Transcript Risks of Antibiotics in Animal Waste

Risks of
Antibiotics in
Animal Waste
Christopher Ohl MD, FACP
Associate Professor of Medicine
Section on Infectious Diseases
Wake Forest University School of Medicine
Winston-Salem, NC
[email protected]
Objectives
• Overview of antimicrobial resistance
• Discuss the 3 origins of antibiotic resistant
infections in humans
• Discuss antimicrobial use in humans and
animals
• Present risk to humans from antimicrobial
use and resistance in food animals and
their environment
• Briefly present governmental and
regulatory response to the problem
Antibiotics Have
Transformed
Human Medicine
Antimicrobial Targets
Only 1 New Antibiotic With a Novel Target in Last 20 Years
Antimicrobial resistant Nosocomial Infections In ICU Patients
1999 compared with 1994-1998, NNIS
Organism
Increase in resistance
VRE
43%
MRSA
37%
MRSE
2%
3rd Ceph E. coli
8%
3rd Ceph K. pneumoniae
-3%
Imipenem P. aeruginosa
56%
Quinolone P. aeruginosa
50%
3rd Ceph P. aeruginosa
10%
3rd Ceph Enterobacter sp.
-4%
Campylobacter jejuni & C. coli
Quinolone Resistance
Engberg et al. 2001. Emerg Infect Dis 7:24
Penicillin-Resistant S. pneumoniae
United States (1979-1997)
40
33%
29%
Intermediate (0.12 to 1.0 µg/ml)
Resistant (>2.0 µg/ml)
30
20
1994-95
1992-93
1990-91
1987
1985
1986
Year
1988-89
Doern GV. Am J Med. 1995;99: 3S-7S.
Jacobs MR, et al. AAC. 1999:43:1901.
Jacobs MR, et al. ICAAC. 1999; Abstract C-61.
1984
1983
1982
1981
1980
0
1979
10
1998
18%
16%
1997
Penicillin Resistant, %
50
IMPACT
Morbidity and mortality of
infections greater for
resistant compared with
susceptible organisms
New drugs designed to
combat bacterial
resistance are
becoming scarce and
more costly
Cost of antibiotic
resistance in the U.S.
estimated in 1996 at
$30 billion
Cycle of
Antibiotic
Resistance
Acquisition
Under
Increasing
Antibiotic
Selection
Pressure
The Farm
Origins of Human
Antimicrobial
Resistance
The Clinic
The Hospital
The Farm
Origins of Human
Antimicrobial
Resistance
The Clinic
The Hospital
Adult Antibiotic Prescriptions by
Diagnosis
30
27
% Rxs
25
20
Sinusitis
20.9
17.6
Other respiratory
16.7
Otitis media
15
Skin
10
5
Pneumonia
5.8 5.2
4.9
Wounds
1.9
0
Bronchitis
Diagnosis
Physician Drug and Diagnosis Audit (PDDA) 1997, Scott-Levin.
All others
The Farm
Origins of Human
Antimicrobial
Resistance
The Clinic
The Hospital
Percent of Cattle that Received
the Following Antimicrobials in Feed or Water
Percent of all cattle
50
40
30
20
10
0
bacitracin
chlortet/sulfamethazine
oxytetracycline
tetracycline
virginiamycin
chlortetracycline
neomycin
sulfas
tylosin
other
Feedlot 1999 – Part III, USDA/NAHMS survey, December 2000
Percent of Sites that Gave Antibiotics to
Weaned Pigs as a Preventative Practice
90
80
70
Percent of 60
50
swine
production 40
sites
30
20
10
0
Feed
Injection
Water
Oral
USDA/APHIS Veterinary Services Info Sheet, March 2002
Most Common Antibiotics (by route)
Percent of Farm Sites
Grower/Finisher Pigs
60
Feed
Injection
Water
50
40
30
20
10
0
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USDA/APHIS Veterinary Services Info Sheet, March 2002
Antimicrobials in Feed to
Grower/Finisher for any Reason
Percent of sites
60
50
40
30
20
10
0
tylosin (62.3 days)
bacitracin (67.7 days)
carbadox (22.6 days)
chlortetracycline (31.7 days)
lincomycin (31.6 days)
Swine 2000 – Part II, USDA/NAHMS survey, August 2001
Antimicrobials in Feed to Poultry
Nontherapeutic, 1998
Percent of broilers
30
25
20
15
10
5
0
Bambermycin
penicillin
erythromycin
lincomycin
chlortetra.
virginiamycin
Mellon, et al. Union of Concerned Scientists, 2001
Antibiotic Use in US: Animals vs Humans
• Current estimated use/year
– Animals: 26.6 million lbs
– Humans: 3 million lbs
• Mellon, et al. Union of Concerned Scientists, 2001
• Reasonable estimate ~50% of all antimicrobials
in North America are given to animals
• Gorbach. 2001. NEJM. 345:1202
• Classes shared: penicillin, cephalosporin (all
generations), macrolides, sulfas,
macrolide/lincosamide/streptogramin,
aminoglycoside, quinolone
Antibiotic Use in US: Animals vs Humans
Compare and Contrast
Animals
Humans
Individual Treatment
Yes, by vet or Yes, by MD
caretaker
Mass Treatment
Yes, often
Very rare
Preventive Treatment
Often
Seldom
“Growth Promotion”
Yes
No
Duration / dose
Long / low
Short / high
Is Antibiotic Use on the Farm Related to
Antibiotic Resistance?
