Emergence and spread of Salmonella Typhimuriam DT104

Since it first emerged more than half a century ago, a particular strain of multidrug-resistant Salmonella has spread all over the world. Now researchers have figured out why this strain, Salmonella Typhimuriam DT104, has been so successful. This new knowledge could prove valuable in combating other successful pathogens, according to the authors. The study is published ahead of print March 4th in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

Salmonella Typhimuriam DT104In order to construct the history of this strain, the investigators performed whole-genome sequencing of samples of DT104 that had been collected from patients over more than 40 years, from 1969 to 2012, in 21 countries, on six continents. Very tiny changes in the genome that took place over time enabled them to construct the strain’s family tree. The sequences have also made it easy to estimate roughly when the pathogen acquired the resistance genes.

DT104’s success was due in no small part to its resistance to at least five antibiotics, including ampicillin, chloramphenicol, streptomycin, sulphonamide, and tetracycline, said corresponding author, Pimlapas Leekitcharoenphon, PhD.

Further abetting its spread, unlike other strains of DT Salmonella, DT104 was able to infect numerous livestock species, including cattle, poultry, pigs, and sheep, said Leekitcharoenphon. “Having multiple hosts increases the chances of dissemination,” she explained. Leekitcharoenphon is a postdoctoral researcher at the Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby.

Using a program that took into account the rate of mutations in DT104, the investigators estimated that it first emerged in 1948 as an antibiotic susceptible pathogen. It is not clear exactly when DT104 first acquired the multidrug resistance-containing transposon. Transposons are mobile genetic elements that can carry antibiotic resistance genes, and that can jump from one genome to another. In the case of DT104, transposons have been identified as the sources of the resistance genes. The study suggests that the first acquisition of antibiotic resistance may have happened in 1972. However, multidrug-resistant DT104 was first reported in 1984 in the United Kingdom.

The new results also illuminated, for the first time, the results of a program in Denmark to eradicate all pigs infected with DT104, which had begun in 1996, but was stopped in 2000 due to financial pressures. It turns out that program was quite successful.

“If we know and understand the past, we might be able to solve the current resistance problems and prevent future ones,” said Leekitcharoenphon.

Antimicrobial resistance spreads in French livestock

Colistin resistance was investigated in 1,696 isolates collected from 2007 to 2014 within the frame of the French livestock antimicrobial resistance surveillance programme.

Cow_KissThe mcr-1 gene was detected in all commensal Escherichia coli isolates with a minimum inhibitory concentration to colistin above the 2 mg/L cut-off value (n=23). In poultry, mcr-1 prevalence was 5.9% in turkeys and 1.8% in broilers in 2014. In pigs, investigated in 2013, this prevalence did not exceed 0.5%. These findings support that mcr-1 has spread in French livestock.

Prevalence Of Mcr-1 In Commensal Escherichia Coli From French Livestock, 2007 To 2014

Eurosurveillance, Volume 21, Issue 6, 11 February 2016

A Perrin-Guyomard, M Bruneau, P Houée, K Deleurme, P Legrandois, C Poirier, C Soumet, P Sanders

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21380

Antimicrobial resistance in Europe

In relation to the 8th European Antibiotic Awareness Day on 18 November, the European Centre for Disease Prevention and Control (ECDC) has published the annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) [1]. On the same occasion, an update with 2014 data of the EARS-Net interactive database on antimicrobial resistance [2] and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) interactive database on antimicrobial consumption [3] was released, on the ECDC website.

ab.res.prudent.may.14The data on antimicrobial resistance showed that the percentages of Klebsiella pneumoniae isolates resistant to fluoroquinolones, third-generation cephalosporins and aminoglycosides, as well as combined resistance to all three antibiotic groups increased significantly at European Union (EU)/European Economic Area (EEA) level over the last four years. A significant increase was also observed for carbapenem resistance in K. pneumoniae.

For Escherichia coli, resistance to third-generation cephalosporins and combined resistance to fluoroquinolones, third-generation cephalosporins and aminoglycosides increased significantly at EU/EEA level. The increase in combined resistance, and the increase in resistance to last line groups of antimicrobials such as the carbapenems, is a serious cause for concern and a threat to patient safety in Europe.

