"Given what we know now, I don't think it's overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective," says  Gautam Dantas. (Credit: Philippa Willitts/Flickr)

antibiotics

Even ‘last resort’ antibiotics are starting to fail

Bacteria frequently implicated in respiratory and urinary infections in hospitals may soon develop complete resistance to antibiotics, even those used as a last resort, experts warn.

A new study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections.

“…we may be looking at the start of the post-antibiotic era…”

Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. Those infections are linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.

“Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works,” says senior author Gautam Dantas, associate professor of pathology and immunologyat Washington University in St. Louis.

“Given what we know now, I don’t think it’s overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective.”

Because of this, experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.

For the study, published in the journal Emerging Infectious Diseases, researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiella pneumonia, and Enterobacter. Some strains of these bacteria don’t cause illness and can help keep the body healthy. But in people with weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be deadly.

1 of 3 ‘most urgent threats’

The Centers for Disease Control and Prevention named carbapenem-resistant Enterobacteriaceae as one of the three most urgent threats among emerging forms of antibiotic-resistant disease. Studies have shown the fatality rate for these infections is above 50 percent in patients with weakened immune systems.

Two genes are primarily responsible for carbapenem-resistant versions of these disease-causing bacteria. One gene, KPC, was detected in New York in 2001 and quickly spread around most of the world, with the exception of India, Pakistan, and other South Asian countries. The gene was present in the bacteria that recently contaminated medical equipment in a Los Angeles hospital where two patients died.

A second carbapenem resistance gene, NDM-1, was identified in 2006 in New Delhi, India. It was soon detected throughout South Asia, and most patients infected by bacteria with NDM-1 have had an epidemiological link to South Asian countries.

Researchers were curious about why the two resistance genes seemed to be geographically exclusive. For the study, they compared the genomes of carbapenem-resistant bacteria isolated in the United States with those of carbapenem-resistant bacteria isolated in Pakistan.

Bacteria delivery truck

Based on the apparent geographic exclusivity of the two resistance genes, the scientists expected to find that bacteria from the two regions were genetically different. Such differences could explain why the two resistance genes weren’t intermingling. But the researchers’ results showed otherwise. The bacteria’s high genetic similarity suggests that the antibiotic resistance genes could be shared easily between bacteria from the two geographic regions.

The researchers also sequenced a special portion of bacterial genetic material called plasmids. Most of a bacteria’s DNA is found in its chromosome, but bacteria also have many extra, smaller and circular bits of DNA known as plasmids that easily can pass from one bacterial strain to another. A plasmid is like a bacterial gene delivery truck; it is the primary way antibiotic resistance genes spread between bacteria.

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The researchers identified a few key instances in which the plasmids carrying NDM-1 or KPC were nearly identical, meaning they easily could facilitate the spread of antibiotic resistance between disease-causing bacteria found in the United States and South Asia. Recent evidence suggests that this intermingling already may be happening in parts of China.

“Our findings also suggest it’s going to get easier for strains of these bacteria that are not yet resistant to pick up a gene that lets them survive carbapenem treatment,” Dantas says.

“Typically, that’s not going to be a problem for most of us, but as drug-resistant forms of Enterobacteriaceae become more widespread, the odds will increase that we’ll pass one of these superbugs on to a friend with a weakened immune system who can really be hurt by them.”

The National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of General Medical Sciences funded the study.

Researchers from the National University of Sciences and Technology in Pakistan contributed to the work.

Source: Washington University in St. Louis

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