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cipars picra - Antibiotic Awareness

Canadian Integrated Program for

Antimicrobial Resistance Surveillance

(CIPARS)

Rita Finley

Public Health Agency of Canada

Antibiotic Awareness Day in Canada

November 18 th , 2010

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Canadian Integrated Program for

Antimicrobial Resistance Surveillance

(CIPARS)

3

• Established in 2002

• Coordinated by PHAC (LFZ 1 , NML 2 , CFEZID 3 )

• Partnerships include:

– Veterinary Drug Directorate, Health

Canada

– Canadian Food Inspection Agency

– Agriculture and Agri Food Canada

– Provincial agriculture and public health

– Academia

– Private industry

1

LFZ – Laboratory for Foodborne Zoonoses; 2 NML: National Microbiology Laboratory;

3

CFEZID: Centre for Food-borne, Environmental and Zoonotic Infectious Diseases


Canadian Integrated Program for

Antimicrobial Resistance Surveillance

(CIPARS)

Objectives

4

– Provide a unified approach to monitor trends in

AMR and AMU in humans and animals

– Generate data to facilitate the assessment of

the public health impact of antimicrobials used

in humans and the agricultural sectors

– Allow accurate international comparisons with

other countries that use similar surveillance

systems (i.e. United States, Denmark)

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


5

EPIDEMIOLOGY

OF ZOONOTIC

BACTERIA

Rendering

Dead

stock

Drinking

water

Farm Effluents and

Manure Spreading

SWINE

Offal

AQUACULTURE

Rivers and

Streams

SOIL

WILDLIFE

Sea /

Lakes

Sewage

Vegetation,

Seed Crops, Fruit

Drinking

Water

Swimming

Industrial &

Household

Antibacterial

Chemicals

HUMAN

Animal

Feeds

SHEEP

VEAL

CALVES

FOOD

ANIMALS

OTHER

FARMED

LIVESTOCK

CATTLE

POULTRY

Commercial

Abattoirs /

Processing

Plants

Meat

Handling

Preparation

Consumption

HOSPITALIZED

EXTENDED

CARE

FACILITIES

COMMUNITY

- URBAN | RURAL

-SICK | HEALTHY

TRAVELLERS

COMPANION

ANIMALS

IMPORTS

Direct

Contact

after Linton AH (1977), modified by Irwin RJ


6

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Abattoir Surveillance

7

• Began in 2002

• National estimates

• Federally inspected abattoir

• Random abattoir selection and sample allocation

weighted by slaughter volume

• Cattle - beef

→ Generic E. coli, Campylobacter

• Swine - market hogs

→ Salmonella, generic E. coli

• Chickens - broilers

→ Salmonella, generic E. coli, Campylobacter (2010)

• Sample size - to generate 150 isolates of Salmonella &

E. coli, 100 isolates of Campylobacter

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Retail Meat Surveillance

Random census division selection and sample allocation

within divisions weighted by census population

8

• 7 provinces

– Ontario, Québec (2003),

Saskatchewan (2005), British

Columbia (2007), Maritimes (Nova

Scotia/New Brunswick/PEI)* (2008)

(* sampled as one province)

• Continuous sampling

– Weekly or every other weekly

sampling in each province

– Goal: 100 isolates/commodity/

province (or region)/year for

antimicrobial susceptibility testing

• Bacteria

– generic E. coli (Chicken/Pork/Beef),

Campylobacter (Chicken),

Salmonella (Chicken/Pork)

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


9

Farm Surveillance

90 Sentinel Sites across 5 Provinces

– Swine farms with

grower/finisher units

– Major swine-producing

provinces: Quebec, Ontario,

Manitoba, Saskatchewan

and Alberta

29 Swine Veterinarians

– Protect biosecurity and

confidentiality

– Collect antimicrobial use

data and faecal samples

2 Supervisory Veterinarians

– Protect confidentiality of

corporate farms

Nationally:

108 Herds

29 Vets

26

8

• AF Lab

15

5

• PDS

Lab

12

3

27

7

28

6

• PHAC-LFZ Lab

• PHAC-LFZ Lab


Human Surveillance

• Full data collection started January 1, 2003

• Provincial public health laboratories forwarding

human Salmonella isolates

– BC, ALTA, ONT, QUE: All isolates (outbreak

and non-outbreak related) received from

the first to the fifteenth of each month, and

all S. Newport and S. Typhi received

throughout the entire surveillance period.