Data on antimicrobial consumption in 2014 show that the overall consumption of antimicrobials in the community in the EU/EEA was 21.6 defined daily doses (DDD) per 1,000 inhabitants and per day. The large inter-country variation in antibiotic consumption observed in previous years remained. When antibiotic consumption was expressed in terms of number of packages (a better estimate for prescriptions) per 1,000 inhabitants and per day, five countries (Denmark, Luxembourg, Slovenia, Spain and Sweden) showed a significant decrease during 2010–2014.

During the same period, antibiotic consumption in the hospital sector (expressed in DDD per 1,000 inhabitants and per day) showed a significant increasing trend. A significant increase in the consumption of specific antibiotic groups, e.g. carbapenems, was also observed during this period at EU/EEA level, and in several countries. Although the vast majority of antibiotics is consumed in the community, i.e. outside hospitals, antibiotic consumption in hospitals is a major driver of the spread of multidrug-resistant bacteria responsible for healthcare-associated infections.

References

European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance surveillance in Europe 2014. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2015. Available from http://ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance-europe-2014.pdf

European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance interactive database (EARS-Net). Stockholm: ECDC. [Accessed 19 Nov 2015]. Available from http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx

European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance interactive database (EARS-Net). Stockholm: ECDC. [Accessed 19 Nov 2015]. Available from http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/esac-net-database/Pages/database.aspx

Ups and downs in report on drug-resistant foodborne bacteria

CIDRAP reports that an annual federal report released this week on drug resistance in bacterial foodborne illness culprits mainly showed encouraging patterns but raised concerns about multidrug resistance in two Salmonella serotypes.

ab.red.aug.15The findings are from the National Antimicrobial Resistance Monitoring System (NARMS), a collaboration of three federal agencies that between them track resistant bacteria in humans, retail meat, and food animals. The respective agencies include the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the US Department of Agriculture (USDA).

The report focuses on foodborne pathogens that resist antibiotics considered crucial to human medicine and on multidrug resistant bacteria—those that resist agents in three or more antibiotic classes. The system screens for nontyphoidal Salmonella, Campylobacter, Escherichia coli, and Enterococcus; Salmonella and Campylobacter are the leading bacterial causes of foodborne illness.

Methodology and testing changes

This year’s report for the first time covers multiple years, 2012 and 2013, and has a new format that includes 10 interactive graphs to help show resistance patterns in Salmonella and Campylobacter in humans, retail foods, and animals through 2013, the FDA said in a press release yesterday. It added that the report also reflects improvements in NARMS testing. For example, animal testing now includes cecal (intestinal) testing of food-producing animals before slaughter, which may provide a more accurate picture of animals’ microbial status in farm settings.

Also, the FDA said it is using epidemiologic cut-off values that move toward global harmonization of Campylobacter surveillance methods as well as updating measurements for cefepime in response to changes made to best practices for international testing. Cefepime is an antibiotic used to screen for extended-spectrum beta-lactamase (ESBL) production, a mechanism linked to drug resistance.

In encouraging findings, the NARMS study found that overall, Salmonella isolates are holding the line against resistance. About 80% of human Salmonella isolates aren’t resistant to any tested antibiotics, a number that hasn’t changed over the past decade. Resistance to the three most important drugs used to treat human Salmonella isolates—ceftriaxone, azithromycin, and quinolones—remains below 3%.

Similarly, Salmonella multidrug resistance in human, cattle, and chicken isolates hasn’t changed in the last 10 years, remaining at about 10%. Also, the number of multidrug-drug resistant Salmonella isolates in retail chicken has decreased to around 3%, according to the report.

For Campylobacter jejuni, the subtype that causes most human campylobacteriosis cases, resistance to ciprofloxacin, the drug most commonly used for treatment, declined to its lowest level in retail chicken to date (11%).

Among the worrisome findings, multidrug resistance in human isolates of the common Salmonella serotype l 4,[5],12:i:- is still rising, and has doubled from 18% in 2011 to 46% in 2013, according to the FDA.

The report also pointed to another concern, an increase in multidrug resistance and ceftriaxone resistance in Salmonella Dublin subtypes isolated from cattle and humans.

EU report provides basis for effective fight against development of resistant bacteria

The European Food Safety Authority reports the use of certain antimicrobials in animals and humans is associated with resistance to these antimicrobials in bacteria from animals and humans. There are also important differences in the consumption of antimicrobials in animals and in humans between European countries. These are some of the findings of the first integrated analysis of data from humans, animals and food in Europe published jointly by the European Centre for Disease Prevention and Control (ECDC), the European Food Safety Authority (EFSA) and the European Medicines Agency (EMA).

