H5N1

UK to urge global clampdown on antibiotics amid public health fears

Via The Guardian: UK to urge global clampdown on antibiotics amid public health fears. Excerpt:

Britain is to urge the G8 to take action against the spread of drug-resistant microbes as medical and veterinary experts warn that co-ordinated international action is needed to prevent soaring rates of potentially lethal infections turning into a public health catastrophe. 

David Willetts, the science minister, will propose far-reaching measures that would clamp down on the overuse of antibiotics by GPs and hospital doctors. He will also try to restrict usage on farms and fisheries, where the drugs are blended with feed to boost yields. 

Willetts will push for a consensus on ways to ramp up the discovery of new drugs to fight bacteria, speed their approval and delivery to patients, and strengthen cross-border surveillance for emerging resistant strains. 

"Across the G8, we should regard the spread of antibiotic resistance as a global challenge that is up there with climate change, water stress and environmental damage, and there are genuine policy consequences that follow from that," Willetts told the Guardian ahead of Wednesday's meeting of science ministers at the Royal Society in London. 

Drug-resistance is an inevitable consequence of antibiotics. The drugs wipe out susceptible infections but leave resistant organisms behind. The survivors multiply and, in time, can become immune to even the strongest antibiotics. Though improved surveillance and hygiene has reduced levels of life-threatening MRSA and C difficile "superbugs" in hospitals, resistant strains are on the rise. 

In Britain, doctors see ever more resistant strains of TB, E coli and Klebsiella, which causes pneumonia. Some 80% of gonorrhoea is now resistant to the frontline antibiotic tetracycline. Of serious concern is the rise of resistance to powerful drugs called carbapenems, the antibiotics of last resort. The first few cases were detected in Britain in 2003, but since then the numbers have soared to 217 cases in the first six months of 2011. 

Willetts has asked England's chief medical officer, Dame Sally Davies, to brief the meeting after she warned in a March report that untreatable infections posed a "catastrophic threat" to the population.

Australia: Hunt continues for people exposed to drug-resistant TB

Via ProMED-mail, an ABC news report: Hunt continues for people exposed to drug-resistant TB.

Queensland Health is still searching for people in the state's far north who may have been exposed to a multi-drug resistant strain of tuberculosis (TB). 

Last month, a woman died in Cairns Base Hospital while being treated for TB. Chief health officer Jeannette Young says anyone who was in contact with the woman for more than eight hours is being screened. 

"The last number I got was something like 60 or so out of the 70, 80 or so people, because as we go and contact-trace people, then they give us information about other people, so the number slowly gets bigger," she said.

ProMED-mail's comments are extensive and enlightening. Excerpt:

The news report above concerns the tracing of contracts of a 20-year-old woman from Papua New Guinea (PNG) who had been hospitalized in Queensland in an isolation ward since May 2012 and who died on 14 Mar 2013 in Cairns Base Hospital with XDR-TB (extensively drug resistant TB). She was said to be part of an ongoing TB epidemic in PNG on Daru Island, capital of PNG's Western Province that is located just north of the Torres Strait and Cape York Peninsula (Far North Queensland) at the tip of the state of Queensland, Australia. ProMED-mail previously posted news reports on this case in 2012 and 2013 (Tuberculosis - Australia: (QL) ex Papua New Guinea 20121020.1355085 and Tuberculosis - Australia: (QL) ex Papua New Guinea, XDR, fatal 20130318.1591289). The news report, however, fails to say whether any of the patient's approximately 60 contacts was thought to have developed latent or clinically active TB and if found, how the infection was managed.

India "has lost" superbug war

Via India Real Time, a blog of the Wall Street Journal: India ‘Has Lost’ Superbug War. Excerpt:

India has lost the war against the toughest forms of antibiotic resistance, largely because of poor sanitation, unregulated use of antibiotics and an absence of drug resistance monitoring, according to the man who discovered a type of drug resistance in bacteria in New Delhi. 

“All these factors add to why it’s going to be so difficult to deal with or even tackle [resistance], you won’t solve it, it’s over,” said Tim Walsh, professor of medical microbiology at Cardiff University in Wales. 

