risks of antibiotics in animal waste christopher ohl md, facp associate professor of medicine...
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Risks of Antibiotics inAnimal Waste
Christopher Ohl MD, FACPAssociate Professor of MedicineSection on Infectious Diseases
Wake Forest University School of MedicineWinston-Salem, [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 TargetsOnly 1 New Antibiotic With a Novel Target in Last 20 Years
Antimicrobial resistant Nosocomial Infections In ICU Patients1999 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. coliQuinolone Resistance
Engberg et al. 2001. Emerg Infect Dis 7:24
Doern GV. Doern GV. Am J Med.Am J Med. 1995;99: 3S-7S. 1995;99: 3S-7S. Jacobs MR, et al. AAC. 1999:43:1901.Jacobs MR, et al. AAC. 1999:43:1901.Jacobs MR, et al. ICAAC. 1999; Abstract C-61. Jacobs MR, et al. ICAAC. 1999; Abstract C-61.
Penicillin-Resistant Penicillin-Resistant S. pneumoniaeS. pneumoniaeUnited States (1979-1997)United States (1979-1997)
0
10
20
30
40
50
Year
Pen
icil
lin
Res
ista
nt,
%
Intermediate (0.12 to 1.0 µg/ml)Resistant (>2.0 µg/ml)
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
-89
1990
-91
1992
-93
1994
-95
1997
1998
29%29%
16%16%18%18%
33%33%
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
IMPACT
Cycle of Antibiotic Resistance Acquisition
UnderIncreasingAntibioticSelectionPressure
The Farm
The Hospital
The Clinic
Origins of Human Antimicrobial Resistance
The Farm
The Hospital
The Clinic
Origins of Human Antimicrobial Resistance
Adult Antibiotic Prescriptions by Diagnosis
20.920.9
17.617.616.716.7
5.85.8 5.25.2 4.94.9
1.91.9
2727
00
55
1010
1515
2020
2525
3030
DiagnosisDiagnosis
BronchitisBronchitis
SinusitisSinusitis
Other respiratoryOther respiratory
Otitis mediaOtitis media
SkinSkin
PneumoniaPneumonia
WoundsWounds
All othersAll others
% R
xs%
Rxs
Physician Drug and Diagnosis Audit (PDDA) 1997, Scott-Levin.
The Farm
The Hospital
The Clinic
Origins of Human Antimicrobial Resistance
Percent of Cattle that Receivedthe Following Antimicrobials in Feed or Water
0
10
20
30
40
50
Per
cen
t o
f al
l ca
ttle
bacitracin chlortetracyclinechlortet/sulfamethazine neomycinoxytetracycline sulfastetracycline tylosinvirginiamycin other
Feedlot 1999 – Part III, USDA/NAHMS survey, December 2000
Percent of Sites that Gave Antibiotics to Weaned Pigs as a Preventative Practice
0102030405060708090
Percent of swine
production sites
Feed
Injection
Water
Oral
USDA/APHIS Veterinary Services Info Sheet, March 2002
Most Common Antibiotics (by route) Grower/Finisher Pigs
0
10
20
30
40
50
60
tylosin
penicillin
oxytetra.
chlortetra.
bacitracin
ceftiofur
lincomycin
carbadox
neomycin
sulfa.
FeedInjection Water
USDA/APHIS Veterinary Services Info Sheet, March 2002
Pe
rce
nt o
f Fa
rm S
ites
Antimicrobials in Feed to Grower/Finisher for any Reason
0
10
20
30
40
50
60
Per
cen
t o
f si
tes
tylosin (62.3 days) chlortetracycline (31.7 days)
bacitracin (67.7 days) lincomycin (31.6 days)
carbadox (22.6 days)
Swine 2000 – Part II, USDA/NAHMS survey, August 2001
Antimicrobials in Feed to PoultryNontherapeutic, 1998
0
5
10
15
20
25
30
Per
cen
t o
f b
roil
ers
Bambermycin erythromycin chlortetra.
penicillin lincomycin 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 HumansCompare and Contrast
Animals Humans
Individual Treatment Yes, by vet or caretaker
Yes, by MD
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 3GAO. RCED 99-74
FDA. www.fda.gov/cvmWHO. www.who.ch
Is Antibiotic Use on the Farm Related to Antibiotic Resistance in Humans?
Colonized Animal
Susceptible Human
Slaughter
Retail Meat
Occ
upat
iona
l
•Soil•Ground water•Surface water•Air
3 Possible Routes
Food borne EnvironmentalVan den Bogaard. 2000. Int J. Antimicrob Agents. 14:327
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
FQ Use in Poultry
Smith, et al. 1999. NEJM 340:1525
Glynn, M. K. et al. N Engl J Med 1998;338:1333-1339
Prevalence of Resistance to Ampicillin, Chloramphenicol, Streptomycin, Sulfonamides, and Tetracycline among Typhimurium Isolates Identified by Surveys of Antimicrobial-Drug
Resistance in Sentinel Counties
Enterococcus faeciumStreptogramin 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 Human-Associated, 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
• 1 or more antibiotics foundin 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.
Antibiotics in Surface Water
Kolpin et al. Environ Sci Technol 2002. 36:1202
US Governmental Response
Release Assessment
ExposureAssessment
Qualitative Risk Assessment
ConsequenceAssessment
Risk Estimation
Risk estimation integrates results from release, exposure and consequence assessments to produce overall measure of risk associated with hazards
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Text only version
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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!”