sponsor day on animal feeding: antimicrobial consumption and emergence of cephalosporin resistant...
DESCRIPTION
Sponsor Day: Seminar on Animal Feeding 15th-16th May 2014 IRTA Mas BoverTRANSCRIPT
Lourdes Migura
Antimicrobial consumption and emergence of
cephalosporin resistant Escherichia coli and Salmonella in pigs
Consumption of antimicrobials
ANTIMICROBIALS (mg/PCU)Tetracycline: 35.9Penicillins: 21.2 Polymyxins: 10.5 Macrolides: 7.6 Lincosamides: 7.5 Pleuromutilins: 4.4 Aminoglycosides: 3.8 (Fluoro)quinolones: 3.41 Sulfonamides: 2.5 Others: 2.1 Amphenicols: 0.5 Trimethoprims: 0.4 3rd-4th gen. cephalosporins: 0.1 (1.5 tonnes)
Sales active ingredient (tonnes)
1,000 Tonnes PCU (food producing animals)
mg/PCU (mg/kg of
meat)Italy 1,663 4,497 370
Spain 1,779 7,135 249Germany 1,819 8,600 211Hungary 147 767 192Belgium 297 1,695 175Portugal 164 1,016 161Poland 471 3,929 120France 896 7,643 117
Netherlands 363 3,186 114Czech Rep 61 732 83
Austria 53 977 54UK 344 6,724 51
Ireland 87 1,770 49Denmark 106 2,479 43Finland 12 520 24Sweden 11 835 13.6Norway 6.2 1,680 3.7
Population correction unit (PCU): multiplying numbers of livestock animals (dairy cows, sheep, sows and horses) and slaughtered animals (cattle, pigs, lambs, poultry and turkeys) by the theoretical weightat the time most likely for treatment
Data obtained from the 3rd ESVAC report (EMA 2011)
OBJECTIVES
To evaluate the possible association between consumption of different antimicrobials (b-lactams, cephalosporins and other unrelated antimicrobial compounds) and occurrence of cephalosporin resistant (CR) E. coli and Salmonella enterica
To assess if the animals are a real reservoir of cephalosporin resistance genes that can spread to the community via the food chain
To characterize both, the resistant population and the genetic determinants coding for resistance genes
• 1st treatment: seven day-old piglets, 6 visits, day 0 (pre-treatment) and days 2, 7, 21, 41 post-treatment
• 2nd treatment: fattening period, 7 visits, day 0 (pre-treatment) and days 2, 7, 14, 22, 45 y 73 (age of 4 to 6 months aprox.)
2nd treatment N=92
Group 1 controln=20
Group 2 Amoxicillin
n=26
Group 4 Ceft+ Amoxi
n=26
Group 3Ceftiofurn=20
+amoxi 10mg/kg lifeweigt/day (14 days)
+amoxi 10mg/kg lifeweight/day (14 days)
1st treatmentN=100
Control group n=50
Ceftiofur group n=50 7 day-old piglets
RESULTSSampling days
Age (days)
Positive animals in the control group (N=50*)
Positive animals in the treated group (N=50)
0 6-8 5 (10%) 6 (12%)
2 8-10 5 (10%) 13 (26%)
7 13-15 1 (2%) 0
14 20-22 1 (2%) 4 (8%)
21 27-29 0 0
41 47-49 0 0
Positive animals in each group after amoxi treatment
Sampling days
Age (days)
Group 1Control(N=20)
Group 2Amoxi(N=26)
Group 3 Ceftiofur(N=20)
Group 4Amox+Ceft
(N=26)
0 70 0 0 0 0
2 72 0 2 (8%) 0 0
7 77 0 7 (27%) 0 0
14 84 0 1 (4%) 0 0
22 115 0 0 0 1 (4%)
45 138 0 1 (4%) 0 0
73 155 0 0 0 0
p=0.03
Fisher test p=0.02
RESULTSDice (Opt:1.50%) (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]PFGE E. coli
