Maryn McKenna

Journalist and Author

More on NDM-1

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One of the frustrations of being a working journalist and a blogger is that, when a big blog-story breaks, you’re likely already to be working on something else. And so it is, unfortunately, with NDM-1: I’m on a magazine assignment and will be off interviewing people when I should be blogging.

(This s a great time to recommend that, for any breaking infectious disease news, you follow Crof at H5N1 (@crof) and Michael Coston at Avian Flu Diary (@Fla_Medic), who are dedicated, thoughtful, nimble and smart.)

Since I last posted, there’s been lots of additional coverage of the “Indian superbug.” Much of it, blog and media, is just echo chamber cannibalizing of the earliest reports (including but certainly not only mine), but there are some important new developments worth noting, which I’ll list below.

There are also some important points that are getting lost in the echo-chamber bounce: First, it is not correct to say that every person who acquired this was seeking cheap medical care or engaged in medical tourism; a few of them were treated on an emergency basis while traveling, and a few have no apparent healthcare tie. So this is not a situation of people seeking to save money and, as some commenters seem to be suggesting, receiving their karmic payback. (C’mon: Seriously?) Second, it is also not correct to say that every case of this has been linked to a hospital — it’s quite clear in the Lancet ID paper that in South Asia, a number of the cases were community infections. So it is not just a case of hospitals that are dirty or have poor infection control (which by the way is a problem in the US as well, right?); NDM-1 is already a community bug, which will make detection and defense much more complex.

OK, curated list:

First, if you’re interested in more from me, CNBC asked me to write up a piece about NDM-1, which ran Thursday; and Friday morning I was on the WNYC-FM (and nationally syndicated) radio show The Takeaway.

Second, the list of potential victims of NDM-1 is growing. Most of them have survived, so marking their cases is really a way of measuring the resistance factor’s previously undetected spread:

The UK has released a new statement, updating its earlier warning, and says it has found “around 50” cases carrying NDM-1, an update from the Lancet ID paper. (Side note: This statement, and the earlier warnings, came from the UK’s Health Protection Agency. The UK has just announced that it will be shutting down that agency in a cost-cutting measure. Great timing.)

The government of Hong Kong has announced that it has seen one case of NDM-1, but the patient recovered.

Canada has disclosed that it has had two cases, not the one mentioned in the Lancet ID editorial, in two different provinces.

Australia says that it has had three cases scattered across the country.

Belgium has announced one death.

And finally — sadly but probably not surprisingly — India is objecting to the stigma of being characterized as the source of NDM-1. The study’s first author has disassociated himself from the paper and members of the government are claiming a “pharma conspiracy.” Medical tourism has become a significant industry in India, and it is true  some of these reports cast doubt on its safety. But still, I find this reaction disappointing.

Evading the stigma of an emerging disease is not a new impulse: Recall how the government of China suppressed for 6 months the news of the start of the SARS epidemic. They did not stop the epidemic, of course — it eventually sicked more than 8000 people across the globe and killed about 775 — but their suppression of the details of its spread kept other jurisdictions from mounting a defense in time. From my teaching gigs in Hong Kong I can testify how much bitterness endures in Hong Kong over this.

China’s actions in 2002-03 led to the enactment of the new International Health Regulations by the WHO, which specify that, because expanding epidemics take no notice of borders, it is inappropriate for any government to attempt to impede the free flow of information about their spread. India is a signatory to the IHRs.

I am not suggesting that India is attempting any suppression of news about NDM-1 — there’s no evidence of that — but the volatile language being used does concern me. I acknowledge that India is an extremely open society, with degrees of political expression that can sound surprising from this distance. But let’s hope the government takes its commitment to the IHRs as seriously as any signatory should.

News break: CDC alert on imported novel resistance

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This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

There’s a troubling item in this afternoon’s issue of the CDC’s Morbidity and Mortality Weekly Report or MMWR: The first report in the United States of a novel resistance mechanism that renders gram-negative bacteria extremely drug-resistant and that has been linked to medical care carried out in India or Pakistan.

