Dr. Randy Singer - The Impact on Public Health of Environmental Contamination with Antimicrobial...
-
Upload
john-blue -
Category
Health & Medicine
-
view
169 -
download
1
description
Transcript of Dr. Randy Singer - The Impact on Public Health of Environmental Contamination with Antimicrobial...
The Impact on Public Health of Environmental Contamination with
Antimicrobial Residues
Randall Singer, DVM, MPVM, PhD
Will not focus on toxicology
How much antimicrobial residue is in the environment?
Is there biological activity of these residues?
How can we predict how much residue will be loaded into the environment?
An example One Health approach
Overview
The Ecological Model (Confusogram)
Residues in the Environment
Residues in the Environment
Residues in the Environment
Residues in the Environment
Residues in the Environment
Residues in the Environment
Ecology of Resistance
Cluster Count AMP AXO FOX TIO AMI GEN KAN STR NAL CIP FLO CHL TET AMC COT FIS Rivers Farms stx 1 stx 2 eae
A-F 1,054 ≥13 ≥13 ≥14 ≥17 ≥14 ≥12 ≥13 ≥11 ≥13 ≥15 ≥14 ≥12 ≥14 ≥13 ≥10 ≥12 318 736 1 11 23G 47 17.0 24.1 22.0 19.3 17.0 16.0 15.1 12.5 19.4 22.0 19.4 19.0 17.8 17.9 20.3 6.3 1 46 0 2 0H 45 19.9 27.0 24.4 22.0 19.0 17.8 18.2 13.7 21.5 29.4 22.7 22.2 7.3 21.0 24.8 20.9 7 38 0 0 1I 9 19.8 26.3 24.2 21.8 19.3 18.0 19.0 14.6 8.0 23.1 25.9 23.1 19.1 22.0 26.6 25.4 0 9 0 0 0J 12 6.0 24.9 24.4 20.3 18.0 16.8 17.1 13.3 21.2 23.9 21.8 21.8 14.6 17.1 25.3 19.4 11 1 0 0 1K 28 18.3 26.6 22.6 21.5 18.9 17.5 18.4 9.7 16.5 26.0 21.9 22.1 6.0 19.6 19.4 6.1 0 28 0 0 0L 16 7.8 25.5 24.5 21.2 18.3 17.2 16.2 8.5 21.9 29.7 22.3 22.1 16.0 18.6 11.2 6.0 11 5 0 0 1M 8 16.6 25.0 23.3 20.0 18.4 17.8 17.8 6.0 20.3 27.4 6.0 6.0 6.0 18.6 17.6 6.0 0 8 0 0 0N 7 6.0 26.0 22.6 20.4 18.4 13.0 10.3 9.4 6.0 10.1 22.9 15.4 6.0 15.1 16.9 13.7 7 0 0 0 0O 3 6.0 10.0 6.0 6.0 13.3 7.7 9.0 9.0 9.7 12.0 6.0 6.0 12.7 9.7 9.7 9.0 0 3 0 0 0
Total 1229 355 874 1 13 26
≤13 ≤13 ≤14 ≤17 ≤14 ≤12 ≤13 ≤11 ≤13 ≤15 ≤14 ≤12 ≤14 ≤13 ≤10 ≤12
Antibiotics Tested Virulence Genes
Breakpoints
Ecology of Resistance
Los Lagos
Valdivia
Mariquina
Máfil
Corral
Lanco
Paillaco
Panguipulli
FutronoLa Unión
PL
PK
PJ
PI
PH
PG
PFPE
PD
PC
PB
PA
0 10 20 30 405Kilometers
.
Clusters
O
N
M
L
K
J
I
H
G
A-F
Ecology of Resistance
WC19
WC18
WC17
WC16
WC15 WC14
WC13
WC12
WC11
WC10
WC09
WC08
WC07 WC06
WC05
WC04
WC03
WC02 WC01
WS10
WS09
WS08
WS07WS06
WS05
WS04
WS03 WS02
WS01
Los Lagos
Valdivia
Mariquina
Máfil
Corral
Lanco
Paillaco
Panguipulli
FutronoLa Unión 0 10 20 30 405
Kilometers
.
Clusters
O
N
M
L
K
J
I
H
G
A-F
Do low concentrations of chlortetracycline or tylosin have a biological effect on the bacterial community in river water?
Samples taken from the Mississippi River
Activity of Antibiotics in the Water
Chemostats inoculated with 8 µg/L, 800 µg/L and 32 µg/ml of chlortetracycline (CTC) or 10 µg/L and 50,000 µg/L of tylosin twice daily for 10 days. One chemostat was used as a control.
