Microbes that cause many of the world's deadliest infections are becoming increasingly immune to the drugs used to treat them. 1 Resistance is rising among a wide range of bacteria, viruses, parasites, and fungi that are responsible for diseases from malaria to AIDS. 2 (See Table 1.) This threatens to reverse a halfcentury of public health improvements, which began with the introduction of the "miracle drug" penicillin in 1943.3

Many diseases are developing resistance not only to first-line drugs but also to second-, third-, and even last-resort treatments. Certain types of tuberculosis (TB) now evade every

existing antibiotic-an arsenal of more than 100 drugs.4 Even common hospital-acquired infections like Staphylococcus aureus (staph) are increasingly lethal, with strains

failing to respond to vancomycin, the antibiotic of last resort. S

Resistance spreads when an antimicrobial agent fails to kill all the germs that cause an infection, favoring the overgrowth of those that are particularly immune. These "super-bugs" acquire their initial resistance through rapid mutations in their own DNA, or from other microbes.6 The resistant strains can then multiply and spread to new human or other hosts through the usual pathways of contagion, including infected blood, saliva, and nasal fluid. 7

A key factor behind emerging resistance is the soaring use of antimicrobial drugs-particularly antibiotics, used to fight bacterial infections.8 In the United States, antibiotic production increased more than 80-fold between 1950 and 1994, and hospitals now administer some 160 million doses daily 9 Though antibiotic use does not always trigger resistance, more frequent use creates greater opportunities for the survival and spread of resistant bacteria. 10

Studies suggest that at least half of all antibiotics used in human medicine are prescribed unnecessarily 11 Many doctors administer these drugs before they are needed, or apply them in situations where they are ineffective, such as to fight colds and other viruses. 12 They may do this in response to patient demand, to speed

patient visits, or under pressure from drug companies or health management groups. 13

In the developing world, misuse of antibiotics is rapidly depleting the arsenal of viable treatments, worsening the tolls of many deadly diseases. In parts of Africa, chloroquine, once the cheapest and most effective anti-malarial, is now taken more frequently than aspirin to treat minor pains-an overuse that has contributed to its rising ineffectiveness on the continent. 14 With many treatments available over-thecounter, patients often purchase pills in single doses and take them only as long as their symptoms persist, enabling the hardiest microbes to survive. IS Such self-dosage is also a large factor behind the rising failure of many anti-TB drugs, which must be taken for at least six months to be fully effective. 16

Surging agricultural use of many of the same antibiotics used for human medicine also encourages resistance. Farmers now use up to 84 percent of all antimicrobials in the United States-some to fight animal disease and prevent bacterial growth on crops or in fish ponds, but the bulk as feed additives to boost livestock growth. 17 Such nontherapeutic livestock use has nearly doubled in the United States since 1985.18 Any resistant infections that develop in animals or the environment can spread to humans through contact with infected creatures or water, as well as through the food chain. 19

The booming use of antimicrobials to kill surface germs on living tissue, water, and everyday objects can also promote resistance. 20 Between 1992 and mid-1998, some 700 new "antibacterial" products were introduced in the United States, among them cleansers, cutting boards, toys, cat litter, and ballpoint pens. 21 But this sanitation revolution has its downside: in 1998, for the first time, scientists isolated strains of the bacteria Escherichia coli that resisted triclosan, a common antiseptic used in soaps and toothpaste. 22

Resistant infections are typically costlier to treat than regular infections, requiring longer medication and hospitalization.23 Treating multidrug-reSistant TB, for example, costs roughly 100 times more than regular TB-at least $2,000

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per patient in the developing world.24 The expense of second-or third-line treatments can be prohibitive in many countries, making the human toll of resistance particularly high.25 In Senegal, for instance, the risk of malaria death to children under 10 has increased nearly sixfold since the early 1980s due to rising resistance.26