CRE

"Nightmare bacteria" with quick-spreading capabilities found on US pig farm

lborkowski — Mon, 12 Dec 2016 10:59:48 +0000

"Nightmare bacteria" with quick-spreading capabilities found on US pig farm

Last week, the journal Antibiotic Agents and Chemotherapy posted an accepted manuscript that contains some very bad news: an easy-to-spread gene that makes bacteria resistant to an important class of antibiotics has been found in samples from a US pig farm.

A team of researchers from Ohio State University, led by Thomas Wittum, collected samples from pigs and buildings at a pig facility over five months in 2015. They found that several of the samples contained carbapenem-resistant Enterobacteriaceae (CRE). Back in 2013, CDC Director Thomas Frieden held a press briefing on this "nightmare bacteria," warning of the alarming increase in hospital-acquired infections resistant to this last-resort class of antibiotics. Enterobacteriaceae is a family of bacteria that includes E. coli. They're often involved in foodborne illness outbreaks and in urinary tract infections.

Two aspects of this new finding are especially alarming. First, the researchers found the carbapenem-resistance factor, IMP, on a plasmid. Plasmids are highly mobile portions of DNA that transfer easily between different bacterial strains. So, a strain of E. coli that's already resistant to a first- or second-line antibiotic could acquire plasmid-borne resistance to a last-resort antibiotic relatively easily. This is why last year's discovery of colistin-resistance gene mcr-1 on a plasmid was so alarming.

The other worrisome thing is that carbapenems aren't approved for use in agriculture. Much of today's antibiotic resistance has been traced to the routine use of antibiotics in livestock for growth promotion, but the facility where Wittum's team found CRE doesn't use carbapenems -- so, the bacteria must have arrived or developed there through another route, possibly involving human-to-animal transmission.

Maryn McKenna at FERN's AG Insider considers what the new findings might mean for public health:

[Wittum's] team did not find any CRE in the finishing barn, where the pigs spend the last part of their lives before being sold, nor in any fecal samples taken from pigs in any of the barns. Since then, however, they have gone back, retested sows and piglets, and found them carrying IMP in their feces — which raises the possibility these highly-resistant organisms could move with pigs when they leave the farm, and could enter the food chain.

... “If they can find this in one farm, and not a huge farm, over and over, then there is probably more of this out there than we realize,” said Tara Smith, a molecular epidemiologist at Kent State University who was the first researcher to identify MRSA, drug-resistant staph, in pigs in the United States.

If carbapenem resistance is spreading in agriculture, she pointed out, we probably won’t know — because the limited testing of animals and meat that occurs in the United States looks for antibiotic resistance only in foodborne organisms such as salmonella and campylobacter. The organisms that Wittum and his co-authors recovered from the barns were random gut bacteria that linger on environmental surfaces: E. coli, citrobacter, morganella and providencia.

McKenna is my favorite source of writing on resistant bacteria (and you should read her whole FERN article about this new finding). When researchers began finding mcr-1 in samples around the world, she offered this helpful analogy:

It’s natural to imagine that antibiotic resistance proceeds step-wise; that in the leapfrog between bug and drug, bacteria gain resistance to one drug, and then the next toughest drug presented to them, and then a last-resort drug after that. But in the wild, the way bacteria accumulate resistance DNA is more like being dealt cards in a hand of poker: one might have a 3, a 5, and a Jack, while another has a King, a Queen and a 10.

In these papers published tonight, researchers are finding bacteria that already possess colistin resistance— call it the Ace—and are accumulating the rest of a winning hand. Only, what looks like winning would be losing, for us.

If CRE isn't already in the US food supply, it's probably only a matter of time before it is. This is how we get closer to a day when a strain of bacteria assembles a winning hand that makes it resistant to all antibiotics. At that point, we'll have to face a post-antibiotics era, when a simple cut can prove fatal and medical procedures that are routine today (dialysis, hip replacements, etc.) become much more likely to kill us.

lborkowski Mon, 12/12/2016 - 05:59

Tags

infectious diseases

carbapenem

CRE

livestock

More bad news about the global spread of antibiotic-resistant bacteria

lborkowski — Mon, 07 Dec 2015 10:10:03 +0000

More bad news about the global spread of antibiotic-resistant bacteria

Last month, researchers from China reported in The Lancet Infectious Diseases that they had identified a gene (MCR-1) that confers antibiotic resistance to a last-resort antibiotic (colistin) and then found that gene in E. coli isolates from pigs, meat, and hospital patients. This prompted Danish researchers to re-examine the genomes of bacteria they had mapped previously, and they found the MCR-1 gene in sample from a patient who suffered a blood infection in 2015. They also found it in five food samples imported between 2012 and 2014.

