Antibiotic Resistance: An Update

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

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

4. PRSP Gram-Positive Resistance - United States, 1980-1999 100 80 MRCNS Percentage of Pathogens Resistant to Antibiotics 60 MRSA 40 20 VRE GISA 0 1975 1980 1985 1990 1995 2000 1997 Paladino JA. Am J Health Syst Pharm 2000;57 Suppl 2:S10-2.

5. FDA Meetings on Resistance General • July, 1998 • October, 1998 • October, 1999 Product-specific • Synercid February, 1998 • Levaquin October, 1999 • Zyvox April, 2000 • AugmentinES January, 2001

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

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. 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. 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. 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. 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. 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. 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.