1. Points for Discussion Anti-Infective Drugs Advisory Committee Meeting March 5, 2003

2. Morning Discussion

3. 3 Points for Discussion u Listing Pathogens of Public Health Importance: –The criteria proposed are intended to identify resistant pathogens of public health importance. Please discuss these criteria and provide comments on the factors that comprise the criteria. –Data were presented for 27 taxa that the Agency plans to evaluate according to these criteria. Are there other pathogens which should be added for evaluation? –Are there other analyses the committee believes would be useful in evaluating multi-drug resistant organisms?

4. 4 Criteria for Developing List 1. Organism of sufficient prevalence in population with disease under study 2. Organism causes serious and severe disease 3. Drug to which organism is resistant is commonly used in disease under study 4. Limited available therapies due to multi-drug resistance 5. Drug used to control spread of disease in population 6. Clinical correlation of in vitro resistance with poor clinical outcomes

5. 5 Prevalence of Clinically Relevant Species from All Specimen Sources Percent of Patients Top 10 Enterobacteriaceae Escherichia coli Klebsiella pneumoniae Proteus mirabilis Enterobacter cloacae Serratia marcescens Enterobacter aerogenes Citrobacter freundii Klebsiella oxytoca Citrobacter koseri Morganella morganii Staphylococcus aureus Coagulase-negative staphylococci Pseudomonas aeruginosa Enterococcus faecalis Enterococcus faecium Acinetobacter baumannii Stenotrophomonas maltophilia Burkholderia cepacia Streptococcus pneumoniae Viridans streptococci Beta-hemolytic streptococci Streptococcus agalactiae Streptococcus pyogenes Haemophilus spp. Haemophilus influenzae Haemophilus parainfluenzae Anaerobic bacteria 5

6. Afternoon Discussion

7. 7 Points for Discussion-1 Data from Studies in One Indication Supporting Studies in a Different Indication: 1. Please discuss the concept of data from studies in one indication supporting studies in a different indication. In your discussions please also discuss the proposed criteria that are intended to identify factors which should be evaluated when considering the evidence from studies in one indication supporting studies in a different indication. Are there factors that should be added, modified, or removed?

8. 8 Points for Discussion -2 Data from Studies in One Indication Supporting Studies in a Different Indication: 2. Please discuss which indications may provide supportive evidence for a single clinical study in another indication. 3. Please discuss whether data for a “more serious” indication can support safety and efficacy in a “less serious” indication. Are there situations where the converse could be considered (“less serious” indication supporting “more serious” indication)?

9. 9 Proposed Criteria - 1 1. Natural history of the disease under study - what is the spontaneous resolution rate and what is the morbidity/ mortality without treatment? 2. Factors other than he antimicrobial which may affect outcome in a given indications –surgical debridement –adjunctive therapies - ABECB 3. Characteristics of the study drug, e.g., pharmacokinetics of the drug - does it reach site of infection? –tissue levels –effects of pH

10. 10 Proposed Criteria - 2 4. Monomicrobial vs. polymicrobial nature of infection –enterococci in a polymicrobial intraabdominal infection 5. Similar site of infection –Lung for CAP and HAP 6. Host effects –Host differences in CAP vs. HAP 7. Similarity in spectrum of organisms causing disease –differences in organism most commonly associated with CAP vs. HAP

11. 11 Relating Indications (?) Related by Organ System u CAP  HAP u CAP  ABECB u cSSSI  uSSSI u cUTI  uUTI u cUTI  Prosatitis Other Relationships. u CIAI  cSSSI u cSSSI  CIAI u cSSSI  HAP u HAP  cSSSI u ABS  AOM u AOM  ABS