NDM-1 Will Reach the U.S. How Will We React?

One of the most threatening forms of antibiotic resistance to have evolved in the last few years is NDM-1 (‘New Delhi metalobetalactamase-1). This antibiotic resistance gene confers resistance to all penicillin derivatives–those drugs that begin with “cef-” and “ceph-” or end with either “-cillin” or “-penem.” Since NDM-1 is found on plasmids–mini-chromosomes that not only can move from bacterium to bacterium, but also carry other antibiotic resistance genes, bacteria that carry NDM-1 often are pan-resistant and difficult or impossible to treat with antibiotics.

Maryn McKenna provides some good background and news from a recent conference:

It’s been more than a year since the “Indian superbug” NDM-1 — not actually a bacterium, but a gene that directs production of an enzyme — hit the news. The enzyme, whose acronym is short for New Delhi metallo-beta-lactamase-1, disables almost all antibiotics directed against it, leaving the bacteria in which the gene appears vulnerable to only two imperfect and sometimes toxic drugs.

The enzyme and its gene, blaNDM-1, were first identified in 2008 in people who had traveled in India or sought medical care in South Asia. Hence its name: Many beta-lactamases, enzymes that denature the very large class of everyday antibiotics known as beta-lactams, are named for countries and cities where they were first identified. Since its identification, NDM-1 has been discovered in patients in more than a dozen countries and has also been found to be widely harboured outside hospitals in India, and in surface waters and sewage there.

The unveiling of NDM-1 clearly caused embarrassment for India, and media and lawmakers there struck back, throwing around intemperate language and claiming the naming of the enzyme was a plot to derail the subcontinent’s medical-tourism industry — even though the Indian doctors had attempted to raise the alarm earlier and had been ignored.

The Indian government’s response can, at best, be described as conflicted. Different agencies (state versus federal) are stating different results regarding the prevalence of NDM-1. The federal response unfortunately appears to still be reflexive and defensive. Meanwhile, the researchers who first characterized the problem claim that NDM-1 might be found in 10% of the non-clinical population. The barn door isn’t only open, the horses are breeding like rabbits . Or something (although in India, the problem seems to stem largely from clinical misuse of antibiotics, not agricultural use).

Suffice it to say, I don’t have much confidence in India’s ability to contain the problem. It will hit the U.S. So how has the U.S. prepared for this?

Not so well.

Here’s the key advice from a 2010 CDC advisory:

Clinicians should be aware of the possibility of NDM-1–producing Enterobacteriaceae in patients who have received medical care in India and Pakistan, and should specifically inquire about this risk factor when carbapenem-resistant Enterobacteriaceae are identified. CDC asks that carbapenem-resistant isolates from patients who have received medical care within 6 months in India or Pakistan be forwarded through state public health laboratories to CDC for further characterization. Infection control interventions aimed at preventing transmission, as outlined in current guidance (5), should be implemented when NDM-1–producing isolates are identified, even in areas where other carbapenem-resistance mechanisms are common among Enterobacteriaceae.

The current hospital protocol is the following (boldface mine):

All patients colonized or infected with CRE or carbapenemase-producing Enterobacteriaceae [E. coli and relatives] should be placed on contact precautions. Acute care facilities should establish a protocol, in conjunction with CLSI guidelines, to detect nonsusceptibility and carbapenemase production in Enterobacteriaceae, particularly Klebsiella spp. and Escherichia coli, and immediately alert epidemiology and infection control staff members if identified. All acute care facilities should review microbiology records for the preceding 6–12 months to ensure that previously unrecognized CRE cases have not occurred. If previously unrecognized cases are identified, facilities should conduct a point prevalence survey (a single round of active surveillance cultures) in units with patients at high risk (e.g., intensive care units, units where previous cases have been identified, and units where many patients are exposed to broad-spectrum antimicrobials) to identify any additional patients colonized with carbapenem-resistant or carbapenemase-producing Klebsiella spp. and E. coli….When a case of hospital-associated CRE is identified, facilities should conduct a single round of active surveillance testing of patients with epidemiologic links to the CRE case (e.g., those patients in the same unit or patients who have been cared for by the same health-care personnel).

…Situations where periodic point prevalence surveys repeatedly fail to identify other colonized patients suggest that infection control measures at the facility are effective in controlling transmission. In such instances, consideration should be given to halting active surveillance cultures in response to clinical cases and replacing them with periodic point prevalence surveys in units with patients at high risk to ensure that carbapenem-resistant or carbapenemase-producing Klebsiella spp. and E. coli do not reemerge.

…Because the prevalence of CRE is low in the majority of U.S. hospitals, routine microbiologic surveillance of persons admitted, such as that performed in some facilities to detect carriage of methicillin-resistant Staphylococcus aureus, is not recommended. However, in some areas of the United States, notably New York City, CRE are routinely recovered, including from many patients who are admitted from the community. In these settings, point prevalence surveys in response to detected clinical cases might be less useful in controlling transmission of CRE. Facilities in regions where CRE are endemic should monitor clinical cases of CRE and implement the intensified (i.e., Tier 2) infection control strategies outlined in the 2006 HICPAC guidelines if rates of CRE are not decreasing (2). The challenges to hospitals of allocating additional resources to prevent and control CRE are balanced by the fact that an aggressive infection control strategy, such as that recommended in this report, offers an opportunity to limit the impact of these problematic pathogens while CRE prevalence remains low in most U.S. hospitals.

What worries me are the 2006 guidelines regarding staff testing (not staph). According to the guidelines, that is basically the last thing one does after exhausting all other possibilities. I think we need to be much stricter: if a ward is shown to have NDM-1, all of the staff on that ward–everybody–is screened, and any carriers are treated for the organism (and obviously not able to work). This is what the Netherlands did (‘search-and-destroy‘) to control MRSA, and it seems to have worked reasonably well.

If we don’t jump on this hard, we’ll have the same kind of problem we’re seeing with MRSA. For once, let’s get out ahead of the problem. If we need emergency funds to pay for the extra financial burden to hospitals, find them.

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2 Responses to NDM-1 Will Reach the U.S. How Will We React?

  1. evodevo says:

    If India is anything like Mexico, the average citizen can buy antibiotics, especially amoxicillin, in any drugstore – no prescription needed. Of course, circumstances like these are perfect for establishing resistant organisms in the population.

  2. Pingback: Why We Can’t Have Nice Antibiotics | Mike the Mad Biologist

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