Microbiologist Vincent Fischetti of Rockefeller University, New York City, doesn't scare easily. He knows all about "galloping gangrene," the flesh-killing bacteria that sounds like a sci-fi script. He has seen it. He has worked with it. It doesn't keep him up nights.
What does is the specter of something less dramatic but more threatening: bacteria that nothing can kill.
Overuse and misuse of antibiotics have allowed many kinds of bacteria to mutate and become immune to their effects. "We may be going back to a pre-antibiotic era," Fischetti cautions.
The Centers for Disease Control and Prevention, in a recent report on emerging infectious diseases, calls drug resistance in the U.S. and abroad "a major public health crisis. . . . Drugs that once seemed invincible are losing their effectiveness" against a range of diseases, including TB, gonorrhea, middle-ear infection and staph infections. Doctors fear the day when patients come to them for help and they have nothing to offer.
Warning lights are blinking. One bacteria, Enterococcus faecalis, which causes bloodstream and heart-valve infection, was once vulnerable to a combination of antibiotics, but is now unfazed by any of them.
In this week's Journal of the American Medical Association, CDC researchers report an increase in pneumococcal infections - the kind that cause adult pneumonia, meningitis and kids' middle-ear infections - that are resistant to penicillin or other drugs normally used against them. This leaves doctors with less effective second-string drugs as their only weapons and often lets the disease do greater damage because of the delay in recognizing drug resistance.
"We could be caught very quickly with a whole population of resistant organisms," Fischetti says. So far, strep organisms, including the kind that causes the dreaded galloping gangrene, "are the only ones that haven't become resistant to antibiotics in general," he says. But if they do, "we could have a serious problem, because strep throat is such a prevalent disease."
Everybody's to blame for this turn of events, experts say, from the patient who takes just a week's worth of a 14-day prescription - which doesn't quite kill the germs, but lets them adapt to the antibiotic - to the doctor who prescribes the equivalent of a neutron bomb when a .22 would do.
"What you get is people using wide-spectrum antibiotics," says Dr. Robert Rapp, professor of pharmacy and surgery at the University of Kentucky, "and they wipe out everything," including good bacteria, leaving the field clear for antibiotic-resistant germs to spread unchecked.
Day-care centers, where children are in close contact, are particularly vulnerable. Patient Care, a journal for primary-care physicians, last month reported several cases of middle-ear infections and diarrhea caused by drug-resistant germs at day-care centers, noting that kids in day care use antibiotics 3-5 times more often than other children. The CDC says the 11 million children in day-care centers are at "a markedly increased risk for enteric infections, such as hepatitis A, giardiasis and cryptosporidiosis; respiratory illnesses; and middle-ear infections."
Many resistant organisms come from countries where antibiotics are sold over the counter, Fischetti says. "These organisms are constantly bombarded with inadequate treatment, and you develop these resistant organisms easily."
Travelers also go "into areas of the world where large numbers of humans didn't go before, and encounter organisms they wouldn't normally come across," says Dr. Joseph John Jr., University of Medicine and Dentistry, New Jersey. They bring home exotic illnesses such as malaria - in drug-resistant strains - yellow fever and Japanese B encephalitis.
Drug companies, meanwhile, have no caped crusader in the wings. "This is the only time I can remember where I can't pick up a list of investigational drugs and see a whole new class of antibiotics coming down the road," Rapp says. "I think the drug industry . . . is very concerned about it, (but) the question is, have they decreased their emphasis on antibiotic research? And the answer is yes, because the ability to make money in that area is not what it was."
Jeff Hoyak, spokesman for drugmaker Lederle Laboratories, says research in new antibiotics is ongoing, but "we're being more selective in the projects we choose to research, mainly because of the environment for business."
It's more profitable to make a drug for a chronic illness than one needed sporadically, Rapp says, "so you change the focus of your drug development. With what's going on today, this is very scary."
Fischetti agrees. Even if a new antibiotic were discovered today, he says, "it would be eight years at least before it's available to the public. The way things are going now, we don't have eight years."
New forms of infection, and old diseases making a comeback, underscore the danger:
-- Tuberculosis. Resurging TB, often in people with HIV, has become a public-health menace. New strains are multi-drug-resistant, difficult and expensive to treat, and can be passed on to others.
-- Hantavirus. A new, deadly strain of a virus known to cause kidney disease cropped up first in the Southwest last year. The new forms - three have been identified - cause sudden respiratory distress and often death.
-- Food- and water-borne infections. Hamburgers contaminated with E. coli and served at a fast-food restaurant caused an outbreak in several states that killed four children and left others ill. Cryptosporidium in the Milwaukee water supply sickened an estimated 403,000 and sent about 4,400 to the hospital.
Scientists are "working hard to decrease the risks from these emerging infections," says John, using new diagnostic techniques that allow quick identification of otherwise baffling illnesses. But there's an onslaught of new enemies, he says, and in some cases, "we don't have a way to treat (them) and we don't have a way to get rid of (them.)"
Lack of money for research and surveillance is a problem, says Gail H. Cassell, president of the American Society for Microbiology. "The public-health infrastructure is crumbling. The infrastructure is no longer there," she says. "In 1992, less than $ 10,000 was spent on antibiotic-resistance surveillance.
"If we continue to ignore the problem," she says, "we'll be in serious trouble, not only in this country but around the world."
Turning the tide of battle
How antibiotics work Som interrupt the construction of the cell wall, making the cell take on water until it bursts:
Others halt the growth of bacteria, allowing the body's immune system to respond.
Antibiotics go through cell wall and can ...
... break down DNA, block instructions for protein synthesis, stop protein production.
How bacteria respond
Bacteria develop several means of defense, including pumping the antibiotic out of the cell, making enzymes that inactivate the drug, or changing their cell-wall structure so the drug can't interrupt the cell-wall assembly.
One way bacteria transfer their resistance genes to others is by exchanging genetic material: 1. Bacterium bearing resistance genes makes a thin protein tube that reaches out to another bacterium and 2. draws them together. 3. The donor passes on copies of resistant genes. 4. Both bacteria then go on to be donors, passing on the resistance exponentially.