In 2010, Mr. Walsh discovered an enzyme that made disease-causing bacteria resistant to antibiotics.  He named the enzyme “New Delhi Metallo 1” (NDM-1) and claims he was banned from working in India after the discovery. 

Bacteria carrying the NDM-1 enzyme are highly resistant to the most powerful group of antibiotics, known as carbopenems, making infections caused by them extremely difficult to treat. 

They can also transfer their resilience to other bacteria, including those that cause infections. “The rapidity and frequency of that transfer is something that we have never seen before in antibiotic resistance,” Mr. Walsh said. 

He estimates that up to 200 million Indians carry NDM-1 on the benign bacteria in their intestines. But a lack of research and scarcity of data make it difficult to gauge in terms of its transfer to disease causing bacteria. 

“We’ve failed to understand how NDM-1 spreads in the community,” Mr. Walsh said, adding that there is also very little understanding about the risks associated with being infected by a bacteria carrying NDM-1. 

“We’ve failed to understand what dominant clones are in hospital and we’ve failed to understand the risk post surgical infections,” he said. 

In almost three years since he published his research in the Lancet medical journal, Mr. Walsh says that India has failed to respond to the “urgent” need to regulate the sale and use of antibiotics, track the incidence of resistance or improve sanitation. 

Antibiotics are for sale without prescription in pharmacies in India and there are no national guidelines for clinicians on their use in hospitals. Bacterial diseases develop resistance to treatment with antibiotics when the drugs are wrongly used to treat viral infections or when a full course of drugs isn’t completed. 

Resistance makes infectious diseases more difficult or impossible to treat. Even simple urinary tract infections when caused by an NDM-1 carrying bacteria cannot be eradicated with antibiotics, Mr. Walsh said. 

When he published his findings in 2010 Walsh says his name “became mud” in political and scientific circles in India. 

“I named the gene after the capital of India which they [the government] weren’t too thrilled about,” he said. It is normal scientific practice to name genes after the cities in which they are found, he added. 

“We were banned from India and India had a massive clamp down on sending [biological] strains out,” Mr. Walsh said. “Indians were banned from working with me, or anybody in Europe the whole thing was a systematic campaign to control research into antibiotic resistance in India.” 

Neither the Ministry of Health nor the Central Drugs Standard Control Organization responded to requests for comment.

Australia: XDR-TB on the doorstep

Via the Medical Journal of Australia: Extensively drug-resistant tuberculosis hovers threateningly at Australia’s door. Excerpt:

It was hoped that extensively drug-resistant tuberculosis (XDR-TB) might never arrive on Australia’s shores. But new cases raise the spectre of death for patients, transmission to others and large costs for Australian taxpayers. Papua New Guinea (PNG) national Catherina Abraham, aged 20 years, “made it” to Australia and hit the headlines in October 2012 because she had been diagnosed with XDR-TB. 

After almost a year in an isolation ward at Cairns Base Hospital, she died on 8 March 2013. Her treatment cost Queensland Health about $500 000 and would have cost $1 million had she lived to complete it. 

Now another PNG national has been diagnosed with XDR-TB in Australia. In the preceding 8 years, only two other XDR-TB cases were recorded in Australia. According to Queensland Health, the most recently diagnosed patient came through the Torres Strait, was referred to Cairns Base Hospital and was transferred to PNG health services before the laboratory diagnosis of XDR-TB was made. 

He or she is currently in Daru Hospital (in PNG’s Western Province, the closest to Cape York). Although TB treatment is meant to be free for patients in PNG, potential exposure to other patients, the cost of sourcing active drugs, and the complexity and length of XDR-TB treatment mean that this patient is at significant risk of dying. 

A recent television exposé of Daru Hospital showed numerous patients with XDR-TB and multi-drug resistant TB (MDR-TB) mixing together and leaving their isolation wards, resulting in the risk of drug-resistant TB spreading through the community. 

Experts believe Abraham would have died within 1 month had she not reached Cairns and also predict that Australia could see its own outbreak of XDR-TB within 5 years. In comparison, 24 patients have been diagnosed with XDR-TB in the United Kingdom since 1995, six of whom were diagnosed in 2011. 