The short item describes three isolates (E. coli, Klebsiella pneumoniae and Enterobacter cloacae) found in three patients in three states between January and June of this year. All three isolates produced New Delhi metallo-beta-lactamase (NDM-1), which has never been recorded in the US before. Because of that novel mechanism, the three isolates were resistant to the carbapenems usually used on the most serious gram-negative infections, in fact to all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams, etc.) except for one monobactam, aztreonam — and they were also resistant to aztreonam through another mechanism that hasn’t been identified yet. All three of the patients found carrying this novel resistance factor had undergone medical care in South Asia recently.

This may be the first finding of this mechanism in the US, but it’s been causing alarm in Europe for at least two years.

The first identification of NDM-1 was in 2008, in a 59-year-old resident of Sweden who was of South Asian origin and had returned to India for several months. The man was not well — he had long-standing type 2 diabetes and had experienced a number of strokes — and while in India he was hospitalized for an abscess, underwent surgery, developed bedsores and was treated for them as well. He returned to Sweden and was hospitalized there in January 2008, where physicians found him to be suffering from a urinary tract infection caused by a Klebsiella strain carrying this never-seen resistance mechanism.

Last July, the UK’s Health Protection Agency put out a national alert about NDM-1, warning that the novel mechanism had gone from never-seen in 2007, to 4 isolates in 2008, to 18 in the first half of 2009. They were not an outbreak, but represented repeated importations: The isolates were clonally diverse and had been collected at 17 different hospitals. They were, instead, a sign that long-standing two-way population movement between England and South Asia — augmented by elective medical tourism (two patients had gone to India for cosmetic surgery) — was bringing the high rates of antibiotic resistance in India back to a UK medical system that is already challenged by serious infection-control problems.

And now it’s here. The special challenge of NDM-1 (which as today’s finding suggests is on a mobile genetic element that has carried the resistance mechanism between species) is not only that it adds to an accumulating rogues’ gallery of resistance factors that are rapidly making gram-negative bacteria ferociously drug-resistant, but also that there are so few drugs under development for gram-negatives that truly untreatable infections are not far off. The UK clearly is already struggling with attempting to use drugs that are old and toxic, untested against these organisms (and therefore with no agreed-upon dosing), or wrong for the organ systems affected:

Treatment presents major challenges. Most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections. Polymyxin is usually active in vitro … but of uncertain clinical efficacy, especially in pneumonia, owing to poor lung penetration. Tigecycline is often active in vitro, but has low serum levels, is unsuitable for urinary infections and, more generally, is of unproven efficacy in severe infections.

The CDC’s alert today asks any clinicians who come up against carbapenem-resistant gram-negatives to ask about contact with India or Pakistan as part of history-taking, and to forward isolates through state public health labs to the the CDC.

Update + fodder: I flipped over to my RSS reader and also discovered this paper posted overnight by Clinical Infectious Diseases, about extended-spectrum beta-lactamases in a particular strain of E. coli (“an important new public health threat”), and this one in Emerging Infectious Diseases, about carbapenem resistance moving between Klebsiella and E. coli.

MRSA in the House of Lords — the silly, the serious

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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

  • better surveillance
  • better infection control
  • consideration of MRSA as a notifiable disease
  • and promotion of both vaccine research and point-of-care diagnostics.

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.

British newspaper discovers ST398, says no UK cases – incorrect

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The UK’s Sunday Express takes note today of “pig MRSA” ST398 (full post archive here) in a story that is both somewhat alarmist and oddly incomplete, since it misses a piece of news that I told you about here last June.

The Express story raises the alarm over ST 398 in pigs in the Netherlands, colonizing farmers and causing human illnesses. There is nothing in it that we have not already discussed here many times, but it is nevertheless worth noting because it appears to be the first report on ST398 in a year in a major UK paper. (Credit for what I think is the first mention of ST398 in the Brit press goes to the Independent.)

