<blockquote>
'The nightmare scenario is that NDM-1 producers are close to becoming true superbugs that are resistant to everything. The horror model is XDR-TB – extensively drug-resistant tuberculosis, which broke out in South Africa in 2006, and is a significant problem in Russia, among other regions. It is reasonable to say that such strains, which for all practical purpose are so hard to treat that sufferers from them might as well be living in the 1930s, have evolved because of poorly controlled anti-TB drug prescribing. The same is true for the prescription of antibiotics in the Indian subcontinent. But it is hard to see changes coming there any time soon. Even in the UK we could do better. And hoping for new antibiotics remains just that.'</blockquote>
Can we stop the Indian superbug?Should the rapid spread in Britain of NDM-1, an antibiotic-resistant enzyme dubbed the 'new MRSA', be a cause for alarm, asks Hugh Pennington.By Hugh Pennington
11 Aug 2010
SourceCarbapenems are very useful antibiotics. Distantly related to penicillin, they can be used to treat a much broader range of bacteria, many of which are difficult to attack because they are naturally resistant to most other antibiotics.
An important group of such microbes is the Enterobacteriaceae, so called because they live mostly in the intestine. Most of the time in healthy people they cause no harm. But members of the group – particularly Escherichia coli and Klebsiella pneumoniae – are important causes of infections contracted by the sick in hospital. So a recent sudden and significant rise in the number of carbapenem-resistant bacteria in this group in Britain set alarm bells ringing.
In January last year, it caused the Health Protection Agency to issue a National Resistance Alert. The focus was on a type of enzyme, carbapenemase, that destroys the antibiotic and makes the bacteria resistant. The Antibiotic Resistance Monitoring and Reference Laboratory in London had seen only eight bacterial samples producing such an enzyme in the years up to 2007. But there were 21 in 2008 and more than 40 in 2009.
The rise in the number of cases infected with these resistant bacteria was not the only development. It was not due to a single kind of bacterium carrying a single type of enzyme – resistance in different species of bacteria was appearing, due to different enzymes. And they were being imported into the UK as on-going infections in people who had been patients in hospitals in Greece, Turkey and Israel.
The most recent development, and the one that has hit the news this week, is that resistant bacteria producing a brand new carbapenemase, NDM-1, have been found in Britain and that some of them have come here from the Indian subcontinent. Some of the implications of the discovery are truly alarming.
The story started in 2008 with a 59-year-old man who had lived in Sweden for many years but was originally from India. He returned to that country many times and was admitted to hospitals there; most recently in New Delhi, in December 2007.
He had diabetes and had developed an abscess. He returned to Sweden in January 2008 and had various tests. Small numbers of Klebsiella pneumoniae bacteria were found in his urine. The bacteria were not causing any problems for the patient – he did not have a bladder or kidney infection – but were of interest and were followed up because they were carbapenem-resistant.
The big surprise was that they were negative for all the known relevant carbapenemase genes. DNA sequencing identified a novel enzyme. Its discoverers called it NDM-1, New Delhi Metallo ß-lactamase.
A paper describing this new enzyme was published last September. It is full of technical molecular detail, but it uses plain English to say things that send shivers down the spine. The Klebsiella carrying the new gene was fingerprinted to find its type. It was ST14, a type almost identical to ST 15, which is branded as being the “new MRSA” due to its wide international distribution and carriage of other antibiotic resistance markers. So the Klebsiella was already particularly good at spreading and travelling long distances.
Just as unsettling was the finding in stools from the patient of a strain of Escherichia coli that was also carrying the NDM-1 gene. It was on a plasmid, a small DNA structure that can transfer quite easily from bacterium to bacterium. It is very likely that it had jumped from the Klebsiella to the Escherichia while they were living quietly in the patient’s bowels (vice versa is possible, but the practical consequences would be no different).
The original Klebsiella plasmid carried other antibiotic resistance genes as well. No surprise there; they often do. So more bad news. The paper doesn’t mince its words: “The rapid dissemination of this plasmid throughout clinical bacteria would be a nightmare scenario."
Bacteria don’t need sex to reproduce, but they indulge nevertheless. They can conjugate, when a physical junction is set up to transfer the DNA, or the DNA can piggyback on a virus, or the DNA can transfer on its own. Cross-breeding between species is common. Promiscuity is the order of the day. So it would be no surprise to find the NDM-1 gene getting about, as it did in the Swedish patient. This week’s news about British patients shows that it is happening.
It is clear that the NDM-1 gene had spread to different bacterial types. NDM-1 production is getting commoner; it is now the commonest kind of carbapenemase being detected in Britain. The only good news – and it hardly qualifies as that – is that there hasn’t been much spread in hospitals, yet.
Seventeen of the 37 patients had a history of travel to India or Pakistan, and 14 had been in hospital in those countries. Some had had plastic surgery, others had received treatment for cancer and other serious conditions. It is also clear that NDM-1-producing bacteria are widespread through the Indian subcontinent.
What can be done? The most important action we can take right now is to make sure that hospital control procedures in Britain are as good as they can be. Stopping the spread of NDM-1 producers from patient to patient is a no-brainer. Keeping the numbers of the bacteria down will also reduce the likelihood of the spread of the gene to other organisms. Handwashing is still paramount as a way of interrupting transmission. Physically isolating patients is crucial.
Health “tourism” is here to stay. But, just as knowing where someone has been is vital in diagnosing a fever, the question also has to be asked of patients who have been in hospital abroad. It has been standard practice for years in Scandinavian countries and the Netherlands for the assumption to be made that patients who have been in hospital in Britain are MRSA-positive until screening test results have come back.
The nightmare scenario is that NDM-1 producers are close to becoming true superbugs that are resistant to everything. The horror model is XDR-TB – extensively drug-resistant tuberculosis, which broke out in South Africa in 2006, and is a significant problem in Russia, among other regions. It is reasonable to say that such strains, which for all practical purpose are so hard to treat that sufferers from them might as well be living in the 1930s, have evolved because of poorly controlled anti-TB drug prescribing. The same is true for the prescription of antibiotics in the Indian subcontinent. But it is hard to see changes coming there any time soon. Even in the UK we could do better. And hoping for new antibiotics remains just that.
There is nothing new about the importation of new bugs. Don’t blame modern globalisation. Syphilis, cholera and plague were ancient imports, and they have been followed in our time by Sars, HIV and influenza. All I can say as a microbiologist is that, whatever the economic climate, my business will continue to flourish.
Hugh Pennington is emeritus professor of bacteriology at the University of Aberdeen