1. 1 Antibiotic Resistance: An Update Janice Soreth, M.D. Director Division of Anti-Infective Drug Products February 20, 2002

2. 2 Antibiotic Resistance: Overview FDA/CDER Meetings Lessons Learned What’s New in 2002

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4. 4 100 80 60 40 20 0 198019751985199019952000 1997 GISA VRE MRSA MRCNSPRSP Percentage of Pathogens Resistant to Antibiotics Gram-Positive Resistance - United States, 1980-1999 Paladino JA. Am J Health Syst Pharm 2000;57 Suppl 2:S10-2.

5. 5 FDA Meetings on Resistance General July, 1998 October, 1998 October, 1999 Product-specific –SynercidFebruary, 1998 –LevaquinOctober, 1999 –ZyvoxApril, 2000 –AugmentinESJanuary, 2001

6. 6 Lessons Learned Regulatory tools may encourage development. Novel approaches to study design need to be considered (e.g., dose-response trial). Enrichment strategies may help. Data from susceptible isolates are an important component of the overall picture. Using positive culture results to enroll patients in a study (e.g., MRSA) can augment a development program with infection-site specific trial (e.g., pneumonia, skin)

7. 7 Lessons Learned (continued) Regulatory tools have helped, but it is still a challenge to accrue organisms. Great resources are spent to develop a drug for resistant pathogens. Historical controls can be used when there is no approved comparator, but they may be problematic. More data do not necessarily equal better data. Bottom line: New drugs are still needed, as is preservation of the already-marketed ones.

8. 8 What’s New? Resources Surveillance Education Future Approaches

9. 9 Resources We have received resources intended specifically for antimicrobial development and resistance activities. We intend to increase our staff who deal with these issues.

10. 10 Surveillance We will augment our access to surveillance information, in collaboration with CDC and the private sector Goal: To better approach antimicrobial drug development and usage.

11. 11 Education Campaign Target both health care professionals and patients. We plan to address antibiotic resistance and prudent use in product labeling. (Proposed Rule) We anticipate an impact on promotional material.

12. 12 Proposed Rule September 19, 2000: Federal Register publication of proposal to amend regulations to require that all systemic antibacterial products intended for human use contain additional labeling information about the emergence of drug-resistant bacterial strains. Intent is to encourage physicians to –Prescribe antibacterials only when clinically necessary. –Counsel patients about proper use of antibacterials.

13. 13 Education Campaign CDER effort is underway to develop advertisements on the prudent use of antibiotics. We envision a variety of media: –print advertisements in professional journals, patient leaflets, public service announcements.

14. 14 Future Approaches to Anti-Infective Development Require creativity and flexibility on our part. Recognize the limits of resources (patients, time, money) that go into developing an antimicrobial product for resistance.

15. 15 Summary We have made progress in getting antimicrobial products to the market for patients with resistant pathogens, but more are needed. We must preserve the antibiotic treasures we do have, through education, prudent use, etc. We need to strike a balance between available resources for performing clinical trials and level of certainty in determining effectiveness.