Journalist and Author
On the heels of the news of totally drug-resistant (TDR) TB being identified in India — and disavowed, unfortunately, by the Indian government — the World Health Organization has released an update on the background situation of drug-resistant TB around the world.
The news is not good. Drug-resistant TB is at the highest rates ever recorded.
In the United States, it’s been “Get Smart About Antibiotics” Week this past week, an annual observance in which the Centers for Disease Control and Prevention and its medical and public health partners try to raise awareness of antibiotic resistance. The real action this week though was in Europe, where individual researchers and the EU’s version of a CDC — the European Centre for Disease Prevention and Control — are speaking out about the problem with unusual candor.
Here’s the short version: In Europe, according to the ECDC, 25,000 people each year die as a result of multi-drug resistant infections, causing an additional cost to society of 1.5 billion Euros ($2.02 billion): 938 million Euros ($1.27 billion) in hospital and outpatient medical costs, and an additional 596.3 million Euros ($806 million) in lost productivity.
Dr. Marc Sprenger, director of the ECDC, said Friday:
This certainly is an underestimate of the true economic impact of antimicrobial resistance. In particular, the figures were based on data for just five multidrug-resistant bacteria.The estimate was also based on a conservative figure for the cost of a day in hospital… We think the real cost of treating a patient with a multidrug-resistant infection would be higher than this. My take home message is that antimicrobial resistance is one of the most serious public health challenges that we face.
A quick post, because I’m on a ferocious deadline, but still can’t let this news go by. In a vote that’s non-binding but high profile and influential, the European Parliament has resolved to end “prophylactic use” of antibiotics in farming, and to prevent any “last resort” antibiotics from being used in animals, in order to keep resistance from developing so that the drugs will still be effective in human medicine.
This is a significant development. The European Union has already banned “growth promotion,” the use of micro-doses of antibiotics that cause meat animals to fatten more quickly. What the Parliament is doing here is asking the European Commission, the EU’s law-making body, to add “disease prevention” use to the ban. That’s the delivery of treatment-strength doses of antibiotics to all animals on a farm in order to prevent their becoming ill as a result of the confinement conditions in which they are held. It accounts for a substantial portion of the antibiotics used in agriculture, and is a major driver of the emergence of antibiotic-resistant organisms.
It’s very odd sometimes watching how the same issues play out in different parts of the world. The French environment ministry confidently ascribes the growth of seaweed choking its beaches to farm runoff. The European Parliament denounces the establishment of very large-scale “meat factories.” China (China!) enacts a ban on growth-promoting uses of antibiotics in agriculture.
Here in the United States, on the other hand, the government gropes unsuccessfully for a way to put controls on confinement agriculture, despite evidence of its environmental harm, while at the same time those farms grow by an estimated 4,600 hogs and 5,800 broiler chickens per day.
For more of that difference between Europe and the US, look this week to England, where the Health Protection Agency has just rejected the zoning application for a hog farm that was small by US standards, with a plan for only 2,500 sows producing about 20,000 piglets. The HPA said:
… those living up to 150 meters downwind of an intensive swine farming installation could be at risk of adverse human health effects associated with exposure to multi-drug resistant organisms. (this .pdf, p.30 of 44)
Well, wow. National legislators stand up to oppose the use of tax revenues to subsidize large-scale confinement pig farms out of concern for food safety and antibiotic resistance, declaring that they are “going to war in defense of pigs.”
In Europe, though.
At the European Parliament today, three national representatives — Janusz Wojciechowski of Poland, José Bové of France and Dan Jørgensen of Denmark — declared their opposition to industrial-scale swine agriculture, positioning themselves for a fight over the European Union’s Common Agriculture Policy, which is up for revision this summer.
Jørgensen represents the country that has done the most to place controls on agricultural antibiotic use; Bové is a farmer and political organizer who famously destroyed a McDonald’s by driving a tractor through it; and Wojciechowski is the son of pig farmers who wrote on his blog today:
Chcemy poruszyć sumienia posłów i doprowadzic do likwidacji tego typu “fabryk miesa” w Unii Europejskiej, no czywiscie takze w Polsce, gdzie takich fabryk jest juz ponad sto.
Chcemy doprorowadzic do tego, aby wielkie fermy nie były wspierane środkami europejskimi, aby wstrzymać lokalizacje nowych obiektów, po czym stopniowo likwidować te, które już istnieją.
Chcemy, żeby na miejsce fabryk miesa powróciła normalna hodowla świń.
We want to move the conscience of members and lead to the liquidation of this type of “meat factories” in the European Union, also in Poland, where such plants are already over a hundred.
We want to ensure that large farms are not supported by the European funds to stop the locations of new facilities, then gradually eliminate those that already exist.
We want “meat factories” returned to normal breeding of pigs. (via GoogleTranslate)
As I’ve written before (long archive here and here),the MRSA strain ST398 arose on Dutch pig farms in 2004, among pigs that had been given prophylactic doses of antibiotics, especially tetracycline. It has since spread through the EU, Canada and the United States, affecting not only farm workers and veterinarians, but also hospital patients with no connection to agriculture.