Activity of Antibiotics in the Water
For chlortetracycline, total bacteria counts did not differ among chemostats (P = 0.51)
High-CTC chemostat selected for CTC resistance (P = 0.03)
Activity of Antibiotics in the Water
0
2
4
6
8
10
0 2 4 6 8 10
Time (Days)
Cou
nt (l
og c
fu /
ml)
Control
8 ug / L
800 ug / L
32000 ug / L
0
2
4
6
8
10
0 2 4 6 8 10
Time (Days)
Cou
nt (l
og c
fu /
ml)
Control
8 ug / L
800 ug / L
32000 ug / L
For tylosin, total bacterial load decreased with increasing concentration (P < 0.01)
No significant difference among chemostats for total growth on plates with tylosin (P < 0.17)
Activity of Antibiotics in the Water
0123456789
10
0 2 4 6 8 10
Time (days)
Cou
nt
(log
cfu
/ m
l)
Control
10 μg / L
50000 μg / L
0
1
2
3
4
5
6
7
8
9
0 2 4 6 8 10
Time (days)
Cou
nt
(log
cfu
/ m
l)Control
10 μg / L
50000 μg / L
High tylosin chemostats had significantly higher ratios of counts on CNA-TYL / CNA (P = 0.025)
High tylosin chemostats had higher ratios on LB-CTC / LB (P = 0.08)
Activity of Antibiotics in the Water
00.10.20.30.40.50.60.70.80.9
1
0 2 4 6 8 10
Rat
io o
f co
un
ts
Time (days)
Control
10 μg / L
50000 μg / L
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0 2 4 6 8 10
Rat
io o
f cou
nts
Time (days)
Control
10 μg / L
50000 μg / L
Activity of Excreted Residues
Activity of Excreted Residues
Medicated pelleted feed used in aquaculture
Florfenicol is a commonly used antibiotic in aquaculture in many countries
Multidrug Resistance Plasmids
Call et al., Antimicrob. Agents Chemother., 2010
Resistance in Aquaculture
Fernández-Alarcón et al., Zoonoses Pub Health., 2010
Activity of Excreted Residues
How do we develop accurate estimates of environmental loading of antibiotics excreted in animal agriculture?
Track concentrations in each compartment to develop excretion profile
Cmax and half-life within each compartment
Volume excreted from each compartment
Estimate percentage of total dose in each compartment to develop excretion profile
Half-life of compound in each compartment
Back-calculate to get estimate of concentration
Modeling Excretion of Residues
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Feca
l Con
cent
ratio
n (µ
g/g)
Feca
l Exc
retio
n (m
g)
Time (days)
Cow Fecal Excretion
Fecal Concentration
Modeling Excretion of Residues
Modeling Excretion of Residues
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Milk
Con
cent
ratio
n (µ
g/L)
Milk
Exc
retio
n (m
g)
Time (days)
Cow Milk Excretion Milk Concentration
Modeling Excretion of Residues
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Feca
l Con
cent
ratio
n (µ
g/g)
Feca
l Exc
retio
n (m
g)
Time (days)
Calf Fecal Excretion
Fecal Concentration
Few data available concerning concentration of compound in each compartment
Older compounds have very sparse data
If environmental loading is of interest, additional trials might need to be conducted
Dairy example highlights dilemma of discarding waste milk or feeding it to the calves
Excretion Data Gaps and Concerns
Background: 20%
Transmission: 0 – 12%
Selection: 20 – 60%
0
0.5
1
1.5
2
2.5
1 1.5 2
Selection Pressure
Ris
k R
atio
Baseline
Scenario 1
Scenario 2
Scenario 3
A One Health Model
A One Health Model
A One Health Model
Ministry of Health
Ministry of Agriculture
Ministry of the Environment
Ministry of Tourism
Ministry of Indigenous Peoples
National Water Authority
NGOs
Private Foundations
Private Business
Salmon Coalition
Academia
A One Health Model
First meeting in January 2013, Panguipulli, Chile
Environmental concerns and waste management will continue to be key issues
Residues will decrease with time in the environment, but the rate of decay will vary with many factors
Biological activity in environment remains highly uncertain
Excretion data from animals is lacking
Take Home Messages
Compounds can bind in the environment, analogous to binding in gut or in serum/plasma
Not a blame game; to minimize impacts of residues in the environment, we must develop methods for attribution
Take Home Messages
United StatesDoug CallTim JohnsonAbigail SalyersTom Shryock
ChileClaudia CampilloSantiago ErnstGerardo GonzalezKeith HoodGuillermo Ramirez
United KingdomPeter Silley
Singer labJanet AndersonClaudia FernándezKevin LangJeannette MuñozSheila Patterson