Transcript Antibiotic Stewardship– Presenter

The Resistance Problem
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PRSP = Penicillin Resistant Strep. pneumoniae
QRSP = Quinolone Resistant Strep. pneumoniae
MRSA = Methicillin Resistant Staph. aureus
VRE = Vancomycin Resistant Enterococci
– VRE in Canada: 1993: first isolated  1997: >800 cases
– MRSA in Ontario: 1992: <100 cases  2000: >9000 cases
• Resistance rates differ dramatically between Canada
and the U.S.
Worldwide Distribution of Penicillin Resistant Pneumococci
The Problem
Russia
7%
Canada
14%
• Graph of Global Resistance patterns?
Israel
54%
USA
41%
Japan
64%
Mexico
53%
Brazil
31%
Kenya
49%
Saudi Arabia
62%
Singapore
53%
South Africa
80%
Hong Kong
80%
Principles of Antibiotic Prescribing
Ideal World
Real World
1. Known organism(s) with
predictable sensitivity
• Organism(s) frequently unknown
• Information often unclear in clinical decision-making
• Spectrum of sensitivity changing, especially due to bacterial
resistance
2. History, physical exam
(+/- simple, available tests) to
establish firm working diagnosis
• May or may not be helpful (e.g., URTI vs sinusitis).
3. Natural history of condition is
known, and drug intervention is
helpful in changing it
• Sometimes true (e.g., AECB), but frequently ignored in
decision making (e.g., acute OM; acute bronchitis)
• Evolving knowledge of disease natural history
4. High likelihood that morbidity
and complications can be
reduced by drug treatment.
• How often do our interventions actually reduce morbidity or
complications?
• Primary care practice is failure-based
• "It won't do any harm"
5. First and foremost, do no harm
‘Primum, non nocere’
• Evidence of real individual and social harm with current
patterns of antibiotic use
• Individual harm: Allergy (lifelong), increased intolerance,
morbidity, increased susceptibility to other infections
Antimicrobial Resistance
• Understanding Resistance:
 Darwin’s theory of natural selection
 Minimum Inhibitory Concentration (MIC)
 Clinical and Laboratory Standards Institute
(CLSI) reporting system based on MIC:
Susceptible (S)
Intermediate (I)
Resistant (R)
Interpretation of Susceptibility Data:
• In vitro susceptibility testing only involves the
bug and the drug
• Antimicrobial resistance vs clinical resistance
• MIC value needs to be considered in context
of patient factors
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Type of infection
Location of infection
Antibiotic distribution
Antibiotic concentration at site of infection
Contributing Factors to Resistance
• Overuse in humans
More than 50% of antibiotics in Canada are
prescribed for viral URTI’s
• Animal and agricultural use:
 Accounts
for 50% of all antimicrobials
 Used for prevention/treatment of infection
and growth promotion
 Evidence of resistant strains in livestock
Implications Of Resistance
• Treatment failure
• Forced to use more toxic alternatives
• Possibility of no alternate agents
(e.g., vancomycin-resistant S. aureus)
• Longer hospital stays
• Forced to use more expensive alternatives
and other increased healthcare costs
S. pneumoniae
• Spectrum of Disease
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Otitis Media
Sinusitis
Bronchitis
Pneumonia
Meningitis
• Treatment
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Penicillin
Cephalosporins
Macrolides
TMP/SMX
Tetracyclines
Quinolones
PRSP - Prevalence
1980s
- < 2.0%
1998
- 16.0% (with up to 5% with
high-level resistance)
1999
- 12.0%
2000
- 12.3 – 16.9%
CMAJ 2002; 167(8)
Figure 1. Percentage of Penicillin Non-Susceptible
S. pneumoniae in Canada: 1988-2007
18
% intermediate resistance
16
% high-level resistance
14
12
10
8
6
4
2
0
1988
1993
1995
1997
1999
2001
2003
2005
2007
Canadian Bacterial Surveillance Network, March 2008
Penicillin Resistant S. pneumoniae Isolates
Ontario 1988, 1993-2005
14
% Intermediate Resistance
12
% High-level Resistance
10
8
6
4
2
0
1988
1993
1995
1997
1999
2001
2003
2005
Canadian Bacterial Surveillance Network, March 2006
Figure 5. Macrolide-Resistant Pneumococci: Canadian
Bacterial Surveillance Network, 1988-2007
20
Erythromycin
Percentage of Isolates Resistant to
25
15
10
5
0
1988
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Canadian Bacterial Surveillance Network, March 2008
Figure 4. Percentage of Non-susceptible Isolates of
S. pneumoniae in Geographic Regions of Canada, 2007
30
25
20
15
10
5
0
BC
PRAIRIES
Levo
ONT
Ceftri (Non-mening)
QUE
Clind
Atlantic
Pen
Eryth
Canadian Bacterial Surveillance Network, March 2008
PRSP – Cause / Spread
JAMA 1998;279:365-370.
