Wednesday, January 5, 2011

NDM-1 Gene Makes Superbugs

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. "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.

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.

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 carbopenems, which are usually used in last-ditch efforts to save patients whose infections fail to respond to standard antibiotics.

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.

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.

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.

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.

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.

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