100
95908580757065
PFGE E. coli
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E1V4C90
E1V1C17a
E1V2C100a
E1V1C80a
E1V2C55a
E1V2C70a
E1V2C35a
E1V1C63a
E1V1C75a
E1V2C72a
E1V2C73a
E1V4C80a
E1V1C97a
E1V2C97a
E1V4C29b
E1V3C29a
E1V1C26a
E1V1C27a
E1V1C28a
E1V1C29a
E1V2C26a
E1V2C27a
E1V2C29c
E1V2C30a
E1V2C96a
E1V1C96a
E1V1C59a
E1V1C65a
E2V6C29c
E1V2C93b
E2V5C75c
E1V4C89c
E2V3C47b
E2V2C31a
E2V3C34b
E2V3C35b
E2V3C40b
E2V2C32c
E2V3C32c
E2V3C33b
E2V3C41c
E2V4C33a
E1V4C59c
E1V4C64a
E1V2C52a
E1V2C53c
E1V2C62a
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A
D
A
B1
B1
B1
A
A
A
A
A
A
B1
B1
A
A
A
A
A
A
A
A
A
B1
B1
A
A
A
A
B1
A
A
A
A
A
A
A
A
A
A
A
A
B1
B1
B1
B1
D
TEM-1
TEM-1,CTXM-14
TEM-1
TEM-1, SHV-12
TEM-1b, SHV-12
TEM-1, SHV-12
TEM-1
TEM-1,CTXM-9
TEM-1,CTXM-9
TEM-1,CTXM-9
TEM-1,CTXM-9
TEM-1,CTXM-1
TEM-1
TEM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM-1,CTXM-1
TEM, SHV-12
CTXM-1
TEM-1,CTXM-1
TEM-1
TEM-1, SHV-12
TEM-1,CTXM-15
TEM-1,CTXM-15
CTXM-14
CTXM-14
CTXM-14
CTXM-14
CTXM-14
CTXM-14
CTXM-14
CTXM-14
CTXM-14
TEM-1
TEM-1
TEM-1
TEM-1
TEM-1
cef
control
cef
cef
cef
cef
control
cef
cef
cef
cef
cef
cef
cef
control
control
control
control
control
control
control
control
control
control
cef
cef
cef
cef
amox
cef
cef+amox
cef
cef+control
amox
amox
amox
amox
amox
amox
amox
amox
amox
cef
cef
cef
cef
cef
Id phylo R genes treatmt Caz Am Cs Su Tm Cm Km Ctx Ci Nal Gm Sm Tc Ff
CONCLUSIONS
Both treatments generated an increase in the proportions of CR E. coli, which was statistically significant during the ingestion of the antimicrobials
The treatment with ceftiofur and amoxicillin was associated to the emergence of CR E. coli, however did not pose enough selective pressure to select for long-term resistant organisms
Both treatments have selected for a wide range of cephalosporin resistance genes: CTX-M-1, CTX-M-9, CTX-M-14, CTX-M-15 and SHV12
CR E. coli were phenotypically resistant to different families of antimicrobials. Half of them were resistant to ciprofloxacin, even though fluoroquinolones were never used to treat these animals
ceftiof
ur
tulat
hrom
ycin
40
40
30
30
Visit 07 day-old
piglets
Visit 148hr post-
treat
Visit 27 days
post-treat
Visit 3slaughter
SalmonellaCR Salmonella
CR E. coliEnumeration
Isolation
STUDY DESIGN
Farm TreatmentSows
Day 0 prior
treatment
48hr post
treatment
7 days post treatment Departure to
abattoir
Positive Control Treated Control Treated Control Treated Control Treated
1*Tulathromyci
n5/6 16.7% 77.5% 30% 65% 30% 82.1% 0 0
2 Ceftiofur 7/7 93.3% 92.5% 96.7% 100% 100% 100% 14.3% 63.3%
3Tulathromyci
n0/7 0 0 0 0 0 0 0 0
4 Ceftiofur 6/7 82.8% 71.8% 86.2% 79.5% 89.7% 87.2% 0 0
5 Ceftiofur 0/7 0 0 0 0 0 0 0 0
6Tulathromyci
n5/7 73.3% 87.5% 100% 100% 90% 85% 20.8% 23.5%
7Tulathromyci
n6/7 86.7% 57.5% 76.7% 77.5% 86.7% 75% 50% 47%
8 Ceftiofur 0/7 0 0 0 0 0 0
CR E. coli RESULTSP=0.001
CR E. coli were found before any treatment, the frequency was variable between farms, and the origin of the grandmothers was associated to the presence of CR E. coli
