Nothing to see here, please move along

It's been a quiet week out here on the edge of the blogging prairie. Some of us are recertifying, some are in the middle of huge grant deadlines and some are chairing a giant meeting planning committee with the meeting imminent. But, we still think about you every second and we miss providing you with up-to-date infection prevention information...

In the interim, we have created a little poll off to the right, which you can use to let us know how you like to read or follow the blog.  Vote early and often.

From the nothing to see here column: We've heard new reports that the NIH KPC outbreak that was halted by whole-genome sequencing is back. On September 7th there was a new case of the KPC strain, the first since January and 19th overall. The blood stream infection resulted in the unfortunate death of boy from Minnesota, the seventh fatality attributable to the strain.

NOW SEE THIS: Registration for ScienceOnline2013 is now officially open. It's the seventh annual un-conference exploring science on the Web and takes place Jan. 30-Feb. 2, 2013, in Raleigh, NC. Registration for the first round of 100 slots is closed for today, but there are two more opportunities to register: Thursday, Sept 20, 2012 at 2:00 PM (EDT) and Friday, Sept 21, 2012 at 11:00 PM (EDT). By rumor I heard that these sessions last only minutes, so log on near those start times and keep refreshing your browser. All seems pretty exciting.

The Rise of the MIC: Microbiological Industrial Complex

Mike "Alexander" Edmond

Note: This is the post I wanted to write regarding the NIH Clinical Center KPC outbreak last week until I noticed the posts and comments blaming the front line infection prevention staff.

"...we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the military-industrial complex (MIC). The potential for the disastrous rise of misplaced power exists and will persist....As we peer into society's future, we-you and I, and our government-must avoid the impulse to live only for today, plundering, for our own ease and convenience, the precious resources of tomorrow. We cannot mortgage the material assets of our grandchildren without risking the loss also of their political and spiritual heritage." - President Eisenhower's Farewell Address January 17, 1961

In microbiology and clinical medicine, the MIC is the "lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation."  I think it's time to recognize a new definition for MIC: the Microbiological Industrial Complex. The MIC encompasses the industry, associated lobbying efforts and government agencies that most benefit from the adoption of expensive and unproven testing and treatment. The MIC has had a tremendous impact on infection prevention practice through economic forces pushing for MRSA active surveillance mandates and perhaps mandatory flu vaccinations of health care workers. This MIC leads to the utilization of expensive (and largely unproven) interventions at great cost both economically and to the well-being of patients.  The more we spend on expensive sequencing, the less we can spend on actual prevention. Hand hygiene might not be sexy, but it does more to prevent the spread of resistant infections than any PCR test.

The latest evidence of the insidious rise of the MIC is the initial discussion surrounding the NIH Clinical Center KPC outbreak. So far, the only paper describing the outbreak covered the miracle of whole-genome sequencing and how it helped halt the outbreak, which it most certainly did not. The outbreak was halted using a grab bag of unproven and expensive interventions including the hiring of 9 hand hygiene "police" that monitored infection control practice 24-7.  Even NIH's Henry Masur speaking today on the Diane Rehm show said that sequencing "didn't conclusively prove" (what caused the outbreak).  Both he and Jule Segre suggested they only stepped up their infection control efforts because of the whole genome sequencing evidence, which is almost certainly not true. They would have used infection control escalation even without expensive testing. (listen to the Diane Rehm show segment here)

To understand the power of the MIC, you don't have to look further than a recent MSNBC report, which noted that the NIH sequencing cost $40,000 and suggested that this technique could spawn a $1 billion industry in the US alone. In discussing the whole genome technique, Dr. Segre was noted to say "When you have patients in your ICU who just paid $100,000 for an organ transplant,"...spending a few thousand dollars to protect them from an outbreak of deadly bacterial infections "doesn't seem like too much to ask."

It seems to me that since there is no evidence that whole genome identified the source of transmission here or elsewhere and even if it did it wouldn't have altered the course of the outbreak, we might better spend our infection control research and clinical dollars elsewhere.  Unfortunately, the MIC has more money and more NIH backing. The NIH has a National Human Genome Research Institute but it doesn't have a "National Infection Prevention Institute", for example.

Almost a year ago, Mike peered through his crystal ball and accurately predicted the future of KPC prevention in the US.  The NIH outbreak and report starts the countdown, and much like MRSA before it, the prevention efforts will be focused on expensive DNA surveillance efforts backed by large industry lobbying efforts and not investments in the research and expansion of basic and simple infection control efforts. It is easy to blame the healthcare worker for not washing their hands and look for a quick scientific panacea (DNA). Sadly, given that there have been only four high-quality hand hygiene improvement studies since 1980, we haven't provided clinicians with the proven tools to improve hand hygiene. If we continue to bow to the pressure of the MIC and avoid the harder tasks of infection prevention, we will be squandering our precious resources of tomorrow (antibiotics), as Eisenhower warned 50 years ago.

