I thought I was done for the time being with “nightmare bacteria” (the US CDC’s characterization of disease organisms resistant to the last-ditch antibiotics called carbapenems), but there are two stories today that deserve to be called out as examples of how rapidly and dangerously these pathogens are spreading.
In my last post I talked about the under-appreciated emergence of “nightmare bacteria” (those are the Centers for Disease Control and Prevention’s words, not mine) that are widely distributed in hospitals and nursing homes around the world and do not respond to a last-ditch small family of antibiotics called carbapenems. That seemed dire enough, but new research suggests the problem, bad as it looks, has been understated.
There’s an ahead-of-print article in Antimicrobial Agents and Chemotherapy whose authors include David Shlaes, a physician-researcher and former pharmaceutical executive, now consultant, and Brad Spellberg, an infectious disease physician on the UCLA medical faculty and author among other books of Rising Plague, about antibiotic resistance. In a commentary examining the Food and Drug Administration’s promised “reboot” of antibiotic development rules, they analyze privately gathered data on resistance in the United States and conclude the incidence of highly resistant bacteria is greater than the CDC has estimated.
Cast your minds back a few months ago, to when the director of the US Centers for Disease Control and Prevention announced, “We have a very serious problem” with “nightmare bacteria,” and the chief medical officer of the United Kingdom backed him up a few days later, describing a “ticking time bomb” that threatens national security as seriously as terrorism.
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.
News, via the Washington Post‘s hard-working health reporter Brian Vastag: After 6 months with no cases, carbapenem-resistant Klebsiella has surfaced again at the Clinical Center of the National Institutes of Health, and has killed a boy from Minnesota who came to the specialty hospital after a bone-marrow transplant meant to address an immune deficiency. This sad event makes the boy the 19th patient to contract the extremely resistant hospital organism, and the 12th to die from it, since the outbreak began.
You can find here my last post analyzing this outbreak (which was originally reported by the Post following a write-up by NIH staff in the journal Science Translational Medicine). I’m looping back to the subject not just because of this new death, but also to add a few new publications to the discussion, one of them mine.
I mentioned in my last post that I’ve been away on assignment and have been trying to catch up to an onslaught of news. One of the things that broke while I was gone was a new paper in Science Translational Medicine describing the ferocious impact on a hospital at the National Institutes of Health of the arrival of carbapenem-resistant Klebsiella pneumoniae, known for short as KPC or CRKP.
Even though the news is now several days old — the paper went live at noon Wednesday and has been covered in most major media since — I think it’s worth doubling back to take a closer look. Because, with all respect to my media colleagues, I think some of this week’s stories have omitted the larger context. So, a different kind of post for me — less news, more analysis, based on this book, this magazine story, and these past posts on antibiotic resistance. Here we go:
Last night, prompted by Michael Coston’s excellent primer on NDM-1 (one of a set of short courses he publishes periodically), I scrolled through the literature to see what had happened recently with the spread of the “Indian superbug” — actually a gene and enzyme that were first spotted in 2008 and create resistance to almost all antibiotics. (My past posts on NDM-1, going back several years, are here.)
There was a lot to see: Cases in countries as varied as Belgium, Japan, Oman, Singapore and China. Indications that transmission of NDM-1, which at first indicated some travel or family connection to South Asia, has become a pan-European problem with clusters in several countries. Concern that international travelers are transporting bacteria containing the gene without realizing it. And, disappointingly, reassurances from within India, in a new study, that it can “easily combat” NDM-1 — though the fact that a study was conducted, as opposed to the problem just being denied out of existence, must be an encouraging sign.
That tour through the literature made me curious what has been happening in the United States since NDM-1 was first identified in patients here two years ago this week, and I made a note to check when I got back to work today. And then the Centers for Disease Control and Prevention forestalled me, by announcing this morning that there have been 13 cases in the United States so far — including two in which the infection apparently spread within the same hospital.
In all the latest bad news about bacteria becoming highly resistant — through carbapenem resistance, or the “Indian supergene” NDM-1 — there has been one hopeful thread: All of the organisms have remained susceptible to one very old, little-used drug called colistin.
That might be about to change. Which would be very, very bad news.
Tomorrow, Thursday, is World Health Day, an annual observance that the World Health Organization uses to focus attention on some critical global-health issue. This year, they’ve chosen antimicrobial resistance as the issue that most needs highlighting. Noting the choice, the Lancet editorialized: “Resistance has joined the front rank of global health concerns.”
On the day, the WHO and some other agencies and organizations will be announcing plans and strategies. I’ll cover those tomorrow. For today, a scene-setter: Why you should care.
Having spent the last couple of years immersed in antibiotic resistance (because, you know, I wrote a book about it), I’m often puzzled why it doesn’t excite more alarm. I’ve concluded our situation is similar to the overused analogy of the frog in the slowly warming water: We don’t realize how bad things have gotten, even when we’re in imminent danger of death.
