This document discusses antimicrobial stewardship, including reasons for inappropriate antimicrobial use, the concept of antimicrobial stewardship programs, strategies for antimicrobial stewardship programs, and metrics for monitoring compliance. It notes that antimicrobial resistance is a global threat and excessive antimicrobial use has contributed to the problem. Antimicrobial stewardship programs aim to optimize antimicrobial use and limit unintended consequences through multidisciplinary teams implementing educational programs, formulary restrictions, prior approval programs, and other strategies while monitoring outcomes.

1. Antimicrobial Stewardship –
Methodology and metrics
Dr. Abhijeet Mane
August 30, 2021 1

2. Index
 Introduction
 Reasons for inappropriate use of
antimicrobials
 Concept of Antimicrobial Stewardship
 Antimicrobial Stewardship program
 Antimicrobial Stewardship strategies
 Monitoring compliance to AMSP
 Role of Microbiologist
 Conclusion
August 30, 2021 2

3. Introduction
 Antimicrobial resistance (AMR) is a global
threat today
 By the year 2050, Asia will have 4.7 million
deaths that could be directly attributed to
AMR
 Excessive use of antimicrobials in early
1940s
 Jawetz (1956) recognised this problem
 60% of all hospitalised patients in USA – 1
dose atleast
 50% of this use is unnecessary
August 30, 2021 3

4. Situation in India
 Antimicrobial resistance rampant in India
 E.coli - 12-59 % ESBL producers, 30% Carbapenemase
producers
 Klebsiella pneumoniae - Upto 50% Carbapenemase and
rapidly increasing resistance to polymyxins
 MRSA - up to 30% of S. aureus isolates nationally
 India is the largest consumer of antibiotics in the world i.e., 13
billion standard units in 2010 and from 2000 to 2010 the per
capita consumption increased by 66%.
 In May 2015, the World Health Assembly adopted a resolution
to endorse a global action plan on antimicrobial resistance.
August 30, 2021 4

5. The 30% rule
 Antimicrobial prescribing facts: the 30%
rule
 30% of all hospitalised inpatients…
 30% prescribed inappropriately
 30% of all Sx prophylaxis inappropriate
 30% hospital pharmacy cost due to
antimicrobials
 10-30% cost can be saved by
Antimicrobial Stewardship Programs
(ASPs)
August 30, 2021 5

6.  In India, drug resistance
emerged to
Carbapenems
 Due to OTC availability
of antimicrobials for use
of human, animal,
industry use
 Guidelines for RNTCP,
NACP, NVBDCP,
present
 Not available for enteric
fever, August 30, 2021 6

7. Role of animals…
 Use of Antimicrobial Avoparcin:
development and amplification of VRE
 Enerofloxacin use approved in many
countries: resulted in Ciprofloxacin
resistant Salmonella spp and
Campylobacter spp --- humans too
 Animal feed supplements with Tylosin –
Erythromycin resistant Streptococci and
Staphylococci in animals and handlers
 WHO called for strict legislation to
minimise use
August 30, 2021 7

8.  Unwanted consequences of
antimicrobial therapy
 MDR organisms
 Increase in resistance rates not
matched by development of newer
antimicrobials
 Hence smart use is advised
August 30, 2021 8

9. Reasons for inappropriate use of
antimicrobials
 Good intentions
 Inappropriate dosing
 Inappropriate prophylaxis
 Use of multiple antimicrobial agents
 Pressure from patient
◦ Treating trivial infections / viral Infections
with Antibiotics
August 30, 2021 9

10.  Time constraints
 Cost and availability of
Radiographic/Lab studies
 Inadequacy of Physicians’ knowledge
of diagnostic procedures
 Fear of litigation
 Pressure/Perks by Pharma companies
 Poverty
August 30, 2021 10

