The NDM-1 “Superbug”: The Next Global Health Crisis?

NDM-1 Structure

Green et al. 2011

With its emergence on the Indian subcontinent, Europe, and now the United States, New Delhi metallo-beta lactamase, the NDM-1 “superbug,” so called for its resistance to nearly every antibiotic currently in use, has garnered significant attention worldwide. NDM-1 should be regarded as both a public health threat and the latest warning of the dwindling efficacy of antibiotics due to their extensive overuse and the vital need for research into alternative antimicrobial treatments.

Though not itself a pathogen, NDM-1 is an enzyme that, when incorporated into a microorganism such as Klebsiella pneumonia or Escherichia coli, the most common pathogen to infect humans, imparts strong resistance against antibiotic agents [1]. Even the carbapenams, our most potent antibiotics and typically the antibiotics of last resort, have been ineffective against pathogens armed with the NDM-1 enzyme. Specifically, NDM-1 acts as a carbapenemase, an enzyme that breaks down the beta-lactam ring that forms the core of carbapenems [2].

Dr. John Conly, co-director for the Snyder Institute of Infection, Immunity and Inflammation at the University of Calgary, reports that at least one of the ten strains of NDM-1 currently known is pan-resistant, in other words, resistant to every antibiotic in use today [1]. Although the drugs colistin and tigecyclin have been used successfully to treat the most resistant NDM-1 strains, colistin has caused toxic side effects in the kidneys of approximately one third of patients that have thus far received this treatment.

In 2009, the first known case of NDM-1 appeared in a Swedish patient who had been hospitalized in New Delhi in 2007. Dominique Monnet of the European Centre for Disease Prevention and Control reports that seventy-seven cases of NDM-1 were diagnosed in thirteen European countries between 2008 and 2010 along with at least three cases identified in the US as of November 2010 [3]. About two-thirds of the European cases have been in Great Britain, where seven patients have died.

NDM-1 Worldwide Distribution

Nordmann et al. 2011.

Given that the majority of European cases, particularly in Britain, have occurred in patients who had recently traveled to and/or received medical care on the Indian subcontinent, this region is believed to be the origin. Each of the three American cases, from different states, had also received medical care in India prior to becoming ill. Healthcare officials have since discovered NDM-1 throughout India, Pakistan, and Bangladesh. A healthcare center in Mumbai ascertained that twenty-two of the twenty-four species of carbapenem-resistant Enterobacteriaceae isolated in the hospital from August to November 2009 produced the NDM-1 enzyme [5].

Additional cases have been found in Austria, the Netherlands, Belgium, the Sultanate of Oman, Kenya, China, Japan, Singapore, Taiwan, Australia, and Canada [4]. Officials have also known for many years that hospitals their patients are reservoirs of multiple-antibiotic resistance. Hospitals’ serving patients with NDM-1 and treating international patients who potentially transport the “super” pathogen home with them perhaps best account for this rapid global spread.

 Dr. Conly maintains that the emergence of NDM-1 underlines the trend of ever-growing global antibiotic resistance [1]. NDM-1 poses a serious threat not only in countries like the US and UK where antibiotic use has become widespread, but also in nations such as China and India, as well as many African and Latin American nations, where antibiotic application is on the rise. Most dangerous may be the excessive use of antibiotics in livestock, which are often the primary hosts of microbes such as E. coli and are then transmitted to human hosts via contact with and consumption of the animals. Some estimates place antibiotic use in feedlots and fisheries at over 1000 times greater in sheer tonnage than that of antibiotic administration to humans [1].

While it would be unrealistic to assume, at least at present, that we could eliminate all NDM-1 bacteria, strides can be made to halt its transmission. The existence of multiple-antibiotic resistance highlights the consequences of excessive use of antibiotics, a most convincing incentive to sharply reduce antibiotic usage in both humans and livestock [4]. The emergence of “superbugs” also emphasizes the importance of research into different types of antimicrobial agents. With such common human pathogens as E. coli bearing the NDM-1 enzyme, the issue becomes even more pressing and should be investigated by scientists around the globe before a pandemic can erupt.

Given that hospitals are likely the focal point of human transmission of NDM-1, other nations may want to consider the policy adopted by the French Health Authority in September 2010, which requires screening international patients for multidrug-resistant bacteria on the day of admission to a medical facility [1]. Perhaps such screening should be added to the standard array of tests conducted for all patients displaying symptoms of a bacterial infection so that infected persons can be treated before spreading NDM-1 to others. Such policies naturally raise concerns about how and where individuals testing positive for multiple-antibiotic resistant bacteria should be treated. Nevertheless, the risk of further spreading NDM-1 worldwide warrants great care in evaluating potential new sources of outbreaks, especially until researchers have formulated safer antimicrobials effective against bacteria armed with carbapenemases.

References

1. Conly, J. 2010. Antimicrobial resistance: revisiting the “tragedy of the commons.” Bulletin of the WHO. 88 (11): 797-876.
2. Green, V. et al. 2011. Structure of New Delhi metallo-beta-lactamase 1 (NDM-1). Acta Cryst. F67: 1160–1164
3. Kelland, K. 2011. “Super Superbug” NDM-1 Spreads in Europe. Clin. Infect. Dis. 52 (4): i-ii.
4. Nordmann, P. et al. 2011. Does broad-spectrum b-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria? J. Antimicrob. Chemother. 66: 689-692.
5. Pillai, D.R. et al. 2011. New Delhi metallo-ß-lactamase-1 in Enterobacteriaceae: emerging resistance. Canad. Med. Assoc. J. 183 (1): 59-64.

Jessica Kowalik is a senior at The George Washington University double-majoring in Biological Sciences and Art History. Follow The Triple Helix Online on Twitter and join us on Facebook.

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