Bugs Behaving Badly
Antibiotics are aging, and bacteria are learning to fight them off
Last month brought fresh evidence that while small, bacteria can certainly look out for themselves. Clostridium difficile, a microbe that can cause serious digestive illness and death in vulnerable patients in hospitals and nursing homes but rarely bothers healthy adults outside healthcare settings, was blamed by the federal Centers for Disease Control and Prevention for doing just that in four states. Like many other germs, it apparently had mutated, under pressure from antibiotics, into a toxic new strain.
As if that wasn't bad enough, a couple of weeks later, the Journal of the American Medical Association suggested that we had aided the resourceful C. difficile by dosing ourselves with pills such as Pepcid and Prilosec that prevent severe heartburn, or reflux, by lowering the acidity of the stomach's gastric juices. That acidity, noted the authors, keeps the upper part of the digestive tract bug free. By reducing the acidity, the pills lowered the barrier.
Unbeatable. Such news was just the latest in a string of misadventures that illuminate the uncommon adaptive power of bacteria. Until about 25 years ago, most disease-causing germs stood little chance against the stream of antibiotics that had emerged from laboratories during the 1940s and '50s. Top researchers at large pharmaceutical companies truly believed that the days of infectious disease were over.
But the flow of unique new classes of antibiotics ebbed and died in the 1960s. Resistant strains of microbes that had crumbled obediently at the touch of drugs like vancomycin appeared. Now some 2 million hospital patients a year get bacterial infections; about 90,000 of them die. The National Institute of Allergy and Infectious Diseases estimates that more than 70 percent of the bacteria that cause these infections are resistant to one or more antibiotics. That complicates care, inflating the cost of treating an infected patient. And so reports such as these are piling up:
Military service members injured in Iraq and Afghanistan increasingly are coming home with Acinetobacter baumannii, a potent microbe that causes pneumonia and blood infections, in their wounds. Plucked straight from soil or water, the bug is naturally resistant, often to multiple antibiotics. Sometimes physicians have to turn to coliston, a drug rarely used since the 1960s because of the high chance of injuring the kidneys and nervous system.
Gonorrhea used to be easily treatable with penicillin, but the bacterium reponsible, Neisseria gonorrhoeae, long ago shrugged it off. Now the newer quinolone class of antibiotics such as Cipro and Floxin, which became the drugs of choice, are being defeated in the United States and in Australia, Canada, Great Britain, and Hong Kong. It has gotten so bad, J. Todd Weber, director of the CDC' s office of antimicrobial resistance, wrote in a JAMA editorial in November, that the usefulness of quinolone drugs to treat and control gonorrhea "is being lost worldwide because of increasing resistance."
Resistant strains of bacteria usually confined to hospitals are finding their way into local communities. In 2003 and 2005, studies fingered Staphylococcus aureus, a microbe that is blamed for many serious heart and lung infections in hospitals and nursing homes and is resistant to the methicillin class of anti-biotics, as the cause of outbreaks of skin abscesses in high school wrestlers in Indiana, members of a Colorado fencing club, and five players on the St. Louis Rams football team.
Methicillin-resistant S. aureus is being transported into hospitals from outside, not just sent into communities from hospitals. A report to be published later this month in the Journal of Infectious Diseases states that as many as 90 million healthy people, or nearly one third of the U.S. population, carry S. aureus as a passenger in their noses. And in more than 2 million of them, the bug is the resistant strain. Based on cultures of nasal samples taken from some 9,600 individuals selected at random in 2001 and 2002 as part of an ongoing national health and nutrition survey, the study was the first to determine the precise extent to which the microbe has made itself at home throughout the population. The answer, clearly, is: very at home.
