ASP News Scan for Sep 09, 2016

Resistance evolution on video
Antibiotic-resistant Salmonella in blood
Prize for drug-resistance tests
Undercount of drug-resistance deaths
AMR genes in household dust
E coli in meat samples
Malaria decline, drug resistance
ESBL E coli on pig farms

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans


Scientist show bacterial resistance evolving in real time

Scientists have filmed the evolution of bacterial drug resistance in real time, noting that the pathogens can mutate to grow resistant to high levels of antibiotics in about 11 days, according to a study published yesterday in Science.

Researchers from Harvard Medical School (HMS) and Technion-Israel Institute of Technology built a 2-by-4-foot petri dish, which they called the Microbial Evolution and Growth Arena (MEGA) plate. They then filled it with 14 liters of agar, a growth medium for bacteria. They divided the MEGA plate into sections, with the outsides containing no antibiotics and each progressive section toward the middle containing 10 times the amount of antibiotic as the previous section.

The first section to hold an antibiotic had just enough to kill bacteria. The center of the plate contained 1,000 times as much antibiotic as the area with the lowest dose.

The team then inoculated the outside of the MEGA plate with Escherichia coli. Video of the plate showed colonies of drug-resistant bacteria gaining a foothold on the neighboring higher-drug section, then establishing themselves and spreading, until mutations allowed colonization of the next higher-dose section.

"What we saw suggests that evolution is not always led by the most resistant mutants," Baym said lead author Michael Baym, PhD, a research fellow at HMS, in a school press release. "Sometimes it favors the first to get there. The strongest mutants are, in fact, often moving behind more vulnerable strains. Who gets there first may be predicated on proximity rather than mutation strength."

The researchers caution that the MEGA plate is not intended to perfectly mirror how bacteria adapt and thrive in the real world, but they say its size allows E. coli evolution to mimic more closely the real-world environments bacteria encounter than do traditional lab cultures, according to a Harvard Medical School press release.

"This is a stunning demonstration of how quickly microbes evolve," said coauthor Tami Lieberman, PhD, now a postdoctoral research fellow at the Massachusetts Institute of Technology. "When shown the video, evolutionary biologists immediately recognize concepts they've thought about in the abstract, while nonspecialists immediately begin to ask really good questions."
Sep 8 Science abstract
Sep 8 HMS news release (includes video)


Study: One fifth of Salmonella blood isolates resistant to antibiotics 

A new study in the Journal of Infectious Diseases shows that 20% of Salmonella isolates collected from blood samples are resistant to antimicrobials, including first-line antibiotics. According to the authors, from the Centers for Disease Control and Prevention (CDC), drug-resistance in nontyphoidal Salmonella is now a serious health threat.

The isolates were collected from blood samples gathered from 2003 to 2013 in the United States through the National Antimicrobial Resistance Monitoring System (NARMS). Men over the age of 65 were at greatest risk for infection with Salmonella resistant to first-line treatments.

Nineteen percent of isolates were resistant to tetracycline, a commonly used antibiotic. Ceftriaxone resistance slightly increased in blood isolates over the study period. Salmonella serotypes Enteritidis, Javiana, Panama, and Typhimurium were more likely to show resistance to antimicrobials than were other strains.

Salmonella is one of the most common bacterial infections in the United States, causing at least 1 million illnesses each year. While most cases resolve on their own, severe cases require antibiotic treatment. The CDC said there are now more than 100,000 cases of drug-resistant Salmonella each year.
Sep 8 J Infect Dis study


HHS offers $20 million for innovative antimicrobial resistance tests

Originally published Sep 8.

The US government is awarding $20 million in prizes for innovative ideas for the development of rapid, point-of-care diagnostic lab tests to quickly identify antibiotic-resistant bacteria, according to a National Institutes of Health (NIH) press release today.

The Antimicrobial Resistance Diagnostic Challenge is sponsored by the NIH and the Office of the Assistant Secretary for Preparedness and Response (ASPR), both parts of the Department of Health and Human Services (HHS). "The diagnostic tests being sought are those that identify and characterize antibiotic resistant bacteria and those that distinguish between viral and bacterial infections to reduce unnecessary uses of antibiotics, a major cause of drug resistance," the NIH said in the release.

