Update on Update on Antimicrobial ResistanceAntimicrobial 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

Antibiotic resistance in pneumococci, Antibiotic resistance in pneumococci, CBSN, 1988-2000CBSN, 1988-2000

0

2

4

6

8

10

12

14

16

Year

Per

cen

t re

sist

ant

isol

ates

Pen(NS)

Cipro

Ery

TS

Antibiotic resistance in pneumococci in Antibiotic resistance in pneumococci in older adults, respiratory specimens, older adults, respiratory specimens,

CBSN, 1988-2001CBSN, 1988-2001

0

1

2

3

4

5

6

7

8

Year

Per

cen

t re

sist

ant

isol

ates

Cipro

Lev

Number of Patients Number of Patients Colonized/Infected with MRSA, Colonized/Infected with MRSA,

Ontario, 1992-2000Ontario, 1992-2000

0100020003000400050006000700080009000

10000

No.

of c

ases

of M

RS

A

1992 1993 1994 1995 1996 1997 1998 1999 2000

.

6866

471 475 566

1426

4212

LPTP Survey, 1996/97/98LPTP Survey, 1996/97/98

80168 252 9345 $25

M

Risk of death from MRSA vs Risk of death from MRSA vs MSSA bacteremiaMSSA 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

Resistance in Resistance in E. coli, E. coli, Baycrest 1997-2002Baycrest 1997-2002

0

5

10

15

20

25

30

35

1997 1998 1999 2000 2001 2002

Per

cen

t o

f is

ola

tes

resi

stan

t

Amp

Cipro

TS

MH, NH #1, March 2001MH, NH #1, March 2001

Admitted to MSH with SOB, ?pneumonia Sputum: E. coli

Ampicillin R

Cotrimoxazole R

Nitrofurantoin R

Cefazolin R

Ciprofloxacin R

G.D. 82yo Male 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 therapyInappropriate antimicrobial therapyImpact on MortalityImpact on Mortality

0

100

200

300

400

500

600

Innapropriatetherapy

Appropriatetherapy

No

. in

fecte

d p

ati

en

ts

Deaths

Survivors

42% mortality

17% mortality

Rel risk 2.495% Ci 1.8,3.1)

Kollef et al. Chest 1999;115:462

ConclusionConclusion 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?What can be done? Surveillance Prevention

– Hand hygiene– Vaccine

Transmission control Reduced/improved antibiotic use

– Public expectations– Provider practice

SurveillanceSurveillance

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, 1997WHO, 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 UKInternational 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, 1997Canada,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 tenTop 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?What can be done? Surveillance Prevention

– Hand hygiene– Vaccine

Transmission control Reduced/improved antibiotic use

– Public expectations– Provider practice

Impact of hand hygiene on infectionsImpact of hand hygiene on infections

Year Author Setting Impact on infections

1982 Maki ICU Decreased

1984 Massanari ICU Decreased

1990 Simmons ICU No effect

1992 Doebbeling ICU Decreased

1994 Webster NICU MRSA eliminated

1995 Zafar Nursery MRSA eliminated

1999 Pittet Hospital MRSA decreased

2000 Hammond Schools Illness/absenteeism decreased

2000 Dyer Schools Illness/absenteeism decreased

2001 Ryan Army base URI decreased

VaccinesVaccines

Influenza (universal) Pneumococcal

– polysaccharide (pneumovax) for high risk children and adults

– conjugate vaccine for children

Effect of influenza vaccine for staff Effect of influenza vaccine for staff and residents of long term care and residents of long term care

facilitiesfacilitiesEffect of

vaccinatingHCW

Effect ofvaccinating

residentsMortality 0.56 (.40,.80) 1.2 (0.81,1.6)

Mortality frompneumonia

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

Annual risk of influenza outbreaks by Annual risk of influenza outbreaks by percentage of staff vaccinatedpercentage of staff vaccinated

05

101520253035404550

Per

cent

of L

TC

Fs

repo

rtin

g in

flue

nza

outb

reak

<25% 25-50% 50-75% >75%

Percent of staff vaccinated

Impact of influenza vaccine on Impact of influenza vaccine on antibiotic useantibiotic use

Pediatrics (Belshe, NEJM, 1998)– 30% reduction in acute otitis media

Healthy adults (Nichols, NEJM, 1995)– 45% reduction in antibiotic prescriptions

Rate of invasive pneumococcal Rate of invasive pneumococcal disease:disease:

Metro/Peel vs. QuebecMetro/Peel vs. Quebec

02468

1012141618

Rat

e pe

r 10

0,00

0 po

pula

tion

1995 1996 1997 1998 1999 2000 2001

Year

Metro/Peel

Quebec

Cases of invasive disease by Cases of invasive disease by vaccine eligibility, Metro/Peel, vaccine eligibility, Metro/Peel,

1995-81995-8

0

50

100

150

200

250

300

350

Nu

mb

er o

f ca

ses

Ineligible Eligible

Vaccine eligibility

1995

1996

1997

1998

1999

2000

2001

Pneumococcal vaccination Pneumococcal vaccination rates, by risk grouprates, by risk group

0

10

20

30

40

50

60

70

<1996 1996 1997 1998 1999 2002Cum

ulat

ive

perc

ent o

f pop

ulat

ion

grou

p v

acci

nate

d

<65, ill

>64, well

>64, ill

What can be done?What can be done? Surveillance Prevention

– Hand hygiene– Vaccine

Transmission control Reduced/improved antibiotic use

– Public expectations– Provider practice

Number of Patients Number of Patients Colonized/Infected with MRSA, Colonized/Infected with MRSA,

Ontario, 1992-2001Ontario, 1992-2001

0100020003000400050006000700080009000

10000

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

No

. o

f ca

ses

of

MR

SA

.

6866

471 475 5661426

4212

QMP/LS Surveys, 1996-QMP/LS Surveys, 1996-20022002

80168252

9345

7684

Number of Patients Number of Patients Colonized/Infected with MRSA, Colonized/Infected with MRSA,

Ontario, 1993-2005?Ontario, 1993-2005?

0100020003000400050006000700080009000

10000

1 2 3 4 5 6 7 8 9 10 11 12

Nu

mb

er

of

pa

tie

nts

02468101214161820

MR

SA

as

% a

ll S

A

OntarioDenmark

.

Number of Patients Number of Patients Colonized/Infected with VRE, Colonized/Infected with VRE,

Ontario, 1992-2001Ontario, 1992-2001

0

100

200

300

400

500

600

700

800

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Year

Nu

mb

er o

f p

atie

nts

2 7

99

589

167

718 685

QMP-LS Surveys, 1996-2002QMP-LS Surveys, 1996-2002

445

230

ALC - Risk Factors for ALC - Risk Factors for ColonizationColonization

Risk Factor Odds Ratio (95% CI)

Tmp-smx, last 3mos 0.11 (.02,.59)

Cip/cef2, last 6mos 3.9 (1.0,15)First floor residence 0.37 (.16,.89)Bath on Sun/Mon 3.8 (1.2,12)3 positive BR mates 2.3 (1.0,5.3)

Public Health RolePublic Health Role

Surveillance Daycare, long term care Communication Co-ordination within regions National, provincial, regional

guidelines

What can be done?What can be done? Surveillance Prevention

– Hand hygiene– Vaccine

Transmission control Reduced/improved antibiotic use

– Public expectations– Provider practice

Improved antibiotic useImproved antibiotic useChallengesChallenges

Dissemination from current programs in the community– Edmonton, Port Hope, Ottawa

Institutions