Antimicrobial stewardship

1. Dr. CHINMOY SAHU
Additional Professor
Department of Microbiology
SGPGI
Antimicrobial Stewardship

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Created on 18th April 2022
PP-MGX-IND-0562 28th July 2022

3. Potential impact of antimicrobial resistance if left unchecked
• By 2050 more than 10 million people across the globe could be
dying per year as the result of an antimicrobial resistant infection.
(More than currently dying because of cancer.)
• Economic cost cumulatively to be more than $100 trillion US.
• Equates to burning $15,000 US for every man, woman, and
child on the planet.

4. Antibiotics
• The development and widespread use of antimicrobial agents has
been among the most important public health interventions in the last
century.
• Not a human invention per se, having been present in the
environment for millennia.
• Humans have co-opted the molecules that microorganisms use to
secure their ecologic niche in a world teeming with competitors.

5. First antibiotic stewardship programme

6. Terminology and usage
• Term coined by John McGowan and Dale Gerding in 1996
• Guidelines to prevent antibiotic resistance published by IDSA in 1997
• IDSA published guidelines for antibiotic stewardship in 2007
• 2014, antibiotic stewardship recommended in all US Hospitals by CDC

7. Saving Antibiotics
• Antibiotics are a shared resource
• Only drugs for which use in one patient impacts effectiveness
in others.
• The use of antimicrobials, however appropriate and
conservative contribute to the development of resistance.
• We need to promote prudent prescribing.
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8. Consequences of Resistance
• Longer duration of illness
• Increased HAI
• Higher mortality
• Treatment with expensive drugs
• Increased burden on the health system
• Patient acts as a reservoir of resistant
organisms for the community
• Estimates of Overuse, Misuse, Abuse
• Antimicrobials account for 30-50% of hospital pharmacy budgets.
• Up to 50% of antimicrobial use is inappropriate.

9. Another Problem…
“Antimicrobial
resistance is
increasing
while the
development of
newer
antimicrobial is
decreasing.”

10. Post antibiotic era
• WHO Director-General Margaret Chan said in March 2012 at a
medical meeting in Copenhagen:
• “A post-antibiotic era means, in effect, an end to modern
medicine as we know it….. Things as common as strep
pharyngitis or a child’s scratched knee could once again
kill……. Some sophisticated interventions, like hip
replacements, organ transplants, cancer chemotherapy, and
care of preterm infants, would become far more difficult or even
too dangerous to undertake.”

11. What is the solution?
• New drug discovery and manufacture
• “10 x ‘20” initiative: Highly challenging
• Reduce cross-infections: Infection Control practices
• Preserve efficacy of available antimicrobials: Antibiotic policy
• Optimize therapy: Antibiotic stewardship

12. Antimicrobial Stewardship
“Coordinated interventions designed to improve and measure the
appropriate use of antimicrobials by promoting the selection of
the optimal antimicrobial drug regimen, dose, duration of
therapy, and route of administration.

13. Antimicrobial Stewardship Philosophy
1. Optimizing clinical outcomes
2. Minimizing unintended consequences of antimicrobial use
• Toxicity.
• Selection of pathogenic organisms such as Clostridium
difficile.
• Emergence of resistance.
• Other adverse events
3. Reducing healthcare costs without adversely impacting the
quality of care.

14. Prerequisites to get started
• Convincing administration
• Sensitizing physicians and reassuring them the freedom to
choose initial therapy
• Providing evidence based data
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15. BUILDING THE STEWARDSHIP TEAM
Team Members
• Infectious diseases physicians
• Clinical and Hospital pharmacists with infectious disease training
• Clinical microbiologists
• Infection control staff
• Hospital epidemiologists
• Information system specialist
• Hospital administrators
• A mistake to delay implementation because of a lack of availability of
participants.

16. Work of a stewardship team
• Surveillance of prescribing practice and clinical outcomes
• Antibiotic use (various measures of quantities)
• Ecological impacts (antibiotic resistance development
and Clostridium difficile infection numbers)
• Clinical outcomes (morbidity and mortality rates).
• Design and implementation of interventions aimed at optimal
antibiotic prescribing.
• Structural
• Restrictive
• Persuasive

17. Stewardship Strategies
• Front-end / pre-prescription authorization approach.
(Restrictive)
• Back-end / post-prescription review and feedback approach
(Persuasive)
Most successful programs generally implement a combination of
both.

18. Front-end/pre-prescription authorization approach
• Uses restrictive prescriptive authority
• Certain antimicrobials are considered restricted and require prior
authorization for use by all except a select group of clinicians.
• For others approval from the steward will be required
Example:
Preauthorization requirements for use of clindamycin during
nosocomial epidemics of C. difficile infection have led to prompt
cessation of the outbreaks.
• Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN. Decrease in nosocomial Clostridium difficile-associated diarrhea by
restricting clindamycin use. Ann Intern Med 1994; 120:272–7

19. Advantages-
• Targets antimicrobials that are overused, misused, or abused.
• Antimicrobials can be approved for a specific duration, thereby
prompting review after culture data have been obtained.
• Immediate reduction in antimicrobial use and costs.
Disadvantages-
• Clinicians believe this approach threatens their autonomy.
• Transfer of patients between facilities with different policies results
in inappropriate therapy.

