1. Antibiotic Resistance
Background information, current issues and policy,
and the veterinarian’s role

2. Outline Recent news and importance of issue
Antibiotics: information, mode of action
Factors that contribute to resistance
In the free environment
In animals
Resistance: a working definition
The Veterinarians role and current policy
Discussion

4. Meropenem, an example of a carbapenem

8. Level of Importance
One of the most important issues for current treatment for human and animal patients
Will probably become the most challenging treatment complication while we are practicing
68% of acute respiratory tract visits were prescribed antibiotics.
Of these, 80% of the prescriptions were unnecessary according to CDC guidelines1.
1) Scott JG, Cohen D, DiCicco-Bloom B, Orzano AJ, et al: Antibiotic use in acute respiratory infections and the ways patients pressure physicians for a prescription. J Fam Pract: 50(10): 853-8, 2001.

9. Pictures from Doug Johnson
Antibiotics
Take advantage of a difference between bacterial cells and host cells to be selectively bactericidal or bacteriostatic
FDA has four approved uses of antibiotics: treatment, prevention, control, and growth promotion/feed efficiency
Gram-positive cell wall
Gram-negative cell wall
Eukaryotic cell membrane
Pictures from Doug Johnson

11. Transpeptidation inhibition
Transpeptidation is the cross-linking of peptides within cell wall. Necessary for cell wall integrity
Penicillin-binding proteins (pbp) catalyze this process
Penicillin and related antibiotics (β-lactams) inhibit this process +
Transpeptidation
by pbp
Penicillin
Cell lysis and death

12. MRSA Methicillin Resistant Staphylococcus aureus
Multiple Resistant Staphylococcus aureus?
Skin infections are common and relatively easy to treat
Infections acquired in healthcare settings, both human and animal, are often more severe
Immunocompromised or vulnerable to infection
Post-operative risk
Presence of many ill individuals
Large reservoir for infection
Most human hospitals have protocols in place for Multiple Drug Resistant Organisms
Animal hospitals are lacking in robust protocols
cdc.gov

13. Tracking Resistance

14. Tracking Resistance
HealthMap.org

15. Resistance – A Working Definition
Antibiotic resistance is the ability of bacteria to resist the effects of an antibiotic. In a clinical setting this means the persistence of disease.
Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections.
Huge selective pressure is placed on bacteria when antibiotics are present
cdc.gov

16. Resistance – possible causes
Mutation – change of drug target
Inevitable mutations that occur normally are enhanced by increased rates of DNA damage
Conjugation – direct transfer of genes
Transformation – eDNA is incorporated into cell
Transduction – transfer of genes via viruses
Destruction or inactivation of drug
Ability to pump drug out

17. Determining Resistance
Disk Diffusion Assay
Aminoglycoside
Quinolone
Tetracycline
Ciprofloxacin
Cephamycin
NARMS Retail Meat Annual Report, 2007

18. Contributing factors to resistance- Biofilms
The extreme majority of microbes do not live as isolated, pure cultures in the planktonic state
Rather they exist in complex communities surrounded by the extracellular polymeric substance (EPS)
The EPS consists of
Protein
eDNA
Sugars
Water
Confocal Scanning Laser Microscopy
Flemming and Wingender. Nature reviews 2010

19. Contributing factors to resistance- Biofilms
Biofilms offer many advantages over planktonic cells:
Protective barrier from direct harm and predation
Complex array of enzymes that otherwise may not be available to a particular species
Retention and storage of water and nutrients
Maintenance of chemical gradients
A diverse set of nuclear material for exchange (horizontal transfer)
Flemming and Wingender. Nature reviews 2010

20. Contributing factors to resistance- Biofilms
Implications for human and animal health
Also consider achieving and maintaining the minimum inhibitory concentration in tissues (different tissue types having the same effect as a biofilm)
Photo from Doug Johnson

21. Contributing factors to resistance- Exposure
Kaufmann et al. 2010

22. Contributing factors to resistance- Exposure
LexA inhibition
Causes for continued low level exposure:
Non-therapeutic dose
Missed dose/early discontinuation
Did not achieve MIC at site of infection
Not the appropriate antibiotic
Kaufmann et al. 2010
Cirz et al. (2005)

23. Briefing on Current Issue
July 3, FDA issued an order that prohibited the extralabel use of cephalosporin drugs in food-producing animals
The AVMA recommended the FDA postponed the ruling until a risk assessment was preformed
Felt there was a lack of scientific evidence
No promise that it would benefit human health
Unintended consequences of animal health, food safety
In November of 2008 the FDA withdrew the order

24. Briefing on Current Issue
The Preservation of Antibiotics for Medical Treatment Act of PAMTA (S.619/H.R.1549)
Eliminate the use of non-therapeutic use of antibiotics that are important in human health, meant to decrease the development of antibiotic resistant bacteria
Non-therapeutic use = use of a drug as a feed or water additive for an animal in the absence of any clinical sign of disease
Drugs listed: penicillin, tetracycline, macrolide, sulfonamide, or any drug that is used in humans to treat and prevent disease

25. The AVMA Position on PAMTA
The AVMA opposes this legislation
Increase in animal disease and death
Compromise disease prevention and control
PAMTA is not risk-based (backed up by a solid risk assessment)
Contrary to the practice of veterinary medicine
Current layers of protection
Conflicting scientific data on risk to humans

26. What YOU can do
Need for more information on to what extent antibiotics in animals play a role in human health
Novel drugs are desperately needed
Properly set up protocols should be established and followed

27. What do you think?
Now everyone has plenty of basic information and a general knowledge of the importance of the issue.
What do you think about …?
PAMTA and the current AVMA position
Current veterinary practices (draw from your own experiences)
Current human medicine practices (draw from your own experiences)
How things will change in the next 10 years (from now to time when some of you may be practicing)
Any general thoughts?