Our ability to treat common bacterial infections with antibiotics goes back only 65 years. Yet increasing resistance to these wonder drugs has already returned us to an era when many strains of bacteria cannot be easily treated. If left unaddressed, antibiotic resistance has the potential to derail the health care system and recreate a world where children and the elderly - and even hometown sports heroes and our fighting armed forces - routinely die from simple bacterial infections. The world could be faced with previously treatable diseases that have again become untreatable, as in the days before antibiotics were developed.

As an indication of the scale of the problem, high-level penicillin resistance in Streptococcus pneumoniae in the United States has experienced a thousand-fold increase in the last 20 years - from 0.02 percent in 1987 to over 20 percent in 2004 (CDC 2005). From 1974 to 2004, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has climbed from roughly 2 percent to more than 50 percent in many U.S. hospitals. Drug-resistant infections affect patients, health care systems, and society by increasing the cost of treating infections and causing greater disability and death. Billions of dollars' worth of avoidable costs accrue to our health care system because resistant infections require longer hospital stays and more expensive drugs. Infections from just six common resistant bacteria cost our health system nearly $2 billion a year – more than the total annual spending on influenza. In addition, modern medicinal procedures, from organ transplants and chemotherapy to basic surgery, require effective drugs that can ward off infection.

The problem of resistance is an evolutionary game played between humans and microbes: we try to stay ahead by creating new antibiotics, and microbes develop resistance to our drugs. Unfortunately for us, microbes evolve resistance to antibiotics faster than we can create new drugs, meaning that, in recent years, bacteria have been winning this “arms race.” Antibiotic use disturbs microbial communities, and in these disturbed environments, the bacteria that thrive are those that are naturally invasive—the equivalent of weeds. Not all bacteria are bad. We are all colonized by bacteria that live on our skin and in our gut, where they do important things like help us process food. They become a medical problem only when they cause an infection—an invasion of otherwise sterile areas, such as the bloodstream, lungs, or urinary tract.

Antibiotics work by killing bacteria. But by mutating, bacteria can become resistant to antibiotics. Antibiotic use selects for resistance in several species of bacteria simultaneously because the drug affects both target (harmful) and nontarget (helpful) species. While their competitors are killed off, those individual bacteria that survive because of some mutation are able to grow unchecked. Bacteria that evolve resistance can ultimately spread to other people just like any other bacterial infection—through personal contact or coughing. Bacteria can also acquire resistance to antibiotics when they share genetic material with related bacteria. Entire sets of genes can move from soil microbes, farm animal bacteria, or even “good” bacteria in the gut into dangerous pathogens . Genes that confer resistance to antibiotics let bacteria become resistant to many related antibiotics all at once. Resistant bacteria can spread on a large scale when intensive use of antibiotics gives them a window of opportunity to colonize a host while sensitive bacteria cannot.

When these advantages are strong enough, resistant bacteria tend to spread. A simple principle thus arises: certain thresholds on the rate of antibiotic use favor resistant bacteria. Since antibiotics are heavily used in health care facilities, patients who transfer to and from hospitals and nursing homes can help spread the pathogens. Evolved mutations have increased the frequency with which resistance emerges, and resistant bacteria have been rapidly spreading. Antibiotic resistance cannot be prevented. But it can be slowed. Biology points to three possible policy objectives:

• delay the emergence of antibiotic resistance;

• slow the spread of resistant bacteria; and

• reduce infections from antibiotic-resistant bacteria.

These are discussed in more detail in the Solutions section.