20. Back-end/post-prescription review and feedback
• Reviews all current antibiotic orders and provides clinicians with
recommendations to continue, adjust, change, or discontinue therapy
based on the available microbiology results and clinical features of
case.
Example-
In a large teaching hospital,
• Resulted in a 37% reduction in the number of days of unnecessary
levofloxacin or ceftazidime use by decreasing the duration of therapy,
• House staff learnt not to initiate unnecessary antibiotic treatment
regimens.
Solomon DH, Van Houten L, Glynn RJ. Academic detailing to improve use of broad-spectrum antibiotics at an academic
medical center. Arch Intern Med 2001; 161:1897–902.

21. Advantages-
• Avoids loss of autonomy for clinicians
• Facilitate direct interaction and feedback with the prescriber.
• Focus is on de-escalation
Disadvantages-
• Compliance with recommendations is voluntary.
• Requires active surveillance by an ASP, which is time
consuming.

22. Supplemental Antibiotic Stewardship Techniques
• Formulary restriction
• Treatment algorithm and clinical guidelines
• Education
• De-escalation
• Pharmacodynamic dose optimization
• IV to oral switch
• Computer surveillance and decision support
• Antibiotic cycling

23. Formulary Restriction
• First step towards stewardship because, making only certain drugs
available is a way to steer clinicians towards the use of those drugs.
• Price of drugs can be negotiated with pharma companies because
of use of more quantity of fewer drugs.
• Can be a challenge when patients transfer to hospitals with different
formularies.

24. Formulary Restrictions
• Step Therapy: Try Drug A first, then Drug B
• Quantity Restrictions: Limited amount of certain drugs

25. In response to an increasing incidence of cephalosporin resistant Klebsiella-
• Formulary restriction resulted in reduction in hospital- wide cephalosporin use,
• 44% reduction in the incidence of ceftazidime-resistant Klebsiella throughout the
medical center,
• And 71% reduction in the ICUs.
However,
• Imipenem use increased 141%,
• Accompanied by a 69% increase in the incidence of imipenem resistant P.
aeruginosa.
Rahal JJ, Urban C, Horn D, et al. Class restriction of cephalosporin use to control total cephalosporin resistance in
nosocomial Klebsiella. JAMA 1998; 280:1233–7.

26. Treatment Algorithms & Clinical Guidelines
• Can be paper or electronic.
• Prompts to make guideline-based antibiotic choices based on
• Relevant clinical factors
• Allergies
• Adjust for renal function
• Cost of therapy
• Order the appropriate tests, monitoring, and consultations.

27. Pocket or online
guidebooks for clinicians,
which contain empiric
antibiotic
recommendations for
common infections,
dosing guidelines etc.

29. Advantages
• Provides the opportunity to incorporate many thought leaders within a
hospital to develop hospital- or network-specific algorithms.
• Ability to reach out to frontline professionals who are not specialists in
infectious disease
• Guidelines use national recommendations but incorporate local trends in
antimicrobial resistance and hospital-specific targets for decreased use.

30. Education
• Designed to influence prescribing behaviour.
• Provide a foundation of knowledge that will enhance and
increase the acceptance of stewardship strategies.

31. De-escalation
• De-escalation is modification of the initial empiric antimicrobial
regimen based on culture data, other laboratory tests, and the
clinical status of the patient.
It includes -
• Changing a broad-spectrum antibiotic to one with narrower
coverage.
• Changing from combination therapy to monotherapy.
• Stopping antibiotic therapy altogether as it becomes more
apparent that these drugs are not needed.

32. Dose Optimization
• Use of PK/PD properties of antimicrobial agents to optimize
drug efficacy based on organism, site of infection, and patient
characteristics.
• Optimal use of antimicrobials may improve outcomes without
increased risk of toxic effects.

