'We Have a Limited Window of Opportunity': CDC Warns of Resistance 'Nightmare'

It’s not often that you get to hear a top federal health official deliberately deploy a headline-grabbing word such as “nightmare,” or warn: “We have a very serious problem, and we need to sound an alarm.”

Dr. Thomas Frieden, director of the US Centers for Disease Control and Prevention, said both Tuesday, during a press conference announcing new CDC statistics on the advance of the highly drug-resistant bacteria known as CRE. His language — plus the fact that he conducted the entire press conference himself, instead of just making a brief opening statement — seem to me a clear signal that the CDC is taking this resistance problem seriously, and hoping we do too.

And we should. Here’s what the CDC announced Tuesday:

  • Healthcare institutions in 42 states have now identified at least one case of CRE.
  • The occurrence of this resistance in the overall family of bacteria has risen at least four-fold over 10 years.
  • In the CDC’s surveillance networks, 4.6 percent of hospitals and 17.8 percent of long-term care facilities diagnosed this bug in the first half of 2012.

Those are dire reports.

Here’s some back-story: CRE stands for “carbapenem-resistant Enterobacteriaceae.” Enterobacteriaceae are a family of more than 70 bacteria which share the characteristic of being gut-dwelling (“entero”); they include Klebsiella, Salmonella, Shigella and E. coli. Carbapenems are a “last-resort” family of antibiotics — imipenem, meropenem, doripenem and ertapenem — which are used against these bacteria when they have become resistant to other drugs. (Carbapenem resistance is conferred by a number of different genes and so sometimes goes by a number of other acronyms, including KPC, VIM, OXA and the “Indian superbug” NDM-1.)

CRE tends to attack in ICUs and other critical care, and also in rehab units and nursing homes. That is for several reasons. First, because patients in those settings are uniquely vulnerable to infection, not just because of their illness but because the protective barrier of their skin has been breached by ports and catheters, and also because they are visited and touched by a lot of people. Second, because they are likely to be receiving heavy-duty antibiotics which put the bacteria in their bodies under evolutionary pressure. Third, because those drugs plus others cause diarrhea, which spreads gut-dwelling bacteria into the air and area. And fourth, because those bacteria are particularly good at surviving on the kind of surfaces — plastic, glass and metal — that you find in health care.

Carbapenem resistance first appeared in the US in 1996, in a single sample containing KPC that the CDC found in a hospital in North Carolina. By the early 2000s, it was causing significant outbreaks in hospitals in New York City; from there, it spread with New Yorkers to “snowbird” vacation locations, and then to Israel, and then started moving around the globe. (You can read that history in a piece I did for Scientific American in April 2012; and my past posts on all this are here.)

The map of CRE in the US now looks like this, as released by the CDC yesterday. Among the outbreaks represented on that map are the “NIH superbug” outbreak last year (described in these two posts and by Carl Zimmer on the magazine side of Wired), and also an outbreak of NDM-1 in a Rhode Island hospital in 2011. But — and the CDC acknowledges this — the map is probably an understatement, for several reasons. CRE is not what public health calls a “reportable disease”; according to the CDC, only six states require that physicians or hospitals tell the rest of the world they have diagnosed it. (Three others are “considering” making it reportable.) Plus, surveillance for CRE is patchy; yesterday’s CDC report comprised data from three different surveillance systems. And also, there are carbapenem-resistant bacteria causing outbreaks in the US which are not counted as CREs because the bacteria are not Enterobacteriaceae. For one example, take a look at the breathtaking trend line in this map of carbapenem-resistant Acinetobacter, put together by the ResistanceMap project at the Center for Disease Dynamics, Economics and Policy.

The tone of the CDC press conference yesterday was unusually somber and blunt. Frieden said:

CRE… pose a triple threat. First, they’re resistant to all or nearly all antibiotics.  Even some of our last-resort drugs.  Second, they have high mortality rates.  They kill up to half of people who get serious infections with them.  And third, they can spread their resistance to other bacteria.  So one form of bacteria, for example, carbapenem-resistant Klebsiella, can spread the genes that destroy our last antibiotics to other bacteria, such as E. coli, and make E. coli resistant to those antibiotics also… We only have a limited window of opportunity.

The underlying risk here is that effectively untreatable CRE will spread out from hospitals and into the wider world, where it will become vastly more common and much harder to detect. That is not an unreasonable fear, given that the Enterobacteriaceae include incredibly common E. coli, which has already been found to be causing bladder infections bearing a slightly less dire form of multi-drug resistance, known as ESBL.

So what’s to be done? In their press push yesterday, the CDC reviewed six steps that they first published last year in a CRE Toolkit and want health care facilities to take:

  • enforce infection-control precautions (that’s hand-washing, gowning and gloving, and so on)
  • group patients with CRE together in one part of a unit or facility
  • reserve certain rooms, pieces of equipment and staff members for CRE patients
  • require hospitals, nursing homes and so on to tell each other when they are transferring a patient with CRE
  • interrogating patients about recent medical care elsewhere, including in other countries
  • and using antibiotics conservatively, so that bacteria don’t get much of a chance to develop resistance to the last-resort drugs.

But an important point is that none of this is required, and none of this is funded. When the Netherlands wanted to beat back the emergence of MRSA, that country passed laws requiring every hospital to test patients before letting them in the door. (That story is told in this book.) When Israel wanted to counter KPC, which was ripping through its hospitals after arriving from the US, it created a national task force and imposed mandatory national measures for detecting and confining the infection. (That program is described in this 2011 paper.) And hospitals are on their own in figuring out how to organize and pay for CRE control. There are no reimbursements, under Medicare, for infection-control as a hospital task; and as infection-prevention physician Eli Perencevich demonstrated two years ago, the National Institutes of Health is not funding resistance-countering research.

(It is well worth reading Perencevich’s response, posted yesterday, to CDC’s CRE announcement. Money quote: “This is not a national response. This is a national tragedy.”)

So what’s the takeaway? Public reaction to news of antibiotic resistance seems to follow a predictable pattern: Instant alarm, followed almost immediately by apathy. Despite writing about this for years, I still haven’t figured out whether people think it will never happen to them, or whether they assume there will always be another drug to save them — both assumptions that are incorrect. But I’ve also written about the CDC for years, and I can’t remember many times when they have made statements as strongly worded as yesterday’s. It will be interesting to see whether the news sinks in this time.

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Maryn

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