When Blood

1
When Blood Guidance Go BadThe Story of
Bacteremia as an Indication

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

2
Outline of Todays Talks

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

3
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.

4
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)

5
Rockville 1990s to present
6
2005 White Oak
7
Hollywood Nothing Is Impossible

• every scientist should remove the word
  impossible from his lexicon. Christopher Reeve
  (1952-2004)

8
HollywoodNothing 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
  .

9
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.

10
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 wouldnt get up.

11
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.
• Dont blame it on my heart, blame it on my youth.

12
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.

13
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?

14
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?

15
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?

16
Issues for Discussion (continued)

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

17
Credits

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