The ECDC/EFSA/EMA first joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals also identifies data limitations that need to be addressed to allow further analysis and conclusions to be drawn. These include additional data on antimicrobial consumption by animal species, data on antimicrobial consumption in hospitals in more European countries and monitoring of resistant bacteria in the normal flora from both healthy and diseased people.

ab.res.prudent.may.14The analysis was carried out at the request of the European Commission and combines data from five European monitoring networks that gather information from the European Union (EU) Member States, Iceland, Norway and Switzerland.

This holistic approach aims to make better use of the existing data and thus strengthen coordinated surveillance systems on antimicrobial consumption and antimicrobial resistance in human and veterinary medicine, and to allow policy makers to decide on the best way to tackle antimicrobial resistance in humans and animals.

The joint report will inform the European Commission’s action plan against the rising threats from antimicrobial resistance. The data will also contribute to establishing strong methodologies and priorities in the fight against the development of antimicrobial resistance.

This is the first in a series of reports that EMA, EFSA and ECDC are planning to publish based on the data collected by various monitoring networks.

Access to accurate data on the use of antimicrobials and the occurrence of antimicrobial resistance is an essential step to develop and monitor policies that minimise the development of resistance and keep antimicrobials effective for future generations.

Ciprofloxacin resistant Campylobacter in broiler chicken in Canada

This case study outlines the patterns of ciprofloxacin resistance in Campylobacter isolated from retail chicken meat in Canada. Campylobacter is the third most common cause of foodborne enteric illness in Canada; it usually causes a self-limited illness, but in some cases antimicrobials may be indicated. Ciprofloxacin (a fluoroquinolone) is an antimicrobial used to treat a number of infections in humans; other fluoroquinolones are used both therapeutically and prophylactically in livestock animals, including broiler chickens.

ab.retail.cdn.foodThe Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) has been testing retail chicken meat samples across Canada for the presence of Campylobacter and for resistant strains since 2003. At the end of 2010, CIPARS documented that retail chicken meat samples in Canada contaminated with Campylobacter ranged from 36% in the Maritimes to 42% in British Columbia. Furthermore, levels of ciprofloxacin-resistant Campylobacter varied across the country, with higher percentages in British Columbia (17% in 2010) and Saskatchewan (11%), in comparison with lower percentages in Ontario (5%), Québec (2%), and the Maritimes (4%). In 2011 and 2012, resistance declined in British Columbia and Saskatchewan, but began to rise in Québec and Ontario. Recently, the Canadian poultry industry developed a policy to eliminate the preventive use of third generation cephalosporins and fluoroquinolones in broiler chickens (meat chickens) and broiler breeder chickens (chickens that produce the eggs that will become the broilers).

CIPARS will continue to monitor trends in antimicrobial use and resistance following this industry intervention. By following good food preparation and hygiene practices, Canadians can reduce the risks of developing a Campylobacter infection (resistant or susceptible) from retail chicken.

Public Health Agency of Canada, CCDR, Volume 40 S-2

A. Agunos, D. Léger, B. Avery, E. Parmley, A. Deckert, C. Carson

R. Reid-Smith, R. Irwin

http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40s-2/dr-rm40s-2-cs-ec-eng.php

Antimicrobial resistance surveillance in Canada: Retail food highlights, 2003-2012

The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is a collaborative, integrated program designed to track antimicrobial resistance (AMR) among enteric bacteria isolated from various livestock commodities along the food-producing continuum (“farm to fork”) and in humans.

raw-chicken-bacteria-537x357Objective: To provide a summary of the prevalence and trends in AMR among select bacteria isolated from raw, fresh chicken, pork, and beef in 2012 at the retail food level and to link these data with other findings from CIPARS.

Methods: Meat samples were collected from randomly selected geographic areas across Canada weighted by population for subsequent isolation of bacteria and interpretation of the associated AMR profiles. Salmonella, Campylobacter and generic Escherichia coli (E. coli) were tested in chicken, and E. coli was tested in beef and pork. Data were analyzed for 2012 and temporal and regional trends were examined between 2003 and 2012 by province/region.

