Update on
Antimicrobial Resistance
Allison McGeer, MD, FRCPC
Mount Sinai Hospital
amcgeer@mtsinai.on.ca
416-586-3118
http://microbiology.mtsinai.on.ca
“This inquiry has been an alarming
experience which leaves us convinced
that resistance to antibiotics...
constitutes a major public health
threat and ought to be recognized as
such”.
UK House of Lords
White Paper, 1999
Percent resistant isolates
Antibiotic resistance in pneumococci,
CBSN, 1988-2000
16
14
12
10
8
6
4
2
0
Pen(NS)
Cipro
Ery
TS
88 993 994 995 996 997 998 999 000 001 002
9
1
1
1
1
1
1
1
1
2
2
2
Year
Percent resistant isolates
Antibiotic resistance in pneumococci in
older adults, respiratory specimens,
CBSN, 1988-2001
8
7
6
5
4
3
2
1
0
Cipro
Lev
88 993 994 995 996 997 998 999 000 001 002
9
1
1
1
1
1
1
1
1
2
2
2
Year
No. of cases of MRSA
Number of Patients
Colonized/Infected with MRSA,
Ontario, 1992-2000
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
8 252 9345
$25M
8016
6866
4212
.
1426
471 475 566
1992 1993 1994 1995 1996 1997 1998 1999 2000
LPTP Survey, 1996/97/98
Risk of death from MRSA vs
MSSA bacteremia
Meta-analysis, 2001
 9 case control studies, 1990-2000


Pooled relative risk:
2.1 (1.7, 2.6)
Whitby, MJA, 2001;175:264-7
Percent of isolates resistant
Resistance in E. coli,
Baycrest 1997-2002
35
30
25
20
15
Amp
Cipro
TS
10
5
0
1997
1998
1999
2000
2001
2002
MH, NH #1, March 2001

Admitted to MSH with SOB,
?pneumonia

Sputum: E. coli
Ampicillin
Cotrimoxazole
Nitrofurantoin
Cefazolin
Ciprofloxacin
R
R
R
R
R
G.D. 82yo Male
ESRF on Hemodialysis-resident of RH
 TO ER with fever, shortness of breath
 T=38.0, WBC-N
 Bibasilar Infiltrate-Rx IV Cefuroxime x24hrs
 Deterioration: Resp Failure +Septic Shock
 ETT suction-Gram-Mod Poly’s, many Gram neg
rodst: culture; heavy MDR E.Coli
 IV Azithro+Meropenem
 Death due to septic shock + Refractory hypoxemia
Inappropriate antimicrobial therapy
Impact on Mortality
No. infected patients
600
17% mortality
500
Rel risk 2.4
400
300
95% Ci 1.8,3.1)
42% mortality
200
Deaths
Survivors
100
0
Innapropriate
therapy
Kollef et al. Chest 1999;115:462
Appropriate
therapy
Conclusion

Antibiotic resistance is
coming
bad for patients
expensive

The only good news is that we can
choose to spend our money on
prevention or on treatment
What can be done?
Surveillance
 Prevention

– Hand hygiene
– Vaccine
Transmission control
 Reduced/improved antibiotic use

– Public expectations
– Provider practice
Surveillance

Measure burden of illness
– incidence, mortality, morbidity, cost
Identify opportunities for prevention
 Evaluating/inform prevention programs

– vaccine, appropriate AB, transmission
prevention

Minimize treatment failures
WHO, 1997
Antimicrobial resistance has increased
dramatically in the last decade,
adversely affecting control of many
important diseases. Antimicrobial
resistance leads to prolonged morbidity,
increased case fatality and lengthens
duration of epidemics. Surveillance is
necessary for national and international
co-ordination.
Canada
UK
International considerations
-
Incidence/severity
Present burden ill health
General population impact
Socioeconomic impact
Socioeconomic burden
Socioeconomic impact
Preventability
Health gain opportunity
Potential to drive policy
-
Risk perception
Public concern
Changing patterns
Potential threat
-
PHLS "added value"
Canada,1998
UK, 1997
3 influenza
5 tuberculosis
15 inv S. pneumoniae
18 inv H. influenzae
23 gonorrhea
24 invasive GAS
35 Campylobacteriosis
2 antibiotic resistance
4 nosocomial infections
5 tuberculosis
8 MRSA
9 salmonellosis
12 campylobacteriosis
14 C. difficile
Top ten
(1,1) S. aureus
(2,2) S. pneumoniae
(3,4) M. tuberculosis
(5,4) Enterococcus spp.
(4,7) N. gonorrhoeae
(8,5) E. coli
(x,6) H. influenzae
(7,8) Salmonella spp.
(9,9) N. meningitidis
(x,6) P. aeruginosa
(10,10) Klebsiella spp
What can be done?
Surveillance
 Prevention