Mike the Mad Biologist found the plasmid and protein sequences of MCR-1 in Genbank, and checked to see whether it had appeared anywhere else. He reports that the identical protein has been found in E. coli from Malaysia isolated in 2013, and also in a Salmonella strain identified in Portugal in 2011.

This gene has now been found in both Europe and Asia, and analyses of bacteria collected on other continents is necessary to know whether it has spread elsewhere. But it’s clear now that this gene is spreading, and if it isn’t in the US already it could be here soon.

A separate but related story comes from the CDC, where researchers report on “nightmare bacteria” CRE (carbapenem-resistant Enterobacteriaceae) isolates collected from US patients between June 2010 and August 2015. They found that 52 CRE isolates collected from patients in 19 states carry enzymes that inactivate carbapenems, a class of broad-spectrum antibiotics used as a last resort for many serious infections. The enzymes are called OXA-48-like carbapenemases, and CDC found them in only one isolate from 2010, but 11 per year in 2013, 2014, and 2015. The Washington Post’s Lena Sun explains why this particular finding is so worrisome:

Unlike more common types of CRE, it carries a plasmid, or mobile piece of DNA, with an enzyme that breaks down antibiotics. And what makes these bacteria even more dangerous is their ability to transfer that plasmid--and that antibiotic resistance--to normal bacteria that are present in our bodies.

… Bacteria develop antibiotic resistance in two ways.

Many can evolve their own genome in ways that deactivate antibiotics, although that ability can't be shared with pathogens outside their own family.

Yet other bacteria rely on a shortcut: They get infected with a plasmid carrying the resistance gene. That makes them more dangerous because plasmids can make copies of themselves and transfer within a family of bugs and as well as jump to other families of bacteria, which can then "catch" the resistance directly without having to develop it through evolution.

This is also what makes the MCR-1 gene so alarming: It can be transferred easily from one type of bacteria to another. Colistin and carbapenems are drugs we often turn to for infections that can’t be treated effectively with other antibiotics – but now these last lines of defense are also under attack.

My George Washington University colleagues at the Antibiotic Resistance Action Center (ARAC) have been studying the spread of antibiotic resistance and how to stop it. In response to the latest bad news, ARAC Director Lance Price recommends:

We must act swiftly to contain the spread of colistin-resistant bacteria, or we will face increasing numbers of untreatable infections. Leaders from every nation should immediately implement a ban on the use of colistin in animal agriculture. While China appears to be the biggest user of the drug, it is approved for use in the the European Union and many other countries. It also is approved for use in food animals in the U.S., but drug companies holding those approvals are not actively marketing the drugs. Drug companies with these approvals should immediately withdraw these label claims to ensure that colistin is never used in U.S. animal agriculture, otherwise our livestock production facilities could become breeding grounds for untreatable superbugs.

In addition, we need to remember why colistin is the last drug available for treating these dangerous infections. We turned to it because the preferred drug class – carbapenems – became powerless against some superbugs due to overuse. Carbapenems are still effective against many bacteria, but for how long? While carbapenems are not approved for use in animal agriculture in many parts of the world, their use is not explicitly banned. World leaders should call for an immediate ban on carbapenems to protect them for future generations.

Colistin and carbapenems are the last lines of defense between humans and some of the most dangerous bacteria. Protecting these drugs is of the utmost importance and urgency. Superbugs are gaining strength because we continue to squander these precious medicines through over use in human medicine and as cheap production tools in animal agriculture.

It seems fitting for this news to come out as world leaders gather at the COP21 Paris climate summit. Antimicrobial resistance and greenhouse gases have both increased rapidly because we’ve pursued cheap, fast production whose costs are spread across the globe instead of being paid by those who reap the benefits. Both problems worsen unseen and can only be addressed effectively with large-scale action. In both cases, I hope the repeated alarming discoveries finally prompt the kind of action we need to keep global health and wellbeing from getting substantially worse.

lborkowski Mon, 12/07/2015 - 05:10

Tags

infectious diseases

antibiotic-resistant bacteria

CRE

It is an interesting race between the global warming and the misuse of antibiotics. Who will get us first. The bets are open.

More bad news about the global spread of evolution.

At least if you believe antibiotic-resistance is 'evolution before our eyes.'

of course sn, only an idiot like you would think it is not evolution.

Layperson question dep't:

Is it pronounced "carba-PEN-ems" or "car-BAP-en-ems" or something else?