Results: Overall, resistance levels to Salmonella in retail chicken varied widely by region and year. For example,  ceftiofur resistance to Salmonella in retail  chicken was significantly lower in 2012 than in 2004 in Ontario and in Québec; however among all regions sampled,  resistance to Campylobacter in retail chicken was relatively low in 2012 (<16%) with the exception of tetracycline resistance. In 2012, ciprofloxacin resistance to  Campylobacter in chicken declined in British Columbia but significantly increased in Ontario, compared to 2011. In 2012, β-lactam resistance to E. coli in retail beef remained low (≤1%) and was also relatively low comparable to previous years in pork.

Conclusion: In Canada, as is the case worldwide, there is evidence of resistance to medically important antimicrobials among bacteria from retail meats. Resistance among organisms isolated from poultry, beef, and pork at the retail food level is characterized by wide variation over time and across different regions.

Public Health Agency of Canada, CCDR, Volume 40 S-2

B. Avery, E. Parmley, R. Reid-Smith, D. Daignault, R. Finley, R. Irwin

http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40s-2/dr-rm40s-2-surv-4-eng.php

Statement of the American Society for Microbiology on the national strategy to combat antibiotic resistant bacteria

The American Society for Microbiology (ASM) congratulates the Obama Administration for its September 18 announced White House National Strategy for Combating Antibiotic Resistant Bacteria (CARB).   The strategy outlines bold steps to slow the public health threat of antibiotic resistant bacteria, including efforts to stimulate innovative research.   Importantly, the Strategy will establish a new Task Force for Combatting Antibiotic Resistant Bacteria which is directed to submit an action plan to the President by February 2015. This elevated attention at the highest level of government is needed because in the United States alone, antibiotic resistant bacteria cause 2 million infections a year and 23,000 deaths.

ab.res.prudent.may.14Innovative research is needed to discover new, effective antibiotics and to ensure existing antibiotics are properly targeted. Research will lead to innovative diagnostics to improve detection and tracking of pathogens, new vaccines targeted to drug resistant organisms and new antibiotics in partnership with private industry. Cutting edge genetic sequencing technologies used at point of care can enhance surveillance of antimicrobial resistance, enabling rapid tracking of genetic signatures and ensure rapid, accurate diagnosis and appropriate use of antibiotics saving lives and reducing resistance resulting from inappropriate treatment.  Because an estimated half of antibiotic prescriptions are inappropriate, encouraging the development of rapid, point of care tests is critical to identifying and tailoring treatment of resistant bacteria and minimizing the use of broad spectrum antibiotics.  

The National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) will play leading roles in the national response. The collaborative efforts of the these agencies will be extremely important to advance development and use of rapid diagnostic tests for identifying drug resistant infections. Enhanced regulatory processes and reduction in approval cycle time will be key. Reimbursement of new diagnostic tests will also be a major incentive for development of new diagnostics by the private sector. The recommended expansion of DNA sequencing capacity and collection of microbial genetic sequences in a centralized National Database of Resistant Pathogens will allow comparison of outbreak stains with the database collection, improving their control.

The emphasis on tracking resistance in humans, animals and food and promoting antibiotic stewardship across the food chain is vitally important, as well as minimizing antibiotic use for non-health purposes. The President’s Executive Order calls for work internationally, recognizing that efforts must be global to reduce the burden of antimicrobial resistance and its spread.

The National Strategy articulates national goals, priorities and specific objectives that provide an overarching framework for federal investments to combat antimicrobial disease. It will be extremely important that new and adequate funding is provided to accomplish this comprehensive agenda. The ASM appreciates the new initiatives and is committed to working with federal agencies and Congress as this ambitious agenda to address the threat of antimicrobial resistance gets underway.

Health Canada’s quiet move to end use of antibiotics to fatten up animals

A cow can get penicillin without a prescription in most parts of Canada, unlike humans who have to see their doctors first.

kelly-croweFarmers can simply go down to the local farm supply store and buy tetracycline and many other antibiotics over the counter.

And the animals don’t have to be sick. Cattle, chickens, turkeys and pigs take antibiotics to prevent them from becoming infected.

For animal producers, antibiotics are an important management tool to keep their herds and flocks healthy and profitable. It’s estimated that up to 80 per cent of the world’s antibiotics are used in agriculture.

But every time a bug comes up against a drug, whether it’s in humans or animals, that’s a fresh opportunity to evolve a new defence.