But here’s what’s odd about the story: It says (italics mine),

A DEADLY new form of MRSA is believed to be spreading from farm animals to humans – already the bacteria has been found in hospitals abroad.
It is the first time the bug has spread in this way and experts believe excessive use of antibiotics in factory-farmed animals may be behind its development.
“Farm animal” MRSA, as it is known, can cause a raft of illnesses including skin infections, pneumonia, bone infections and endocarditis. …
The new MRSA bug, known as ST398, could reach hospitals in the UK, causing serious illness and death among vulnerable patients. (Byline Lucy Johnstone and Martyn Halle)

However as constant readers here already know, ST398 has already has been found in UK hospitals: in three unrelated patients — one adult and two newborns — in a Scottish hospital, none of whom had any relationship to pig-farming.

Credit for pushing the story of ST398 in the UK goes to the organic/sustainable farming group the Soil Association, who have aggressively monitored and lobbied for the extremely slow reveal of ST398 by the British government. As the issue now stands, the UK tested British pigs for ST398 colonization in 2008, but has not revealed the results. It has not yet tested retail meat in the UK, some of which is imported from the Netherlands, the location where the most ST398 has been found.

While that sounds like foot-dragging, it is still ahead of the US: Except for the study published in January by Tara Smith’s team at University of Iowa (paper here, my Scientific American story here), there has been no testing of pigs in the US, certainly none by government agencies.

(Hat-tip to Pat Gardiner for alerting me to the Sunday Express article.)

“Sick as a pig” – from ST398

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Constant readers, I am at the annual meeting of the Society for Healthcare Epidemiology of America, where there is a lot of news about MRSA in hospitals. I hope to post on that over the next few days.

In the meantime, though, I want to pass on several pieces of news about ST398, the “pig strain” that we have talked so much about.

First, the Soil Association, the British organic/sustainable farming group that has done much work elucidating the spread of ST398 and making the link between that bug and antibiotic use on farms, has released an online documentary about ST398 called Sick as a Pig. You can watch it here, and here is the Soil Association’s press release:

…40% of Dutch pigs and up to 50% of Dutch pig farmers are now carrying the new strain, which is also spreading to the wider population. Although this type of MRSA was first detected in humans in the Netherlands as recently as 2003, it now causes almost one in three cases of MRSA treated in Dutch hospitals.
It is not yet known whether any British pigs are affected by the new strain of MRSA (called ST398) since the results of testing, which was required by the EU and carried out in 2008, have not been made public.
Several countries have already published the results of their own tests revealing significant levels of MRSA in national pig herds. The European Food Safety Authority has said that, ‘It seems likely that MRSA ST398 is widespread in the food animal population, most likely in all Member States with intensive animal production’.

Second, here is a paper from last fall that somehow slipped by me: in the CDC journal Emerging Infectious Diseases, a report of two cases of ST398 infection in men in Sweden. Neither had any contact with farming or animals.

The first patient, a previously healthy 36-year-old male physiotherapist, sought medical care in March 2006 for a small abscess in his axilla. Culture of the abscess grew MRSA. Presence of mecA gene was confirmed by PCR. During the next 2 months, furunculous [sic] developed twice, caused by the same strain. His youngest child, adopted from China, had been found to be MRSA positive (throat, perineum, and a small wound) a month earlier during routine screening for adopted children. During subsequent screening of the family, the older sister, adopted from South Korea, was also found positive (throat). Both parents were negative for MRSA at that time, which suggests that the father was newly infected when his abscess developed and that he had not acquired the strain abroad. Also, spa typing indicated that the children carried different strains from that of the father and from each other (t286, t1434). Subsequent screening of family members for MRSA on several occasions found only the father to be repeatedly positive.
The second patient, a 43-year-old male clerk, also previously healthy, sought medical attention during the summer of 2007 for a MRSA-infected elbow wound. Follow-up examination determined that he carried MRSA also in the perineum and in a chronic external otitis eczema. He was later hospitalized for a larger abscess that required surgical drainage. His family members reported no symptoms and were thus not screened for MRSA.

Of note, the men’s strain (ST398, t034) carried the two genes that express the toxin PVL, which is unusual in ST398, though characteristic of CA-MRSA USA300, the dominant community strain in the US. The role that PVL plays is very controversial: Some research groups believe it is responsible for the rapid tissue destruction that can accompany USA300 infection (in penumonia and some soft-tissue infections, for instance), while others vociferously disagree.

Did MRSA kill an Ontario nurse?