– SASK, MAN, NB, NFLD, NS, PEI: All human

Salmonella isolates (outbreak and nonoutbreak)

received throughout the entire

surveillance period.

• Over 25,000 isolates processed as of mid 2010

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

Programme intégré canadien de surveillance de la résistance aux antimicrobiens

10

CIPARS


11

Antimicrobial Drug Use Surveillance

Data

Data

Retail pharmacies

• ~5092 sampled,

~7980 represented

(2008)

• All provinces

• Enter data on

dispensed

prescriptions

IMS Health

• Data collection &

aggregation

• Projection of

sample data to

“universe”

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

PHAC

• Data classification,

analysis, &

interpretation

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


12

ANTIMICROBIAL

CLASSIFICATION SYSTEM

Drugs of Human Health Importance – The

Veterinary Drugs Directorate Classification System

(April 2009)

Rationale for Classification:

• Spectrum of activity of antimicrobials

• Mode of action

• Mechanism of resistance

• Availability of alternative antimicrobial therapy

• Potential for transfer of resistance


13

ANTIMICROBIAL

CLASSIFICATION SYSTEM

Drugs of Human Health Importance 1

Category I: Very High Importance (e.g. amoxicillin-clavulanic acid,

ciprofloxacin, ceftiofur, ceftriaxone)

Category II: High Importance (e.g. amikacin, gentamicin, nalidixic

acid, ampicillin, cefoxitin)

Category III: Medium Importance (chloramphenicol, sulfisoxazole,

tetracycline)

Category IV: Low Importance (ionophores, colistin)

1

http://web.hc-sc.gc.ca/dhp-mps/consultation/vet/consultations/amr_ram_hum-med-rev-eng.php

Veterinary Drugs Directorate, Health Canada. 2009.

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Surveillance and Research

Findings

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Human antimicrobial consumption

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Human Systemic Anti-bacterials Dispensed in Canada:

Total Number and Cost/1000 Inhabitants per Year, 2009

16

800

Number of prescriptions/1,000 inabitants

Total cost/1,000 inhabitants

$23,000.00

700

$20,853.20

$21,007.78

$20,699.63

$21,576.86

$21,053.14

$21,573.93

$21,369.13

$20,337.69 $20,480.99

$20,744.97

$21,000.00

$19,000.00

Total number of prescriptions/1000 inhabitants

600

500

400

300

$17,000.00

$15,000.00

$13,000.00

$11,000.00

$9,000.00

Total cost/1000 inhabitants

200

$7,000.00

100

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

$5,000.00


Percentages of total number of defined daily doses

(DDDs) per 1,000 inhabitant-days for oral antimicrobials

dispensed by retail pharmacies in Canada, 2009

17

Macrolides and lincosamides

(J01F)

23%

Penicillins with extended

spectrum (J01 CA)

25%

Sulfonamide combinations (excl.

trimethoprim) (J01RA)

0%

Other antimicrobials (J01XX)

0%

ß-lactamase resistant penicillins

(J01CF)

1%

Tetracyclines (J01AA)

13%

ß-lactamase sensitive penicillins

(J01CE)

3%

Nitrofuran derivatives (J01XE)

4%

Fluoroquinolones (J01MA)

11%

Cephalosporins (J01DB-DE)

10%

Trimethorpim and trim. +

sulphonamides (J01E)

5%

Combinations of penicillins, incl.

ß-lactamase inhibitors (J01CR)

4%


18

Antimicrobial consumption (DDDs/1,000 inhabitant-days) in

30 European countries and Canada: European Surveillance of

Antimicrobial Consumption and CIPARS 2008.

50.00

45.00

40.00

35.00

30.00

25.00

20.00

DDD/1000 inhabitants

15.00

10.00

5.00

0.00

Greece

Cyprus

Italy

France

Belgium

Luxembourg

Lithuania

Slovakia

Croatia

Portugal

Ireland

Israel

Poland

Iceland

Bulgaria

Spain

Finland

Canada

Czech_Republic

United_Kingdom

Denmark

Norway

Hungary

Austria

Slovenia

Sweden

Germany

Estonia

Netherlands

Latvia

Russian_Federation

Penicillins (J01C) Tetracyclines (J01A) Quinolones (J01M)

Cephalosporins and other b-lactams (J01D) Macrolides, lincosamides, Country and steptogramins (J01F) Sulphonamides and trimethoprim (J01E)

Others (J01B+J01G+J01X+J01DF+J01DH)


