Antibiotic resistance: NDM-1 alarm in the UK

My understanding is that about 16% of infections are now resistant to multiple classes of antibiotics. The Scientist polls readers on the topic (79% real danger, 21% media hype):

The front page of The Guardian featured an article highlighting the apparent waning efficiency of antibiotic efficiency due to the global spread of certain drug-resistant bacteria.

(…)

The Guardian interviews one of the principal authors of The Lancet paper:

A new gene conferring high levels of resistance to almost all antibiotics has been found to be widespread in forms of gut bacteria that can cause potentially life-threatening pneumonia and urinary tract infections.

In just three years, says Professor Tim Walsh of Cardiff University who discovered the gene, it has grown in prevalence from being rarely observed at all to existing in between 1% and 3% in patients with Enterobacteriaceae infections in India.

“It is absolutely staggering,” said Walsh. “Because of international travel, globalisation and medical tourism, [the gene] now has the opportunity to go anywhere in the world very quickly.”

Some of the comments are useful, e.g., this one from UK molecular biology researcher Jim Caryl whose Gene Gym profile reads “Bad bugs, drugs and antibiotic resistance, all in a day’s work at The Gene Gym, brought to you from the gym floor by a researcher (fitness instructor) in bacterial evolution“:

I would find it hard to answer either way. I think multidrug resistance is a serious and potential threat, and there have been recommendations for some time that reports, such as that published by Walsh et al. in Lancet Infectious Diseases, be published and acted upon.

Molecular epidemiological studies are a crucial underpinning to work on predicting antimicrobial resistance (PAR), especially when these elements are associated with, or are in the same ecological niche, as promiscuous mobile genetic elements, and arising in nosocomial environments.

However, whilst the a/biotic pipeline could certainly have been considerably better stocked, the efforts of numerous small biotechs and academic researcher looking at alternatives to the rather poultry introduction of new a/biotic classes, seems to be chronically undervalued. There are valiant efforts to target bacterial virulence, the mechanisms of horizontal transfer, and to inhibit the means by which bacteria resistant antibiotics – in all cases rendering more time for new drug discovery, but crucially more time in clinical therapy.

“Is it likely that we will be dealing with infections in the UK that are completely resistant to antibiotics within 10 years? Or is this simply a case of media hysteria?”

Yes, if the funding is not made available and we rely on the efforts of a (majority) disinterest of large pharmaceuticals to invest in new drug class leads, we will be dealing with increased prevalence of multidrug resistance – as we already are in isolated pockets with some strains of Gram (+)ve bacterial pathogens.

Media hype should be reflective, and not doomsaying. They should be pointing out the threats, but identifying the huge efforts being taken to provide alternative solutions – brought about by the lack of real investment. We know so much more about bacteriology, molecular epidemioloigy and drug discovery now than we did in the heyday of a.biotic discovery. A/biotics were used for years without a full understanding of their mechanisms, nor the mechanisms of resistance. Many instances of a/biotic resistance spread could (and should) have ben predicted and prevented.

Ironically, some of the systems biology, high-throughput infrastructures that have been stealing so much of the research funding pot (that could have gone into a/biotic and resistance research), could actually now be of some considerably use in speeding up the whole process of recognising new resistance determinants, tracking their spread and identifying resistance trends that can be exploited to clinical benefit.

Jim’s Gene Gym blog looks to be an excellent resource on antibiotic resistance. Back to the UK NHS brief on NDM-1, who says “not to worry just yet” but:

(…) The NDM-1-positive samples from the UK and India also came from a diverse range of bacterial strains, which means the presence of NDM-1 was not confined to a few common strains of E. coli and Klebsiella pneumonia (the most common types of Enterobacteria carrying NDM-1). Worryingly, this suggests that this was not just a single international outbreak with the same strain of a particular bacterium. This finding supports the fact that the NDM-1 gene, being located on the bacterial plasmid, can be easily transferred to other bacteria. As one of the researchers says, the NDM-1 gene may have “an alarming potential to spread and diversify among bacterial populations.”

The authors say that the emergence of NDM-1 positive bacteria could be a serious global public health concern as there are few antibiotics that are effective against NDM-1. It is also worrying that the isolates in India came from people presenting with common community-acquired infections, suggesting the bacteria with this enzyme may be widespread in the environment, in India at least.

As the researchers conclude, there is the potential of NDM-1 to be a worldwide public health problem, and coordinated international surveillance is necessary.

So don’t be going to India and Pakistan for that cheap surgery. The Lancet paper that is the cause of this UK alarm is Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study (available to the public as a service). From the Summary:

Interpretation: The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.

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