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Here is a story that was flagged by several commenters (welcome, Canadian readers), and is being reported by a number of Canadian news outlets: A nurse who worked in the critical care unit at Victoria Hospital in London, Ont. has died, possibly of MRSA, and the Ontario Ministry of Labor is investigating whether her death is an occupational exposure — that is, whether she caught the bug in the process of working in the hospital.

There’s not a lot of detail in the stories published so far. The St. Thomas (Ont.) Times-Journal, the London (Ont.) Free Press and the Canadian Press suggest that the nurse was a patient in her own hospital and acquired the infection while a patient. The Toronto Globe and Mail, on the other hand, casts the story as the nurse working, becoming sick, and then becoming a patient.

Occupational infections with MRSA have certainly been recorded. A Texas firefighter and EMT died of invasive MRSA in 2006, and his widow alleged it was because of his exposure to MRSA patients; an Illinois EMT almost lost a leg to the infection in 2007.

Let’s stipulate that this Ontario nurse’s death is terribly sad. The question will be whether it is also scientifically confounding. A hospital is going to have a substantial background rate of MRSA, in infected patients, colonized patients and colonized personnel. If her death turns out to be caused by MRSA, it will be important to ascertain both the timeline — did she become sick while working, or while undergoing care for some other health problem — and also the microbiology: Did she have whatever strain is predominant in her hospital? Or was it on the other hand a strain that is circulating in the community (provided that community strains have not moved into hospitals in Ontario as they have in the US)?

That sort of microbiological differentiation provided an important clue in the death of Maribel Espada, a British nurse who died of invasive MRSA in 2006, six days after giving birth at the hospital where she worked. Unusually for the UK, Espada was infected with a PVL+ strain of MRSA, something that is very common in US community strains, but unusual in the UK until recently. That allowed her infection to stand out from the background, and suggested that she had been infected by a patient in her hospital:

The Health Protection Agency said it was investigating the possibility Mrs Espada caught PVL MRSA from a patient who died at the hospital in March.
A spokesman for University Hospitals of North Staffordshire NHS Trust said all staff who had come in contact with the two people originally diagnosed with PVL MRSA had been screened by the hospital’s infection control team.
A further nine cases were subsequently identified, of which one was a former patient.
The eight other cases were either members of staff or people staff had come into contact with. (BBC News)

Seriously, a global problem

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Serendipitously, as I was preparing the previous post (an intro to GlobalPost.com, which will be featuring posts from SUPERBUG), an auto-push email from the National Library of Medicine‘s PubMed service landed in my inbox.

For those of you whose bedtime reading is not obscure medical journals (I know: This is what you have me for), PubMed is a search interface that allows you to pull articles for medical journals wordwide. It also offers a push option: Set a search term, fill in your email, and links to the latest articles on your term of choice are delivered. I have my search set to “MRSA” and have the results pushed once a week; there are never fewer than 25 new papers, which is a great gauge of how active an area of research — and how important a topic — MRSA is.

The latest push — 26 articles — vividly reminded me that, as NIAID Diretor Dr. Anthony Fauci said a few months ago, we are in the midst of “a global pandemic.”

Here is a sampling of those latest papers, from, again, a single week:

No question, constant readers: What we are talking about here is an international problem, a truly global bug.

Brilliant entrepreneur asks: “So why CAN’T you fix this?”

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Constant readers, you’ll note that posting has slowed down a bit: I am deep into a chapter that is giving me some difficulty. (And I seem to be playing holiday host to an unexpected bout of bronchitis. I’m sure I didn’t need both lungs…)

But here’s something that crossed my monitor this morning, and it’s worth looking at. Sir Richard Branson, founder of Virgin Air and many other extremely successful entrepreneurial efforts. has accepted a post as vice-president of the Patients Association, a nationwide nonprofit that advocates for hospital patients in the UK. Speaking up in his new position, Branson gave an interview to the BBC in which he talked about hospitals’ failure to curb MRSA:

It feels like they have tinkered with the problem rather than really got to the heart of the problem. The hospitals are there to cure people. They are not there to kill people.