11. Antimicrobial Stewardship
 Coined in 1996
 Stewardship: the activity or job of
protecting and being responsible for
something (Marriam – Webster
dictionary)
 Antimicrobial Stewardship: “Processes
designed to optimize the appropriate use
of antimicrobials by ensuring that every
patient receives an antibiotic only when
one is needed, with right agent, at right
dose, by right route, right duration, in
order to improve patient care and
optimize health care outcomes while
minimizing unintended consequences”
August 30, 2021 11

12. AMSP –Indian Scenario
 ICMR survey among 20 tertiary health care
institutes (HCI) about AMSP components,
implementation and outcome:
◦ only 40% of HCIs had AMSP written documents,
◦ 75% of HCIs had HIC guidelines and
◦ 65% had antimicrobial agents (AMA) prescription guidelines
◦ 30% HCIs had AMSP implementation strategies.
 Private HCI better performance compared to
Government HCI in AMSP: accreditation process.
 Survey report: absence of ID physicians and CPs
in institutions.
 This shows the huge lacunae for AMSP in India
and the dire need to implement AMSP on priority.
August 30, 2021 12

13. Antimicrobial Stewardship (AS)
program
 Running an AS program needs an :
◦ AS team
◦ AS strategies
 AS team:
◦ Multidisciplinary team with core membership
of
◦ An ID physician
◦ A Clinical Microbiologist
◦ A Clinical Pharmacist with expertise in ID
◦ Other members: ICNs, Hospital
Epidemiologist, Director (IT), Infection
August 30, 2021 13

14. Infrastructure support
 Essential to initiate pathogen directed
Rx
 Support from Microbiology laboratory
◦ Automations – Automated culture (Bactec
/ BacT/Alert), Identification (MALDITOF),
AST (Vitek) should be available
◦ Biomarkers – procalcitonin, CRP
◦ Molecular tests – Biofire FilmArray
multiplex PCR
◦ Emergency laboratory
Hospital Information System – fully
functional August 30, 2021 14

15. Framing antibiotic policy
 Should be unique to each hospital
 Available in form of pocket handbook,
e-book
 Should be prepared by AMS team in
consultation with clinicians,
microbiologists, administrators
 Should be acceptable by all
stakeholders
 Compliant to standard national /
international antimicrobial guidelines
August 30, 2021 15

16. Antimicrobial Stewardship
strategies
 Educational
Programs
◦ Hallmark activity of
ID physician
◦ Staff conferences,
lectures by visiting
Professors,
newsletters,
bulletins, email
alerts, etc.
◦ Continuous
reinforcement
necessary
 Antimicrobial
formulary
restrictions
◦ Most direct method
◦ Prohibit use of
newer, more
expensive antibiotics
◦ Landmark study by
Woodward et al:
cost saving of USD
24000/month for all
antibiotics
August 30, 2021 16

17.  Prior approval programs
◦ Telephone approval
◦ Antibiotic order forms
◦ Automatic stop orders
◦ Direct interaction with AS team
◦ Cost per treatment day, cost per
admission and total doses differed
significantly from pre-study periods
August 30, 2021 17

18. August 30, 2021 18
 Prospective audits and feedback
programs
◦ Feedback to be educational & evidence
based
◦ i/v to oral Rx: switch or stepdown Rx
(fluoroquinolones, metronidazole,
clindamycin, trimethoprim-
sulfamethoxazole, fluconazole)
◦ Broad spectrum to Narrow spectrum
(streamlining) may be tried

19.  Computer assisted
stewardship
programs
◦ Instant feedback,
education and
prescription alteration
◦ LDS hospital in Salt
Lake city, Utah, USA
◦ Epidemiology, detailed
info, warnings, etc.
◦ www.theradoc.com
◦ WHONET
 Antibiotic rotation
(cycling)
◦ Due to HAIs
◦ Rationale
◦ Kolleff et al: switched
empiric therapy of
suspected GN
infections from Ceftaz
to Cipro at 6 month
intervals
◦ Led to decrease in
VAP from 11.6% to
6.7% and lowered
bacteremia
August 30, 2021 19

