Drug Resistant Infections

Superbugs; The new generation of resistant infections is almost impossible to treat by Jerome Groopman

Before the development of antibiotics, the threat of infection was urgent: until 1936, pneumonia was the No. 1 cause of death in the United States, and amputation was sometimes the only cure for infected wounds. The introduction of sulfa drugs, in the nineteen-thirties, and penicillin, in the nineteen-forties, suddenly made many bacterial infections curable. As a result, doctors prescribed the drugs widely—often for sore throats, sinus congestion, and coughs that were due not to bacteria but to viruses. In response, bacteria quickly developed resistance to the most common antibiotics. The public assumed that the pharmaceutical industry and researchers in academic hospitals would continue to identify effective new treatments, and for many years they did. In the nineteen-eighties, a class of drugs called carbapenems was developed to combat gram-negative organisms like Klebsiella, Pseudomonas, and Acinetobacter. “They were, at the time, thought to be drugs of last resort, because they had activity against a whole variety of multiply-resistant gram-negative bacteria that were already floating around,” Moellering said. Many hospitals put the drugs “on reserve,” but an apparent cure-all was too tempting for some physicians, and the tight stewardship slowly broke down. Inevitably, mutant, resistant microbes flourished, and even the carbapenems’ effectiveness waned.

Now microbes are appearing far outside their environmental niches. Acinetobacter thrives in warm, humid climates, like Honduras, as well as in parts of Iraq, and is normally found in soil. An article published in the military magazine Proceedings in February reported that more than two hundred and fifty patients at U.S. military hospitals were infected with a highly resistant strain of Acinetobacter between 2003 and 2005, with seven deaths as of June, 2006, linked to “Acinetobacter-related complications.” In 2004, about thirty per cent of all patients returning from Iraq and Afghanistan tested positive for the bacteria. “It’s a big problem, and it’s contaminated the evacuation facilities in Germany and a lot of the V.A. hospitals in the United States where these soldiers have been brought,”

The practice of “clinical tourism,” in which patients travel long distances for more advanced or more affordable medical centers, may introduce resistant microbes into hospitals where they had not existed before.

Meanwhile, antibiotic use in agricultural industries has grown rapidly. “Seventy per cent of the antibiotics administered in America end up in agriculture,” Michael Pollan, a professor of journalism at Berkeley and the author of “In Defense of Food: An Eater’s Manifesto,” told me. “The drugs are not used to cure sick animals but to prevent them from getting sick, because we crowd them together under filthy circumstances. These are perfect environments for disease. And we also have found, for reasons that I don’t think we entirely understand, that administering low levels of antibiotics to animals speeds their growth.” The theory is that by killing intestinal bacteria the competition for energy is reduced, so that the animal absorbs more energy from the food and therefore grows faster. The Food and Drug Administration, which is often criticized for its lack of attention to the risks of widespread use of antibiotics, offers recommended, non-binding guidelines for these drugs but has rarely withdrawn approval for their application. A spokesman for the Center for Veterinary Medicine at the F.D.A. told me that the center “believes that prudent drug-use principles are essential to the control of antimicrobial resistance.” A study by David L. Smith, Jonathan Dushoff, and J. Glenn Morris, published by PLoS Medicine, from the Public Library of Science, in 2005, noted that the transmission of resistant bacteria from animal to human populations is difficult to measure, but that “antibiotics and antibiotic-resistant bacteria (ARB) are found in the air and soil around farms, in surface and ground water, in wild-animal populations, and on retail meat and poultry. ARB are carried into the kitchen on contaminated meat and poultry, where other foods are cross-contaminated because of common unsafe handling practices.” The researchers developed a mathematical model that suggested that the impact of the transmission of these bacteria from agriculture may be more significant than that of hospital transmissions. “The problem is that we have created the perfect environment in which to breed superbugs that are antibiotic-resistant,” Pollan told me. “We’ve created a petri dish in our factory farms for the evolution of dangerous pathogens.”

A recent assessment of progress in the field, from U.C.L.A., concluded, “FDA approval of new antibacterial agents decreased by 56 per cent over the past 20 years (1998-2002 vs. 1983-1987),” noting that, in the researchers’ projection of future development only six of the five hundred and six drugs currently being developed were new antibacterial agents. Drug companies are looking for blockbuster therapies that must be taken daily for decades, drugs like Lipitor, for high cholesterol, or Zyprexa, for psychiatric disorders, used by millions of people and generating many billions of dollars each year. Antibiotics are used to treat infections, and are therefore prescribed only for days or weeks. (The exception is the use of antibiotics in livestock, which is both a profit-driver and a potential cause of antibiotic resistance.)