(Self-promotion alert: This may be a good time to tell you that my book SUPERBUG: The Fatal Menace of MRSA, which tells the full story of the emergence and spread of ST398, has just been released in paperback.)
In advance, this morning the trade paper Farming UK wrote this about the planned European Parliament announcements:
(Members of the European Parliament) will hear evidence that European taxpayers’ money is being used by the European Bank for Reconstruction and Development, together with Common Agriculture Policy payments, to subsidise industrial pig farming even though there is increasing concern over the impact on human health. With a vote this summer over reforms to the Common Agricultural Policy, MEPs will come together to take a stance against the crisis in agriculture with critically low prices for pork, poor labelling, and widespread disregard for animal welfare laws.
MEPs and NGOs will condemn the overuse of antibiotics in factory farms which has led to the emergence of antibiotic-resistant bacteria such as MRSA and ESBL E. coli. A recent report by the Dutch Food Standards Agency estimated that one third to one half of all antibiotic resistance in human diseases in the Netherlands derives from farm antibiotic use. American scientists recently found that flies and cockroaches from intensive pig farms carry bacteria resistant to the same antibiotics routinely used in pig farming, and warned that the insects were likely to be able to spread the disease from the farms to local people.
The event was co-organized by Tracy Worcester, who is both a British aristocrat and director of a documentary, Pig Business, that has not yet been shown in the US. Here’s its trailer:
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In both medicine and agriculture, Europe has been ahead of the US in addressing concerns about antibiotic resistance. This morning’s announcements are yet more evidence of just how far ahead they are.
Odd but interesting fact: Scandinavia takes antibiotic resistance incredibly seriously. Denmark has one of the most thorough programs for preventing antibiotic misuse in agriculture; Norway has very tough regulations regarding antibiotic stewardship in hospitals (as captured in this AP story last year). Sweden has pressed the issue as well; drug resistance was a major issue for the Swedish Presidency of the European Union in the last half of 2009 and led to a major conference there on creating incentives to bring antibiotic manufacturers back into the market.
The presidency has since been relinquished to more southern countries (Spain in the first half of this year and now Belgium) but the Swedish focus on resistance persists, pushed along by the nonprofit organization ReAct, based at Uppsala University. Earlier this week, ReAct hosted a three-day international conference on antibiotic resistance in Uppsala. They haven’t posted the full conference report yet, but they have come out with a closing press release, which says some interesting things (emphases mine):
At a historic three day conference at Uppsala University, Sweden,
190 delegates representing 45 countries and many leading stake holders – civil society, academia, industry, governments, authorities, supranational organizations – agreed on Wednesday to turn a new page and move towards concerted action on antibiotic resistance…
The new signals from the Uppsala meeting include:
– A shared conviction that antibiotic resistance is a universal problem.
Like global warming, it requires joint action, not least by governmental alliances.
– A clear signal from the pharmaceutical industry that
return of investment on research and development of new antibiotics and diagnostic tools will have to be de-linked from market sales in order to boost necessary innovation while yet limiting the use of antibiotics. This requires a new business model where private and public sectors cooperate.
– A strong recommendation to all stakeholders to
speed up the efforts to limit unnecessary use of antibiotics, while at the same time making the medicines affordable and accessible in developing countries.
– A commitment to
improve the monitoring of antibiotic resistance across the world, through shared data and increased efforts. A global network of surveillance will require common methods, and is crucial for both prudent use and needs driven development of new agents.
The release also mentions some promising events coming next year:
– A final report from TATFAR, The Transatlantic Task Force on Antibiotic Resistance.
– A policy meeting on antibiotic resistance in Delhi, India.
– A WHO Action Plan on Antibiotic Resistance.
– A number of regional initiatives, including in Southeast Asia, Africa and The Middle East.
(Hmm. Surely it is time for me to go back to India…)
People who’ve worked in this field for a long time will know, of course, that up-front commitments are easy to make; it’s downstream action, carried out over the long term, that makes a difference. But this looks like a promising start: Even just stimulating international recognition of the program is an encouraging beginning.
Until the final conference report is posted, you can see video of the opening and final sessions here.
Folks, I told you Tuesday about a Congressional hearing on antibiotic resistance, featuring NIAID Director Dr. Anthony Fauci and CDC Director Dr. Thomas Frieden. Not much new was said, but it’s encouraging that the hearing was held at all. (Fauci testimony here, Frieden here.)
Coincidentally, constant reader Pat Gardiner of the UK alerted me to a gathering being held on the same day in Ireland, by the quasi-government agency SafeFood—which reports to the North-South Ministerial Council of Ireland, which deals with whole-island issues under the Good Friday agreement, which is more about the Irish political structure than you probably ever wanted to know.