20. Monitoring compliance to
AMSP
 If you cannot measure it, you cannot
improve it
 Process indicator
◦ Policy adherence indicator
 Outcome indicator
◦ Antimicrobial usage outcome indicator
◦ AMR outcome indicator
◦ Clinical outcome indicator
◦ Financial outcome indicators
August 30, 2021 20

21.  Policy adherence indicator
 Achieved by conducting AMS audit
◦ Prescription compliance
◦ Administrative compliance
August 30, 2021 21

22. Process indicator
Prescription compliance Administrative compliance
 % of time the empiric Abx
given is as per infective
syndrome suspected
 % of time the empiric Abx
is modified as per AST
report
 % of time cultures are
taken before start of Abx
 % of time SAP is given
as per Abx policy
 % of time the Abx
administered in correct
dose, frequency, route
 % of time the SAP is
administered in correct
dose, time, frequency
August 30, 2021 22

23. Outcome indicator
 Antimicrobial usage outcome indicator
◦ Defined Daily Dosage (DDD)
◦ Days of therapy (DOT)
 AMR outcome indicator
◦ Change in AMR pattern analysed by
periodic AMR surveillance
August 30, 2021 23

24. Outcome indicator
 Clinical outcome indicator
◦ Morbidity (eg length of stay)
◦ Mortality (eg infection related deaths)
 Financial outcome indicator
◦ Antimicrobial cost per day
◦ Antimicrobial cost per year
◦ Antimicrobial cost per admission
August 30, 2021 24

25. Defined Daily Dose (DDD)
 Is average maintenance dose per day
for a drug used for its main indication
in adults
 The DDD is a unit of measurement
and does not necessarily correspond
to the recommended or Prescribed
Daily Dose (PDD)
 DDD cannot be used in estimating Abx
consumption in pt. with renal failure,
paediatric pt., because daily dose is
lower than average dose defining the
DDD August 30, 2021 25

26. How does DDD help us?
 Examine changes in drug utilization over
time
 Evaluate the effect of an intervention on
drug use
 Document the relative therapy intensity
with various groups of drugs
 Follow the changes in the use of a class
of drugs
 Evaluate regulatory effects and effects of
interventions on prescribing patterns.
August 30, 2021 26

27. Calculation
No. of DDD =
Therapeutic dose (No. of tablets /vials used x gm per
tablet / vial)
---------------------------------------------------
WHO defined DDD of the antimicrobial agent
Ex. – Levofloxacin is administered as 750 mg PO
daily for 7 days. The WHO assigned DDD for
levofloxacin is 0.5 gm
Therefore, the number of DDD is calculated as:
= (0.75 g dose x 7 days / 0.5 g DDD) = 10.5 DDDs
August 30, 2021 27

28. Days of Therapy (DOT)
 Is the number of days that patient
receives at least one dose of that
antibiotic
 Used in estimating Abx consumption
in pt. with renal failure, paediatric pt.,
 Preferred over DDDs
August 30, 2021 28

29.  E.g. A pt. has received
◦ Meropenem 1gm, twice daily for 3 days;
the DOT is 3
◦ Meropenem 0.5 gm, thrice daily for 3
days; DOT is 3
◦ Meropenem 1gm, twice daily and
Vancomycin 1gm thrice daily for 3 days;
DOT is 3+3 = 6
August 30, 2021 29

30. Rational use of Antimicrobial
agents
 Advice on following aspects to be given to clinicians
 Prescribe only when indicated
 Culture of cultures
 Empirical vs. Targeted therapy
◦ Escalation vs. De-escalation Approach
 Site specific antimicrobials
 Avoid administration errors
 MIC guided therapy
 Therapeutic drug monitoring
 Timely stoppage of antimicrobial
 Biomarkers guided therapy
 Misuse of antimicrobials
August 30, 2021 30