• On the Farm: Yes
–
–
–
–
–
Controlled challenge studies
Farm animal microbiologic surveys
Farm environmental microbiologic surveys
Abattoir investigations
Retail meat
• Pathogens of human interest
– Campylobacter sp. (Resis. to FQ’s, macrolides)
– Salmonella typhimurium, S. newport; (multidrug
resistant common, FQ Resis. rare in US)
– Enterococcus sp. (R Streptogramins, tetracyclines,
vancomycin, macrolides)
– E. coli (tetracyclines, cephalosporins, aminoglycosides,
trimethoprim-sulfamethoxazole, FQs)
APUA/FAAIR: 2002. Clin Inf Dis. 34: supplement 3
GAO. RCED 99-74
FDA. www.fda.gov/cvm
WHO. www.who.ch
Is Antibiotic Use on the Farm Related to
Antibiotic Resistance in Humans?
Colonized Animal
Retail Meat
Occupational
Slaughter
Food borne
Van den Bogaard.
2000. Int J.
Antimicrob
Agents. 14:327
•Soil
•Ground water
•Surface water
•Air
Environmental
Susceptible Human
3 Possible Routes
FQ Use in Poultry
Quinolone Resistant
C. jejuni
Minnesota 1992-1998
• 4953 isolates from ill
humans
• 1997: 14% of retail
chicken meat with
quinolone resistant
C. jejuni
• Human and chicken
isolates related
molecularly
• Only 15% of cases
could be explained
by prior human
quinolone use or
foreign travel
Smith, et al. 1999. NEJM 340:1525
Prevalence of Resistance to Ampicillin, Chloramphenicol, Streptomycin, Sulfonamides, and
Tetracycline among Typhimurium Isolates Identified by Surveys of Antimicrobial-Drug
Resistance in Sentinel Counties
Glynn, M. K. et al. N Engl J Med 1998;338:1333-1339
Enterococcus faecium
Streptogramin Resistance
• Common in chicken retail meat, but rare in humans:
microbiologic survey of stools submitted to clinical
laboratories show 1% colonized.
– McDonald. 2001. NEJM 345:1155
• Challenge study in 6 humans with streptogramin resistant E.
faecium spiked chicken or pork
– Sorensen. 2001. NEJM. 345:1161
• Recent risk assessment by FDA-CVM
– “ assuming a food pathway attribution of 10%, the
average risk to a random member of the US population of
having SREF attributable to animal uses of virginiamycin
and that may result in impaired Synercid therapy ranges
from 7 chances in 1 billion to 14 chances in 100 million in
one year”
– FDA-CVM. 2004. www.fda.gov/cvm
Possible Animal Origin of HumanAssociated, MDR uropathogenic E. coli
• Multistate outbreak of
TMP-SXT resistant E. coli
urinary tract infections
• PFGE and PCR
fingerprinting
• 1 isolate from a cow was
found in a cluster of
human isolates
• Conclusion: origin of this
drug resistant strain
potentially has an animal
origin
Occupational and Farm Resident Risk
• Tetracycline resistant E. coli transferred to farmers and farm
families (31.3% compared with 6.8% of neighbors)
– Levy. 1976. NEJM 295:583
• Macrolide resistant S. aureus and Streptococci as well as
Enterobacteriaceae resistant to quinolone, TMP-SXT,
tetracycline and aminoglycoside more common in pig
farmers than controls
– Aubry-Damon et al. 2004. Emerg Infect Dis. 10:873
• Enterococci resistant to streptogramins or vancomyin
transferred from chicken and turkey flocks to farm workers
– Willems et al. 2000. J. Infect Dis. 182:816
– Van den Boggard et al. 1997. NEJM. 337:1558
• Ceftriaxone resistant S. typhimurium transferred from cattle
to 12 y.o. farm resident causing severe intestinal illness.
– Fey et al. 2000. NEJM. 342:1242
Antibiotics in Surface Water
• 1 or more antibiotics found
in 48% of streams sampled.
• 14 of 22 antibiotics detected at least once.
• Concentrations generally low (<0.5 ppb).
• Most frequently detected antibiotics:
trimethoprim (27.4%), erythromycin-H2O
(21.5%), lincomycin (19.2%), sulfamethoxazole
(19.0%), tylison (13.5%).
• Antibiotics found in streams downstream of both
intensive urban (68%) and livestock (39%)
activity.
Kolpin et al. Environ Sci Technol 2002. 36:1202
US Governmental Response
Qualitative Risk Assessment
Release
Assessment
Exposure
Assessment
Risk Estimation
Consequence
Assessment
Risk estimation integrates results from release,
exposure and consequence assessments to produce
overall measure of risk associated with hazards
_____________________________________________________________________________________________________
Text only version
Press Release: Antimicrobial Animal Drugs
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Can Risk Be Reversed?
Danish Growth Promoter Withdrawal Experience
• Complete withdrawal of antimicrobials for growth promotion
or disease prevention but not therapeutics by end of 1999
• Antimicrobial use decreased 54% from 1994 to 2001
• Some increase in therapeutic use in pigs but not poultry
• Dramatically reduced food animal reservoir AR enterococci
• Possible increase in tetracycline resistance in food animal
salmonella
• No measurable change in food-borne pathogen AR in
humans (illness or commensal)
• Minimal impact on animal welfare
• Economic impact: Modest decreased feed efficiency in
weaners and poultry. GDP 0.03% decrease. (~1 euro/pig)
WHO/CDS/CPE/2FK/2003.1
“I say we do it
…
and trichinosis
be damned!”