Further Reading:
(1) Maryn McKenna: The ‘NIH Superbug’: This Is Happening Every Day
(2) Ed Yong:  Genome detectives unravel spread of stealthy bacteria in a hospital
(3) Dr. Judy Stone: The NIH Superbug Story-A Missing Piece
(4) Mike the Mad Biologist: Some thoughts on the CRE Superbugs

Image source: wikimedia commons

Not a failure, a lesson. The NIH KPC Outbreak

Mike posted about this yesterday and I'm sure we'll have more posts concerning the deadly KPC outbreak that occurred last year at the NIH Clinical Center. Since the whole report is behind a paywall (why is that??), I thought I'd describe the interventions taken to control the outbreak and also let you peruse the description of the 18 cases and 11 deaths (See table below).

The kitchen sink: the problem
and the current solution

Infection control measures used:
1) Index patient placed on enhanced contact isolation on admission.
2) All ICU patients during the outbreak were placed on universal enhanced contact precautions during their entire stay
3) A wall was built in the ICU, so that all KPC+ patients could be placed in a new six-bed unit
4) Infection control compliance monitors were hired (peak use was 9 monitors) who ensured that all healthcare workers entering the rooms practiced enhanced contact precautions and hand hygiene. Suboptimal monitors were fired
5) A private firm was hired to decontaminate the ICU and all KPC+ patient rooms using hydrogen peroxide vapor
6) Staff were cohorted so that staff did not care for both KPC+ and KPC negative patients
7) When the KPC was found in a sink, they tore out the plumbing
8) Active surveillance culturing using rectal and throat swabs was utilized

What an amazing effort by Tara Palmore and others at NIH. Why did it take so long to control the outbreak? It's not their fault. I was in a similar situation with an acinetobacter outbreak in 2002. What I faced in 2002 and what Dr. Palmore faced last year is that there is almost no science behind infection prevention interventions. We literally don't know what works or where in works. What this outbreak demonstrates is what happens when you make little investment in infection control science in decades. We don't know how to prevent these outbreaks, so we throw the kitchen sink (literally in this case) at them hoping something works.

Not every hospital can afford to undertake all of the expensive construction and staffing interventions that the NIH did, especially since it isn't clear what works and what doesn't. Unless we make serious efforts in understanding the science behind hand hygiene compliance improvement, optimal use of contact isolation, environmental cleaning and other "unstudied" areas, this scene will continue to be repeated over and over again. These outbreaks are happening every day in the US and patients are dying (see below). We need science in infection prevention just as much as we need novel antibiotics.  The lesson needs to be that we fund CDC and other agencies to direct the infection prevention studies necessary to prevent and terminate these terrible outbreaks.

The wrong lesson is to blame frontline infection prevention staff for fighting an outbreak with one hand behind their back and not being successful. We need to stop blaming clinicians and start funding the science to assist our infection prevention efforts.  If we won't have novel antibiotics for 10-20 years, we better start getting serious about infection prevention.

Scary KPC outbreak at the NIH

Today's Washington Post contains an article that will send chills down the spine of every hospital epidemiologist and infection preventionist in the world. It describes an outbreak of carbapenem-resistant Klebsiella pneumoniae (KPC) at the hospital of the National Institutes of Health in Bethesda. Over a 6-month period last year, 17 patients became colonized or infected with KPC; of these 8 developed bloodstream infections. A total of 11 patients died; 6 of these deaths were attributed to the infection.

The outbreak was terminated using typical interventions (cohorting of patients and staff, active surveillance cultures, contact precautions, and enhanced cleaning protocols). Further details can be found in a report in Science Translational Medicine (abstract here, full text requires subscription). This report outlines how the outbreak was able to be tracked using whole genome sequencing, which allowed the epidemiologists to determine that the entire outbreak could be traced to a single patient. Traditional molecular typing with PFGE would not have provided enough discriminatory power to do this.

KPC is a horrible organism. As shown here, over half of colonized patients developed bloodstream infection and three-quarters of those died. This bug makes MRSA look like a teddy bear. We desperately need new antibiotics to combat this organism as many strains are resistant to all available antibiotics.

Detecting and preventing carbapenem-resistant Enterobacteriaceae (CRE)

Late last week, the CDC issued new guidance for control of CRE. You can read my 2009 post for thoughts on their initial guidance. This update expands on that guidance, providing tailored recommendations for different settings, ranging from regions where no CRE have been reported to those in which CRE are common. The guidance also emphasizes regional control and the role of long term care (and “long term acute care”) in the epidemiology of CRE.