• 941 children in observational study
• Nasopharyngeal carriage of S.
pneumoniae determined
• Low doses and long duration of ßlactam treatment was associated with
increasing penicillin resistance
PRSP – Cause / Spread
BMJ 2002; 324 - 461 children in Australia
• Examined nasopharyngeal carriage of S. pneumoniae
• Likelihood of carrying PRSP doubled in children who
had used a beta-lactam in the previous 2 months
• >7 days of antibiotics resulted in higher PRSP carriage
• PRSP present even in children who had not taken
antibiotics for 6 months (likely acquired through
transmission from others)
Message #1
1) Penicillin exposure selects resistance
with S. pneumoniae
Widespread use of antibiotics selects for
resistant strains, allowing them to proliferate
and spread genes to other bacteria
Message #2
1) Penicillin exposure selects resistance
with S. pneumoniae
2) Penicillin resistance is associated with
multi-drug resistance
Quinolone Resistant S.pneumoniae
Quinolone Resistant S.pneumoniae
Antibiotic
Resistance (%)
1988
Resistance (%)
1997/8
0
1.7
Penicillin
2.4
13.9
Macrolides
1.2
6.7
Cotrimoxazole
1.8
11.6
Tetracycline
2.4
6.9
Quinolones
Figure 6. Fluoroquinolone-Resistant Pneumococci:
Canadian Bacterial Surveillance Network, 1997-2007
Moxifloxacin
% Resistant
2
Levofloxacin
1.5
1
0.5
0
1997
1998
1999
2000
2001 2002
2003
2004
2005
2006
2007
Canadian Bacterial Surveillance Network, March 2008
Figure 7. Fluoroquinolone-Resistant Pneumococci in
Respiratory Isolates from Adults >64 years: 1988-2007
4.5
3.5
Levofloxacin
Moxifloxacin
3
2.5
2
1.5
% Resistant isolates
4
1
0.5
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1988
0
Year
Canadian Bacterial Surveillance Network, March 2008
PRSP - Significance
• Recommendations:
– quinolones be reserved for treatment
failure or known resistance
– standard -lactam treatment is effective in
sensitive and intermediate resistant
pneumococci
Arch Intern Med. 2000; 160: 1399-1408.
Message #3
1) Penicillin exposure selects resistance with S.
pneumoniae
2) Penicillin resistance is associated with multidrug resistance
3) Resistance is relative and can be overcome
with increasing doses of penicillins, if tolerated.
However, S. pneumoniae resistance to
macrolides and TMP-SMX is high level and
cannot be overcome by increasing dosages.
Resistance – What can be done?
• Finland:
Year
DDD/1000 inhabitants
macrolide consumption
Resistance of
group A strep to
erythromycin
1991
2.40
16.5%
1992
1.38
8.6%
N Engl J Med, August 1997
Anti-infective Guidelines
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Independent physician panel
Arms length from government, industry
Focus on optimal patient care
Best available evidence, including
Canadian references
• Published 1994, 1997, 2001, 2005
Penicillin: Resistance Rates and Prescriptions
(Canadian Bacterial Surveillance Network. 1988, 1993-2005)
Penicillin use
18
45
16
40
14
35
12
30
10
25
8
20
6
15
4
10
2
5
0
0
1988
1990
1992
1994
1996
1998
2000
2002
Annual rate of prescriptions
(per 100 pop'n)
Percent of isolates
not susceptible to penicillin
Penicillin non-susceptibility
2004
Canadian Bacterial Surveillance Network, Feb. 2006
Erythromycin: Resistance Rates and Prescriptions
(Canadian Bacterial Surveillance Network. 1988, 1993-2005)
20
6
4
4
2
2
0
0
20
05
6
20
04
8
20
03
8
20
02
10
20
01
10
20
00
12
19
99
12
19
98
14
19
97
14
19
96
16
19
95
16
19
94
18
19
93
18
19
88
Percent of resistant isolates
Macrolide use
Prescriptions per 100 pop'n
Erythromycin non-susceptibility
20
Canadian Bacterial Surveillance Network, Feb. 2006
Take Home Messages
Antibiotics are good drugs, when used properly
• Always consider if infection is Bacterial vs Viral
• Try to use NO antibiotic or 1st line antibiotics first
• Narrow vs broad spectrum antibiotics
• Care about the consequences of prescribing
antibiotics (resistance, side effect, C.difficile, cost)
• Provide professional/community leadership
• Partner with and educate/support your patients