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Correction to This Article
This article incorrectly said that a recently identified gene in certain bacteria enables the microbes to destroy most antibiotics. The gene enables the microbes to destroy antibiotics known as carbopenems, which are usually used in last-ditch efforts to save patients whose infections fail to respond to standard antibiotics.
A VERY SCARY GENE

By Rob Stein
Washington Post Staff Writer
Tuesday, October 12, 2010; E1

Urinary tract infections, pneumonia and other common ailments caused by germs that carry a new gene with the power to destroy antibiotics are intensifying fears of a fresh generation of so-called superbugs.

The gene, NDM-1, which is apparently widespread in parts of India, has been identified in just three U.S. patients, all of whom had received treatment in India and recovered. But the gene's ability to affect different bacteria and make them resistant to many medications marks a worrying development in the fight against infectious diseases, which can mutate to defeat humans' antibiotic arsenal.

"The problem thus far seems fairly small, but the potential is enormous. This is in some ways our worst nightmare," said Brad Spellberg, an infectious-disease specialist at LA Biomed (the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center) and author of "Rising Plague," a book about antibiotic resistance. "You take very common bacteria that live in all of us and can travel from person to person, and you introduce into it some of the nastiest antibiotic-resistance mechanisms there are."

The bacteria, which include previously unseen strains of E. coli and other common pathogens, appear to have evolved in India, where poor sanitation combines with cheap, widely available antibiotics to create a fertile environment for breeding new microorganisms.

The infections were then carried to the United States, Britain and more than a half-dozen other countries, often through "medical tourism," which involves foreigners seeking less expensive, more easily accessible surgery overseas.

"We need to be vigilant about this," said Arjun Srinivasan, a medical epidemiologist at the Centers for Disease Control and Prevention, which has been monitoring the spread of the microbes. "This should not be a call to panic, but it should be a call to action. There are effective strategies we can take that will prevent the spread of these organisms."

Experts fear the germs will follow the path of other multi-drug-resistant bugs and become a common scourge in medical centers and perhaps even among otherwise healthy people.

"It's an acute example of how bacteria can outwit people," said Stuart Levy, a professor of molecular biology at Tufts University School of Medicine and president of the Alliance for Prudent Use of Antibiotics.

So far, the highly resistant gene has not jumped into bugs spread by coughing or sneezing, and the three U.S. patients did not transmit their infections to anyone else. But the microbes can spread readily through other common ways, including contaminated sewage, water and medical equipment and lax personal hygiene such as inadequate hand-washing. Many patients eventually recover, but it remains unclear how many people have died and what the mortality rate is.

Indian roots?

The origin of the microbes is politically sensitive. The Indian government has condemned the reports saying the bugs arose in that country, arguing that the tale was concocted by Western pharmaceutical companies and others to discredit India's burgeoning medical tourism industry, which is attracting more than 450,000 patients a year and could generate annual revenues of $2.4 billion by 2012, according to some estimates.

"They say it's found in patients who visit India and Pakistan," said India's health minister, Ghulam Nabi Azad. "It was nowhere mentioned if the bacteria are found even before those persons visited India."

The resistance gene - NDM-1 stands for New Delhi metallo-B-lactamase 1 - was first identified in 2008 in bacteria in a Swedish patient who had been hospitalized in New Delhi. The gene produces an enzyme that destroys most antibiotics, including so-called carbopenems, which are usually used in last-ditch efforts to save patients whose infections fail to respond to standard antibiotics.

"We really are already running out of antibiotics," said Richard Wenzel, an infectious-disease specialist at Virginia Commonwealth University and former president of the International Society for Infectious Diseases. "It's potentially very, very worrisome."

The patient in Sweden was infected with bacteria called Klebsiella pneumoniae, a common cause of pneumonia and other frequent infections in hospitals.

The gene was also found in Escherichia coli in the patient's body. E.coli is ubiquitous. While it often is carried harmlessly in people's bodies, it can cause a host of health problems, including urinary tract and gastrointestinal infections. It has also been identified in more than a half-dozen other so-called gram-negative bacteria, including salmonella.

"What is different about NDM so far is the genetic background is very variable," said Robert Bonomo, a professor of medicine at Case Western Reserve University. "It's in many different organisms. There seems to be an unpredictable manner in which it's moving around."

In June, the CDC reported the first three cases of NDM-1 infections in the United States, advised doctors to watch for it and recommended steps to try to prevent the germs from spreading, including isolating infected patients. The three patients, who were treated in Illinois, Massachusetts and California between January and June, had all apparently gotten urinary tract infections when they received medical care in India. One had been hospitalized after a traffic accident.

An international team of researchers reported in August in the journal Lancet Infectious Diseases that the gene was not limited to hospital patients in India but was commonly found in the community in both India and Pakistan. Moreover, the bacteria had been carried home by British visitors, including some who had come specifically for elective surgery. Most of the infections were resistant to every antibiotic except tigecycline and colistin. Some were invulnerable even to those. Most patients recovered, but some died.

'Tip of the iceberg'

"What we saw is almost certainly the tip of the iceberg," said Timothy R. Walsh, a professor of microbiology and antibiotic resistance at Cardiff University in the United Kingdom, who helped discover the gene. "For every person in the hospital, you can imagine there are a vast majority of people out there carrying NDM around. It's a kind of silent-sleeper situation. "

The August report led to a flurry of interest in the germs, including intensive discussion of the problem at a scientific meeting in Boston last month. Cases have now been reported in Australia, Canada, Germany, France, the Netherlands, Austria, Hong Kong, Japan, Singapore, Taiwan, Oman and Kenya, Walsh said.

"That's the frightening thing about this," Walsh said. "It appears to be spreading fast."

Experts are quick to note that the bugs are far from the first highly resistant microbes.

Another similar resistance gene, Klebsiella pneumoniae carbapenamase, or KPC, makes organisms as difficult to treat as NDM-1 does. Discovered in North Carolina in 2000, KPC infections have been found in at least 35 states and have triggered outbreaks in other countries, such as Israel. So far, KPC infections are limited to hospitals.

But experts fear that NDM-1, which appears capable of jumping more easily from one type of bacteria to another, will travel to many other organisms because it is on a piece of DNA known as a plasmid, which can move easily among different microbes.

"These plasmids are very, very promiscuous," Walsh said.

NDM-1 could follow the pattern of methicillin-resistant Staphylococcus aureus, or MRSA, a difficult-to-treat wound infection that began by plaguing hospital patients but has now spread widely to populations as disparate as prisoners, children in day care centers, soldiers and high school football players and wrestlers.

"It's good that it's been recognized and detected early, and people have been alerted to it," said Thomas O'Brien, a microbiologist at the Brigham and Women's Hospital in Boston who helps track resistant microbes for the World Health Organization. "In the past, a lot of the antibiotic-resistance problems have not been noticed early and have spread fairly widely before anyone paid any attention."

Special correspondent Rama Lakshmi contributed to this report from India.

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