# Presentation: 236765

## When Blood & Guidance Go Bad:The Story of Bacteremia as an Indication

- Janice Soreth, M.D.
- Director
- Division of Anti-Infective Drugs
- US Food & Drug Administration

## Outline of Today’s Talks

- The District, Rockville, and White Oak
- Hollywood
- The Washington Redskins
- National Hockey League (NHL) Lockout
- Monday Morning Quarterbacking
- Credits

- Soreth  October 15, 2004

## District of Columbia, pre- 1965

- Bacteremia, sepsis, bacteremic sepsis, septicemia, primary bacteremia, and secondary bacteremia discussions began a long time ago, since the FDA was located in the District of Columbia.
- Org chart: Bureau of Biological and Physical Sciences, Division of Pharmacology, Branch of Antibiotics
- My knowledge of this era is derivative.

- Soreth  October 15, 2004

## Rockville: 1970s and 1980s

- Language for “bacteremia”, “septicemia” made it into package inserts.
- Org chart changed:
- Bureau of Biological & Physical Sciences/Div of Pharm →
- Bureau of Drugs & Biologics/Div of Anti-Infectives  →
- Center of Drug Evaluation & Research/Div
- Division of Anti-Infectives then regulated
- 	antibiotics, antiparasitics, topicals, dermatologics, ophthalmologics, antifungals, TB drugs, antivirals
- 					↓ *split*
- 	Division of Anti-Viral Drugs (1988)

- Soreth  October 15, 2004

## Rockville: 1990s to present

- Soreth  October 15, 2004

## 2005: White Oak

- Soreth  October 15, 2004

## Hollywood: Nothing Is Impossible 

- “...every scientist should remove the word ‘impossible’ from his lexicon.” Christopher Reeve (1952-2004)

- Soreth  October 15, 2004

## Hollywood:Nothing Is Impossible

- ...except maybe when it comes to breakdown of the skin, invasion of the bloodstream, and infection of the patient, followed by cardiac arrest, heart failure, coma, and death.
*Superman was no match for a bloodstream infection .*

- Soreth  October 15, 2004

## AIDAC Meeting: October 14, 2004

- 	It takes extraordinary individuals to recognize that investment and effort in the discovery of new antibiotics, and in treatments for serious infections like S. aureus bacteremia, are worth it in the long run.

- Soreth  October 15, 2004

## The Washington Redskins and Catheter-Related Infections Guidance

- What do Joe Gibbs and the FDA have in common?
- Just like Joe Gibbs, we thought we had put all the right pieces together with the CRBSI guidance.
- Just like Joe Gibbs, we watched
- as the Monster just wouldn’t get up.

- Soreth  October 15, 2004

## CRBSI Guidance

- Discussed at AIDAC meeting 1999
- US stats: 200-400K episodes per year
- Mortality 12-25%
- Definable case definition
- Sponsors now tell us there are numerous reasons why they have hit the boards.
- Don’t blame it on my heart, blame it on my youth.

- Soreth  October 15, 2004

## NHL Lockout and S. aureus Bacteremia

- Success, beyond being tied to a salary cap, is determined not by knowing where the puck *is*...
- ...rather, knowing where the puck *is going to be*, sometimes unpredictable.
- Increasing incidence of S. aureus bacteremia, paralleled by rise in infective endocarditis, foreshadows where major players need to position themselves to win.

- Soreth  October 15, 2004

## Issues for Discussion

- Should  primary bacteremia due to *S. aureus* (PBSA) be an indication? What exactly would a healthy development program look like?
- What patient populations would be  included in such a program?
- Should endocarditis due to *S. aureus* be a separate indication?

- Soreth  October 15, 2004

## Issues for Discussion (continued)

- Should we grant a CRBSI indication in its own right? Or fold it into a more general experience (PBSA or Complicated Skin Infections)?
- If separate, what additional information would you suggest be collected on treating serious *S. aureus* infections?

- Soreth  October 15, 2004

## Issues for Discussion (continued)

- What role do preclinical and early clinical studies play in setting the stage for later, larger clinical trials?
*Sweat the Small Stuff*: How many positive blood cultures are required prior to study entry in a PBSA clinical trial?

- Soreth  October 15, 2004

## Issues for Discussion (continued)

- Screening patients for admission into clinical trials is complicated.  Any thoughts as to a general approach?

- Soreth  October 15, 2004

## Credits

- AC Staff:	Shalini Jain
- Office:	Mark Goldberger
- 			John Powers
- 			Edward Cox
- 			Leo Chan
- Division:	Lillian Gavrilovich
- 			Sumathi Nambiar
- 			Janice Pohlman
- 			Fred Sorbello

- Soreth  October 15, 2004