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Tougher Germs, at Home and On the Farm.

Almost all major infectious diseases are becoming resistant to existing medicines, according to a June 2000 World Health Organization report (see "Super-bugs Arrive," March/April 1999). In the United States alone, an estimated 14,000 people are dying each year from drug-resistant microbes that infect them in hospitals. Much of this resistance is caused by inappropriate medical use of antibiotics. (In the developing world, sick people may be able to afford only partial treatment--enough to kill susceptible germs while leaving the hardier ones to thrive. In the developed world, overuse of drugs is speeding up the rate at which microbes adapt, just as indiscriminate use of insecticides encourages the development of tougher bugs.) In addition to these medical problems, there is growing evidence of resistance caused by the use of antibiotics in agriculture and by antimicrobial consumer products

Sales of antimicrobial hand soaps, dishwashing liquids, and other such products are booming, particularly in the United States, where the market for antimicrobial and disinfectant chemicals is expanding at 3.6 percent annually and is expected to reach $620 million by 2003. Despite manufacturers' success in capitalizing on consumer fear of germs, there is little evidence that any of their products actually prevent infection. The U.S. Environmental Protection Agency, which regulates U.S. sales of cutting boards, dish sponges, and other products treated with antimicrobials, maintains that it "has seen no evidence that these products prevent the spread of germs and bacteria in humans." In April 1997, the EPA fined Hasbro, the manufacturer of Playskool toys, for claiming that an antimicrobial agent in its products helped to protect children's health.

In scientific studies, antimicrobial personal-care products seem to fare no better than the cutting boards. The American Medical Association recently reviewed the studies conducted thus far and found no evidence that antimicrobial soaps, lotions, mouthwashes, or other such products confer any infection-fighting benefit. What the AMA did find was evidence of growing resistance to many common antimicrobial agents. Although these antimicrobials are too toxic to be taken as drugs, some research suggests that antimicrobials could promote "cross resistance": some strategies that bacteria adopt to ward off antimicrobials, such as chemical pumps that eliminate the deadly substances, also work against antibiotics.

Widespread use of the products could help pathogens in another way as well, by killing off the beneficial bacteria that live on or inside us and that help repel pathogens. This suppression of bacteria in general--rather than just the serious pathogens--is a special concern in infants, since it may hinder the development of their immune systems. That concern got an additional boost when researchers in Sweden recently discovered that triclosan, a commonly used antimicrobial agent, is persistent enough in the human body to be detectable in breast milk.

At its annual meeting in June, the AMA passed a resolution urging tighter regulation of antimicrobial consumer products, although the Cosmetics, Toiletry and Fragrance Association, an industry trade group, persuaded the AMA to remove a recommendation actively discouraging the use of these products.

If the problems with antimicrobial consumer products are only beginning to emerge, the danger of widespread antibiotic use in agriculture has become alarmingly clear. Each year, an estimated 29 million pounds of antibiotics are consumed by agriculture in the United States and Europe (countries where statistics on the practice are most readily available). Much of this material consists of drugs similar to the ones that people rake. On the farm, some of it is used to treat sick animals, but most of it is mixed into feed to promote growth or prevent disease in highly crowded "factory farms"--applications that account for an estimated 80 percent of agricultural antibiotics used in the United States.

This continual, low-dose treatment creates ideal conditions for culturing resistance, so it's hardly surprising that farm animals are often found to harbor antibiotic-resistant bacteria. Humans are at risk when they ear or handle the contaminated meat. In June 1998, for example, an outbreak of drug-resistant Salmonella in Denmark was traced back through a particular slaughterhouse to a herd of pigs that had been infected by the drug-resistant strain. This dynamic is particularly troubling when the drugs involved are relatively new. In the 1990s, there was a surge of bacterial infections resistant to fluoroquinolone antibiotics, shortly after farmers received approval to use the drugs in chickens. Experts are concerned that agricultural use may limit the useful life of many of the newer drugs for fighting human infections.

The U.S. Food and Drug Administration is currently revising its guidelines for the use of antibiotics in agriculture. The FDA may tighten restrictions on especially valuable drugs--those that are the last line of defense against certain infections. The European Union has already banned the agricultural use of several antibiotics outright. The most recent ban, which went into effect in July 1999, covered four drugs. One of these, virginiamycin, is similar to an especially valuable antibiotic known as Synercid, which is the drug of last resort for about 70,000 potentially deadly infections every year. There are signs that such restrictions work. A study in the Netherlands found that two years after the 1997 EU ban on the agricultural drug avoparcin, the prevalence of bacterial resistance to a related human drug, vancomycin, had dropped by half in both livestock and people.

That may seem like a rather incremental form of progress, but in the current medical context it is extremely important. Since the early 1980s, all "new" antibiotics have been modified versions of existing drugs, instead of truly novel compounds. Pharmaceutical companies are now scrambling to develop entirely new formulations. But in the meantime, human health will increasingly depend upon our skill in conserving the dwindling power of the drugs currently at our disposal.

What makes bacteria resistant?

Some bacteria may acquire a degree of resistance from just a few simple mutations--a process that could occur within a couple of hours. In other cases, resistance mechanisms have evolved over the course of millennia, in response to the natural antibiotics produced by a variety of microorganisms (including some types of bacteria). The result is a range of drug-fighting "strategies," for example:

* A stronger cell wall may keep drugs out.

* Chemical "pumps" may allow a bacterium to expel a drug.

* Enzymes may inactivate drug molecules.

* A drug's target structure may be altered, preventing the drug from detecting it.

Sometimes these mechanisms work against more than one compound, so resistance can be caused by a chemical that is not a human drug--and still be effective against one or several compounds that are.

Once it acquires resistance, a bacterium may transfer that power--not just to its offspring but to other species of bacteria. These cross-species transfers can also happen in several ways:

* Bacteria may temporarily "dock" like spacecraft, and exchange bits of DNA.

* Viruses may infect bacteria and transfer DNA from one host to the next.

* A dying bacterium may rupture and release its genes, which may then be scavenged by another bacterium.

This portability property means that resistance can develop in a harmless bacterium--and wind up in a serious human pathogen.
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Author:Hwang, Ann
Publication:World Watch
Date:Sep 1, 2000
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