Magazine article American Scientist

How to Fight Back against Antibiotic Resistance

Magazine article American Scientist

How to Fight Back against Antibiotic Resistance

Article excerpt

Not so long ago, it seemed like the fight against infectious diseases was nearly won. The discovery of penicillin in 1929 gave clinicians their first weapon to combat common ailments like pneumonia, gonorrhea, and rheumatic fever. In the decades that followed, medical researchers discovered more than 150 other types of antibiotics. These widely hailed "wonder drugs" were so successful that U.S. Surgeon General William Stewart announced in 1967, "The time has come to close the book on infectious diseases."

Stewart and most of his contemporaries greatly underestimated the ability of bacterial pathogens to adapt to these life-saving medicines. Almost as soon as clinical use of penicillin began in 1946, the first drug-resistant pathogens appeared. During the golden age of antibiotic development (the 1940s to the 1960s), the spread of antibiotic resistance was balanced by the continued discovery and deployment of new classes of antibiotics. But starting in the 1970s, a dwindling interest and ability of the pharmaceutical industry to develop new antibiotics resulted in a 40-year period when virtually no new broad-spectrum classes of antibiotics were brought to the market. Instead, companies focused on modifying the chemical scaffolds of already approved classes of antibiotics.

During this innovation gap, bacterial evolution did not cease. Consequently, drugs that were previously effective in treating a broad spectrum of infectious bacteria are now useful for fewer and fewer infections. Certain bacteria, including strains of Escherichia coli and Klebsiella pneumonia, are now resistant to all major antibiotics- even carbapenems, which have long been the drug of last resort to treat afflictions such as lung infections. With dwindling treatment options, the mortality rate from those infections in the United States is approaching 50 percent. In effect, for some diseases we are now living in a post-antibiotic age.

According to a September 2013 report from the U.S. Centers for Disease Control and Prevention (CDC), treatment of antibiotic-resistant infections adds $35 billion in health care costs and 8 million hospital days per year in the United States. A recent drugresistant Salmonella outbreak due to contaminated chicken meat was linked to nearly 300 illnesses across 18 states, sickening infants and nonagenarians alike. At least 23,000 Americans die each year from infections, many caused by the superbug methicillinresistant Staphylococcus aureus (MRSA), because doctors have run out of drugs with which to treat them.

Government agencies are belatedly considering incentives to support renewed antibiotic drug development, but these initiatives have not yet had a direct impact on the drug development pipeline. As a result the number of antibiotics approved by the Food and Drug Administration (FDA) hit a record low of one new antibiotic in the five-year period from 2008 to 2012, down from 16 new drugs in the years from 1983 to 1987 (see the figure on page 44). CDC Director Tom Frieden recently warned, "If we don't act now, our medicine cabinet will be empty and we won't have the antibiotics we need to save lives." In reality, the development of new antibiotics is only part of the solution, as pathogens will inevitably develop resistance to even the most promising new compounds.

To save the era of antibiotics, scientists must figure out what it is about bacterial pathogens that makes resistance inevitable. By studying the suite of genes-collectively known as the resistome-that can tum a susceptible pathogen into a superbug, researchers may be able to uncover the Achilles heel of these multiple drug-resistant strains. Although most studies on drug resistance have focused on diseasecausing pathogens, recent efforts by the two of us and by a number of our colleagues have shifted attention to the resistomes of nonpathogenic bacteria. Importantly, over the past decade advances in DNA sequencing have enabled us to explore the genomes of both pathogenic and non-pathogenic bacteria across a variety of different natural habitats. …

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