“The Enemy Within: A New Pattern of Antibiotic Resistance”

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The Story

“The Enemy Within: A New Pattern of Antibiotic Resistance”
http://www.scientificamerican.com/article.cfm?id=the-enemy-within [abstract; subscription required for full access]
by Maryn McKenna
Scientific American, April 2011

The Pitch

[In an interview at The Open Notebook, McKenna describes how she pitched this story:

Christine Gorman [health editor at Scientific American] and I had been acquainted for years because we wrote about many of the same topics but in different venues: I was a newspaper person and she was a magazine person. We knew each other’s bylines and then we talked a few times after she left Time and went freelance. Then I left newspapers and became a freelancer also. When she went to SciAm she let me know and asked for pitches. I sent two or three ideas to her—quick notes, a paragraph each— and she came back and said, “This is the one that most resonates.” And then we went through the formal pitch process of a memo and subsequently an outline. If there’s a lesson in that, it’s: Never lose track of people. That has been reinforced for me in the five years I’ve been a magazine writer. There are editors I know who have been in three jobs in those five years. Maybe someone won’t take something from you at Magazine X, but don’t lose their email—a year from now they may be at Magazine Y.]

When the journal Lancet Infectious Diseases published a paper Aug. 11 on the identification and rapid spread of a novel resistance mechanism in gram-negative bacteria, New Delhi metallo- beta-lactamase (or NDM-1), the reaction was electric. The enzyme, transported on a plasmid, renders E. coli, Klebsiella pneumoniae and other Enterobacteriaceae — some of the most common causes of severe hospital-acquired infections — almost untreatable, by conferring resistance to the drug class called carbapenems, generally considered the “drugs of last resort” for gram-negative bacteria.

By the time the Lancet ID paper saw print, NDM-1 had been spreading for several years. It was first identified in 2008 in Sweden, in a man of South Asian origin who had been hospitalized in India. By 2009, the Health Protection Agency of the United Kingdom was publishing a national alert, and two months before the Lancet paper, the US Centers for Disease Control and Prevention put out its own bulletin, identifying NDM-1 in three patients in three states, each infected with a different gram-negative bacterium. In every country, the spread of NDM-1 was
linked to people moving back and forth to South Asian, and especially to medical treatment there. The government of India reacted furiously to that interpretation and to the naming of the enzyme, denouncing a Western “pharma conspiracy” intended to undermine the subcontinent’s burgeoning medicaltourism industry.

In the ensuring month, some of the heat has died down. At the same time, NDM-1 is unquestionably spreading — currently, to Japan, Canada, Hong Kong, Australia and Belgium so far. But what’s been missed in the furor is that NDM-1 is only one of multiple carbepenem- resistance factors, otherwise known as carbepenemases, that have been moving across the globe with much less fanfare than this one.

Collectively, they pose the question: Once antibiotic resistance factors begin to move from their point of emergence, can anything be done to stop them?

The stage was set for these new resistance factors by the emergence in the 1980s of the extended-spectrum beta-lactamases (ESBLs), which confer resistance not only to antibiotics possessing the four-atom beta-lactam ring that originated with natural penicillin, but also to the most recent generations of cephalosporins. That left medicine reliant on the carbepenems — but in this decade, carbepenem resistance has spread via multiple mechanisms. In Europe and the Mediterranean, the silent culprit is oxacillinases. In the United States — and now in South America, Israel and China — the problem is K. pneumoniae carbepenemases or KPCs, first identified in a single isolate in North Carolina in 1996 and now endemic in New York City.

Why is this wave of carbepenem resistance, of which NDM-1 is just the most recent, so “worrying” and “insidious,” to use papers’ own language? Because carbepenemases are fostered by a unique array of conditions:

They were originally found in bacteria that are common human gut flora, and therefore evade surveillance and can be carried undetected across borders.
They spread easily via mobile genetic elements, between bacterial genera but
also across classes (as vancomycin resistance did in the 1990s from Enterococcus to S. aureus, creating VRSA).
They are spreading with particular speed in countries where antibiotics are easily accessed over the counter; before NDM-1 emerged, other carbepenemase resistance was flagged by researchers in India.
They confer very high-level resistance, a particular problem for gram-negative bacteria, for which almost no new drugs are in the pipeline because they are more complex to develop than drugs for gram-positives.

The story of carbepenemases touches problems of population movement, disease surveillance, antibiotic misuse, healthcare economics and market conditions for drug development. It describes a more profound challenge that the battle to control MRSA, considered the leading organism in the international epidemic of drug resistance. And without exaggeration, it raises the possibility that the 70 years of the antibiotic miracle may be coming to an end; for most carbepenem-resistant strains, only a few older and highly toxic drugs still work, and for one strain of NDM-1, no drugs work at all.

Maryn McKenna is the author of SUPERBUG: The Fatal Menace of MRSA, a narrative account of the 50-year history of drug-resistant staph, published in March 2010 by Free Press/Simon & Schuster. She is a journalist for national magazines and a former staff member at the Center for Infectious Disease Research and Policy at the University of Minnesota. Previously, she was the senior medical writer at the Atlanta JournalConstitution, where she was the only US journalist assigned to full-time coverage of the CDC. She is also the author of BEATING BACK THE DEVIL: On the Front Lines with the Disease Detectives of the Epidemic Intelligence Service (Free Press 2004).

Papers likely to be referenced in this article:

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study Karthikeyan K Kumarasamy MPhil, Mark A Toleman PhD, Prof Timothy R Walsh et al. The Lancet Infectious Diseases – 1 September 2010 (Vol. 10, Issue 9, Pages 597 – 602) DOI: 10.1016/S1473-3099(10)70143-2

Goren MG, Carmeli Y, Schwaber MJ, Chmelnitsky I, Schechner V, Navon-Venezia S. Transfer of carbapenem-resistant plasmid from Klebsiella pneumoniae ST258 to Escherichia coli in patient. Emerg Infect Dis 2010 Jun. Available from http://www.cdc.gov/EID/content/16/6/1014.htm

Krishna B. New Delhi metallo-beta-lactamases: A wake-up call for microbiologists. Indian J Med Microbiol 2010;28:265-6

Nordmann P, Cozon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemanse- producing bacteria. Lancet Infect Dis 2009; 9: 228–36

Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: An emerging public-health concern. Lancet Infect Dis 2008;8 :159-66.

Bratu, S., Landman, D., Haag, R., Recco, R., Eramo, A., Alam, M., Quale, J. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: A new threat to our antibiotic armamentarium (2005) Archives of Internal Medicine, 165 (12), pp. 1430-1435.

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