33. IV to Oral Switch
• Difficult to remember which medications are highly bio-available orally.
• Patients who are clinically stable and consuming a normal diet and
other oral medications are automatically switched by pharmacists to
oral drugs.
Fluoroquinolones
• Metronidazole
• Macrolides (azithromycin, erythromycin)
• Doxycycline
•Clindamycin
•Rifampin
•Linezolid
•Fluconazole

34. Computer Surveillance and Decision Support
• Provides unique opportunity for:
• Instantaneous feedback
• Education
• Alteration in prescription patterns
• Linked to patients records
• Presents epidemiologic information
• Warnings
• Assists in the selection of antibiotics

35. Computerized physician order entry (CPOE) is the process of electronic
entry of medical practitioner instructions for the treatment of patients under
his care.
These orders are communicated over a computer network to the medical
staff or to the departments (pharmacy, laboratory, or radiology) responsible
for fulfilling the order.
• Decreases delay in order completion,
• Reduces errors related to handwriting or transcription,
• Allows order entry at point-of-care or off-site,
• Provides error-checking for duplicate or incorrect doses or tests,
• Simplifies inventory and posting of charges

36. Example-
In a pediatric study, a Web-based automated clinical decision support tool
provided real-time communication with prescribers of antibiotics.
• This system resulted in an 11.6% reduction in doses of antibiotics
prescribed during 1 year and
• an increase in satisfaction of prescribers and pharmacists.
• The cost savings using this system was estimated at $370,069.
(Agwu AL, Lee CK, Jain SK, et al. A World Wide Web-based antimicrobial stewardship program improves
efficiency, communication, and user satisfaction and reduces cost in a tertiary care pediatric medical
center. Clin Infect Dis. 2008;47(6):747-753)

37. However, it introduces new types of errors-
• Gaps in antimicrobial therapy resulting from automatic discontinuation orders
• Inexperience may cause slower entry of orders at first
• Slower than person-to-person communication in an emergency situation
• Physician to nurse communication can worsen if each group works alone at
their workstations.
• Automation causes a false sense of security.
• Frequent alerts and warnings can interrupt work flow.

38. Antibiotic Cycling
Scheduled removal and substitution of specific antimicrobials
or antimicrobial classes in a given patient care unit.
• By removing specific classes of antimicrobials on a regular basis,
the development of resistance can be avoided.
• Inadequate studies to demonstrate its benefit.

39. If you cannot measure; you cannot improve.
-- Kelvin --
Process and Outcome
Measurements

40. Process
measure
Did the intervention
result in the desired
change in
antimicrobial use
Useful in determining
impact of the program
on antimicrobial use
and resistance pattern
Outcome
measure
Did the process
implemented reduce
or prevent unintended
consequence
Measure of quality
improvement

41. Process Measures
• “Process measurements” determine the degree to which the
intervention to change the use of an antimicrobial has been
successfully implemented, compared with baseline levels.
Did the intervention result in the desired change in antimicrobial
use?
• The units used are
1. Defined daily doses (DDD)
2. Days of therapy (DOT)

42. Process Measures contd…
Defined Daily Dose (DDD) =
Total number of grams of an antimicrobial agent used (per 1000 patients)
Number of grams in an average adult daily dose of the agent.
Disadvantage is that it does not account for
• Alternative dosing regimens due to renal dysfunction/age.
• Result in either overestimation or underestimation of drug
consumption.

43. How to calculate DDD

44. How to calculate DDD

45. How to Calculate DDD

46. How to calculate DDD

47. Days of Therapy

48. Hospital Statistics

49. Hospital Statistics

50. Process Measures
Antimicrobial consumption and expenditure-
often do not account for
• drug wastage,
• unused doses returned to pharmacy,
• fluctuations in institutional price
• discounts.

51. Outcome Measures
• “Outcome measurements” express the extent to which introduced
changes have reduced resistance or other unintended
consequences of antimicrobial use.
Did the process implemented reduce or prevent resistance or
other unintended consequences of antimicrobial use?

52. Outcome Measures contd……
Define the degree to which outcomes are altered (Point prevalence study)
• Antimicrobial resistance
• Adverse drug events
• Cost
• Unintended consequences, such as rates of C. difficile infection
• Clinical outcome variables- duration of hospitalization, mortality

53. Role of a Clinical Microbiologist
• 1970s – CDC formally recognized relationship of microbiology with
infection control
• Constantly changing spectrum of MDR pathogens and availability of
newer technologies -
• Need of regular communication between the microbiologists and
ID specialists
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54. Role of a Clinical Microbiologist
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•From Conventional……….
• Monitoring HAIs and environmental sampling
• Compiling antimicrobial susceptibility data

55. …….Evolving Role
• HIC team member– intervention strategies
• Antimicrobial stewardship
• Rapid and molecular lab diagnosis , early identification of emerging
pathogens
• Training medical students, doctors and nurses
• Antibiotic policy revision
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56. Stewardship: In-vitro Susceptibility Test
• Selecting antimicrobial agents
• Reporting results using interpretative criteria which is mainly based
on usual dosage and regimens
• Selective reporting ?
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57. Problems in Constituting a Team
• Infectious disease physicians Only handful in entire country.
• Clinical pharmacist Only involved in dispensing
• Clinical microbiologist Mostly confined to labs
• Infection control professional/ nurse No formal training
• Hospital epidemiologists Non-existent

59. “I did not fail one thousand times;
I found one thousand ways how not to
make a light bulb.”
---Thomas Edison---

60. Thank
You