Overload. What has exacerbated matters is Americans' well-documented tendency to think they need an antibiotic for every cold or cough or child's sore throat or earache. And physicians tend to go along, arguing that they don't have time to educate patients on the folly of taking an antibiotic. The larger the quantity of antibiotics prescribed, the greater the opportunity for bacteria to form resistant mutations. Yet in an analysis in JAMA published in November, more than half of children who came to a doctor's office, a hospital outpatient department, or an emergency room between 1995 and 2003 because of a sore throat left with an antibiotic.
Such reflexive prescribing is unsound medicine. Most sore throats are caused by viruses, which don't respond to antibiotics, so the majority of the children wouldn't have been helped. And many of the kids who did take an antibiotic, the JAMA analysis found, were prescribed one that was not among those specifically recommended by physician groups and the CDC.
Surely a prescription is justified for an adult who's been coughing for more than a week, is running a fever, and--skip ahead to the next sentence if squeamish--is hacking up greenish phlegm. But no. The largest study to date of the merits of antibiotics for such patients, published in JAMA in June, found the cough didn't go away or the severity of the symptoms lessen any sooner in a group of patients on antibiotics than in another group that didn't get them. "Perhaps it is not a coincidence," suggested family physician Mark Ebell in an accompanying edi-torial, "that manufacturer-sponsored placebo-controlled trials of newer anti-biotics for acute bronchitis in healthy adults are absent from the literature."
Some researchers, among them Stuart Levy, a microbiologist at Tufts University School of Medicine and founder and president of the Alliance for the Prudent Use of Antibiotics, worry about another source of antibiotic resistance: antibacterial household products. Between 300 and 550 germ-fighting products, such as liquid soaps, laundry detergents, and even toothbrushes, have been introduced every year since 1999, according to Datamonitor, a Naples, N.Y., market research firm.
Levy cautions that trying to stamp out germs in healthy households could breed tougher bugs that might also resist anti-biotics. A study he coauthored, published in October in Emerging Infectious Diseases, found no such problem in 224 households after a year of use. But Levy argues: "That wasn't long enough. Vancomycin was used for years before resistance emerged." It's worth noting that the cleaners aren't anything special. The study found them no better at exorcising bacteria than plain soap.
Empty shelves. The solution to larger issues of antibiotic resistance is more and better drugs. If that doesn't happen, warns "Bad Bugs, No Drugs," a report issued in 2004 by a task force of the Infectious Diseases Society of America, whose 8,000 members are mostly physicians and scientists, the country--and the world--face a brewing crisis in which millions of people could die. "The shelf is very sparse," says John Bartlett, a physician who chaired the task force and is founding director of the Center for Civilian Biodefense Strategies at the Johns Hopkins School of Public Health. "When we go on rounds every day, we are continually reminded that we're running out of drugs."
Why few new antibiotics are emerging, says George Talbot, a task force member and consultant to drug manufacturers, is simple: "Big companies decided that there are more fertile fields. They needed to have blockbuster drugs." Antibiotics are expensive to develop--putting a new one on the market would cost at least $800 million and take as long as 10 years--and offer a lower return than that offered by medications for chronic illnesses, such as heart disease, Alzheimer's, and depression. Potent new antibiotics, notes Talbot, "are put on the shelf to be used in reserve. It may make sense clinically, but it's not exactly an incentive to companies to develop new drugs."
The task force concluded that Congress has to give large pharmaceutical manufacturers a good reason, in the form of tax breaks and other financial carrots, to get back into antibiotic R&D. Several bills that would do so, however, languish in committee. And so a perfect storm well may be in the making, as microbes gain in strength while current antibiotics, unbolstered by reinforcements, are defeated one by one.
MUSCLING UP
Two types and one whole class of bacteria are getting tougher to defeat, as shown by the rise in strains found in hospital intensive care units that are resistant to the usual antibiotics.
STRAINS WITH RESISTANCE
Staphylococcus aureus
Enterococci
Pseudomonas aeruginosa
[labels]
0
10
20
30
40
50
60 pct.
1980
2002
1990
Source: Centers for Disease Control and Prevention
This story appears in the January 9, 2006 print edition of U.S. News & World Report.