I constantly follow the public health news but occasionally something like this comes along and I'd rather not sound like a silly goose by mispronouncing it;-)

In case anyone here is wondering why public health scientists don't get together and start pestering presidential candidates to put AB abuse in their platforms: whoever puts it in a platform is going to catch major flak from the AB abusers in agriculture. So, better to keep it mum until after the election. In any case we can all guess, and be within an infectious sneeze's distance of an answer, what they would do about this once they get into office.

G, I believe it's car-ba-PEN-em. But I've certainly read the word a lot more often than I've heard it pronounced.

Outmaneuvering Antibiotic Resistance

milhayser — Tue, 09 Jun 2015 11:56:37 +0000

Outmaneuvering Antibiotic Resistance

A groundbreaking study published in PLOS ONE offers hope that scientists can reverse the development of antibiotic resistance among bacteria with the help of "a mathematical model that pinpoints optimal antibiotic cycling patterns." On The Pump Handle, Kim Krisberg writes, "the research comes at a time of widespread concern that without a coordinated, well-funded response to growing antibiotic resistance, medicine could lose some of its most effective, life-saving tools." The collaboration between biologists and mathematicians yielded a piece of software dubbed "Time Machine" that "computes which antibiotic goes with which mutation at which point in time to best manage the evolution of resistance."

The promise of this software comes as the problem of antibiotic resistance becomes ever more urgent. On The Pump Handle, Liz Borkowski details a WHO report that documents strains of resistant pneumonia, E. coli, staph, tuberculosis, malaria, and flu worldwide. Borkowski also covers the recent outbreak of a "nightmare bacteria" called CRE due to contaminated medical equipment at a Los Angeles hospital. Meanwhile, last year, the CDC issued a warning about the threat of drug-resistant gonorrhea.

On Aetiology, Tara C. Smith provides some historical perspective, noting that the discoverer of penicillin warned about evolving resistance in 1945. Smith considers the possibility of moving beyond traditional antibiotics entirely, instead using viruses to consume bacteria, or using antimicrobial peptides like those produced by our immune systems to mutilate bacterial cell walls. But as Smith writes, "the peptides of our innate immune system are one of our first lines of defense against an immense variety of pathogens, and we don’t know what the outcome may be if we compromise this essential level of protection."

milhayser Tue, 06/09/2015 - 07:56

Tags

Misc

Antibiotic resistance

Antimicrobial Peptides

I would think the folks here, other than me, would accept an alternative title for this article:
“Outmaneuvering Evolution”.

Yes?

All I know is that if this lives up to the potential . . . sounds like a slam dunk Nobel to me...

See Noevo, that's entirely accurate. Might even be better as "Shepherding Evolution". And why exactly wouldn't you accept it? Young Earth type?

Practicing medicine in an era of antibiotic resistance: Duodenoscope edition

lborkowski — Mon, 23 Feb 2015 10:17:08 +0000

Practicing medicine in an era of antibiotic resistance: Duodenoscope edition

Last week, FDA warned healthcare providers that the complex design of a piece of endoscopy eqiupment may make it hard to fully disinfect -- which means that using it, even in accordance with the manufacturers' instructions, might allow dangerous bacteria to spread between patients. The warning follows reports of seven patients from UCLA's Ronald Reagan Medical Center becoming infected with the drug-resistant "nightmare bacteria" CRE (Carbapenem-Resistant Enterobacteriaceae) after undergoing procedures using ERCP endoscopes, or duodenoscopes. Of these seven patients, two died, and "the infection was a contributing factor in the death of two patients," UCLA said in a statement. The health system notified 179 patients that they may have been exposed to CRE bacteria during diagnostic or treatment procedures performed between October 3rd and January 28th, and offered free home testing kits to see if they are infected.

In a piece for National Geographic's Phenomena, Maryn McKenna notes that the UCLA episode follows outbreaks in other states, and that the weeks or months that can elapse between patients' exposures and infection symptoms can make it hard to stop outbreaks quickly. She also interviewed CDC medical epidemiologist Dr. Alexander J. Kallen, who highlighted these alarming aspects of recent duodenoscope-associated CRE outbreaks (emphasis added):

... the outbreak we investigated in Illinois in 2013, which we reported in the Journal of the American Medical Association, is the first time that we know of where there was transmission of a highly resistant pathogen, from a scope, unrelated to an infection-control breach. You almost always see that someone forgot this step or that step. But in these last three outbreaks, there was persistent contamination despite not identifying a breach, and that is fundamentally different. It starts to raise the suspicion this is more a fundamental issue with these types of scopes, rather than just failures to adhere to recommendations for cleaning.