The occurrence of CR E. coli increased before weaning and decreased with the age of the animals
There were not significant differences in the proportions of animals excreting CR E. coli neither between the two different treatments, nor between the control and the treated groups
Only in one farm, at finishing time the proportion of animals shedding CR E. coli in the group treated with ceftiofur was significantly higher than in the control group
These results suggest that control measures to reduce the prevalence of CR E. coli should be applied in a case by case situation
CONCLUSIONS
Results CR Salmonella (on going)
66 Salmonella enterica from 5 different farms
4 CR Salmonella containing blaCTX-M-1 and blaCTX-M-14 (all from the same farm) before treatment with ceftiofur
Serotype Nº %Salmonella Rissen 39 59Salmonella Typhimurium monophasic
9 14
Salmonella Panama 7 11Salmonella Brandenburg 7 11Salmonella Anatum 3 5Salmonella Derby 1 2Total 66 100
SALMONELLA RESULTSDice (Opt:2.00%) (Tol 2.0%-2.0%) (H>0.0% S>0.0%) [0.0%-100.0%]
10
0
80
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E3G3V4C19
E3G3V2C57
E3G3V4C17
E3G2V4C25
E3G2V4C63
E3G3V4C16
E3G3V4C46
E3G3V4C48
E3G3V1C1
E3G3V1C35
E3G3V2C1
E3G3V1C67
E3G2V1C5
E3G2V1C7R
E3G2V1C10
E3G2V1C41
E3G2V1C42
E3G2V1C45
E3G2V1C48
E3G2V1C50R
E3G2V1C53
E3G2V1C54
E3G2V1C55
E3G1V1C51
E3G1V1C62
E3G1V2C61
E3G1V2C67
E3G1V2C70
E3G1V3C62
E3G1V3C67
E3G1V3C70
E3G6V4C23
E3G5V4C6
E3G5V4C41
E3G5V4C44
E3G5V4C48
E3G5V4C63
E3G2V1C19
E3G2V1C33
E3G2V1C34R
E3G2V1C30
E3G2V1C46
E3G2V1C49
E3G2V2C30
E3G2V2C34
E3G2V1C404.
E3G2V2C22
E3G1V4C48
E3G1V4C19
E3G2V1C56
E3G2V1C57
E3G2V1C60
E3G2V2C7
E3G2V2C8
E3G2V2C41
E3G2V2C45
E3G2V2C48
E3G2V2C50R
E3G2V3C10
E3G2V3C50
E3G1V4C36
E3G1V4C42
E3G3V1C591.
E3G3V2C59
E3G3V2C63
E3G6V4C13
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Panama
S.Panama
S.Panama
S.Panama
S.Panama
S.Panama
S.Panama
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Anatum
S.Anatum
S.Anatum
S.Brandenburg
S.Brandenburg
S.Brandenburg
S.Brandenburg
S.Brandenburg
S.Brandenburg
S.Brandenburg
S.Derby
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Rissen
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Tiphymurium mo.
S.Tiphymurium mo.
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CTXM-14
CTXM-1
CTXM-1
CTXM-1
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CONCLUSIONS
It was not observed any increase in the percentage of samples positive for CR Salmonella during treatment with ceftiofur
This preliminary study suggests that it is not necessary to implement additional control measures focused on reducing the load of CR Salmonella of pig origin
Edifici CReSA. Campus UAB. 08193 Bellaterra (Barcelona) Spain.Tel. (+34) 93 581 32 84 Fax. (+34) 93 581 44 90e-mail: [email protected] - www.cresa.cat
Acknowledgments :
Project AGL2011-28836 (MINECO)
Farm companies
Karla Cameron-Veas
Lorenzo Fraile Miguel Angel Moreno