Canadian province-level risk factor analysis of

macrolide consumption patterns (2000-2006)

19

Macrolide DDDs per capita

0.28

0.24

0.20

0.16

0.12

(a)

240 260 280 300 320 340 360 380

Health workers per 10 000 individuals

Erythromycin DDDs per capita

0.016

0.012

0.008

0.004

0.000

(b)

6 8 10 12 14 16 18

Percent education

Azithromycin DDDs per capita

0.04

0.03

0.02

0.01

(a)

6 8 10 12 14 16 18

Percent education

Clarithromycin DDDs per capita

0.16

0.14

0.12

0.10

0.08

0.06

(c)

50 55 60 65 70 75 80

Median family income (1000's)

Macrolide DDDs per capita

0.32

0.28

0.24

0.20

0.16

0.12

(d)

10 12 14 16 18 20 22

Percent low income

Azithromycin DDDs per capita

0.05

0.04

0.03

0.02

0.01

(b)

50 55 60 65 70 75 80

Median family income (1000's)

Macrolide DDDs per capita

0.28

0.24

0.20

0.16

0.12

(e)

2 4 6 8 10 12 14 16 18 20

Percent unemployment

Macrolide DDDs per capita

0.24

0.22

0.20

0.18

0.16

0.14

0.12

0.10

(f)

0.0 0.5 1.0 1.5 2.0

Reported influenza cases per 10 000

Azithromycin DDDs per capita

0.05

0.04

0.03

0.02

0.01

(c)

10 12 14 16 18 20

Percent low income

Glass SK, Pearl DL, McEwen SA, Finley R. 2010. A Canadian province-level risk factor analysis of

macrolide consumption patterns (2000-2006). Journal of Antimicrobial Chemotherapy. 65: 148-155


20

A province-level risk factor analysis of fluoroquinolone

consumption patterns in Canada (2000-2006)

Fluoroquinolone DDDs per 1000

60

50

40

30

20

10

(a)

50 55 60 65 70 75 80

Median family income (1000's)

Norfloxacin DDDs per 1000

90

75

60

45

30

15

0

(b)

50 55 60 65 70 75 80

Median family income (1000's)

Fluoroquinolone DDDs per 1000

44

40

36

32

28

24

(c)

10 12 14 16 18 20 22

Percent low income

Ofloxacin prescriptions per 1000

0.11

0.10

0.09

0.08

0.07

0.06

0.05

(d)

240 260 280 300 320 340 360 380

Health workers per 10 000 individuals

Levofloxacin DDDs per 1000

1.2

1.0

0.8

0.6

0.4

0.2

(e)

6 8 10 12 14 16 18

Percent education

Ciprofloxacin prescriptions per 1000

5.1

4.6

4.1

3.6

3.1

2.6

(f)

6 8 10 12 14 16 18

Percent education

Glass SK, Pearl DL, McEwen SA, Finley R. 2010. A province-level risk factor analysis of fluoroquinolone

consumption patterns in Canada (2000-2006). Journal of Antimicrobial Chemotherapy. 65: 2019-2027.


Burden of illness associated with

antimicrobial susceptible and resistant

Campylobacter infections in the Perth and

Wellington-Dufferin-Guelph Health Units

(2002-2004)

21

Prescribed an antibiotic for their campylobacteriosis:

– 135 cases (54%)

Culture Results available prior to antimicrobial treatment

– 39 cases (30%)

Culture Results available prior to symptoms ending:

– 48 cases (21%)

Before your illness had you heard of Campylobacter as a

problem in food or water

– Yes 35 (14%)

– No 212 (85%)

– Don’t Know 2 (1%)


22

Antimicrobial use in laboratory confirmed cases

of campylobacteriosis 2002-2004, n=135

amoxicillin

azithromycin

cephalexin

Antimicrobial

ciprofloxacin

clarithromycin

doxycline

erythromycin

metronidazole

sulfonamides

tetracycline

0 10 20 30 40 50

Number of Cases

before fecal results available after fecal results available

* 12 cases reported treatment with more than one antimicrobial


Animal antimicrobial consumption:

Farm Surveillance

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Antimicrobial use by importance to human

medicine (VDD) 1 : Count of Farms; 2008.

