1. Antibiotic Overuse – how much does it matter? Thursday 1/17/08

2. Spread of resistance Antibiotic pressure Human to human transmission

3. Mechanisms by which Antibiotic use can induce resistance Lipsitch & Samore EID 2002

4. Antibiotic selection of resistant mutants Ab treatment => outgrowth of resistant subpopulations or acquire de novo resistance

5. Antibiotic pressure => increased load or resistant bacteria

6. By eradicating a susceptible strain making the host more susceptible to new acquisition of strains

7. Indirect effect – reduced transmission of susceptible strains to other susceptible hosts

8. Antibiotics are drugs with externalities (like pollutants) By treating an individual with antibiotics – other individuals in the society are influenced Antibiotic treatment – maybe beneficial for an individual but deleterious for society.

9. Types of studies that examine the relationship between Ab use and Ab resistance Ecological studies Individual level studies –Case-control –Quasi-experimental studies –Longitudinal studies Mathematical models

10. Total Ab use in 26 European countries in 2002/ Goosens et al. Lancet 2005

11. Total Ab use in 2004 / Goosens CID 2007

12. Correlation between Pen use and PRSP / Goosens et al. Lancet 2005

13. Do all antibiotic classes induce resistance similarly? The pneumococcus paradigm / Dagan et al. PIDJ 2006

14. Antibiotic use as a risk factor for MRSA (in ED) / Moran et al. NEJM 2006

15. Antibiotic consumption and MRSA, an ecologic study (EID 2004)

16. FQ use and FQ-R MRSA and E. coli (community and HA)/ MacDougall et al. CID 2005

17. Is there overuse/non-judicious use of antibiotics? ~50% of Ab prescriptions are non-judicious What is non-judicious use? –Ab for viral infections –Wrong dose –Wrong duration –Wrong Ab class –Broad ab class when narrow is as good

18. Why is there non-judicious use? Lack of knowledge Patient demand Uncertainty (of Dx, of risks and benefits) Medico-legal issues – fear from lawsuit Low awareness to Ab resistance problem

19. Effect of antibiotic use in agriculture Over 50% of Ab produced in US are used for agricultural purposes Use for growth promotion and treatment of food animals FQ used to treat chicken: –Identical strains of FQ-R Campylobacter found in raw chicken as those in humans

20. Agriculture use and Ab resistance: Quantifying the effect Animal use can be a selective force responsible for the assembly of resistant gene clusters Reservoir for resistance-encoding plasmids (or other genetic elements) in animal commensal bacteria Bacteria that are shared by food animals and humans (VRE).

21. Is it not too late? Regulation now may have little or no effect. Waiting for conclusive evidence may result in a missed opportunity to prevent damage!