Patients with XDR-TB and the still-challenging MDR-TB in the UK are largely migrants from Eastern Europe, Africa and Asia. Last year, the UK government began requiring new entrants from TB-prevalent nations to have a chest x-ray with them on arrival to be granted a visa to enter the UK. 

Yet, owing to the UK’s porous air and sea borders and its accessibility and proximity to Europe, it is much more vulnerable than Australia to receiving patients with MDR-TB and XDR-TB. According to the UK’s Health Protection Agency, screening new entrants for latent TB would also be desirable. 

However, Australia is unlikely to enact a similar policy since it would produce many positive results for latent infection without identifying which patients would progress to active or drug-resistant disease (Justin Waring, Chair of the National Tuberculosis Advisory Committee, personal communication). So apart from the Qld–PNG border, it is difficult to predict where other XDR-TB or MDR-TB cases may appear in Australia, since migrants with latent infection can reside in any Australian city or region. 

In Australia, significant resources can, at present, be directed at patients with XDR-TB. Yet in PNG, all forms of TB compete for resources with a catalogue of other health and social problems, including high rates of diarrhoeal illness, pneumonia, HIV (many patients with HIV are co-infected with TB), malaria, maternal mortality, and widespread and crippling poverty.

The famous epidemiologist Charles Dickens made the point in Bleak House, published in 1853: Let disease spread among the poor, and it will inevitably spread to the rich. We have been amazingly obtuse about this simple observation for 160 years.

The Lancet on World Tuberculosis Day

The Lancet has published a special issue today. The executive summary:

To commemorate World TB Day 2013, The Lancet Infectious Diseases publishes a Series of papers on tuberculosis, a disease that has long plagued human beings and was declared a global emergency in 1993 by WHO. 

Without concerted action from political leaders, health policy makers, funders, and others, health systems worldwide are at risk of being overwhelmed by increasing numbers of patients with treatment-resistant tuberculosis. 

As new diagnostic tests, drugs, and drug regimens become available that have the potential to radically improve the detection and management of tuberculosis, the papers in the Series explore the challenges for successful implementation of these interventions.

South Africa: New totally resistant TB identified

Just in time to ruin World Tuberculosis Day on Sunday, a report via allAfrica.com from Health-e: South Africa: Further Resistance to TB Drugs Identified in SA. Excerpt:

Researchers have identified a new strain of tuberculosis in 17 patients in the Eastern Cape which is totally resistant to the all current drug regimens. 

When an earlier study of extensively drug resistant (XDR) TB in the Eastern Cape showed that patients weren't responding to treatment - 58 percent of patients died within a year and only 8.4 percent became un-infectious after more than four months of treatment – epidemiologists at Stellenbosch University (SU) decided to investigate the bacteria that seemed to be more resistant against the available drugs. The Eastern Cape cases are the first to be identified in South Africa, and the fourth country in the world to report totally drug resistant (TDR) TB – it was discovered in India last year, and in Italy (2003) and Iran (2009). 

What they found was an emerging strain of TB even more resistant to drugs than XDR, which is already resistant to all first line drugs and some second line drugs. This new strain has shown resistance to at least 10 anti-TB drugs currently in use in the health sector. 

According to Prof Tommy Victor, from SU's Division of Molecular Biology and Human Genetics, the World Health Organisation and many experts in the field, including him, think the name "totally drug-resistant" (TDR), which is currently used in scientific literature, is not appropriate. They believe there may be a cure for TDR among some of the new drugs currently being developed, or old medication not in use anymore. 

"We really are facing bacteria that has become increasingly resistant, and there are now some bacteria that are hyper resistant, irrespective of the definition," said Victor who was one of the authors of the study. 

In the scientific paper, which was published in the Emerging Infectious Disease Journal in March this year, they used molecular techniques to study cultures of the tuberculosis bacterium of just under 400 Multi-drug resistant (MDR) TB patients in the Eastern Cape. Among these a large number were pre-XDR and XDR's, and 17 cases of TDR. 

There are approximately 18 000 new MDR cases diagnosed each year and "there may be be more TDR cases in South Africa ," says Victor, explaining that 17 cases emerged from only 400 MDR samples tested. 

