Antibiotics are most common therapeutic agents used in hospitals across world, however, microbial world is becoming resistant day by day, posing special challenges to clinicians specially working in ICU set ups. There are multiple ways to curb this menace, if approached together in antibiotic stewardship way, can bring about wonders and retain therapeutic potentials of these drugs.

1. In critical care

2. In critical care

3. Points of this talk..
• Antibiotic resistance and its high prevalence
• Solution: Antimicrobial Stewardship
• Impact of antimicrobial stewardship program

5. Antibiotic resistance
• Prevalence of nosocomial infections in ICU:
10-30 %.
• 50% to 60% of all nosocomial infections are
caused by antimicrobial-resistant strains of
bacteria.
• Increasing resistance make the selection of
appropriate antimicrobial therapy extremely
challenging.

6. Sir Alexander Fleming
New York Times
June 26, 1945

8. Antibiotic resistance is worldwide

9. Indian perspective
Bad bugs rate 40 % higher in Indian
ICUs than general ward

10. 25 % critically ill patients acquired infections.
The initial empiric choice of antibiotic started was
inappropriate for 52% organisms.

11. Isolated bacteria showed a very high rate of resistance to the Cephalosporins
namely Cefuroxime, Ceftazidime, Cefixime, Cefpodoxime
0
10
20
30
40
50
60
Percent
Isolates ICU Infection rate 28.3 %

12. NDM-1 gene originated in India
New Delhi metallo-beta-lactamase-1 is a gene
(DNA code) carried by some bacteria.
A bacterium carrying the NDM-1 gene is the
most powerful superbug around.
No current antibiotics to combat NDM-1
Europeans who have undergone hospitalization
in the Indian subcontinent have brought NDM-1
back to Europe.

13. Top Six MDROs
ESKAPE ESCAPE
• Enterococcus faecium
• Staphylococcus aureus
• Klebsiella pneumoniae
• Acinetobacter baumannii
• Pseudomonas aeruginosa
• Enterobacteriaceae
• Enterococcus faecium
• Staphylococcus aureus
• Clostridium difficile
• Acinetobacter baumannii
• Pseudomonas aeruginosa
• Enterobacteriaceae
2007 2009
Clin Infect Dis. 2009;49(6):992-993

14. Why is Antimicrobial resistance becoming major public health concern?
Antimicrobial
Resistance
Public Health Concern
Genetic
plasticity of
bacteria
Acquisition of
resistant
bacterial
infections
Market
failure of
antibiotic
development
Overuse and
misuse of
antibiotics

15. Bad bugs no drugs !!
Superbugs
New
antibiotics

17. 0
2
4
6
8
10
12
14
16
1983-
1987
1988-
1992
1993-
1997
1998-
2002
2003-
2007
2008-
2011
Newantibacterialagents
Number of New Molecular Entity (NME) Systemic Antibiotics
Approved by the US FDA Per Five-year Period, Through 3/11
Clinical Infectious Diseases 2011;52(S5):S397–S428

18. To solve pipeline problems

19. ICUs are epicenters of antimicrobial
resistance in hospitalized patients
• Heavy use of antibiotics
• Previous exposure to antibiotic
• Presence of invasive devices
• Prolonged length of hospital stay
• Immune suppression
• Malnutrition
• Cross-contamination helps in spread

21. Defining Initial Inadequate Therapy
• The antibiotic did not cover the infecting pathogen(s)
• The pathogen was resistant to the antibiotic
• Dosing was not adequate
• Combination therapy was not used, if indicated.
1Kollef MH et al. Chest 1999;115:462-474.
2Ibrahim EH et al. Chest 2000;118:146-155.
Initial therapy is considered to be inadequate if:

22. Impact of AMA
resistance
Higher
mortality
rates
Longer length
of ICU and
hospital stays
Higher
medical
costs

24. ANTIMICROBIAL
RESISTANCE
What are the solutions?
ANTIMICROBIAL STEWARDSHIP Prevention and
control of
Nosocomial
infections

25. What is antimicrobial stewardship?
• For improving the overall use of
antimicrobials and reducing the problems
of Antimicrobial Resistance & drug
toxicities.

26. Primary Goal of antimicrobial stewardship
To optimize clinical outcomes while minimizing
unintended consequences of antimicrobial use.

27. Improved techniques for Diagnosis of infections
Improved Dosing of antimicrobials
Decreased duration of antimicrobial therapy
Use of Combination Antimicrobial Therapy
Use of antimicrobial Protocols and Guidelines,
Scheduled antimicrobial rotation or “Cycling,”
Hospital formulary-based Antimicrobial Restrictions,
Early involvement of infectious disease experts in management of
infectious diseases

28. Rapid Diagnosis: Impressive in ED
PCR and other molecular based
techniques may be helpful
Evaluate patient for noninfectious
sources of fever.
Obtain appropriate specimens for
culture & susceptibility testing.

