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Infection experts warn of more U.S. superbug cases in coming months
by Ransdell Pierson

NEW YORK (Reuters) - After two confirmed U.S. cases of a superbug that thwarts a last-resort antibiotic, infectious disease experts say they expect more cases in coming months because the bacterial gene behind it is likely far more widespread than previously believed.

Army scientists in May reported finding E. coli bacteria that harbor a gene which renders the antibiotic colistin useless. The gene, called mcr-1, was found in a urine sample of a Pennsylvania woman being treated for a urinary tract infection.

On Monday, researchers confirmed preliminary findings that E. coli carrying the same mcr-1 gene were found in a stored bacterial sample of a New York patient who had been treated for an infection last year, as well as in patient samples from nine other countries.

The report came from a global effort called the SENTRY Antimicrobial Surveillance Program, led by Mariana Castanheira of JMI Laboratories based in North Liberty, Iowa.

The mcr-1 superbug has been identified over the past six months in farm animals and people in about 20 countries, including China, Germany and Italy.

The bacteria can be transmitted by fecal contact and poor hygiene, which suggests a far wider likely presence than the documented cases so far, according to leading infectious disease experts.

Health officials fear the mcr-1 gene, carried by a highly mobile piece of DNA called a plasmid, will soon be found in bacteria already resistant to all or virtually all other types of antibiotics, potentially making infections untreatable.

"You can be sure (mcr-1) is already in the guts of people throughout the United States and will continue to spread," said Dr. Brad Spellberg, professor of medicine at the University of Southern California.

Dr. David Van Duin, an infectious disease expert at the University of North Carolina in Chapel Hill, said he expects more documented U.S. cases of mcr-1 in coming months because it is already here and will spread from abroad. "We will see a lot more of this gene."

Colistin causes kidney damage, but doctors have opted for it as other antibiotics increasingly fail. Its overuse, especially in overseas farm animals, has allowed bacteria to develop resistance to it.


To track the mcr-1 gene, U.S. hospitals are working together with state and federal agencies to test bacteria samples of patients that have recently been treated for infections. Many of the largest research hospitals are examining samples of antibiotic-resistant bacteria that have long been stored in their freezers.

Gautam Dantas, associate professor of pathology at Washington University Medical Center in St. Louis, has tested hundreds of U.S. samples of archived bacteria in recent months and has not yet detected mcr-1. But he expects dozens of confirmed cases of the gene will be documented by next year in the country, mostly among current patients.

The concern of many disease experts is that mcr-1 could soon show up in bacteria also resistant to carbapenems, one of the few remaining dependable classes of antibiotics. In that event, with colistin no longer a last-ditch option, some patients would have to rely on their immune systems to fight off infection.

"Within the next two to three years, it's going to be fairly routine for infections to occur in the United States for which we have no (effective) drugs available," Dantas said.

Castanheira also believes mcr-1 will find its way into carbapenem-resistant bacteria, formally known as carbapenem-resistant enterobacteriaceae (CRE).

In an interview, she said the resulting virtually impervious bacterium would likely spread slowly inside the United States because CRE themselves are not yet widespread in the country, giving drugmakers some time to create new antibiotics.

Beginning in August, the U.S. Centers for Disease Control and Prevention will use $21 million to expand surveillance at laboratories operated by all 50 state health departments and seven larger regional labs. The federal funding will help pay for more-sensitive equipment to test for antibiotic resistance in bacteria samples provided by hospitals.

A 'slow catastrophe' unfolds as the golden age of antibiotics comes to an end
by Melissa Healy

In early April, experts at a military lab outside Washington intensified their search for evidence that a dangerous new biological threat had penetrated the nation’s borders.

They didn’t have to hunt long before they found it.

On May 18, a team working at the Walter Reed Army Institute of Research here had its first look at a sample of the bacterium Escherichia coli, taken from a 49-year-old woman in Pennsylvania. She had a urinary tract infection with a disconcerting knack for surviving the assaults of antibiotic medications. Her sample was one of six from across the country delivered to the lab of microbiologist Patrick McGann.

Within hours, a preliminary analysis deepened concern at the lab. Over the next several days, more sophisticated genetic sleuthing confirmed McGann’s worst fears.

There, in the bacterium’s DNA, was a gene dubbed mcr-1. Its presence made the pathogen impervious to the venerable antibiotic colistin.

We’re seeing more drug-resistant infections. And people will die. — William P. Hanage, Harvard University infectious disease epidemiologist

More ominously, the gene’s presence on a plasmid — a tiny mobile loop of DNA that can be readily snapped off and attached to other bacteria — suggested that it could readily jump to other E. coli bacteria, or to entirely different forms of disease-causing organisms. That would make them impervious to colistin as well.