The conference was titled Antimicrobial resistance and food safety and featured government officials and academic researchers from across Ireland. Here’s the agenda, and here’s the press release with the names of key speakers. Even more important, here are links to a report on antibiotic resistance in food that Safefood released in advance of this conference: executive summary and whole thing. I especially recommend from p.25 in the big report for an accessible discussion of the connections between ag antibiotic use and human health. Key quote among many:
The majority of the evidence acquired through outbreak and epidemiological investigations of sporadic infections, field studies, case reports, ecological and temporal associations and molecular sub-typing studies support the causal link between the use of antimicrobial agents in food animals and human illness. A few papers have questioned this but these have not survived detailed scrutiny.
It’s refreshing to see a government body engage seriously with this emerging issue, which we’ve been talking about for, well, years now, on this blog (sometime this month we passed our 3-year anniversary). I wish, wistfully, that the government doing the discussing was ours.
This is a little outside our usual subject matter, but:
What looks like a marvelous new documentary exploring environmental damage and human illness from pesticides and other farming chemicals is coming out in France, but needs assistance to get onto the international festival circuit. It’s called Nos enfants nous accuseront (Our Children Will Hold Us Responsible), and among other things, looks at the efforts of a French village to make all the food served in its schools organic — which, even in food-centric France, is much harder than it sounds.
You can view the trailer here. The more clicks, the more the film will be taken to have support, and the higher its rankings will go for festival consideration.
It comes well-recommended by friends of mine in Paris, so I hope you’ll take a look.
From the January issue of Emerging Infectious Diseases, published by the CDC (and therefore free. Must I keep urging you to read it? Go, already), here’s a roundup of bad news about bad bugs.
In Canada, researchers from that country’s Public Health Agency have found a “strong correlation” between the use of ceftiofur, a third-generation cephalosporin, in chickens; the rates of a resistant strain of Salmonella in chickens; and the appearance of that same strain in humans. The strain is Salmonella enterica serovar Heidelberg, one of the most common salmonella strains in North America, and one which can be nasty: It may cause mild illness, but also causes septicemia and myocarditis and can kill. Quebec created an unplanned natural experiment: Hatcheries there were broadly using ceftiofur until 2004, backed off from its use in 2005 and 2006, and then began using it again in 2007 in response to a growing problem with a particular infection. When the drug was withdrawn, resistant infections in birds and humans plunged; when it was reintroduced, they rose again. (Look at the black and red lines in the graph above left.)
Meanwhile, broiler chickens in Iceland are passing fluoroquinolone-resistant E. coli to humans there. Researchers at the University of Iceland were puzzled by an earlier finding that bacteria resistant to fluoroquinolones (a family that includes the human drug Cipro) were increasing among chickens raised in Iceland, despite strict controls on antibiotic use in food animals and stringent disinfection in chicken batteries after cohorts of birds were sold for slaughter and removed. They have two findings: The source of the resistant bacteria in the birds appears to be feed contaminated with resistant E. coli; and resistant bacteria in Iceland residents are microbiologically indistinguishable from those in the birds. Because E. coli is a very diverse organism, the very close resemblance between the isolates from chickens and the isolates from humans pins chickens as the likely source.
And just to make clear we’re not blaming every microbiological evil on farming: Seagulls in Portugal have been found carrying multi-drug resistant E. coli in their feces. The public health concern here is obvious: Just think back to the last time you were at a beach, or anywhere else seagulls frequent, and envision a seagull perch — and the masses of seagull droppings streaking it. Now imagine those droppings transmitting antibiotic-resistant E. coli into the surrounding environment: the boardwalk, the beach, the towels… Additional problem: Seagulls are migratory birds, so the resistant bacteria easily cross borders and oceans.
We’ve talked before about the shrinking number of drugs available to treat MRSA and about the challenges of getting new drugs to market. Well, it’s not just a problem in the United States.
A new report from the European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMEA) — that’s the CDC and the FDA of the European Union — analyzes the bench-to-market “pipeline” of new drug development in the EU and finds… not good news. Out of 167 antibacterial agents that are somewhere in the pipeline of development, only 15 look likely to improve treatment of resistant organisms over drugs that already exist — and 10 of those 15 are in early-stage trials and will not come to market anytime soon.
That leaves 5 potential new drugs, for an epidemic of antibiotic resistance that, just in the EU, causes 25,000 deaths and $1.5 billion Euros ($2.27 billion) in extra healthcare spending each year.
(Within that epidemic of resistance, by the way, the single most common organism is MRSA.)
It’s worth understanding how the agencies conducted their analysis. When we look for new drugs to treat resistant organisms, we ideally need several things:
Here’s what the EU pipeline looks like:
If you’re wondering whether you should be depressed, the answer is Yes.
… it is unclear if any of these identified agents will ever reach the market, and if they do, they may be indicated for use in a very limited range of infections.
The agencies call for a concerted government effort to turn this around, and ask for quick action because it takes years to get drugs through the pipeline:
…a European and global strategy to address this serious problem is urgently needed, and measures that spur new antibacterial drug development need to be put in place.
This echoes a call that has already been made in this country by the Infectious Diseases Society of America, which has asked for changes in incentives to drug-makers, and has backed what’s known as the STAAR Act (STrategies to Address Antimicrobial Resistance). With this latest EU report — which comes on the heels of a US-ER agreement to work cooperatively on resistance — the IDSA is asking for an international commitment to bringing forth 10 new drugs in 10 years, what they are calling 10 x ’20.