The goal is to be able to identify pathogens and resistance factors within hours, rather than the 2 to 3 days or longer that the standard culture tests require.

Concepts must be submitted by Jan 9, 2017, for the first phase of the competition, when up to 20 semifinalists will be chosen to receive up to $50,000. In the second phase, on Dec 3, 2018, up to 10 finalists will receive up to $100,000.  These funds can be used to develop prototypes for evaluation by two independent laboratories, which will be considered when final winners are selected and announced on Jul 31, 2020.  The competition specifies that up to three winners can be selected, and winners will share an amount equal to or greater than $18 million.

"The growing incidence of serious infections from antibiotic resistant bacteria presents a critical risk to the public health of our nation," said NIH Director Francis S. Collins, MD, PhD. "My hope is that this competition will spur exceptional innovators to rise to the challenge and deliver effective tools to help manage this significant problem."
Sep 8 NIH news release
Antimicrobial Resistance Diagnostic Challenge home page


US failing to accurately track drug-resistant infection deaths, report says

Originally published Sep 7.

A yearlong investigation by Reuters alleges that thousands of US deaths from antibiotic-resistant infections are going uncounted because federal and state health agencies are doing a poor job of tracking them.

In the first part of a series on "superbugs," the news service today outlines how, in several cases, the death certificates of patients who died as the result of a bacterial infection contracted in the hospital fail to include any mention of the infection.

This happens for several reasons; for example, doctors might not want to wait for laboratory confirmation of an infection, or the patient may have been suffering from several other conditions. But Reuters also found that hospitals are reluctant to acknowledge hospital-acquired infections because of potential legal liability, loss of insurance reimbursements, and public-relations damage.

And this is just one part of the problem. Even when deaths from antibiotic-resistant infections are recorded, many still go uncounted at the state level. A Reuters survey of all 50 state health departments found that 24 states and the District of Columbia do not regularly track deaths caused by drug-resistant infections. And the states that do track such deaths do so inconsistently, and only for a few types of infections.

In the survey, those states reported a combined total of 3,300 deaths due to drug-resistant infections from 2003 to 2014. A Reuters analysis of death certificates from the same period, in contrast, found that drug-resistant infections played a role in 180,000 deaths.

Meanwhile, because there is no unified national surveillance system to monitor drug-resistant infections and related deaths, those deaths recorded at the state level often don't make it into federal health statistics. As a result, Reuters found that the widely cited national estimates of antibiotic-resistant infection deaths provided by the CDC—23,000 a year—are "mostly guesswork," an extrapolation based on small samplings of infections and deaths collected from 10 states in 2011. CDC officials acknowledged to Reuters that those estimates are limited.

Comparing the battle against antibiotic-resistant infections to the fight against HIV/AIDS, Reuters argues that an accurate count of where and when antibiotic-resistant infections and deaths are occurring will prompt national action and enable public health agencies to "quickly allocate money and manpower where they are needed."
Sep 7 Reuters story


Study links household antimicrobial chemicals to antibiotic resistance

Originally published Sep 7.

A new study has found a connection between antimicrobial substances found in household dust and levels of antibiotic resistance genes.

In the study, published today in Environmental Science & Technology, researchers collected 44 dust samples from a mixed-use athletic and educational facility, then analyzed the samples for antimicrobial chemicals, microbial community profiles, and antibiotic resistance gene profiles.

Among the chemicals they found were triclosan, which is a common ingredient in over-the-counter antibacterial soaps and has been linked to antimicrobial resistance in drinking water and wastewater. They also identified several antibiotic resistance genes, with the three most abundant genes covering resistance to a wide range of antibiotics.

Overall, the dust contained low levels of triclosan and low concentrations of antibiotic resistance genes. But further analysis revealed six positive associations between the concentration of an antimicrobial chemical and the relative abundance of an antibiotic resistance gene. In particular, the investigators found a link between higher concentrations of triclosan and higher levels of a macrolide resistance gene.

The authors of the study note that while their findings show only a correlation between the presence of antimicrobials in household dust and an increase in antibiotic resistance genes, they suggest that antimicrobials may have an influence on the promotion and retention of antibiotic resistance genes. They recommend further studies.