31. Prescribe only when indicated
 Antibiotics not required –
◦ Diarrhea – ORS is mainstay. Moreover,
most diarrhea is viral etiology
◦ URTI – common cold, sore throat
 Primary cause viral (except Streptococcal sore
throat, Diphtheria etc. suspected)
◦ Prophylaxis – routine antibiotic
prophylaxis not to be given to prevent
infection (except Cotrimox – HIV)
August 30, 2021 31

32. Culture of cultures
 Abx always after site specific cultures
specimens collected
 False negative if collected after
 Not help targeted therapy
August 30, 2021 32

33. Empirical therapy
Empiric therapy
 Not to be given
randomly
 Based on 3 important
elements
 Infective syndrome
likely to be present
 Common etiological
bacterial agents for
that infective
syndrome
 Local antibiogram for
those organisms with
AMR patterns
Indicated ONLY in
 Febrile neutropenia
 Severe sepsis and
septic shock
 Community acquired
pneumonia
 Ventilator associated
pneumonia
 Necrotizing fasciitis
August 30, 2021 33

34. Targeted therapy
 Empiric therapy to be modified
subsequently based on AST report
 Modifications
◦ Escalation
◦ De-escalation
August 30, 2021 34

35. Escalation vs. De-escalation Approach
 Approach needs to be chosen based
on local AMR pattern and spectrum of
activity of the antibiotic
 Antibiotic for an organism can be
ranked based on their spectrum of
activity and local AMR
August 30, 2021 35

36. Site specific antimicrobials
 Abx active at site of infection to be
prescribed
◦ Lungs – Daptomycin not active as gets
inactivated by surfactants
◦ CSF – Any oral Abx, 1st and 2nd GC,
tetracyclines, macrolides, quinolones,
clindamycin not active in CSF
◦ Urine – Chloramphenicol, macrolide, clindamycin
don’t achieve adequate urinary concentrations
August 30, 2021 36

37. Avoid administration errors
 Abx should be administered at correct dose,
frequency and duration
 Loading dose – concentration dependent Abx
(AGs, Vancomycin, Colistin) should be
administered with a loading dose
 Infusion – Vancomycin – efficacy better when
mixed with saline and given as iv infusion over 2-3
hours
 Renal adjustment – Nephrotoxic drugs (AGs,
Vancomycin, Colistin) to be adjusted as per
Creatinine clearance
August 30, 2021 37

38. MIC guided therapy
 AST
◦ KBDD method or MIC method
◦ MIC – more accurate and reliable
 Situations where Abx therapy is MIC
guided
◦ Endocarditis, pneumococcal
meningitis/pneumonia, etc.
◦ Vancomycin for S.aureus – Vancomycin
should be avoided if MIC > 1ug/mL
August 30, 2021 38

39. MIC guided therapy…
 MIC helps to select
most appropriate
antibiotic
 Lower the MIC, better
is therapeutic efficacy
 If >1 AMA susceptible,
then antibiotic having
lowest MIC (when
compared with
susceptibility
breakpoint) should be
chosen for Rx
 Better calculated by
Therapeutic Index
 Therapeutic Index
 Ratio of susceptibility
breakpoint divided by
MIC of test isolate
 Higher the TI, better is
the efficacy of AMA
August 30, 2021 39
E.coli Meropene
m
Amikacin
MIC 1 ug/ml (S) 8 ug/ml (S)
Break
point
1 ug/ml 16 ug/ml
TI 1/1=1 16/8=2
Amikacin superior to Meropenem, in this case

40. Therapeutic Drug Monitoring
 Therapeutic efficacy depends on
 In vitro MIC and in vivo activity
 Which depends on PK/PD of AMA
 On basis of PK/PD, Abx classified as
◦ Concentration dependent
◦ Time-dependent
August 30, 2021 40

41. Conc. dependent
 E.g.
Aminoglycosides
 Work better if drug
conc. in serum
much higher than
its MIC
 Usually given as
loading dose.
Time dependent
 E.g. beta lactams
 Work better if drug
conc. in serum
higher than MIC for
longer duration
 Hence given
frequently (tds)
August 30, 2021 41