It was a milestone public health officials have been anticipating for years. In a steady march, disease-causing microbes have evolved ways to evade the bulwark of medications used to treat bacterial infections. For a variety of those illnesses, only colistin continued to work every time. Now this last line of defense had been breached as well.

A second U.S. case of E. coli with the mcr-1 resistance gene was reported this week in the journal Antimicrobial Agents and Chemotherapy. Researchers are still working to determine whether it, or any of 18 other samples from around the world, contained the gene on an easy-to-spread plasmid.

Note: See the source for a graphic on the failing of antibiotics.

In 1928, British bacteriologist Alexander Fleming discovered that an errant penicillin mold growing in one of his petri dishes had the power to kill staphylococcus, a type of bacteria that causes pneumonia, skin infections and food poisoning. It took scientists, industrialists and the pressures of a world war to convert the mold into a mass-produced medicine, which was ready in time for troops to pack on D-Day.

More than 100 antibiotic compounds have been introduced since. But almost as soon as they were given to patients, scientists began finding evidence that disease-causing bacteria were developing resistance to these new wonder drugs.

Bacteria meet, mate, compete and evolve inside living bodies. When an antibiotic is added to the mix, only the strongest survive.

Humans have accelerated this natural process by indiscriminately prescribing antibiotics and by routinely feeding the drugs to livestock, scientists say. Multiply the number of humans and animals taking these drugs, and you multiply the opportunities for antibiotic-resistant strains to emerge.

Until very recently, few made the connection between antibiotic use in individual cases and the emergence of antibiotic resistance, said Dr. Susan Bleasdale, an infection-control expert at the University of Illinois in Chicago. Patients with earaches, sinus pressure and sore throats demanded antibiotics, and physicians tended to oblige.

The results have been deadly. Each year, more than 2 million people in the U.S. are infected with a bacterium that has become resistant to one or more antibiotic medication designed to kill it, according to the federal Centers for Disease Control and Prevention. At least 23,000 people die as a direct result of antibiotic-resistant infections, and many more die from other conditions that were complicated by an antibiotic-resistant infection, the agency says.

As medicines such as tetracycline, erythromycin and vancomycin lost much of their effectiveness, colistin continued to overwhelm trouble-making bacteria such as Salmonella, Klebsiella and E. coli.

Colistin is toxic to the human kidney, and doctors largely stopped using it in the 1970s when safer medications became available. But now that so many antibiotics have lost their ability to vanquish E. coli and other bacterial invaders, colistin has become the only hope for some desperate patients.

It’s not apocalyptic until it is. Shame on us if we wait till bodies are in the street. — Peter Pitts, president of the Center for Medicine in the Public Interest

The slow, steady march of antibiotic resistance doesn’t cause people to bleed to death in the streets, the way the Ebola virus does. It doesn’t cause heart-rending birth defects, as the Zika virus does.

And it rarely makes headlines. A survey released in June by the Infectious Diseases Society of America found that only 30% of Americans believe that antibiotic resistance is a significant problem for public health.

Yet officials at the World Health Organization warn that gonorrhea “may soon become untreatable” because of growing resistance to the antibiotic ceftriaxone, a member of the cephalosporin class. The WHO also notes that extensively-drug-resistant tuberculosis is now circulating in 100 countries, and that worldwide resistance to carbapenem antibiotics has weakened physicians’ last line of attack against life-threatening intestinal enterbacteriacaea infections.

“It’s a slow catastrophe,” said Army Col. Emil Lesho, director of the Defense Department’s Multidrug-resistant Organism Repository and Surveillance Network.

The problem goes beyond treating infections. As bacterial resistance grows, Lesho said, “we’re all at risk of losing our access” to medical miracles we’ve come to take for granted: elective surgeries, joint replacements, organ transplants, cancer chemotherapies. These treatments give bacteria an opportunity to hitch a ride on a catheter or an unwashed hand and invade an already vulnerable patient.

The struggle to sustain the effectiveness of antibiotics is a never-ending arms race. If humankind were regularly finding new anti-microbial agents and turning them into medicines, there might be less cause for worry.

Researchers haven’t identified a new class of antibiotic medication since 1987. As a result, while bacteria have continuously evolved new ways to thwart antibiotics, the medicines have not gained new mechanisms to fight back.

The economics of drug development are partly to blame.