It’s not very likely that people will be eating much pork today — OK, maybe some pancetta in the Brussels sprouts — and that’s good, because there’s lots of news today about MRSA in pigs.
(In fact, there’s a ton of news just this week. Make it stop.)
The European Food Safety Authority has published a long-awaited, European Union-wide survey looking for the presence of MRSA in pigs. Here’s the key points: Investigators found MRSA on 1 out of 4 farms where pigs were being raised and in 17 of the 24 EU states. (Two non-member states were included in the analysis.)
Strictly speaking, this is not a survey of MRSA in pigs; the study samples not the pigs themselves, but the dust in pig-raising sheds. The sites were 1,421 breeding farms and 3,176 farms where pig are raised to slaughter age. By far the most common strain was MRSA ST398, though other strains were detected, including some known human strains. The prevalence in various countries went from a low of 0 to as high as 46% of farms. (Highest, in descending order: Spain, Germany, Belgium, Italy, Portugal. The Netherlands, where St398 was first identified, had a prevalence of 12.8%. Countries reporting no MRSA: Bulgaria, Cyprus, Denmark, Estonia, Finland, Hungary, Ireland, Latvia. Lithuania, Luxembourg, Sweden, the United Kingdom, Norway and Switzerland.)
The report closes by recommending comprehensive monitoring of pigs for MRSA, as well as monitoring of poultry and cattle.
About the potential of ST398 crossing to humans, it has this to say:
In humans, colonisation with MRSA ST398 originating from pigs has been identified as an occupational health risk for farmers and veterinarians and their families. Although MRSA ST398 represents only a small proportion of the total number of reports of human MRSA infections in the EU… in some countries with a low prevalence of human MRSA infection, CC398 is a major contributor to the overall MRSA burden.
In most cases, colonisation with MRSA ST398 in humans is not associated with disease, although clinical cases associated with MRSA ST398 have been reported. MRSA ST398 can be introduced into hospitals via colonised farmers and other persons in a region with intensive pig farming. Therefore, MRSA ST398 may add substantially to the MRSA introduced in health care settings. However, it seems that the capacity for dissemination in humans (patient-to-patient transmission) of livestock-origin MRSA, in particular ST398, is lower as compared to hospital-associated MRSA).
… Food may be contaminated by MRSA (including ST398), however there is currently no evidence for increased risk of human colonisation or infection following contact or consumption of food contaminated by ST398 both in the community and in hospital.
Britain’s Soil Association, which pressed for the study to be done, has released a statement quoting the food safety agency warning that the testing method may have underestimated MRSA’s presence on farms, and warning that if ST398 is not yet in England, it is certainly soon to arrive. Germany’s Federal Institute for Risk Assessment also released a statement, admitting that ST398 in German pig stocks is “widespread.”
The report is here, executive summary here, and press release here. All well worth reading.
UK and EU readers can hug themselves with self-congratulation this morning (OK, admittedly, for you it’s afternoon already): It’s Antibiotic Awareness Day across the European Union, featuring a slate of public-awareness activities, public-service announcements, educational efforts, and random appearances by the charming little hedgehog above (kicking antibiotics, don’t you see). It’s all meant to convince people that antibiotics are a precious resource and that misusing them encourages antibiotic resistance.
The campaign is organized by the European Centre for Disease Prevention and Control (the EU equivalent of the US CDC) and is being carried out by an enviably long list of national agencies within the EU. It’s accompanied by the publication in the journal Eurosurveillance of an article setting out the challenges of controlling antibiotic resistance across such diverse nationalities and geographies.
There are materials on the site that would be useful for anyone attempting to get the message of antibiotic stewardship across to physicians, family members or friends: There’s a fact sheet for the general public, one for physicians and other experts, and one that specifically addresses the temptation to take antibiotics in cases of H1N1 flu.
There’s also a short film explaining the genesis of Antibiotic Awareness Day and the basics of antibiotic resistance, and a marvelous set of pull-no-punches short video spots. This one — comparing antibiotics to a lightbulb slowly burning out — is my favorite.
Constant readers, we’ve often talked about MRSA and other resistant pathogens as a global problem (cf. these posts for resistance issues in Europe and these for resistance around the world).
But now there has been formal recognition that resistant bacteria respect no borders. On Nov. 3, the US government and the European Union signed an agreement to form a joint task force to investigate and combat antibiotic resistance. From the Joint Declaration, posted on WhiteHouse.gov:
[We therefore agree}… To establish a transatlantic task force on urgent antimicrobial resistance issues focused on appropriate therapeutic use of antimicrobial drugs in the medical and veterinary communities, prevention of both healthcare- and community-associated drug-resistant infections, and strategies for improving the pipeline of new antimicrobial drugs, which could be better addressed by intensified cooperation between us.