And the links are now clear. Antibiotic use on farms is creating superbug infections in humans.

The World Health Organization warns that unless antibiotic use is reined in, the world is headed for a dystopian future where routine infections are deadly. So it’s a surprise to learn that Canada has no coordinated national system to control antibiotics in agriculture.

There is no way of monitoring what drugs are being used and how farmers are using them, and no reliable statistical data on the volumes of antibiotics being given to food animals.

I discovered all of that as I was researching what seemed to be a simple good news story: that Health Canada is about to stop letting farmers use antibiotics as growth promoters.

On the surface, it sounded like a breakthrough. Public health advocates have been calling for an end to the use of antibiotics for growth promotion for years. It’s a practice that has been banned in most of Europe.

ab.res.prudent.may.14But I soon learned that many believe the change won’t significantly reduce the amount of antibiotics used on Canadian farms. That’s because it’s estimated that most of the antibiotics in feed are intended for disease prevention. And that use will still be permitted.

It was curious how quietly this change came about. No press release, no news conference or ministerial announcement. Just a short “Notice to Stakeholders” posted on the Health Canada Veterinary Drug Directorate website.

But one of the biggest stakeholders — the animal drug manufacturers  — didn’t need any notice, because the whole thing was their idea, according to Jean Szkotnicki from the Canadian Animal Health Institute, the trade association that represents the drug companies who make and sell antibiotics for animals.

In March, the trade association approached Health Canada with an offer to change the labels on 140 animal antibiotics that are the same or similar to human drugs.

They offered to remove claims for growth promotion, to bring their products in line with the U.S. Food and Drug Administration.

Health Canada apparently agreed. But what does it mean in practice?

When I tried to answer that question, I ran up against the wall that is Health Canada media relations.

Health Canada won’t let me talk directly to a policy maker, so, in what has become a familiar pattern, a media person emailed me a short written response to my initial inquiries, raising more questions than it answered:

“The removal of the production claims from the labels is anticipated to eliminate such use of the relevant antimicrobials whereas other claims which are considered prudent and necessary for animal health would remain.”

Translation (after making a lot of calls to veterinarians and others outside of government): this change is unlikely to substantially reduce the amount of antibiotics used in food animals, according to people who will be involved in implementing these changes.

“We’re not going to achieve anything if we stop at the growth promotion discussion,” says Dr. Greg Douglas, Ontario’s chief veterinarian.

“In other jurisdictions, they’ve found that, the drugs are not used for growth promotion, wink, wink, they’re used for disease prevention.”

Nanoparticles: a new bug killer?

The use and overuse of antibiotics have, according to The Economist, led to bacteria evolving resistance to many medications. Dealing with multi drug-resistant strains of Staphylococcus aureus (which causes MRSA infections) and Escherichia coli (linked to food poisoning) requires complex and costly care. The emergence of totally drug-resistant tuberculosis threatens a return to a time before antibiotics, when many life-threatening conditions were largely untreatable.

fda-antibiotics-agricultureNanotechnology could be one way of avoiding, or at least postponing, such a nightmare. Many nanoparticles, which are substances smaller than 100 nanometres (billionths of a metre) have antimicrobial properties, disrupting bacteria and either preventing them from spreading or killing them outright. Silver nanoparticles, in particular, interfere with bacterial replication and the tiniest specks physically abrade and disrupt membrane walls. The most powerful nano-attacks, however, appear to involve reactive oxygen species (ROS). These chemically active molecules are the shock troops of the biological world, rampaging through DNA, oxidising enzymes and damaging many of the cells and proteins essential for life.

The problem is that the mechanisms that allow nanoparticles to kill bacteria pose a risk to the very people they are intended to protect. Inhaled nanoparticles of metal oxides or silver can persist in the lungs and migrate to the kidneys, liver and brain with toxic effects. And ROS have been linked to genetic damage, heart problems and Alzheimer’s disease.

Now Philip Demokritou and Georgios Pyrgiotakis at the Centre for Nanotechnology and Nanotoxicology at the Harvard School of Public Health have come up with a way of creating safer nanoparticles, literally from thin air, using a process called electrospraying. A cooling element chills a tiny needle to condense a minuscule drop of water vapour from the atmosphere. Applying a high voltage to the needle then explodes the drop into a spray of droplets, each just 25 nanometres in size, containing water and ROS.