Antimicrobial class

Antimicrobial

Administration route

Any route Feed Water Injection

I Extended-spectrum cephalosporins Ceftiofur 20 0 0 20

Aminoglycosides Neomycin 1 1 0 0

Lincosamides Lincomycin 40 34 3 11

Tiamulin 10 6 0 4

Marcolides Erythromycin 1 0 0 1

Tulathromycin 6 0 0 6

II

Tylosin 52 46 0 11

Amoxicillin 2 0 2 0

Penicillins Ampicillin 3 0 0 3

Penicillin G 64 5 15 52

Phenoxymethyl penicillin 6 0 6 0

Streptogramins Virginiamycin 0 0 0 0

Trimethoprim/sulfamethoxazole Trimethoprim-sulfadoxine 13 0 3 11

Aminoglycosides Spectinomycin 3 1 0 2

Bacitracins Bacitracin 1 1 0 0

Phenicols Florfenicol 6 0 0 6

III Sulfonamides Sulfonamide (unspecified) 8 5 3 0

Tetracyclines Chlortetracycline 45 43 3 0

Oxytetracycline 14 1 0 13

Tetracycline hydrochloride 7 0 7 0

Flavophospholipids Bambermycin 7 7 0 0

IV

Ionophores Salinomycin 12 12 0 0

1 http://web.hc-sc.gc.ca/dhp-mps/consultation/vet/consultations/amr_ram_hum-med-rev-eng.php

Veterinary Drugs Directorate, Health Canada. 2009.

24


Agri-food antimicrobial

resistance results


Resistance to antimicrobials in Escherichia coli isolates from

swine, chicken and beef cattle; Abattoir Surveillance, 2009.*

26

Amoxicillin-clavulanic acid

Swine (n=160)

Categorization of antimicrobials based on importance in human medicine

I

IV III II

Ceftiofur

Ceftriaxone

Ciprofloxacin

Amikacin

Ampicillin

Cefoxitin

Gentamicin

Kanamycin

Nalidixic acid

Streptomycin

Trimethoprim-sulfamethoxazole

Chloramphenicol

Sulfisoxazole

Tetracycline

Chickens (n=171)

Beef cattle (n = 119)

* Preliminary data

0% 20% 40% 60% 80% 100%

Percentage of isolates resistant and 95% confidence interval


Integration of human and agri-food

surveillance data

Use of ceftiofur and resistance in

Salmonella and E. coli

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


28

Ceftiofur resistance in chicken E. coli and human and

chicken S. Heidelberg by trimester – rolling average

80%

Prevalence of ceftiofur resistance

70%

60%

50%

40%

30%

20%

10%

Ceftiofur in

76% of lots

Voluntary withdrawal of

ceftiofur in -ovo use

Zero use

Retail Chicken E. coli

Retail Chicken S. Heidelberg

Human S. Heidelberg

Unknown use

Partial reinstitution of ceftiofur use

*

0%

3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4

2003 2004 2005 2006 2007 2008 2009

Québec

preliminary

Province, Year, Quarter

* Lines represents rolling averages of current and past 2 quarters

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens


Acknowledgements

29

CIPARS, Public Health Agency of Canada

Agnes Agunos

Brent Avery

Carolee Carson

Linda Cole

Danielle Daignault

Anne Deckert

Andrea Desruisseau

Chad Gill

Sheryl Gow

Nicol Janecko

David Leger

Antoinette Ludwig

Jane Parmley

Michelle Tessier

CIPARS Program Coordinators

Dr. Rebecca Irwin & Dr. Richard Reid-Smith,

Rita Finley and Dr. Michael Mulvey

Provincial Public Health Laboratories

• British Columbia Centre for Disease Control

• Provincial Laboratory of Public Health, Alberta

• Saskatchewan Laboratory and Disease Control

Services

• Cadham Provincial Laboratory, Manitoba

• Ontario Ministry of Health and Long-Term Care

• Institut national de santé publique du Québec

• New Brunswick Enteric Reference Centre

• Microbiology Laboratory, Queen Elizabeth II Health

Sciences Centre, Nova Scotia

• Laboratory Services, Queen Elizabeth Hospital,

Prince Edward Island

• Newfoundland Public Health Laboratory

Canadian Food Inspection Agency

Health Canada, Veterinary Drug Directorate

Abattoir-Industry Participants

Retail Surveillance Participants & Field Staff

Participating Swine Veterinarians and Producers

Provincial Animal Health Labs

Collaborating laboratories

Canadian Integrated Program for Antimicrobial Resistance Surveillance

PICRA

CIPARS

Programme intégré canadien de surveillance de la résistance aux antimicrobiens

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