Mycobacterium (above) are becoming increasingly resistant to antibiotics. Courtesy of the Acid Fast Club. (That's not a new diet -- the name reflects a technique for washing bacteria in dilute acid to fix a microscopy stain.)
What a beauty -- it's E. coli (right) Courtesy of University of Cincinnati Department of Biological Sciences
What happened to antibiotics? Once considered the universal answer to infectious disease, we now know the effective life span of these once-miraculous drugs is limited. The problem, simply, is that we "got complacent," says Barry Kreiswirth of the Public Health Research Institute, who makes a living analyzing strains of tuberculosis that resist as many as nine antibiotics.
It's not just TB. "The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potentially crisis proportions." That's the word from the American Medical Association (AMA), which studied the issue in 1995, and seldom fulminates (defined) in such alarmist terms.
The very success of antibiotics accounts for part of the resistance problem, argues Julian Davies of the University of British Columbia. The life-saving drugs have "changed the way diseases have been treated." It's not only that they are sometimes used to treat viral infections, against which they are impotent. It's also that they are used as "props" when safer methods [think of sanitation or quarantine (defined) might be preferable.
The experts are sounding the alarm about antibiotic resistance because of grim new evidence:
Resistance happens quickly, in parallel with the use of antibiotics. An 11-year study of cancer patients at a hospital in Switzerland (see the 4/28/94 New England Journal of Medicine) found that no strains of Escherichia coli (a common intestinal bacteria that can be pathogenic) resisted any of the fluoroquinolone antibiotics between 1983 and 1990. But between 1991 and 1993, 28 percent of the strains tested were resistant to all five of them. During the study period, the percentage of patients getting antibiotics rose from 1.4 percent to 45 percent.
(Updated 1 May, 1998: Under a new National Institutes of Health grant, scientists have begun examining whether harmless bacteria carry resistance genes and transmit them to pathogens. Already, it's thought that the bacterium Haemophilus influenzae, which causes ear infections, gained resistance to the antibiotic ampicillin during a gene transfer from Escherichia coli, during the 1970s. Why would a harmless bacterium acquire such resistance? Because any organism exposed to antibiotics faces the same selective pressure that causes pathogens to become antibiotic resistant. One leader of the new research group, University of Illinois at Urbana-Champaign microbiologist Abigail Salyers, said resistance can lurk undetected in harmless organisms. She called the presence of resistance in pathogens "the tip of the iceberg compared to what's out there in the environment." See "New Hunt for the Roots of Resistance," Science, 3 April 1998, p. 27. End update.)
It's widespread. In Atlanta, a 1994 study of infections caused by Streptococcus pneumonia found that 25 percent of 431 patients had a bug that resisted penicillin, and that 25 percent of all cases were resistant to several antibiotics.
It spreads fast: thanks in part to jet planes. Resistant tuberculosis has spread from New York City to Denver, Florida, Nevada and Paris.
Bacteria learn from our mistakes: Once resistance develops, all offspring of that bacterium get it. "Once the resistant strain is made, everybody who is infected with it will have that resistance problem," says Kreiswirth. And because these organisms then pick up further resistance to other drugs, he says, "All it's going to do is get worse." You can skip ahead to our coverage of the mechanisms of resistance.
Hospitals serve as centers for the formation and transmission of drug-resistant organisms. About 2 million Americans are infected in hospitals each year and more than half of these infections resist at least one antibiotic, according to Dennis Maki, a University of Wisconsin-Madison expert in hospital infections. In 1992, 13,300 hospital patients were killed by drug-resistant bacteria in the United States.
Resistance is an especially vexing problem for people with impaired immune systems, such as AIDS, and cancer patients, and recipients of organ transplants. About 90 percent of AIDS patients who get multiple-drug resistant TB die.
Even the last-ditch antibiotics are being overwhelmed. Of particular concern is Vancomycin resistance, which is becoming fairly common in certain strains of enterococcus, a common gut bacteria. While enteroccocci generally do not cause life-threatening disease, the gene for the resistance may spread to more deadly organisms like Staphylococcus aureus. That transfer has already taken place in a lab dish and could occur elsewhere.
Multiple resistance, multiple causes
Any time bacteria are exposed to an antibiotic, they are under "selective pressure" that allows only resistant forms to survive and reproduce. So the basic rule in slowing the evolution of resistance is reducing the unnecessary use of antibiotics.
A key problem is the routine feeding of antibiotics to farm animals: Davies notes that, by weight, half of all antibiotics are given to livestock and fish in a prophylactic attempt to prevent disease. That argument gets support from a new report by the CDC Morbidity and Mortality Weekly Report, on Multidrug-Resistant Salmonella, serotype Typhimurium. Let's quote from this alarming document:
"A drug-resistant Salmonella Typhimurium subtype, associated with severe human illness, has emerged in the United States... A new emerging subtype, known as S. Typhimurium Definitive Type 104 (DT 104), characterized by multiple antimicrobial resistance, has been present in the United Kingdom since 1984... Studies in the United Kingdom showed that S. Typhimurium is present in animals (farm, wild, and pets), and that it can be transmitted from farm animals and pets to humans. Those studies also showed that eating beef, pork, or poultry products have been associated with outbreaks of disease in people... S. Typhimurium DT 104 has been detected recently in the United States, and its incidence and distribution are being actively studied to assess and address the threat to public health."
In at least half the world, antibiotics can be sold over-the-counter, Davies adds. That's something many experts suggest should be avoided.
Overuse at your peril
Yet even in places where antibiotics require a physician's prescription, there's a tendency to overuse them, Davies says. One danger zone, he says, is the prophylactic (defined) use of antibiotics during surgery. "Surgeons are not infectious disease people, and while they may rightly feel that their patients are at risk if they don't use antibiotics prophylactically, whether that's really good, I don't know." Again, such widespread use is likely to foster the evolution of resistant strains.
Instead of relying on antibiotics, Davies suggests that surgeons "ought to be able to set up an operating theater so it is sterile, so there is no opportunity for infection. That should not be out of the question."
Surgeons have been changing their practice over the past few years, according to Joe Cranston of the American Medical Association. "Clearly there was a move toward shorter time frame for prophlyaxis" in surgery, with as little as one dose being given just before surgery begins.
So what do we know about how bacteria perform these nasty transformations?