It appears that UCLA followed the FDA-validated disinfection instructions for the scopes, but two of the facility's seven scopes harbored CRE bacteria anyway. Kallen also told McKenna that certain cleaning procedures might work to disinfect new equipment during FDA's lab tests, but the same procedures might not be sufficient with older equipment as used and cleaned in practice. In any case, it's a frigthening thought that a facility's staff can do exactly what they're supposed to do, but their patients can still end up with fatal infections.

FDA has recommendations for facilities, staff, and healthcare providers -- and also for patients. "Discuss the benefits and risks of procedures using duodenoscopes with your physician," the FDA Safety Communication suggests. "For most patients, the benefits of ERCP outweigh the risks of infection. ERCP often treats life-threatening conditions that can lead to serious health consequences if not addressed."

As McKenna warned in her excellent and terrifying Medium piece "Imagining the Post-Antibiotics Future," the spread of antibiotic-resistant bacteria means that medical procedures that are routine today, from dialysis to hip replacements, could become far more likely to result in fatal infections. FDA reports that US healthcare providers perform more than 500,000 ERCP procedures using duodenoscopes each year, because these are procedures are "the least invasive way of draining fluids from pancreatic and biliary ducts blocked by cancerous tumors, gallstones, or other conditions." If cases of duodenoscope-linked CRE infections keep mounting, though, patients and providers might have to start rethinking treatments.

In his FY 2016 budget, President Obama has proposed a $1.2 billion federal investment in combating and preventing antibiotic resistance. That seems like reasonable sum to spend on something that could let us slow the arrival of the post-antibiotics future.

lborkowski Mon, 02/23/2015 - 05:17

Tags

Public Health - General

antibitiotic resistance

bacteria

CRE

CDC classifies three antibiotic-resistant bacteria as urgent threats

lborkowski — Fri, 20 Sep 2013 10:29:56 +0000

CDC classifies three antibiotic-resistant bacteria as urgent threats

Antibiotic-resistant infections kill 23,000 people in the US and sicken two million each year, and the problem is getting worse, warns a new report from the Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013 ranks several strains of bacteria according to their current and projected health and economic impacts. It describes 18 microorganisms whose threat levels are "urgent," "serious," or "concerning."

CDC identifies three bacteria as urgent threats: Clostridium difficile, Carbapenem-resistant Enterobacteriaceae (CRE), and Drug-resistant Neisseria gonorrhoeae. C. diff is included on the list even though most infections from it aren't resistant to typical treatments, because most of these infections "are directly related to antibiotic use and thousands of Americans are affected each year." (The fact that C. diff infections often arise after a course of antibiotic treatment has prompted a few clinicians to treat persistent cases with "fecal transplants" -- essentially, trying to repopulate patients' guts with a mix of normal bacteria that can keep C. diff in check.) CDC's report offers snapshots of each of these bacteria:

Clostridium difficile causes life-threatening diarrhea, and mostly infects hospitalized or recently hospitalized patients who've recieved antibiotics. A stronger strain of the bacteria emerged in 2000, demonstrating resistance to fluoroquinaolone antibiotics (a common treatment for other infections). C. diff causes 250,000 infections, 14,000 deaths, and $1 billion in excess medical costs each year.
Carbapenem-resistant Enterobacteriaceae (CRE) include Kleibsella and E. coli bacteria that are resistant to carbapenams, which are often used as antibiotics of last resort. The bacteria are resistant to all or nearly all of the antibiotics available, and nearly half of hospital patients who get CRE bloodstream infections (a minority of healthcare-associated CRE cases, at the moment) die. CRE causes 9,000 infections and 600 deaths each year.
Drug-resistant Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea, which is the second most commonly reported notifiable infection in the US, and is showing resistance to the antibiotics normally used to treat it, including tetracycline and cefixime. Out of an estimated 820,000 US gonorrhea cases in 2011, 246,000, or nearly one-third, were resistant to at least one antibiotic.

The 12 "serious" threats include multidrug-resistant Acinetobacter, drug-resistant Campylobacter, Vanomycin-resistant Enterococcus (VRE), and the poster bug of antibiotic resistance, Methicillin-resistant Staphylococcus Aureus (MRSA).

CDC recommends four core actions to address these threats:

Preventing Infections, Preventing the Spread of Resistance: Avoiding infections in the first place reduces the amount of antibiotics that have to be used and reduces the likelihood that resistance will develop during therapy;
Tracking: CDC gathers data on antibiotic-resistant infections, causes of infections and whether there are particular reasons (risk factors) that caused some people to get a resistant infection;
Improving Antibiotic Use/Stewardship: Perhaps the single most important action needed to greatly slow the development and spread of antibiotic-resistant infections is to change the way antibiotics are used;
Development of Drugs and Diagnostic Tests: Because antibiotic resistance occurs as part of a natural process in which bacteria evolve, we will always need new antibiotics to keep up with resistant bacteria as well as new diagnostic tests to track the development of resistance.

