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Perspective

Pathogens have attacked humans throughout history. Before the middle of the twentieth century, we relied on our immune systems to survive those attacks. The unlucky and the weak died. Our immune systems were strengthened by improvements in diet, and the frequency of some pathogen attacks was reduced by sanitation and water purification. For other pathogens, vaccines were developed that further decreased the overall burden of infectious disease. Insecticides provided local protection from being bitten by mosquitoes and other disease-carrying vectors. But our fear of pathogens was eliminated only by antibiotics. By taking pills for a few days, we could quickly recover from most bacterial diseases. Resistance is bringing back our fear of the "bugs."

Many of our resistance problems derive from the cumulative effects of several complex factors. One has been our cavalier attitude. For example, in early 2009, American supermarket chains began to advertise free antibiotics to attract customers. The underlying message was that antibiotics cannot be very valuable and worth protecting. Another factor is lack of stewardship. Drug resistance is discussed widely among health officials, but a coherent plan has not emerged. Hospitals are beginning to oversee their own use, but agricultural and community antibiotic use is largely uncontrolled after the drugs are approved by governmental agencies. For years, medical scientists, notably Fernando Baquero, Stuart Levy, Richard Novick, and Alexander Tomasz, wrote and spoke passionately about the dangers posed by resistance. The medical community now uses education as a strategy to limit antibiotic use. As a part of this effort, the Centers for Disease Control (CDC) formulate and distribute plans for restricting the emergence of resistance in particular environments. In one survey, neonatal intensive care units failed to adhere to the guidelines about 25% of the time.31 Outside hospitals individual patients continue to insist on antibacterial treatments for viral infections, a behavior that stimulates the emergence of resistant bacteria and upsets the balance of microbial ecosystems. In the Latino immigrant community, the prescription process is commonly bypassed.32 , 33 Thus, the educational effort needs to be intensified. A third factor is the philosophy behind the choice of dosage. Doses are kept low enough to cause few side effects but high enough to block susceptible cell growth or kill susceptible cells. Conditions that block the growth of susceptible cells but not that of mutants are precisely those used by microbiologists to enrich mutants. Conventional dosing strategies lead directly to the emergence of resistance.

Understanding the factors that drive the emergence and dissemination of antibiotic resistance is central to controlling resistance. In the following chapters, we describe how antibiotics are used, how pathogen populations become resistant, and what we as individuals can do about resistance. We begin by considering aspects of pathogen biology relevant to antibiotic treatment.

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