De-escalation.De-escalation.
-- changing achanging a broad-spectrumbroad-spectrum antibiotic toantibiotic to narrow spectrumnarrow spectrum
- changing from- changing from combinationcombination therapy totherapy to monotherapymonotherapy, or, or
-- stopping antibioticstopping antibiotic therapy altogether as it becomes moretherapy altogether as it becomes more
apparent that these drugs areapparent that these drugs are not needednot needed..

20. Supplemental AntimicrobialSupplemental Antimicrobial
Stewardship Strategies/TechniquesStewardship Strategies/Techniques
– Education: clinical guidelines, infectionEducation: clinical guidelines, infection
control.control.
– Antimicrobial order formsAntimicrobial order forms
– IV-PO switchIV-PO switch
– Dose optimization via PK-PDDose optimization via PK-PD
– Antimicrobial cyclingAntimicrobial cycling

21. Educational StrategiesEducational Strategies
• Educational programs, active interventionEducational programs, active intervention
(A-III, B-II)(A-III, B-II) Guideline & algorithm dissemination.Guideline & algorithm dissemination.
• Guidelines and clinical pathways –Guidelines and clinical pathways – seek multi-seek multi-
disciplinary involvement and approvaldisciplinary involvement and approval (A-I)(A-I)
– Incorporate local antimicrobial resistanceIncorporate local antimicrobial resistance patternspatterns
(A-I)(A-I)
– ProvideProvide education and feedbackeducation and feedback to practitionersto practitioners
(A-III)(A-III) idea ?idea ? Microbiology Newsletter.Microbiology Newsletter. Questions of theQuestions of the
week/monthweek/month

22. Antimicrobial order forms (B-II)Antimicrobial order forms (B-II)
Shown to be effective component of the programShown to be effective component of the program
and canand can facilitate planningfacilitate planning intointo practice.practice.
HelpsHelps auditaudit andand feedback.feedback.
– ensuresensures guideline-basedguideline-based appropriateappropriate empiricempiric
antibioticantibiotic ordering.ordering.
– Day 3 reviewDay 3 review bundlebundle based on investigations andbased on investigations and
clinical profile.clinical profile.
– Streamlining orStreamlining or de-escalationde-escalation therapytherapy (A-II)(A-II)
Antimicrobial order formsAntimicrobial order forms

23. Day 3 Antibiotic Review BundleDay 3 Antibiotic Review Bundle
Pulcini et al, JAC, 2008Pulcini et al, JAC, 2008

24. Parenteral to Enteral conversionParenteral to Enteral conversion (A-I)(A-I)
– As soon as the patient’s condition allowsAs soon as the patient’s condition allows
• Reduces length of stayReduces length of stay && healthcare costshealthcare costs
I.V. to oral switch overI.V. to oral switch over
Dose optimization via PK-PDDose optimization via PK-PD
Dose optimizationDose optimization (A-II)(A-II)
Based onBased on Organ dysfunctionOrgan dysfunction..
Patient characteristicsPatient characteristics (wt, age, sex,(wt, age, sex,
ethnicity),ethnicity),
CausativeCausative organismorganism ((virulencevirulence),),
SiteSite of infection (drug delivery to that site)of infection (drug delivery to that site)

25. – Hypothesis:Hypothesis: byby removing specific classesremoving specific classes ofof
antimicrobialsantimicrobials on a regular basison a regular basis, the, the
development of resistance can be avoided.development of resistance can be avoided.
Antimicrobial cycling – isAntimicrobial cycling – is not recommendednot recommended
because ofbecause of insufficient datainsufficient data (no ranking)(no ranking)
Antimicrobial cyclingAntimicrobial cycling
………………………………….

26. Barriers to Implementing AntibioticBarriers to Implementing Antibiotic
stewardship programmestewardship programme

27. The Vicious Spiral:
The Prescriber’s dilemma
--Must get right at allMust get right at all
cost.cost.
-Blanket cover is less-Blanket cover is less
stressful.stressful.
-Lack of faith in tests-Lack of faith in tests
-Defensive medicine-Defensive medicine
↑↑ use of newuse of new
drugsdrugs
↑↑ Use of broadUse of broad
spectrum drugsspectrum drugs
↑↑ C.difficleC.difficle
↑↑ costcost
↑ResistanceResistance

28. Barriers to Implementing AntibioticBarriers to Implementing Antibiotic
stewardship programmestewardship programme
Lack of understanding of problem…Who cares..Lack of understanding of problem…Who cares..
– Staff may not want to assume “added”Staff may not want to assume “added”
responsibility.responsibility. (No compensation)(No compensation)..
– The paradoxThe paradox:: higherhigher thethe antibiotic demandantibiotic demand moremore
earning,earning, happierhappier thethe beneficiariesbeneficiaries..
– ““ManyMany clinicians might feel offendedclinicians might feel offended to their rightto their right
to prescribe antibiotics freely (unrestricted)”to prescribe antibiotics freely (unrestricted)”
-Sunenshine RH, et al.-Sunenshine RH, et al. Clin Infect DisClin Infect Dis 2004;38:934-38.2004;38:934-38.
-Arvind Kejriwal-Arvind Kejriwal IACIAC

29. We can still do much without problem.
Every ounce of stewardship countsEvery ounce of stewardship counts
– start small,– start small, think bigthink big!!

30. We can still do a lot…..We can still do a lot…..
• Form anForm an Antibiotic stewardship teamAntibiotic stewardship team withwith
Hospitalists interested in infectiousHospitalists interested in infectious
diseasedisease..
• Educate:Educate: clinical guidelines, algorithms,clinical guidelines, algorithms,
infection control techniques.infection control techniques.
• Day 3 Antibiotic Review form.Day 3 Antibiotic Review form.

31. Day 3 Antibiotic Review form
Pulcini et al, JAC, 2008
-IV-PO switch.IV-PO switch.
-De-escalation.De-escalation.
-Audit and feedback.Audit and feedback.

32. We can still do a lot…..We can still do a lot…..
• Form anForm an Antibiotic stewardship teamAntibiotic stewardship team withwith
Hospitalists interested in infectious diseaseHospitalists interested in infectious disease..
• Educate:Educate: clinical guidelines, algorithms, infectionclinical guidelines, algorithms, infection
control techniques.control techniques.
• Day 3 Antibiotic Review form.Day 3 Antibiotic Review form.
-- IV-PO switch.IV-PO switch.
- De-escalation.- De-escalation.
- Audit and feedback.- Audit and feedback.
• PosterPoster ofof empiric treatment guidelineempiric treatment guideline..
• Microbiology newsletterMicrobiology newsletter with microbial resistancewith microbial resistance
review and feedback.review and feedback.
………………………….

34. A Disturbing Trend
1930 1940 1950 1960 1970 1980 1990 2000 2010
Sulfa, BL, AG,
Chloramphenicol
TCN, MAC, Vanc,
RIF, FQ, TMP
No new classes.
Modification of existing agents.
LZD,
DAP,
TIG
CBP; DAL;
New Entities
Limited
PCN-resistant S. aureus
MRSA
VRE
VISA in 7 states
VRSA
LZD-R S. aureus
MDR Pseudomonas and Acinetobacter, metallo-beta-lactamases, carbapenemases
Half of US and Japanese companies END
drug discovery

35. Computer Surveillance
• Sentri7
• SafetySurveillor-Pharmacy
• TheraDoc
• CPOE
• Benchmarking
• Antimicrobial use