Biotechs Wage War on Superbugs

Multidrug-resistant infections are the new plague. The most publicized, methicillin-resistant Staphylococcus aureus (or MRSA), causes nearly 19,000 deaths in the United States each year -- more than AIDS. Today, 70% of infections are impervious to at least one antibiotic, prompting many clinicians to prescribe multiple drugs. And new antibiotics aren't the answer: Bacteria often begin to show resistance during clinical trials, before doctors have even had a chance to administer the drugs. The Achilles' heel of antibiotics? They poison most bacteria, but allow the hardiest to survive and breed drug-resistant progeny.

Our best hope of defeating antibiotic resistance, says Georgetown University immunologist Michael Zasloff, is to develop drugs that kill bacteria so immediately and thoroughly that they can't evolve resistance. "A drug like penicillin targets an enzyme, and it's easy for an organism to develop a single mutation to get past that," he says. "But when a drug destroys a bacterium's entire membrane, it's very difficult for the bacterium to redesign it." Here, three biotechs that have adopted a scorched-earth approach.

Illustration by Headcase Design

VIRAL WEAPONS

Eastern European doctors have long recognized the power of phages -- naturally occurring bacteria-eating viruses -- to treat antibiotic-resistant infections. The United States hasn't quite caught on yet, but Intralytix, a Baltimore company that manufactures phage-based products to kill bacteria on food, is looking to change that. "We're concentrating on fighting multidrug-resistant bacteria and on building a drug that's effective against MRSA," says CEO John Vazzana. "Enormous amounts of data show phages really do work."

Phages destroy bacteria from the inside out. They enter a bacterium through its membrane (I) and deposit DNA inside, where the phages replicate (II). Baby phages burst out of the bacterium, exploding it like a water balloon (III), and head after other bacteria. Intralytix recently concluded a Phase I human trial at a Texas wound-care clinic, which showed that phage therapy is safe, and is seeking funding for a Phase II trial to demonstrate efficacy against infections like MRSA.

One potential sticking point: the Food and Drug Administration. Since each species of phage attacks one specific type of bacteria, phages work best in a cocktail custom-mixed to combat the particular bacteria causing a patient's infection. FDA policy calls for trials of each combination of phages. But FDA guidelines have accommodated flu vaccines, which must be changed several times a year to keep up with the evolving virus. "I'm an eternal optimist," Vazzana says. "I think that within five years, the FDA will approve a phage-based drug."