You may not have heard much about it here, but in Europe, this declaration was big news. Here’s a story from the Swedish newspaper Arbetarbladet (Sweden currently holds the EU Presidency) and another from the Irish Times. But while it merited barely a blink in the US mainstream media, US nonprofits were deeply involved in the declaration, notably the Infectious Diseases Society of America and the Pew Charitable Trusts:
“Antimicrobial resistance and the lack of new antimicrobial agents to effectively treat resistant infections are problems that no country can deal with alone — they threaten the very foundation of medical care,” said Richard Whitley, MD, FIDSA, president of the Infectious Diseases Society of America (IDSA). “Without effective antimicrobial drugs, modern medical treatments such as operations, transplants, intensive care, cancer treatment and care of premature babies will become very risky if not impossible.” Dr. Whitley joined with Javier Garau, MD, president of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Shelley A. Hearne, managing director of the Pew Health Group in welcoming the multi-country initiative.
…”Antibiotic resistant bacteria respect no political borders, so we must work together to combat them,” Dr. Hearne said. “Resistance takes a terrible toll on health worldwide and is measured in lives lost, greater suffering and higher health care costs. One way that U.S. leaders can demonstrate their commitment to solving this issue is by immediately joining the EU in banning non-judicious antibiotic uses in food animal production.” (Pew press release)
This fresh focus on the problem of resistance will be sharpened in Europe this week with the celebration of European Antibiotic Awareness Day. (We should be so lucky.) More on that on Wednesday.
Well, constant readers, didn’t expect to be gone *that* long. Many apologies. There was a good reason — actually, several: I attended a journalism meeting, and spoke at a second meeting. But most important, I received, marked up, and returned the galleys of SUPERBUG. Yes, it’s really starting to look like a book now. There will be things to share, soon.
Meanwhile, I’ll try to roll out some of the many, many pieces of news and research related to staph that have emerged in the past few weeks. Today: News on animals, and our old opponent, MRSA ST398.
First: A team from the Universidad de La Rioja reports in the Journal of Antimicrobial Chemistry the first finding of MRSA ST398 (“pig MRSA,” archive here) in food in Spain. They tested 318 raw meat and wild-game samples (chicken, pork, veal, lamb, turkey, rabbit, game bird, wild boar, deer, hare) and found ST398 and other MRSA strains in 5 of them, an incidence of 1.6%. The authors write: “Although MRSA prevalence in raw food is low, the risk of its transmission through the food chain cannot be disregarded.”
Importantly, one of the other strains found in the meat of these animals is an uncommon variant, ST125-t067, that has already been implicated in large numbers of hospital infections in Spainand is resistant to ciprofloxacin (Cipro), erythromycin and a third antibiotic, tobramycin, in addition to the usual suspects. The other non-ST398 strain is ST217, which is a variant of a long-known hospital strain, and is also resistant to Cipro, a very valuable drug for skin and soft-tissue infections. So it appears the contamination may cross both ways, from animals, and to animals as well.
No link, but the cite is: Lozano, Carmen, et al. Detection of methicillin-resistant Staphylococcus aureus ST398 n food samples of animal origin in Spain. Journal of Antimicrobial Chemistry. e-pub Oct. 21 2009 AOP doi:10.1093/jac/dkp378
Next: If the prevalence of ST398 is so low in food, why do we care? We care because of where those organisms go next — into hospitals, among other places. A Dutch/German team that includes the original identifier of ST398 in humans are reporting that they have found an association between the density of pig-farming in parts of Germany and the probability that patients admitted to hospitals will be carrying ST398 with them, creating a possible source for nosocomial infections. R. Kock and colleagues screened 1,600 pigs on 40 German farms, and also reviewed screening results for every MRSA-positive patient admitted to the University Hospital-Munster from 2005 through 2008. They found ST398 on 70% of the farms, and also found that ST398 represented 15% of the MRSA isolates at the hospital in 2005, rising to 22.4% in 2008. The key association: The patients carrying St398 were more likely to have contact with pigs in their daily lives, and also with cattle, than patients who had other forms of MRSA or no MRSA at all.
The cite for that paper: Kock, R. et al. Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German farms and import of livestock-related MRSA into hospitals. European Journal of Clinical Microbiology and Infectious Diseases, e-pub Aug 25, 2009. DOI 10.1007/s10096-009-0795-4
And finally: How do you stop the evolution and spread of antibiotic-resistant organisms in livestock? One good way is to stop giving teh livestock antibiotics in the first place. In a column at the Huffington Post, Laura Rogers, project director of the Pew Campaign on Human Health and Industrial Farming, takes on the oft-repeated assertion that you can’t farm without them without risking the lives and market place of your livestock, and offers the example of Denmark, which did ban antibiotics in animals, and which has healthier, more profitable livestock as a result:
American agribusiness often has criticized Denmark’s 1998 ban on antibiotics, calling it an outright failure. But compelling new research presented by a Danish scientist earlier this year showed the opposite, revealing that antibiotic use on industrial farms has dropped by half while productivity has increased by 47 percent since 1992. Danish swine production has increased from 18.4 million in 1992 to 27.1 million in 2008. A decrease in antibiotic-resistant bacteria in food animals and meat has followed the reduced use of these vital drugs.
