Friday, August 12, 2011

NDM-1: One Year Later



# 5751



Inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. – CDC PHIL.


Although the antibiotic resistance enzyme now known as NDM-1 (New Delhi metallo-ß-lactamase-1) was first detected three years ago in a Swedish patient (with Indian origins), its notoriety truly didn’t begin until one year ago today with the publication of a controversial, and eye-opening research paper in The Lancet.


The NDM-1 enzyme confers resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems. And Carbapenems are often our drug of last resort against a variety of bacterial infections.


Of particular concern, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).


One year ago, the following research article was published in the Lancet on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries (see NDM-1: A New Acronym To Memorize).


Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

Dr David Livermore, Prof Timothy Walsh, et al.


Published Online: 11 August 2010



The reaction from officials out of India was both swift and disappointing. Rather than taking immediate action against a growing public health threat, they took umbrage instead.


They condemned of the use of `New Delhi’ in the naming of this resistance gene, called the paper a `conspiracy theory’, and issued broad denials of its prevalence in India or that medical tourism to their nation was responsible for its spread.


It is worth noting that the naming convention for pathogens that invoked so much ire traditionally incorporates its place of discovery or emergence.


In 2001 a similar gene was discovered in Brazil and was dubbed SPM-1 (Sao Paulo metallo-beta-lactamase). Another, discovered in 1999 in Italy, is called VIM (Verona integron-encoded metallo-β-lactamase), while SIM stands for Seoul imipenemase found in Korea.


The day after this paper was published Health agencies around the world began voicing their concerns over the emergence of this new form of antibiotic resistance (see Public Health Agencies On NDM-1).


Under pressure from the International community and editorializing in Indian newspapers, the Indian Health Ministry announced in October 2010 that they would impose new restrictions on the sale of 90 currently over-the-counter antibiotics.


But as of today, amid strenuous protests from pharmacies, those restrictions have yet to be enforced according to this article in the Times of India.


With the specter of a new, more virulent, emerging forms of antibiotic resistance on the horizon, last fall the ECDC and EMEA produced a 54 page joint technical report called The Bacterial Challenge: Time To React to coincide with European Antibiotic Awareness Day in November 2010.




The World Health Organization (WHO) and the CDC - along with other public health organizations around the world – used this year’s World Health Day – 7 April 2011 to promote sane antibiotic usage and awareness of antimicrobial resistance.


Arrow hits the bulls-eye of a target with slogan: Combat drug resistance - no action today, no cure tomorrow


Six months after the first Lancet article in April, 2011, the same researchers published a new study that found the NDM-1 enzyme in 4% of New Delhi’s sampled drinking water sources, and 30 per cent of the sewage tested.


The Lancet Infectious Diseases, Early Online Publication, 7 April 2011


Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study

Prof Timothy R Walsh PhD , Janis Weeks BS, David M Livermore PhD , Mark A Toleman PhD


And alarmingly, the researchers also identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.


Once again the reaction out of India was one of denial (see Hopefully, It’s Just A Stage They Are Going Through)


One year after the Lancet report on the spread of NDM-1 out of India and Pakistan, concerns over its emergence and spread have not diminished. While the end of the antibiotic era is not yet at hand, the fear is we may be drawing closer to that day.


In April of this year, Margaret Chan – Director General of the World Health Organizationin a speech for World Health Day 2011, issued this stark warning:


In the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.


The implications go beyond a resurgence of deadly infections to threaten many other life-saving and life-prolonging interventions, like cancer treatments, sophisticated surgical operations, and organ transplantations. With hospitals now the hotbeds for highly-resistant pathogens, such procedures become hazardous.



Short of seeing an extremely high mortality influenza pandemic, I can think of no looming medical crisis more dire than the growing threat of antimicrobial resistance. 


For more on these issues, you may wish to revisit:


Carbapenemases Rising

Eurosurveillance On Antimicrobial Resistance
WHO: The Threat Of Antimicrobial Resistance


And for a far more complete (and eye-opening) discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA.


And Maryn’s SUPERBUG Blog, part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

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