The Seeds of Change
There isn’t just one reason this rush is on. There are at least four motivators. Foremost is the growing sense of urgency to find ways to stem the advancing strains of bacteria no longer killed by major antibiotics. “Drug resistance is just an increasing problem in essentially every kind of bacterium that causes infection,” says Michael Lancaster, section chief for antimicrobial resistance in the division of hospital infections at the U.S. Centers for Disease Control and Prevention (CDC). Among the diseases caused by drug-resistant bacteria are pneumonia, tuberculosis, ear infections, sexually transmitted diseases, diarrhea, and bloodstream and wound infections. “We are clearly in a public health crisis,” says Stuart B. Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine, “and on the road to an impending public health disaster.”
“Vancomycin-resistant enterococci (VRE) probably are the biggest resistance problem,” says Lancaster. The VRE microbe, which can kill patients with weakened immune systems if it enters their bloodstreams, has been causing growing problems in hospitals. Among patients who got enterococci infections while in hospitals, the incidence of VRE rose from 0.3 percent in 1989 to 14.2 percent in 1996, according to the CDC. What makes VRE so significant is that vancomycin is not the first drug of choice to treat the microbe, but the last. Not only is VRE resistant to vancomycin, it is usually also resistant to all other drugs commonly used to treat it, says Lancaster. The fallback treatment is investigational drugs or high doses of combinations of drugs already on the market.
Microbiologists believe much antibiotic resistance is the result of natural selection. Resistant microbes tend to appear where an antibiotic is used frequently. As the bacteria reproduce, some mutations occur; eventually one bacterium is changed in a way that allows it to survive the drug. For instance, the mutant might have grown a thicker cell wall, making it impossible for the drug to permeate it. Or tiny cellular pumps that were used to get rid of waste products may acquire a new instruction that will now dump the antibiotic right out. This mutant, which can shield itself from the lethal drug, is the one that lives on.
Unfortunately for humans, mutating is not the only way bacteria develop antibiotic resistance. What scares public health officials even more is that bacteria can also transfer their genetic instructions for avoiding an antibiotic to other bacterial species. They have been most concerned that VRE will pass its high resistance to vancomycin over to a common and even more virulent and more aggressive bacterium, Staphylococcus aureus. That could be a huge problem because there are cases of staph bacteria that have proved resistant to every drug except vancomycin, Lancaster explains. Staph, which causes a range of problems from boils to pneumonia, toxic shock syndrome, and bloodstream infections, is the leading cause of infections patients get while they are in hospitals.
Last year a strain of staph that was moderately resistant to vancomycin showed up in Japan. This past August the CDC reported that for the first time in the United States a slightly different, moderately resistant strain had surfaced in Michigan. The CDC warned that this could be the harbinger of a fully resistant strain. Later, another moderately resistant strain showed up in New Jersey. The strains are all thought to be rare mutants. VRE has not yet passed its high resistance on to staph, but the watch is on.
Drug-resistant bacteria are not confined to hospitals and nursing homes. In the last decade, says Alex Rakowsky, a medical officer for the Food and Drug Administration (FDA), health officials have learned that certain resistant bacteria occur more heavily in the suburbs, probably because affluent residents there take large numbers of antibiotics. Other pockets of highly resistant bacteria have been found in poor rural areas, for reasons not clear to health officials.