Maryn McKenna's Superbug blog is always the first place I go for expert analysis of bacteria-related news, and she has two great posts about the report: "CDC Threat Report: ‘We Will Soon Be in a Post-Antibiotic Era’" summarizes the report's findings and the pace of progress to address the threats; "CDC Threat Report: Yes, Agricultural Antibiotics Play a Role in Drug Resistance" highlights the report's many references to the role of large-scale livestock operations in antimicrobial resistance. Perhaps most striking is the report's graphic on the development of antibiotic resistance:

McKenna also notes, "Out of the 18 drug-resistant organisms the report highlights as alarming, four are foodborne organisms that become drug-resistant as the foods that carry them are produced or grown: Campylobacter (p. 61), E. coli (p. 65), Salmonella (p. 70) and Shigella (p. 75)."

The report lists action steps CDC, states and communities, healthcare leaders and providers, and patients and their families can take to reduce the development of antimicrobial resistance and the spread of resistant bacteria. In addition, Congress could pass the Preservation of Antibiotics for Medical Treatment Act, and FDA could collect and publish better data on use of antibiotics in livestock and restrict livestock operations' use of antibiotics to therapeutic purposes (i.e., let producers give antibiotics to infected animals but not routienly dose the whole herd for growth promotion). The decisions we all make today will determine how quickly we recover -- or die -- from infections in the future.

lborkowski Fri, 09/20/2013 - 06:29

Tags

infectious diseases

antibioic-resistant bacteria

Sounding the alarm on "nightmare bacteria" CRE

lborkowski — Thu, 14 Mar 2013 18:36:06 +0000

Sounding the alarm on "nightmare bacteria" CRE

Last week, CDC Director Thomas Frieden opened a press briefing by saying, "It's not often that our scientists come to me to say that we have a very serious problem, and we need to sound an alarm." What scientists found, and reported in CDC's Morbidity and Mortality Weekly Report, is that a growing proportion of Enterobacteriaceae (a family of bacteria known for causing hospital-acquired infections) are resistant to carbapenems, a type of antibiotics that's typically been the last line of attack against stubborn infections. Frieden explained why these carbapenem-resistant Enterobacteriaceae (CRE) are a "nightmare bacteria":

They pose a triple threat. First, they're resistant to all or nearly all antibiotics. Even some of our last-resort drugs. Second, they have high mortality rates. They kill up to half of people who get serious infections with them. And third, they can spread their resistance to other bacteria. So one form of bacteria, for example, carbapenem-resistant klebsiella, can spread the genes that destroy our last antibiotics to other bacteria, such as E. coli, and make E. coli resistant to those antibiotics also. E. coli is the most common cause of urinary tract infections in healthy people. So we only have a limited window of opportunity to stop this infection from spreading to the community and spreading to more organisms.

In the first half of 2012, CRE infections were only reported in 4.6% of US acute-care hospitals; what's troubling is the rate of increase. We have a limited window of opportunity to stop CRE from becoming widespread and getting out into community settings. The key is for hospitals to act swiftly and implement recommendations from CDC's CRE Toolkit. These include detecting and communicating about patients' CRE infections; enforcing infection-control measures; and grouping patients with CRE together and reserving staff and equipment to treat them.

Maryn McKenna at Superbug (who has written extensively about carapenem-resistant bacteria) explains why it might not be so simple to implement these recommendations:

But an important point is that none of this is required, and none of this is funded. When the Netherlands wanted to beat back the emergence of MRSA, that country passed laws requiring every hospital to test patients before letting them in the door. (That story is told in this book.) When Israel wanted to counter KPC, which was ripping through its hospitals after arriving from the US, it created a national task force and imposed mandatory national measures for detecting and confining the infection. (That program is described in this 2011 paper.) And hospitals are on their own in figuring out how to organize and pay for CRE control. There are no reimbursements, under Medicare, for infection-control as a hospital task; and as infection-prevention physician Eli Perencevich demonstrated two years ago, the National Institutes of Health is not funding resistance-countering research.

If we don't act now, we're setting ourselves up for a future in which a minor surgical procedure and short hospital stay carries a high risk of catching an incurable infection -- and even people who go nowhere near a hospital could pick up a deadly bacteria.

lborkowski Thu, 03/14/2013 - 14:36

Tags

infectious diseases

antibiotic-resistant bacteria