– Hand hygiene
– Vaccine
Transmission control
 Reduced/improved antibiotic use

– Public expectations
– Provider practice
Impact of hand hygiene on infections
Year
Author
Setting
Impact on infections
1982
1984
1990
1992
1994
1995
1999
2000
2000
2001
Maki
Massanari
Simmons
Doebbeling
Webster
Zafar
Pittet
Hammond
Dyer
Ryan
ICU
ICU
ICU
ICU
NICU
Nursery
Hospital
Schools
Schools
Army base
Decreased
Decreased
No effect
Decreased
MRSA eliminated
MRSA eliminated
MRSA decreased
Illness/absenteeism decreased
Illness/absenteeism decreased
URI decreased
Vaccines
Influenza (universal)
 Pneumococcal

– polysaccharide (pneumovax) for high risk
children and adults
– conjugate vaccine for children
Effect of influenza vaccine for staff
and residents of long term care
facilities
Mortality
Effect of
Effect of
vaccinating
vaccinating
HCW
residents
0.56 (.40,.80) 1.2 (0.81,1.6)
Mortality from
pneumonia
0.60 (0.37,.97) 0.83 (0.5,1.3)
LRTI
0.69 (0.40, 1.2)0.67 (0.39, 1.4)
Potter et al. JID 1997;175:1-6
Percent of LTCFs
reporting influenza
outbreak
Annual risk of influenza outbreaks by
percentage of staff vaccinated
50
45
40
35
30
25
20
15
10
5
0
<25%
25-50%
50-75%
Percent of staff vaccinated
>75%
Impact of influenza vaccine on
antibiotic use

Pediatrics (Belshe, NEJM, 1998)
– 30% reduction in acute otitis media

Healthy adults (Nichols, NEJM, 1995)
– 45% reduction in antibiotic prescriptions
Rate per 100,000
population
Rate of invasive pneumococcal
disease:
Metro/Peel vs. Quebec
Metro/Peel
Quebec
18
16
14
12
10
8
6
4
2
0
1995
1996
1997
1998
Year
1999
2000
2001
Cases of invasive disease by
vaccine eligibility, Metro/Peel,
1995-8
Number of cases
350
300
1995
1996
1997
1998
1999
2000
2001
250
200
150
100
50
0
Ineligible
Eligible
Vaccine eligibility
Cumulative percent of population
group vaccinated
Pneumococcal vaccination
rates, by risk group
70
<65, ill
>64, well
>64, ill
60
50
40
30
20
10
0
<1996
1996
1997
1998
1999
2002
What can be done?
Surveillance
 Prevention

– Hand hygiene
– Vaccine
Transmission control
 Reduced/improved antibiotic use

– Public expectations
– Provider practice
Number of Patients
Colonized/Infected with MRSA,
Ontario, 1992-2001
No. of cases of MRSA
9345
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
8016
8252
7684
6866
4212
.
471 475 566
1426
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
QMP/LS Surveys, 1996-2002
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
20
18
16
14
12
10
8
6
4
2
0
Ontario
Denmark
.
1
2
3
4
5
6
7
8
9 10 11 12
MRSA as % all SA
Number of patients
Number of Patients
Colonized/Infected with MRSA,
Ontario, 1993-2005?
Number of Patients
Colonized/Infected with VRE,
Ontario, 1992-2001
800
718 685
Number of patients
700
589
600
445
500
400
230
300
167
200
99
100
0
2
7
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Year
QMP-LS Surveys, 1996-2002
ALC - Risk Factors for
Colonization
Risk Factor
Odds Ratio (95% CI)
Tmp-smx, last 3mos
0.11 (.02,.59)
Cip/cef2, last 6mos
First floor residence
Bath on Sun/Mon
3 positive BR mates
3.9
0.37
3.8
2.3
(1.0,15)
(.16,.89)
(1.2,12)
(1.0,5.3)
Public Health Role
Surveillance
 Daycare, long term care
 Communication
 Co-ordination within regions
 National, provincial, regional
guidelines

What can be done?
Surveillance
 Prevention

– Hand hygiene
– Vaccine
Transmission control
 Reduced/improved antibiotic use

– Public expectations
– Provider practice
Improved antibiotic use
Challenges

Dissemination from current programs
in the community
– Edmonton, Port Hope, Ottawa

Institutions