Last week, the Food and Drug Administration announced a ban on triclosan and 18 other antimicrobial and antiseptic chemicals commonly found in over-the-counter soaps.
Sep 7 Environ Sci Technol study
Sep 2 CIDRAP News story "FDA: No antimicrobial agents in over-the-counter soap"


Study finds resistant E coli common in UK poultry, pork samples

Originally published Sep 6.

A new study out of England has found antibiotic resistant Escherichia coli bacteria in nearly a quarter of pig and poultry meat samples purchased at UK supermarkets.

The study, which was commissioned by the Alliance to Save Our Antibiotics and conducted by researchers at the University of Cambridge, analyzed 189 UK-origin pork and poultry samples bought at seven of the UK's largest supermarkets.

In their analysis, the researchers found that 24% of the chicken samples tested positive for extended spectrum beta-lactamase E coli, which are resistant to cephalosporin antibiotics. Cephalosporins are commonly used in the treatment of E coli infections in the urinary tract and the bloodstream.

The researchers also found that 51% of the E coli found in the pork and poultry samples were resistant to trimethoprim, which is commonly used to treat lower urinary tract infections, while 19% showed resistance to gentamicin, an antibiotic used in upper respiratory tract infections. No resistance to fluoroquinolones or colistin was found in any of the E coli isolates.

The authors of the study said it's the first comprehensive study of the levels of antibiotic resistance in E coli found in UK supermarket meat, and that the findings suggest some of the resistance to key antibiotics in human E coli infections is coming from farm animals. Trimethoprin is commonly used to mass medicate farm animals via feed and water. Cephalosprins and gentamicin, while not licensed for use in farm animals in the United Kingdom, are commonly used off-label to treat animal infections when no suitable antibiotics are available.
Sep 5 Alliance to Save Our Antibiotics/Cambridge University study


WHO: Asian nations see drop in malaria, but artemisinin resistance a concern

Originally published Sep 6.

A new report from the World Health Organization (WHO) says that the six countries of the Greater Mekong subregion—China, Vietnam, Cambodia, Laos, Myanmar, and Thailand—cut their malaria incidence by 54%, and saw an 84% drop in malaria deaths, from 2012 to 2015.

Myanmar achieved the greatest reduction (62%) in malaria cases, followed by Vietnam (52%). Significant declines were also recorded in Thailand (24%) and Cambodia (18%), while Laos and China's Yunnan Province saw spikes in cases and deaths.

The WHO attributes the declines to the targeted provision of core malaria tools to those populations that are most at risk for the disease. Those tools include long-lasting insecticide treated nets, rapid diagnostic tests, and artemisinin-based combination therapies (ACTs).

The good news comes despite the development and spread of resistance to artemisinin, the core compound of the best available antimalarial medicines. The WHO report say that artemisinin resistance in the Plasmodium falciparum parasite, which accounts for most malaria cases and deaths, has now been detected in Cambodia, Laos, Myanmar, Thailand and Vietnam.

As a result of this increasing resistance, the agency says it's focusing on protecting ACTs as the front-line treatment for P falciparum malaria. One of the ways countries can do this is by phasing out the use of artemisinin-based monotherapies, the WHO says.

In addition, the report says that affected countries are shifting their malaria strategy from containment to elimination.

In related news, the WHO's South-East Asia Regional Office (WHO SEARO) yesterday declared that Sri Lanka has been certified by the WHO as free of malaria.
September 2016 WHO Bulletin: "WHO's emergency response to artemisinin resistance"


Study notes high rates of ESBL E coli on Chinese swine farms

Originally published Sep 6.

More than half of farm pigs and one in five workers on those farms harbor extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli, according to a small study in the Journal of Food Protection.

Researchers obtained rectal swabs from 60 pigs on four pig-fattening farms in Shandong province in eastern China and from 40 workers on the farms. The same number of animal and human samples was taken on each farm. They then characterized ESBL-carrying E coli isolates by genotype, antibiotic susceptibility, and other factors.

The investigators found that 34 of 60 pigs (56.7%) and 8 of 40 farm workers (20%) tested positive for ESBL-producing E coli. And the swine isolates had the same genotypes, antibiotic resistance profiles, and other factors as the human isolates.

They concluded, "These findings were suggestive for transfer of ESBL-producing E. coli between animals and humans."
September J Food Prot abstract

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