The New Antiseptics

By LEON JAROFF

Sepsis, which is what happens to the body when an infection goes bad, is one of mankind's oldest and most intractable foes. It attacks 500,000 Americans annually and kills nearly half of them; around the world, about 1,500 people die from septic shock every day. Now help may be on the way. A new drug has stopped the progression of sepsis in clinical trials of dangerously ill victims, while another shows promise of halting the disease before it gets out of control.

The deadly agents of sepsis are so-called endotoxins, poisons produced by bacteria infecting the body through wounds, burns or during surgery. But it is the body's overreaction to these toxins that really does the damage. The resulting massive inflammation, accompanied by blood clots in small blood vessels, damages tissues and organs and lowers blood pressure. In its most severe form, called septic shock, it shuts down vital organs.

For years drug companies have been searching in vain for an effective antisepsis potion. Then late last month Eli Lilly & Co. sounded an optimistic note. Clinical trials of a new Lilly drug called Zovant were abruptly halted when it became clear that the death rate of desperately sick patients infused with Zovant was significantly lower than that of counterparts receiving a placebo. When news of this development reached Wall Street, Lilly's stock jumped more than 14 points, to 102, in one day. "We'll know when we get all the data what the drug is truly capable of doing," says Dr. William Macias, medical director of Lilly's Zovant product-development team. "But we hypothesize that it quiets down the inflammation, breaks up the clots and prevents additional clots from forming."

Cautious optimism also pervades the Rogosin Institute in New York City, where Dr. Bruce Gordon, an expert on treating high cholesterol, became intrigued with the fact that cholesterol and blood lipids (fats) in people with severe illness or injury tend to drop to abnormally low levels. This makes them more vulnerable to sepsis, he reasoned, because one of the lipids' functions is to bind to and neutralize endotoxins. His unorthodox solution (especially for someone known for fighting high cholesterol): try to raise lipid levels in sepsis victims.

Working with a lipid emulsion derived by Rogosin researchers from soybeans, Dr. Joseph Parrillo, a leading authority on sepsis at Chicago's Rush medical center, infected 19 pigs with bacteria containing endotoxin, then infused the Rogosin emulsion into eight of them. The results were striking. All 11 of the untreated pigs died, while seven of the treated animals survived. Says Parrillo: "It's kind of convincing."

Indeed, convincing enough that Gordon has just completed a successful safety trial on human volunteers. Scheduled next is a human trial for the efficacy of the compound that may someday, if all goes well, not only contain sepsis but perhaps even prevent it.