It's a chilling notion: deadly bacteria that drugs can't kill. These "superbugs" almost claimed the life of a 55-year-old diabetic being treated for a blood infection last winter at New Jersey's East Orange V.A. Medical Center. Doctors tried their most powerful antibiotics, yet nothing would defeat the relentless microbe.
Fortunately, Lisa Dever, chief of the hospital's infectious diseases clinic, was testing an experimental agent from Rhone-Poulenc Rorer called Synercid. She used it on the fading patient, who after two weeks of injections emerged cured. Dever says the compound can zap other seemingly invulnerable killers that cause, among other things, pneumonia and meningitis.
After years of doing little to combat superbugs, giant pharmaceutical companies once again are putting their muscle into multimillion-dollar counterattacks. Rhone and other drugmakers, including Upjohn, Pfizer, Schering-Plough, and Eli Lilly, are improving older antibiotics, racing new ones through clinical tests, and fine-tuning methods to identify and screen new drugs faster. To bolster their efforts, they're forging partnerships with science labs and biotech startups that are expert in drug-resistant microbes. In December, for instance, Schering-Plough Corp. said it would sink $44 million into Genome Therapeutics of Waltham, Mass., which is searching for genes that could be chinks in the bacteria's armor.
The need for new drugs could not be more urgent. In 1985, just 0.02% of infections around the U.S. showed resistance to penicillin, says Rockefeller University microbiologist Alexander Tomasz, who was one of the first to sound alarms. By 1993, drug-resistant infections were killing 10,000 Americans a year.
What has rendered penicillin and other time-honored blockbusters impotent? Scientists blame the explosion of drug-resistant microbes on everything from overuse of antibiotics in medicine and agriculture to the spread of invasive surgical procedures to urban crowding.
Drugmakers themselves deserve some censure. According to industry magazine Scrip, 50% of antibiotics manufacturers in the U.S. and Japan curtailed development in the mid-1980s, assuming victory in the battle against microbes.
In the race to recoup lost ground, the first important new drug on the shelf may be Rhone's Synercid. It could win Food & Drug Administration approval for some uses as early as 1997, if the agency agrees to fast-track clearance. Close behind: a group of compounds called oxazolidinones, which Upjohn has developed to jam the superbugs' ability to multiply. And Lilly is improving vancomycin, one of the few effective superbug-busters. It seeks expedited FDA approval for a new version that may be 100 times more potent.
PROFIT PICTURE? As strong as the need is for the new drugs, however, their profit potential is unclear. A drug typically costs about $200 million to develop. Merrill Lynch & Co. senior analyst Richard Vietor says patients may not take enough of the superbug fighters to bring a company financial reward--only up to 15 days' worth to defeat drug-resistant bacteria, vs. years for the drugs that fight chronic maladies, such as hypertension.
Physician Dever argues that a single broad-spectrum antibiotic from Merck & Co., called Primaxin, can account for as much as 10% to 20% of a hospital's pharmacy budget--and isn't even effective against many resistant strains. And manufacturers can charge a premium for newer, more powerful compounds. Better technology also should bring down costs.
In the battle of drug companies vs. the microbial kingdom, the good guys have gained some ground. But the war is hardly won.