Let’s go back for a moment to what I think of as the “third epidemic” of MRSA: ST398 and the other strains that reside in animals and cross to humans. (In my personal taxonomy, the first and second epidemics are hospital-acquired and community-associated.)
Via Emerging Infectious Diseases, the open-access journal published by the CDC (Do I have to keep telling you to read it? It’s free. It’s good. Your tax dollars pay for it.), comes a report of surveillance for MRSA colonization of pig-farm workers, conducted in Belgium by researchers from Erasmus Hospital of the Free University of Brussels, and the Veterinary and Agrochemical Research Centre of Brussels. The group persuaded 127 farm workers on 49 farms to be tested for colonization, or asymptomatic carriage, of MRSA; at the same time, they tested 30 randomly selected pigs on each farm.
They found very high rates of colonization, higher than have been found in patients in hospitals or residents of nursing homes: 38% of the farm workers carried MRSA ST398, the pig strain (plus, an additional 17% carried various strains of MSSA, drug-susceptible staph). There was a clear association between colonized farmers and colonized pigs: Out of 1500 pigs sampled, 44% carried ST398 — and half of the workers on farms with colonized pigs were colonized also, compared to only 3% of workers on farms where pigs did not carry the bug.
In a bit of good news, the researchers found only one farm worker who had suffered any MRSA disease from ST398, a man with a lesion on his hand. There was no invasive disease, though ST398 has been associated in the past with pneumonia and endocarditis.
Workers were more likely to acquire the bug if they had regular contact with pigs, dogs or horses, which makes intuitive sense. But in an odd finding, their odds of acquiring ST398 did not go down if they wore protective clothing — which is to say, aprons, gloves and masks did not protect them from picking up the bug, leading the researchers to wonder whether airborne spread or contaminated surfaces are playing a role in transmission.
So what does this mean? The lack of invasive disease in this population must be good news; and it’s consistent with a number of papers that have reported low rates of disease from ST398 even when colonization is present. But to me, the high rate of colonization must be bad news. The more of this bug there is (and every researcher who looks for it seems to find it), the more chance there is of the bug adapting in an unpredictable — potentialy more resistant, potentially more virulent — way. If that did happen, it could well go undetected for a while — because as swine flu has been teaching us, disease surveillance in animals is patchy at best, and new pathogens can and do arise and ciruclate for years before being detected.
For more on the paucity of surveillance in animals, see my CIDRAP colleague Lisa Schnirring’s story here. For a complete archive of posts on “pig MRSA” ST398, go here.
The cite is: Denis O, Suetens C, Hallin M, Catry B, Ramboer I, Dispas M, et al. Methicillin-resistant Staphylococcus aureus ST398 in swine farm personnel, Belgium. Emerg Infect Dis. 2009 Jul; [Epub ahead of print] DOI: 10.3201/eid1507.080652.
Thanks to constant reader Pat Gardiner, we have the transcript of the UK House of Lords discussion on community MRSA, called there PVL-MRSA after the toxin. (Go to the linked page, and click down to the time-mark 3.16 pm.) It’s encouraging to see some members of a government taking MRSA seriously. The members are asking for
Hear, hear to Baroness Masham of Ilton for bringing it up.
To get to that discussion, though, you’ll have to click down through some silliness (the ghost of Monty Python is never far from the British government, is it?): a discussion at time-stamp 3.07 p.m. of whether a House of Lords restaurant can afford to serve British bacon, rather than Dutch bacon, given that British bacon is almost twice as expensive and Dutch pigs are associated with MRSA ST398:
Lord Hoyle: My Lords, I thank the noble Lord for that reply, although there is more than a whiff of hypocrisy about it. After all, I and many others on all sides of the House have argued that it should not be a matter of price. We have urged the British consumer to buy British bacon because of the higher welfare standards that are applied in this country. Will the noble Lord also take into account the presence in Dutch bacon of a deadly form of MRSA, ST398, which can cause skin infection, heart trouble and pneumonia? Is he not putting people in this country at risk, particularly as the strain has passed from animals to humans? Indeed, when Dutch farmers go into hospital, they go into isolation. Why is he putting the British consumer and those who buy bacon in this House at risk in this way?
The discussion quickly devolves into foolishness about British Tomato Week — but if you read carefully, you’ll see that behind the silliness, there are serious issues at stake: animal welfare, farming standards, truth in labeling (the Lord Bishop of Exeter advances the very newsworthy claim that pork imported from other countries is subsequently labeled “British” only because it is packaged in the UK) and movement of zoonotic pathogens across national borders thanks to globalized trade.
Sadly, the leader of the discussion — the Chairman of Committees, AKA Lord Brabazon of Tara (no, really) — appears not to have been keeping up with the news, since he notes of ST398:
As far as MRSA is concerned, I read the article in, I think, the Daily Express a couple of weeks ago. I do not think that it has been followed up by anybody else.
Apparently the Lord’s staff have not been keeping up, since MRSA in pigs in the EU has been covered by the Daily Mail, the Independent, comprehensively by the Soil Association, and by, ahem, us.