29. a. Consider known/probable site of infection and most likely
pathogens.
b. Consider colonization versus infection when evaluating culture
results.
c. Consider rates of antimicrobial resistance among potential
pathogens.
d. Consider need for combination antimicrobial therapy versus
monotherapy.
e. Initial therapy should be broad spectrum, parenteral, and at
appropriately aggressive doses.
1. Consider pharmacokinetic & pharmacodynamic properties
2. Consider age, organ dysfunction, and site of infection when
determining proper dose.
3. Consider potential drug-related adverse effects and toxicities.
4. Consider potentially relevant drug/drug or drug/diseas

30. a. Monitor culture and susceptibility test results.
b. Known pathogen: narrowest spectrum AMA.
c. Combination therapy
d. Appropriately aggressive doses.
(1) Pharmacokinetic and pharmacodynamic properties
(2) Age, organ dysfunction, and site of infection when determining
proper dose.
(3) Potential drug-related adverse effects and toxicities.
(4) Potentially relevant drug/drug or drug/disease state
interactions.
(5) Use of less expensive agents when appropriate

31. a. Patients clinically respond to parenteral therapy.
b. Patients have functional gastrointestinal tracts.
c. Suitable oral alternatives to parenteral therapy
are available.

32. a. Evaluate for clinical resolution of signs and symptoms
and evidence of response to therapy.
b. Evaluate for changes in organ function that may
require change in drug-dosing regimen.
c. Monitor serum drug concentrations when appropriate.
d. Evaluate for drug-related adverse effects and toxicities.
e. Evaluate for potential adverse drug interaction

33. a. Evaluate patient for unidentified or new sources/sites of
infection or superinfection.
b. Obtain additional specimens for culture and susceptibility
testing.
c. Evaluate drug regimen for proper spectrum of activity
against known or presumed pathogens.
d. Consider emergence of antibiotic resistance among certain
pathogens (e.g., Pseudomonas aeruginosa).
e. Evaluate drug regimen for proper dosing of individual
antimicrobial agents.
f. Consider pharmacokinetic and pharmacodynamic
properties of agents and potential need for increased daily
doses or alternative dosing methods.

34. a. Short courses are desired over long courses in patients
who have promptly responded to antimicrobial therapy.
b. In patients with no documented infection/pathogens,
discontinue antimicrobials after appropriate course of
therapy and assess continued need for treatment

35. • By utilizing relevant patient information, drug
history and microbiological laboratory results,
these systems aim to improve physician
antibiotic drug selection.

36. Significant improvement in susceptibility of Pseudomonas

37. AST
members
Infectious
disease
physician
Clinical
Pharmacist
Infection
control
MicrobiologyEpidemiologist
Staff and
residents
P &T
Committee

38. http://chennaideclaration.org/aboutus.htm
first ever joint meeting of medical societies in India addressing antibiotic
resistance, held in Chennai in August 2012

39. Impact of antibiotic stewardship
• Reduced emergence of antibiotic resistance
• Reduced drug related adverse events
• Reduced cost
• Reduced mortality
Surg Infect (Larchmt). 2011 Feb;12(1):15-25.

40. Impact of antibiotic stewardship
• In a study of two ICUs in the United States that
implemented a comprehensive antimicrobial
stewardship program, the proportion of hospital-
acquired infections (HAI) caused by certain
multidrug resistant gram-negative bacilli,
including P. aeruginosa, A. baumannii, and ESBL-
producing Enterobacteriaceae decreased from
37.4 percent in 2001 to 8.5 percent om 2008,
whereas the proportion of HAIs caused by
susceptible isolates increased from 34.1 to 53.2
percent
Surg Infect (Larchmt). 2011 Feb;12(1):15-25.

41. • Similarly, in a study of an ICU in Melbourne,
Australia, which implemented an antimicrobial
stewardship program, 2838 gram-negative bacilli
were isolated from clinical cultures over seven
years, and over this time, there was significant
increases in susceptibility of P. aeruginosa to
imipenem (18.3 percent/year, p= 0.009) and
gentamicin (11.6 percent/year, p=0.02) compared
with trends recorded prior to the stewardship
program
J Antimicrob Chemother. 2010 May;65(5):1062-9.

42. • Restricted and judicious antibiotic utilization,
often implemented, as part of a global
institutional antimicrobial stewardship
program, can decrease selective pressure that
promotes emergence of resistant bacterial
strains.

43. Appropriate Early Antibiotic Therapy Reduces Mortality
Rates In Patients With Suspected VAP
Iregui et al. Chest 2002;122:262–268
Mortality (%)
Hospital mortality Mortality attributed
to VAP
0
60
80
20
40
p<0.01
p<0.001
Initially delayed antibiotic treatment
Early appropriate antibiotic treatment

44. Antimicrobial stewardship in ED
• Rapid turn over
• Busy environment
• Liberal use/ overuse of
antibiotics
• Lack of time for follow
up
Difficult task !!!
fear of missing an infection

45. What’s next after antibiotics

46. Summary
• Role in preventing inappropriate antibiotic
use.
• Small skin abscesses can be treated with I & D
alone: antibiotics not needed.
• Emergency physicians are on the front lines
of antibiotic prescribing.