A shortcoming of the study, which was acknowledged by the authors, is that they only studied the cultures from the infected patients, and don't have any data on patient outcomes – so they don't know how long they may have survived, or if any have been cured. Although a related study on the Eastern Cape cohort showed that patients responded quite badly to even the fiercest treatment.

UK: New wave of 'superbugs' poses dire threat, says chief medical officer

Via The Guardian: New wave of 'superbugs' poses dire threat, says chief medical officer. Excerpt:

Antibiotic-resistant bacteria with the potential to cause untreatable infections pose "a catastrophic threat" to the population, the chief medical officer for Britain warns in a report calling for urgent action worldwide. 

If tough measures are not taken to restrict the use of antibiotics and no new ones are discovered, said Dame Sally Davies, "we will find ourselves in a health system not dissimilar to the early 19th century at some point". 

While antibiotics are failing, new bacterial diseases are on the rise. Although the "superbugs" MRSA and C difficile have been reduced to low numbers in hospitals, there has been an alarming increase in other types of bacteria including new strains of E coli and Klebsiella, which causes pneumonia. 

These so-called "gram negative" bacteria, which are found in the gut instead of on the skin, are highly dangerous to older and frailer people and few antibiotics remain effective against drug-resistant strains. 

As many as 5,000 patients die each year in the UK of gram negative sepsis – where the bacterium gets into the bloodstream – and in half the cases the bacterium is resistant to drugs. 

"Antimicrobial resistance poses a catastrophic threat," said Davies. "If we don't act now, any one of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection that can't be treated by antibiotics. And routine operations like hip replacements or organ transplants could be deadly because of the risk of infection. 

"That's why governments and organisations across the world, including the World Health Organisation and G8, need to take this seriously." 

There has been an 85% reduction in MRSA (methicillin-resistant Staphylococcus aureus), which has meant that many large, acute hospitals have no more than two or three cases a year. But there are now 50 to 100 cases of gram-negative bacteria infection for every MRSA case, according to Professor Mike Sharland of St George's hospital in London, an adviser to the Department of Health on the use of antimicrobials (antibiotics and antivirals) in children. 

"This is your own gut bugs turning on you. Between 10% and 20% are resistant to drugs. We do not yet know why they are on the rise, although some hospital procedures, such as the use of catheters, may be implicated. Many are in the very young or older population," he said. 

"There is a lot of work going on through Public Health England and the Department of Health to try to work out why it has suddenly risen." 

In the second volume of her annual report, Davies calls for politicians to treat the threat of the new bugs and the failing antibiotics as seriously as they did MRSA. She wants action across government departments – involving the Department for Environment, Food and Rural Affairs in particular – because of the use of antibiotics in farming. 

She is asking for the threat to be added to the government's strategic risk register, which will make it easier to raise as an issue abroad. Drug resistance is a global problem as the resistant strains of bacteria travel the world.

Still another doctor's take on CRE

Via the blog Controversies in Hospital Infection Prevention, Dr. Eli Perencevich has some Further thoughts on CRE. Click through for the full post and a lot of links. Excerpt:

I have some further thoughts on where we should go. First, as I said earlier this week, we need a national response to CRE and antimicrobial resistance in general. This response needs to be horizontal in approach, as Mike Edmond and Dick Wenzel recommended several years ago. For it is quite clear that if we follow the vertical approach recommended by the CDC and others, swab for CRE and isolate, that this will bankrupt hospitals and ultimately fail. 

This surveillance approach will bankrupt us, because CRE isn't the only "nightmare" in our hospitals. Back in 2010, when Dan was discussing MRSA on NPR, he said so eloquently: "MRSA is not the only bad bug out there. It's just the most famous." 

And along with MRSA, we have VRE and ESBL and C. difficile and Acinetobacter and MDR-Pseudomonas. You see, we might not be able to take this single-hospital outbreak approach and extrapolate it to the entire country and 10+ pathogens. 

And if there is one lesson we should be taking away from the NIH CRE outbreak it's not that new-fangled whole genome sequence stopped the outbreak (because it didn't), it's that the outbreak spread and killed many patients despite herculean efforts to detect and eliminate it. 