Swine flu continues to dominate the headlines, but other pathogens don’t read the papers. Case in point: New news about a US community strain being found and treated in a woman in Italy — better treated, as it turns out, than she was in California, where she was infected.
In a new letter in Emerging Infectious Diseases (a free journal published online and in print by the CDC — it’s your tax dollars at work, just read it, already), Carla Vignaroli, Pietro E. Varaldo, and Alessandro Camporese of the Polytechnic University of Marche in Ancona amd the Santa Maria degli Angeli Regional Hospital, Pordenone report the case of
a 36-year-old Italian woman (who) was seen at Pordenone Hospital (northeastern Italy) for spider-bite–like skin lesions on the face, characterized by rapid evolution to furuncles and small abscesses. The infection had started ≈1 month earlier in California, where she had spent several months on business (wine import-export), and where she had been treated empirically with amoxicillin/clavulanate for 10 days (1 g, 3×/day), with no clinical improvement.
(At this point, I know every clinician reader and everyone who has had a MRSA skin infection is shaking his or her head. Surely by now the knowledge that “spider bite” is practically diagnostic for CA-MRSA has penetrated? But apparently not, since she was given amoxicillin/clavanulate, AKA Augmentin, which is partially penicillin-based.)
When the woman’s lesions were cultured, they turned out to be caused by USA400, the original community strain, which back in the 1990s was known as MW2. That’s interesting, especially in California, since USA300 has become such a dominant strain. Nevertheless, the key point is that USA400, as with USA300, has barely been recorded in Italy:
All 3 previously reported cases of CA-MRSA infection in Italy were caused by type IV SCCmec, PVL-positive strains, none of which, however, belonged to the ST80 clonal lineage that predominates in Europe (7). The first case (in 2005) was a necrotizing pneumonia caused by an ST30 isolate; the 2 other cases (2006) were severe invasive sepsis and a neck abscess, both caused by ST8 (USA300) isolates.
The concern, of course, is that once imported, they will not remain rare:
The case we note here documents the importation of a US pathogen into a country in Europe, from an area where the pathogen is widespread and has been highly virulent since the late 1990s, to an area where its penetration in the past has been poor.
The cite is: Vignaroli C, Varaldo PE, Camporese A. Methicillin-resistant Staphylococcus aureus USA400 clone, Italy [letter]. Emerg Infect Dis. 2009 Jun; [Epub ahead of print]. DOI: 10.3201/eid1506.081632
There’s a letter in the upcoming issue of Emerging Infectious Diseases (hat tip Pat Gardiner) alerting the medical community that “pig MRSA” ST398 has been found in Italy, adding t the steadily enlarging list of countries where this strain has been identified.
(NB: Because most of these surveys are one-offs, we don’t yet know whether ST398 is truly expanding its range, or has always been there, but no one looked until now.)
Angelo Pan and colleagues of the Cremona Hospital and other institutions report that a pig-farm worker was discovered to have a severe pyomyositis (abscess buried in muscle):
The case-patient was a 58-year-old man admitted to a surgical department in Cremona, Italy, on July 30, 2007, because of a 1-week history of fever and intense pain in his right buttock. He worked on a pig farm, was obese, consumed high volumes of wine (1.5 L/day), was taking medication for hypertension, and had not had recent (Based on clinical and magnetic resonance imaging data, the diagnosis was cellulitis, pyomyositis, and pelvic multiloculated abscess of the buttock. A needle aspiration of the abscess, guided by computed tomography, was performed. Because of persistent fever (38.5°C), oral ciprofloxacin was added to the patient’s treatment regimen on day 3. Blood and abscess cultures yielded MRSA that was sensitive to glycopeptides, rifampin, linezolid, gentamicin, and mupirocin and resistant to co-trimoxazole, macrolides, clindamycin, and fluoroquinolones. After treatment was switched to vancomycin plus rifampin, the patient’s general condition improved; he was discharged from the hospital after 24 days.
An investigation was launched, and the results were intriguing:
Two fellow workers were colonized with S. aureus, 1 with methicillin-sensitive S. aureus (MSSA) and the other with MRSA. The pig farm, a farrow-to-finish production farm with 3,500 pigs, was screened for MRSA … Dust swabs were taken from 5 areas of the farm; 7 MRSA isolates were detected.
The isolate from the patient belonged to spa type t899, was ST398, carried an SCCmec type IVa cassette, and was PVL negative. The isolate from the MRSA-colonized worker was a t108 strain carrying SCCmec type V. The isolate from the MSSA-colonized worker was identified as t899. The dust swabs yielded 7 isolates: 2 belonged to t899 and carried SCCmec IVa; 5 belonged to t108 and carryied SCCmec V. The isolates obtained from the patient, farrowing area 7, and gestation area 1 were indistinguishable (i.e., same spa type, SCCmec type, and ST profile; Table), thus confirming the animal origin of transmission.
So, we have:
None of these are good news.
