Increased resistance due to”non-human” antibiotic use

(veterinary and zootechnical use)

Christina GrekoDept of Antibiotics

National Veterinary Institute (SVA)Uppsala, Sweden

C. Greko, SVA

Why use antibiotics for animals?

Therapy

Prophylaxis

Growth promotion

C. Greko, SVA

Feed additives for performance enhancement, 70/524/EEC

spiramycin (-99) tylosin (-99) virginiamycin (-

99) avoparcin (-97) ardacin (-97) bacitracin (-99)avilamycin

carbadox (-99) olaquindox (-99)flavofosfolipolmonensinsalinomycin

C. Greko, SVA

Some indications for veterinary use

Dairy cows mastitis S.aureus, CNS, streptococci

Calves pneumonia enteritis

Mannheimia sp Pasteurella spp E.coli

Swine pneumonia enteritis

Actinobacillus, Mycoplasma E.coli, Brachyspira spp

Chicken sepsis

E.coli

C. Greko, SVA

Antibiotics approved for use in bovines and/or porcines (Sweden 2001)

Individual medication penicillin-G penicillin-DHS amoxicillin ceftiofur macrolides (16-M) pleuromutilins trim/sulph. tetracyclines fluoroquinolones aminoglycosides

Group medication macrolides (16-M) pleuromutilins tetracyclines fluoroquinolones

From: FASS VET. 2001

C. Greko, SVA

Sales of antibiotics for animals, EU 1997 asg antibiotic/tonnes of livewheight slaughtered

0

40

80

120

160

200

UK

Greec

eSpa

in NL

Be+Lu

x

Franc

e

German

yIta

ly

Portug

al

Denmar

kIrla

nd

Sweden

Finlan

d

Austri

a

g/to

nnes

ani

mal

s Theraputicals

Growth promoters

Calculated from data in: EMEA/CVMP/342/99-Final, table 17 (FEDESA data)

C. Greko, SVA

Resistance to APE in E.faecium from broilers in Denmark

0

25

50

75

100

95 96 97 98 99 '00

% re

sist

ance

Vancomycin

Avilamycin

Virginiamycin

From: DANMAP 95,96,97,98,99,00 (www.svs.dk)

C. Greko, SVA

Penicillin resistance among S.aureus from clinical mastitis in cows and sales of penicillin

0%

10%

20%

resis

tan

ce (

%)

0

5

10

15

20

25

g/d

air

y c

ow

resistance (%)

penicillin

Data as cited in Greko, 1996 KSLA 135 (15) p27- and SVARM 2000 (www.sva.se)

Transfer of

zoonotic bacteria

C. Greko, SVA

Antibiotic resistance,S. Typhimurium from animals

0%

20%

40%

60%

80%

100%

GB (n=864) Dk, cattle (n=53)Dk, pig (n=216) Se (n=46)

Data from: DEFRA: Salmonella in livestock production 2000, DANMAP 2000 and SVARM 2000

C. Greko, SVA

Quinolone resistance in Campylobacter (NL)

0%

10%

20%

30%

1987 1988 1990

Chickens

Humans

From: Endtz et al, 1991, JAC, 27:211-217

C. Greko, SVA

Resistance to nalidixic acid among C. jejuni, Denmark

0

10

20

30

97 98 99 '00

resis

tan

ce

(%

)

Humans (domestic) Chickens (Dk)

Source: DANMAP 00 (www.svs.dk)

C. Greko, SVA

Quinolone resistance in Campylobacter jejuni (DK, 1999)

0

5

10

15

20

25

Humans

(domestic)

Chickens Chicken

meat Dk

Chicken

meat

imported

% re

sist

ance

From: DANMAP 99 (www.svs.dk)

C. Greko, SVA

Fluoroquinolones - human vs veterinary use in Sweden

Fq:s, kg Liveweight,1000 tonnes

Fq:s/ liveweight

Vet. med.(1993)

173 825 0.2

Human med(1994)

4323 540 7.4

Ratio human/vet 35

Data from Naturvårdsverket, 1994 and Statistics Sweden

Transfer of

resistance genes

C. Greko, SVA

Food as source - tetracycline resistance in coliforms of helthy volunteers on control or sterile diet

0

1

2

3

4

5

6

7

8

Control Sterile

log

CFU/g

tet R p<0.001

From: Corpet, NEJM 1988, 318:1205-

C. Greko, SVA

Transfer of genes - spread of streptothricin-resistance (Tn1825), GDR

Origin 82 83 84 85 86 87

Pigs (E.coli from gut) - + + + + +Farm personel (Ec, gut) - - + + + +Family of farm pers. (Ec,gut) - - + + + +Healthy adults (Ec, gut) - - - + + +Human urinary tract inf, Ec - - - + + +Human Salmonella, Shigella - - - - - +

From: Witte, 1996 (Ciba Foundation Symposium 207)

C. Greko, SVA

Transfer of genes- base pair variants of Tn1546 from VRE

Source n T G

Pigs 33 32 1

Poultry 193 0 193

Humans 45 16 29

From: Jensen, AAC 1998 42:2463

Effect of interventions - withdrawal

of growth promoting antibiotics

C. Greko, SVA

Sales of antibacterials for animal use (Sweden)

0

10

20

30

40

50

60

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000

To

nn

es a

ctiv

e

sub

stan

ce

Feed additives

Group medication

Individual medication

Compiled from published data, references given in SVARM 2000 (www.sva.se)

C. Greko, SVA

Resistance among E. faecium – SVARM 2000 vs DANMAP 97

0

20

40

60

80

100

resi

stan

ce (

%) Se DkPig Chicken

(Pig: Se n=48, Dk n=54; chicken: Se n=151, Dk n=207)

C. Greko, SVA

Resistance to vancomycin in E.faecium from chicken and chicken meat, Denmark

0

25

50

75

100

95 96 97 98 99 '00

% r

esis

tanc

e

Chicken

Chicken meat

From: DANMAP 95,96,97,98,99,00 (www.svs.dk)

C. Greko, SVA

Avoparcin and vancomycin resistant enterococci (VRE) of vanA type

VRE easily found in animals (and food)

in most countries - but NOT in Sweden

Community carriage in humans EU 2-

5%?

Community carriage in Sweden <0.1%

(1/670; Torell et al, JCM 1999, 37:3509)

C. Greko, SVA

The flow of resistance genes

monitor use

monitor resistance

promote prudent use

control infectious diseases

increase knowledge