So here’s a round-up to remind us, drawn just from recent news.
In hospitals: Very large hospital systems are using more broad-spectrum last-resort drugs. Last weekend, representatives of the Veterans Health Administration disclosed that over 5 years, vancomycin use has gone up 79 percent, and carbapenem use, 102 percent. Vancomycin is the only affordable drug of last resort for MRSA; carbapenems are the drugs of last resort for gram-negative infections such as Klebsiella. The use of those drugs is growing because organisms are becoming multi-resistant to less-powerful drugs, but they are becoming resistant to the big guns too. Carbapenem resistance in Acinetobacter, a bacterium that afflicts ICU patients and gravely wounded military members, rose from 5 percent of isolates in US hospitals in 2000 to 40 percent in 2009. Israeli scientists reported this month that carbapenem-resistant Klebsiella pneumoniae (CRKP, subject of my Scientific American article this month) caused a nationwide outbreak in 2007 and 2008, sickening 1,275 patients in 27 hospitals before it was brought under control. [Read more…]
Remember NDM-1, the “Indian supergene” that created a media furor last fall and then fell below the news horizon? This is worse.
I have a story in the April Scientific American (“The Enemy Within,” just previewed online) about a new and very troubling form of antibiotic resistance: Carbapenem resistance, spreading through Gram-negative bacteria such as Klebsiella (above, from the CDC) and E. coli.
Carbapenems are drugs of last resort for Gram-negatives, which include many of the bacteria that cause potentially deadly infections in debilitated ICU patients and frail elderly in nursing homes. Gram-negatives have been becoming ever-more resistant to antibiotics, but the carbapenems remained reliable drugs of last resort for even the most serious cases. Then, in 1996, researchers at the Centers for Disease Control and Prevention spotted the first signal that carbapenems were under threat: A single bacterial sample, found in a patient in a North Carolina hospital, that was resistant to the carbapenems and could only be treated by a few remaining drugs that were much less effective or so toxic that medicine had put them on the shelf years ago.
By 2000, that same resistance pattern surfaced in hospitals in Manhattan: first one, then another, then a third and fourth. Then it began to spread to cities where New Yorkers vacation, and then to countries where they travel. Now, more than a decade later, it has reached at least 37 states and at least a dozen countries around the world.
It is spreading much faster than drugs to combat it could be developed — if there were such drugs. One of the difficulties, indeed tragedies, of carbapenem resistance is that there are very few such drugs left — because, for reasons I’ve explored before, drug development in the United States has ground to a halt. For resistant Gram-negatives, there are almost no drugs left, and none on the immediate horizon. If that scares you, well, it should.
Here’s a quick snip from the article:
The end of the antibiotic miracle is not a new theme. For as long as there have been antibiotics, there has been antibiotic resistance: The first penicillin-resistant bacteria surfaced before penicillin was even released to the marketplace in the 1940s. And for almost that long, doctors have raised the alarm over running out of drugs, sparked by the global spread of penicillin-resistant organisms in the 1950s and followed by methicillin resistance in the 1980s and vancomycin resistance in the 1990s.
This time, though, the prediction of post-antibiotic doom comes from a different part of the microbial world. The genes that confer carbapenem resistance have appeared over the past decade or so in a particularly challenging grouping of bacteria called gram-negatives.
Gram-negative bacteria are promiscuous: They facilely exchange bits of DNA, so that a resistance gene that arises in Klebsiella, for example, quickly migrates to E. coli, Acinetobacter and other gram-negative species. Gram-negative germs are also harder to dispatch with antibiotics because they have a double-layered membrane that even powerful drugs struggle to penetrate, and possess certain internal cellular defenses as well. In addition, fewer options exist for treating them. Pharmaceutical firms are making few new antibiotics of any type these days. For the protean, stubborn gram-negatives, they have no new compounds in the pipeline at all.
Carbapenem resistance has already brought hospital-acquired infections to the brink of untreatable. The imagined future that keeps health authorities awake at night is the undetected dissemination of carbapenem resistance genes into organisms that cause everyday maladies—such as E. coli, which is responsible for most of the millions of urinary tract infections in the U.S. every year.
Carbapenem resistance in Klebsiella — which is sometimes called KPC or CRKP for short — got a spike of attention last week just as my piece hit the web. Coincidentally, the article posted just as the Los Angeles County Department of Public Health released results of a survey showing 356 cases just between June and December 2010 just in LA County medical facilities.
This SciAm piece is the first that we know of to tell the whole tangled, troubling story. I hope you’ll take a look.
And while you’re there, please read SciAm’s brave and cogent editorial against antibiotic overuse in industrial-scale agriculture. It’s marvelous.