Furthermore, if we target MRSA like many hospitals are now doing with chlorhexidine (CHG) baths, this approach could select for Gram-negative bacteria like CRE. 

My recommendations: 

(1) Invest significantly in antimicrobial discovery. Apart from the need for new treatment options, optimal control of resistant pathogens may depend on availability of effective antibiotics. 

(2) Invest in studies to improve compliance with hand hygiene – only 4 studies on this topic since 1980 per a recent Cochrane Review. Compliance is terrible, but currently the approach is to blame healthcare workers and not figure out how to help them easily clean their hands. 

(3) Study universal gowning and gloving (several studies are ongoing). Dentists wear gloves with every patient, why not doctors? 

(4) Undertake studies to further optimize environmental source control 

(5) Actually study antimicrobial stewardship. Stop yelling at patients and clinicians to not use antimicrobials. Actually fund studies that use advertising and other other messaging techniques that have a chance to be effective.

This is the most interesting online debate I've seen in ages.

McKenna on the CDC's "nightmare"

Via her blog Superbug, Maryn McKenna writes: "We Have A Limited Window Of Opportunity": CDC Warns of Resistance "Nightmare". Excerpt:

It’s not often that you get to hear a top federal health official deliberately deploy a headline-grabbing word such as “nightmare,” or warn: “We have a very serious problem, and we need to sound an alarm.” 

Dr. Thomas Frieden, director of the US Centers for Disease Control and Prevention, said both Tuesday, during a press conference announcing new CDC statistics on the advance of the highly drug-resistant bacteria known as CRE. 

His language — plus that fact that he conducted the entire press conference himself, instead of just making a brief opening statement — seem to me a clear signal that the CDC is taking this resistance problem seriously, and hoping we do too.

And we should. Here’s what the CDC announced Tuesday: 

• Healthcare institutions in 42 states have now identified at least one case of CRE. 

• The occurrence of this resistance in the overall family of bacteria has risen at least four-fold over 10 years. 

• In the CDC’s surveillance networks, 4.6 percent of hospitals and 17.8 percent of long-term care facilities diagnosed this bug in the first half of 2012. 

Those are dire reports. 

Here’s some back-story: CRE stands for “carbapenem-resistant Enterobacteriaceae.” Enterobacteriaceae are a family of more than 70 bacteria which share the characteristic of being gut-dwelling (“entero”); they include Klebsiella, Salmonella, Shigella and E. coli. 

Carbapenems are a “last-resort” family of antibiotics — imipenem, meropenem, doripenem and ertapenem — which are used against these bacteria when they have become resistant to other drugs. (Carbapenem resistance is conferred by a number of different genes and so sometimes goes by a number of other acronyms, including KPC, VIM, OXA and the “Indian superbug” NDM-1.) 

CRE tends to attack in ICUs and other critical care, and also in rehab units and nursing homes. That is for several reasons. First, because patients in those settings are uniquely vulnerable to infection, not just because of their illness but because the protective barrier of their skin has been breached by ports and catheters, and also because they are visited and touched by a lot of people. 

Second, because they are likely to be receiving heavy-duty antibiotics which put the bacteria in their bodies under evolutionary pressure. 

Third, because those drugs plus others cause diarrhea, which spreads gut-dwelling bacteria into the air and area. 

And fourth, because those bacteria are particularly good at surviving on the kind of surfaces — plastic, glass and metal — that you find in health care.

CIDRAP: News scan for March 4

Via CIDRAP: XDR-TB detention, fungal infection total grows, West Nile in Greece. Excerpt:

Six more infections and one more death have been linked to a fungal meningitis outbreak in patients treated with contaminated injectable steroids, the US Centers for Disease Control and Prevention (CDC) said today. The new developments push the number of infections to 720 and the death total to 49. 

So far 240 of the illnesses were meningitis only, 138 involved spinal or paraspinal infections with meningitis, 6 involved stroke without lumbar puncture, 302 were paraspinal or spinal infections only, 32 were peripheral joint infections only, and 2 involved a paraspinal or spinal infection along with a peripheral joint injection. 

Health officials have traced the infections to three tainted lots of methylprednisolone acetate injections produced by the New England Compounding Center, which were used to teat back and joint pain.