It’s a marvelous interview — read the whole thing, it’s not long — because it’s such a breath of fresh air. Branson is an outsider to health care, but he knows how to make businesses work. And as the head of an airline, he’s extremely familiar with what we in the US call “never events”:

Sir Richard says the health service could learn a lot from the airline and rail industries on how to avoid mistakes.”In the airline industry if we had that kind of track record we would have been grounded years ago,” he said.”In the airline industry if there is an adverse event that information is sent out to every airline in the world. And every airline makes absolutely certain that that adverse event doesn’t happen twice.”

So his advice is brutally practical: Health care workers carry MRSA? Screen and swab them. Workers are positive for MRSA? Treat them, and take them out of direct patient contact for two weeks. That costs money? Spend the money: It’s less costly in the end than killing your patients.

File under Unintended Consequences, 2

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Via the BBC comes a report, from a conference hosted by the journal Lancet Infectious Diseases, that some healthcare-infection experts in the UK are publicly questioning efforts to reduce hospital-acquired MRSA.

The argument is that, by focusing so tightly on MRSA, hospitals neglect other drug-resistant HAIs to such an extent that the overall rate of illness in the hospital remains approximately the same. They argue instead for a broader focus on all resistant and nosocomial organisms:

“It’s not clear that overall things have got better,” … said [Dr Mark Millar, a medical microbiologist at St. Bartholomew’s Hospital and the London NHS Trust].
“Rates of E. coli are going up and it almost compensates for MRSA.
“All you’ve done is replaced one problem with another one,” he said. … “”There’s no evidence that overall we have fewer hospital infections or fewer people are dying.” (Byline: Emma Wilkinson)

This is a highly contentious debate in the US as well, with no resolution in sight. I’ve covered some aspects of it here, and there is a long point-counterpoint from Infection Control and Hospital Epidemiology here and here.

British infection control: Epic fail

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Via the Guardian comes news that British hospitals are failing miserably at hygiene and infection-control targets set by the Healthcare Commission, a government-funded but independent watchdog agency somewhat analogous to the United States’ Joint Commission (formerly called JCAHO).

While community-associated MRSA is still a somewhat new story in the the UK, hospital or nosocomial MRSA is a major epidemic, with resistant Clostridium difficile (“C.diff”) coming close behind. So there has been significant attention paid in the UK to improving infection control programs in hospitals, through the vehicle of benchmarks set for the National Health Service trusts (essentially, regional organizational groupings of hospitals).

And the results, according to unannounced spot-checks made by the UK commission, are appalling. Only 5 of 51 trusts ( 51 = 30% of all acute-care hospitals in the UK) that were checked hit the mark. For those slow at math, that means 3% of UK hospitals are doing what they should to protect patients from infections they cause. (UPDATE: To be fair, if we assume the “5 out of 51” holds true across the NHS, then 10% are doing what they should. That’s still appalling.)

“At nearly all trusts we have found gaps that need closing,” said Anna Walker, the commission’s chief executive. “It is important to be clear that at these trusts we are not talking about the most serious kind of breaches. But these are important warning signs to trust boards that there may be a weakness in their systems.” (Byline: Sarah Boseley)

How weak? This weak, according to the commission’s own report:

  • 27 of the 51 trusts inspected were failing to keep all areas of their premises clean and well maintained. These lapses covered issues ranging from basic cleanliness, to clutter which makes cleaning difficult, to poorly maintained hospital interiors.
  • One in five trusts in this sample did not comply with all requirements for the decontamination of instruments and other equipment used in the care of patients. Trusts that breached this duty tended to have no clear strategy for decontamination or to lack an effective process to assure compliance.
  • In one in eight trusts, the provision of isolation facilities was not adequate. The containment of infections is extremely important to managing outbreaks. Hospitals without adequate facilities must ensure they have contingency plans so that the risk of infections spreading between patients is minimised.
  • For over one in five trusts there were issues related to staff training, information and supervision. While training on preventing and controlling infection was often in place, boards could not always ensure that training days were well attended or that staff used their knowledge in practice.

UK hospitals have until next April to learn to hit these benchmarks or be held accountable under a new Care Quality Commission.

For infection-control geeks, the full text of the “hygiene code” which the hospitals must abide by is here. Details of inspections at individual trusts are here.