To offset the millions of dollars they pour into research, clinical trials and the FDA approval process, pharmaceutical companies aim to develop blockbuster drugs, said Dr. Anthony Fauci, director of the National Institute for Allergies and Infectious Diseases. An ideal candidate would be used by millions of people every day for the rest of their lives, like pills to keep cholesterol or blood pressure in check.

Antibiotics won’t pay the freight. They should be prescribed sparingly and only used for about a week. They could be rendered obsolete at any time by resistance genes. Worst of all, they compete in a field of inexpensive generics.

Without government policies that encourage investment in the antibiotics, “there’s very little incentive” for companies to do it themselves, Fauci said.

Other approaches can help. Under Fauci, the NIAID is funding the development of tests that would speed the diagnosis of infections and prompt more careful use of antibiotics by physicians and hospitals.

New vaccines to prevent bacterial infections are under study, and existing vaccines could be more widely used. The use of bacteria-killing viruses — an approach called phage therapy that revives an idea largely abandoned in the 1930s — is getting a second look.

The Pennsylvania patient whose infection was impervious to colistin was able to beat back the bacteria in her urinary tract with the help of other antibiotics. She survived.

Others have not been so lucky. Hospital patients infected by antibiotic-resistant bacteria are twice as likely to die as those infected by the non-resistant strains of the same bacteria, studies show.

Experts say it’s just a matter of time before other disease-causing bacteria pick up the fateful mcr-1 gene. Since its discovery was first reported in China in November 2015, it has spread to human, animal, food and environmental bacteria on every continent.

“It’s not apocalyptic until it is,” said Peter Pitts, president of the Center for Medicine in the Public Interest and former associate commissioner of the FDA. “Shame on us if we wait till bodies are in the street.”

Follow me on Twitter @LATMelissaHealy and "like" Los Angeles Times Science & Health on Facebook.

Superbug E. Coli Found for Just Second Time in US
by Gillian Mohney

For just the second time in the U.S., researchers have found evidence of E. coli bacteria that are genetically resistant to a last-resort antibiotic, according to a report published today in the medical journal Antimicrobial Agents and Chemotherapy.

The superbug has a gene that makes it resistant to treatment with colistin, an antibiotic often used by doctors as a last resort for antibiotic-resistant infections, the report states.

In this case, the bacteria were genetically resistant to colistin but not to other forms of antibiotics that could be used to kill the E. coli. However, researchers are concerned that these bacteria could transfer genes to other E. coli and different bacteria that are already resistant to all forms of antibiotics except colistin, leading to the chance of a fully antibiotic-resistant strain of bacterium. Researchers are especially concerned about the possibility that the gene could be transferred within the Enterobacteriaceae family of bacteria, which includes E. coli. Some strains in that family are already largely resistant to many kind of antibiotics in the U.S.

Researchers found the strain by testing 13,562 E. coli strains collected at hospitals across the globe. They found 19 strains had the gene mcr-1, which makes E.coli resistant to colistin. In one case, that strain was found in the U.S.

Researchers said the global findings are alarming because it means there may be an increasing likelihood of having outbreaks of E. coli bacteria that are totally resistant to antibiotics.

"The fact that the gene has been detected in food livestock and raw meat is also concerning," said report co-author Mariana Castanheira, the director of micro- and molecular biology at JMI Laboratories.

Dr. Frank Esper, a pediatric infectious disease specialist at University Hospitals Case Medical Center, said the report was alarming but not surprising for infectious disease experts.

"It's basically a wake-up call," he told ABC News. "It's only going to be a matter of time where the perfect storm happens ... Next thing you know, you throw your hands up and say we're out of ammunition" to fight certain infections.

Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center, said health experts have been worried for years that there will be a rise in completely drug-resistant bacteria, especially since there have been few antibiotic breakthroughs in recent years.

He said there are several things that need to happen to minimize the chance of creating antibiotic-resistant bacteria.

"[No. 1], we prescribe antibiotics much more prudentially ... No. 2, we have to stop using antibiotics as freely as we do in our food industry," said Schaffner. "No. 3, we need to energize and create environments so pharmaceutical companies will once again start" developing antibiotics.

He said many pharmaceutical companies have little incentive to find and test new antibiotics, since they are usually used sparingly for a limited time and because the bacteria immediately start to become resistant to them, making them more likely to be rendered useless.

But Schaffner emphasized that more needs to be done to develop new antibiotics because there could be a spike of antibiotic-resistant bacteria outbreaks in the coming years.

"Developing new antibiotics is a long-term commitment, and we think in terms of five to 10 years," he said. "As that Chinese proverb states, the longest journey begins with first steps. We ought to make those steps now, because we're going to need those new antibiotics years from now."

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