The authors very sensibly call for more public-health attention to this strain, which — we have contended before — is long overdue:
…attention should be given to the emergence of MRSA strains among animals, and continuous surveillance in humans should monitor the extent of disease from MRSA ST398, especially in areas of intensive animal farming. Collaboration between infectious disease specialists, microbiologists, and epidemiologists, on both the human and the veterinary sides, should be strengthened and readied for appropriate action whenever complex, zoonotic, public health issues occur.
The cite is: Pan A, Battisti A, Zoncada A, Bernieri F, Boldini M, Franco A, et al. Community-acquired methicillin-resistant Staphylococcus aureus ST398 infection, Italy [letter]. Emerg Infect Dis [serial on the Internet]. 2009 May. DOI: 10.3201/eid1505.081417
One of the challenges of disappearing down the rabbit hole of a gnarly chapter — gee, it’s dark down here — is that I get behind on my RSS feeds, and suddenly every entry in my Google Reader is at 1000+ and it’s all just too daunting.
So, trying to catch up a bit, I found two related, interesting and troubling stories from the Associated Press (4 April) and the online magazine Grist (7 April — yes, I said I was behind…).
Synopsis/synthesis: Corn-based ethanol, former darling of the energy and large-scale agriculture industries, suddenly doesn’t look like such a good idea – and not just because the market for it is crashing. Turns out that ethanol is made by adding yeast and sugar to corn mash; the yeast convert the carbohydrates to the alcohol that is the basis of the fuel. (Yes, just like making beer.) However, the mash is particularly attractive to Lactobacillus and other bacteria that produce lactic acid as a waste product rather than alcohol, and a tank full of lactic acid doesn’t make very good fuel. So, to keep the bacteria under control, ethanol producers add antibiotics. Specifically, penicillin and erythromycin — you’ll recognize those — and tylosin and virginiamycin, two macrolides, related to erythromycin, that are approved in the US for veterinary use.
Now, the problem with this practice, as you might predict, is that if the mash is not appropriately dosed, the presence of antibiotics within it can prompt some of the bacteria to develop resistance. (Here’s an article from the trade magazine Ethanol Producer discussing just that possibility.)
And the further complication of this is that the leftover mash, now called “distillers’ grains,” is sold as animal feed. Ask yourself: Where in animal production are animals most likely to eat grains? Answer: At finishing, in feedlots. In other words, fermented grains that may contain antibiotic residue, and may contain resistant bacteria, are being sold as feed to animals that are already being raised in conditions that have been shown to foster the development of resistant bacteria through subtherapeutic and prophylactic antibiotic use. In fact, some research has drawn an explicit link: Kansas State University scientists have found higher levels of E. coli O157 in the guts of cattle that were fed distillers’ grains.
All of this was new to me, but there’s an additional facet to the story that the AP and Grist pieces don’t highlight, and that just makes my head hurt: the use of virginiamycin. For those new to the story, virginiamycin is an allowed, widely used veterinary antibiotic in the US. However, it is not used in the European Union: It was banned there in 1998 because the EU’s ag authorities believed that it promoted resistance to the drug Synercid (quinupristin+dalfopristin), which is a drug of last resort against vancomycin-resistant bacteria such as VRE. (Here’s a Lancet paper that talks about that resistance mechanism.) Synercid was approved by the FDA in 1999 — two years after Synercid resistance had already been found in the US. (For a long but cogent explanation of the complex story of virginiamycin, see the book The Killers Within.)
So, just to recap: We have an industry whose long-term earnings are shaky, whose economic survival is partially secured by the sale of its waste product, and which via that waste product is putting antibiotic residues and antibiotic-resistant bacteria into the environment, and is conveying them into food animals, and is making particular use of an antibiotic that other countries have banned because they believe that, via its use in animals, it exerts an adverse impact on human health.
Something to remember the next time ethanol subsidies come up.
A brand-new report, in a letter to the International Journal of Antimicrobial Agents, indicates that ST398 “pig MRSA” has been found in Portugal for the first time.
Constanca Pomba and colleagues from the Technical University of Lisbon swabbed and cultured the noses of pigs and veterinarians on two pig farms in different regions of Portugal, and also checked the air at both farms.
What they found:
Strains from both farms were resistant to tetracycline; this is turning out to be a great marker for these strains having emerged due to antibiotic pressure in animals, because tetracycline is very commonly used in pigs. but not much used for MRSA in humans. The strains have the genes tetK and tetM, so they are resistant not just to tetracycline itself, but to the whole class of tetracyclines including doxycycline and minocycline. The Farm B strains also carried the gene ermC, which encodes resistance to erythromycin.
So what does this tell us?
Of note, the European Union is running a study now that is supposed to report ST398 prevalence at any moment (as they have been saying since 2007). It is not expected to be comprehensive, since it was piggy-backed onto another study, but it is something. The US government has not been so enterprising.
The cite is: Pomba, C. et al. First description of meticillin-resistant Staphylococcus aureus (MRSA) CC30 and CC398 from swine in Portugal. Intl J Antimicrob Agents (2009), doi: 10.1016/j.ijantimicag.2009.02.019
