Risks of Antibiotics in Animal Waste

1
Risks of Antibiotics inAnimal Waste

• Christopher Ohl MD, FACP
• Associate Professor of Medicine
• Section on Infectious Diseases
• Wake Forest University School of Medicine
• Winston-Salem, NC
• cohl_at_wfubmc.edu

2
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

3
Antibiotics Have Transformed Human Medicine
4
Antimicrobial TargetsOnly 1 New Antibiotic With
a Novel Target in Last 20 Years
5
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
6
Campylobacter jejuni C. coliQuinolone
Resistance
Engberg et al. 2001. Emerg Infect Dis 724
7
Penicillin-Resistant S. pneumoniaeUnited States
(1979-1997)
Penicillin Resistant,
33
29
Intermediate (0.12 to 1.0 µg/ml) Resistant (gt2.0
µg/ml)
18
16
1986
1979
1980
1981
1982
1983
1985
1987
1984
1992-93
1997
1998
1988-89
1990-91
1994-95
Year
Doern GV. Am J Med. 199599 3S-7S. Jacobs MR,
et al. AAC. 1999431901. Jacobs MR, et al.
ICAAC. 1999 Abstract C-61.
8
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
9
(No Transcript)
10
Cycle of Antibiotic Resistance Acquisition
Under Increasing Antibiotic Selection Pressure
11
The Clinic
The Farm
Origins of Human Antimicrobial Resistance
The Hospital
12
(No Transcript)
13
The Clinic
The Farm
Origins of Human Antimicrobial Resistance
The Hospital
14
Adult Antibiotic Prescriptions by Diagnosis
30
27
Bronchitis
25
Sinusitis
20.9
20
Other respiratory
17.6
Rxs
16.7
Otitis media
15
Skin
10
Pneumonia
5.8
Wounds
5.2
4.9
5
All others
1.9
0
Diagnosis
Physician Drug and Diagnosis Audit (PDDA) 1997,
Scott-Levin.
15
The Clinic
The Farm
Origins of Human Antimicrobial Resistance
The Hospital
16
Percent of Cattle that Receivedthe Following
Antimicrobials in Feed or Water
Feedlot 1999 Part III, USDA/NAHMS survey,
December 2000
17
Percent of Sites that Gave Antibiotics to Weaned
Pigs as a Preventative Practice
USDA/APHIS Veterinary Services Info Sheet, March
2002
18
Most Common Antibiotics (by route)
Grower/Finisher Pigs
Percent of Farm Sites
USDA/APHIS Veterinary Services Info Sheet, March
2002
19
Antimicrobials in Feed to Grower/Finisher for any
Reason
Swine 2000 Part II, USDA/NAHMS survey, August
2001
20
Antimicrobials in Feed to PoultryNontherapeutic,
1998
Mellon, et al. Union of Concerned Scientists, 2001
21
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. 3451202
• Classes shared penicillin, cephalosporin (all
  generations), macrolides, sulfas,
  macrolide/lincosamide/streptogramin,
  aminoglycoside, quinolone

22
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
23
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 FQs, 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
24
Is Antibiotic Use on the Farm Related to
Antibiotic Resistance in Humans?
Colonized Animal
Slaughter

• Soil
• Ground water
• Surface water
• Air

Occupational
Retail Meat
Food borne
Environmental
Susceptible Human
Van den Bogaard. 2000. Int J. Antimicrob Agents.
14327
3 Possible Routes
25
Quinolone Resistant C. jejuniMinnesota 1992-1998
FQ Use in Poultry

• 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 3401525
26
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
19983381333-1339
27
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 3451155
• Challenge study in 6 humans with streptogramin
  resistant E. faecium spiked chicken or pork
• Sorensen. 2001. NEJM. 3451161
• 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

28
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

29
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 295583
• 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.
  10873
• Enterococci resistant to streptogramins or
  vancomyin transferred from chicken and turkey
  flocks to farm workers
• Willems et al. 2000. J. Infect Dis. 182816
• Van den Boggard et al. 1997. NEJM. 3371558
• Ceftriaxone resistant S. typhimurium transferred
  from cattle to 12 y.o. farm resident causing
  severe intestinal illness.
• Fey et al. 2000. NEJM. 3421242

30
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 (lt0.5 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. 361202
31
US Governmental Response
32
Qualitative Risk Assessment
Release Assessment
Risk Estimation
Exposure Assessment
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 FDA Home Page Search FDA Site
FDA A-Z Index Contact FDA Privacy
Accessibility Slide 11 of 21 Back to Slide 1
33
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
34
I say we do it and trichinosis be damned!