42. August 30, 2021 42

43.  Timely stoppage
of antimicrobial
 AMA must be
stopped at
appropriate time
 Determined by
◦ Clinical
improvement or
◦ After negative
culture or
◦ Using biomarkers
 Biomarkers-
guided therapy
 E.g. Procalcitonin
(PCT) or C-reactive
protein (CRP)
 PCT more reliable
than CRP
August 30, 2021 43

44. Misuse of Antimicrobials
 Common examples of misuse-
◦ Avoid overlapping spectra
◦ Redundant antibiotic
◦ Ineffective antibiotic
◦ Inferior antibiotic
August 30, 2021 44

45. Role of Microbiologist
 Antibiogram reporting
◦ Conducts surveillance on local antimicrobial
resistance trends among microbial pathogens
◦ Collection, organization and communication
of resistance data : Antibiogram
◦ Antibiograms provide critical information to
ASPs
◦ Individual physicians can refer to their
institution antibiogram for guidance
◦ Antibiograms can be used for developing
specific guidelines for prescribing
◦ Cumulative antibiograms helpful
August 30, 2021 45

46.  Example 1:
 Drug A overall
susceptibility <80%
 All LTCFs showed
low susceptibility
 Microbiologist
investigated
 Conclusion
August 30, 2021 46

47.  Example 2:
 Susceptibility of
Drug A decreased
10%
 Change in empiric
therapy advised
 Microbiologist
investigated
 Conclusion
August 30, 2021 47

48.  Hence, patient demographic factors
such as differences in age, co-
morbidities, hospital exposure and
prior antibiotic exposure significantly
impact cumulative antibiogram reports
 Hence Microbiologist should be
included in ASP as core member
August 30, 2021 48

49.  Specimen & Reporting quality
 Labs should ensure that high quality
specimens are only processed
 Promotion of appropriate specimen
collection
 Sample rejection
August 30, 2021 49

50. Tenets of Specimen
Management
 Reject poor quality specimens
 Don’t report “everything that grows”
 “Background noise” to be avoided
 Lab requires a specimen, not swab of
specimen
 Follow lab procedure manual religiously
 Collect specimen prior to antibiotics
 AST on clinically significant isolates only,
not all
 Specimens to be labeled accurately
August 30, 2021 50

51.  Improving patient care with rapid
diagnostics
 MALDI – TOF
 Quantitative PCR, etc
 Greatly reduce time to pathogen
identification
August 30, 2021 51

52.  Communication is the key
 May be verbal or written
 Reporting should be timely, clear,
understandble and accessible to
clinicians
 New test started – educate clinicians
 Lab rounds:
◦ Microbiologist: discusses culture growth
◦ Clinician: clinical details of patient
August 30, 2021 52

53. Conclusion
 Healthcare is changing
 High quality care in cost constrained
environment
 Although data still evolving,
comprehensive ASPs have potential to
decrease costs while improving
patient care and institutional outcomes
53 53

54. References
 Mandell, Douglas, and Bennett’s Principles and practice of
infectious diseases 7th edition 2010
 Baron et al. A guide to utilization of the microbiology Laboratory
for diagnosis of infectious diseases: 2013 recommendations by
the infectious Diseases society of america (IDSA) and the
American society for microbiology (ASM) Clinical Infectious
Diseases 2013
 Srivastava BK. National policy for Containment Of Antimicrobial
resistance. India 2011
 Redell M. The Microbiologist as an Active Member of the
Antimicrobial Stewardship Team: A Value Proposition. CLSI
communities. www.clsi.org
 Dellit TH et al. Infectious Diseases Society of America; Society
for Healthcare Epidemiology of America. 2007.Infectious
Diseases Society of America and the Society for Healthcare
Epidemiology of America guidelines for developing an
institutional program to enhance antimicrobial stewardship. Clin.
Infect. Dis. 44: 159 –177.
 Apurba Sastry. Essentials of Medical Microbiology. 3rd edn. 2021
August 30, 2021 54

55. Thank you!!!
August 30, 2021 55