New Antibiotic Resistance Gene NDM-1: A Worrisome Peek Into the Future?

Paul G. Auwaerter, MD, MBA


September 09, 2010

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Hi. I'm Paul Auwaerter. I wanted to talk to you about a new antibiotic resistance gene that's been making some considerable news since its discovery last December 2009: NDM-1. This is an enzyme code for a novel metallo-beta-lactamase. This is an enzyme that renders carbapenemases useless -- a drug that we have come to count on, offered for treating our more resistant gram-negative infections.

There have been a number of papers now that have suggested that this particular gene is spread by plasmid to a number of gram-negatives, and is therefore something that we may be seeing more of. Initial reports, so far, have suggested and looked for bacteria carrying this enzyme in both Pakistan and India. There have also been reports of finding this enzyme in the United Kingdom and 3 reports in the United States from patients who had gone to India to receive medical care.[1] It's not quite clear where this originally started. However, what's probably most important and most impressive to me is that this very resistant kind of bacteria has been described, in the most recent Lancet Infectious Diseases,[2] as a cause of community-acquired infection. This certainly bears some very close watching. It's transmitted on a plasmid, which means that its potential for spread is considerably greater than if it was located on a chromosome.

Also, I'm afraid that this may be a peek into the future. Typically, as an infectious disease specialist or anyone caring for people in the hospital, we spend time considering whether people have community- or so-called hospital-acquired infections. Hospital-acquired infections are the kind where we typically use antibiotics that have a better range of coverage and can fight resistant organisms. Here, we have an enzyme that might be transmitted to bacteria. If this problem spreads, we will have issues in which community-acquired infections may be no different than those acquired in the hospital.

As many of you are aware, we have a very limited pipeline in terms of new drugs to fight gram-negative infections for bacteria that are carrying this particular carbapenemase. It looks as though aztreonam, tigecycline, and colistin have generally had activities against these isolates. But this is a fairly limited menu and certainly something that bears very close watch. Indeed, I think many people are now looking to see and track this.

We've already known that global health issues can be affected by the very rapid and dynamic travel that occurs in our world. For example, we have seen gonorrhea develop resistance in Southeast Asia to fluoroquinolones, and we've had to make a number of changes to treatment responses to infection that's indeed community-acquired.

Whether this will actually happen to the gram-negatives, which can cause all sorts of problems in terms of pneumonia or intra-abdominal infections, will remain to be seen. But do stay tuned. NDM-1 is something that we will be hearing more of. Thanks for listening.


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