I think the new guidance is on the mark, and should be helpful as we struggle with how to respond to these bad bugs. As was the case back in 2009, my main concern relates to the screening recommendations. Not all CRE are created equal, and the test methods available to most laboratories are not good at differentiating among the really nasty (e.g. KPC- and NDM-producers) and the moderately nasty (e.g. chromosomal cephalosporinase + porin protein mutation). The former have much greater outbreak and local-regional spread potential, which is why the modified Hodge Test (MHT) has been used to single them out. But the MHT is not always easy to interpret, can have falsely positive and negative results, and seems to perform especially poorly in detecting certain carbapenemases (e.g. NDM). The CLSI has issued lower MIC breakpoints to better detect CRE, but these breakpoints are (appropriately) designed to guide therapy for individual patients, not to provide detailed information about resistance mechanisms for infection prevention or public health purposes. Lower breakpoints means more CRE detected, most of which do not carry mobile resistance elements like KPC and NDM. Do we respond to them in the same way (they are still resistant, after all….)?

I favor making CRE (at least those due to carbapenemases) reportable, as a couple states have done, along with periodic regional prevalence surveys to help facilities and public health departments understand local and regional epidemiology of CRE (and to help detect emerging new resistance mechanisms). These surveys would need to rely on culture, with referral of all isolates that have a CRE phenotype to state or regional labs that can do the molecular work to determine the underlying mechanism(s).

Predicting the future

There's a perspective in this month's Emerging Infectious Diseases on carbapenemase-producing Enterobacteriaceae (full text here). For the most part, it's a well written piece that focuses on the geographic spread of these organisms. Near the end, however, the authors make a pitch for active surveillance:

The prevention of spread of carbapenemase producers relies on early detection of carriers. Patients who undergo screening should include patients who were hospitalized while abroad and then transferred to another country, and patients at risk (e.g., patients in intensive care units, transplant patients, immunocompromised patients). Screened patients should be kept in strict isolation before obtaining results of the screening (at least 24–48 hours). Because the reservoir of carbapenemase producers remains the intestinal flora, fecal and rectal swab specimens are adequate for performing this screening. 

Yikes! If I followed their advice my hospital would probably be doing a few hundred tests per week. I'll leave the thorny problem of what test to do to Dan, our blog's microbiologist. But more active surveillance means more contact precautions. And we love contact precautions!

Photo: Managed Care Matters

So let me look into my crystal ball and predict the future for our readers:

• A diagnostic testing company will develop a rapid test for the detection of these organisms
• The diagnostic testing company will become a strategic partner to A Group that Represents Infection Preventionists (AGRIP)
• AGRIP will survey all of its members on whether they have ever seen such organisms in their hospitals
• A paper will be published along with a press release revealing the shocking news from the survey that these organisms are much more prevalent than anyone ever imagined
• The strategic partner (bless their heart!) will help AGRIP educate the infection control community and the public on the dangers of this horrible organism
• I'm a little fuzzy on this prediction, but there may be a second survey
• States will pass laws requiring testing of patients admitted to hospitals to protect their citizens from the horrible organism
• The strategic partner will hire a new vice president and all will live happily ever after

I will now put the crystal ball away, return to my regular life as a horizontalist, and simply scream, WASH YOUR HANDS, PEOPLE. WASH YOUR HANDS!!!

Regional Control of a large KPC outbreak: The Israeli Experience

The oubreak DID NOT occur here.
However, it IS St. Patrick's Day.

Hello everybody.  I hope you're all having a great St. Patrick's Day and a great Match Day.  Not sure those two days should be combined, at least for the safety of the future of the medical profession, but for some reason, that decision is not left up to me...

There is a report out electronically in CID (scheduled for April 1) by Mitch Schwaber et al. that describes the containment of a country-wide, carbepenem-resistant Klebsiella pneumoniae outbreak in Israel.  The outbreak of a highly-resistant strain, typically susceptible only to gentamicin and colistin, began in 2006 in multiple Israeli hospitals. The resistance was mediated by KPC-3 and local efforts to control the outbreak were largely unsuccessful. By March 31, 2007 there had been 1275 patients in 27 hospitals affected (13,040 beds).

In March 2007, the Israel Ministry of Health implemented a 3 component intervention: 1) Mandatory reporting of every patient with a carbepenem-resistant Enterobacteriaceae (CRE); 2) mandatory contact isolation of all known CRE carriers within self-contained nursing units in single rooms or cohorts with dedicated equipment AND dedicated nursing; and 3) creation of a nationwide task-force with statutory authority to intervene as necessary to control the outbreak.

Did it all work?  Well, they probably wouldn't have published this if it didn't work. They'd still be working too hard trying to stop the problem!  From the peak of 185 cases (56 cases/100,000) in March 2007 (92% of CREs were Klebsiella) infections fell to a low of 45 (12 cases/100,000) in May 2008, a 79% decline. I have pasted the incidence curve below. So it worked, but there are still too many CREs. If they let their guard down, the outbreak could easily reoccur.

As far as the study design, the usual caveats apply.  Despite great statistical control, they did not include a non-equivalent control group, etc, so perhaps these findings could be partially explained by regression to the mean or other biases, such as non-recorded interventions. Do I think that is what is going on here?  No.  I think the nationwide effort probably worked and their analysis and interpretation are correct.  This overwhelming response might be needed more often in the future given the lack of new antimicrobials, poor overall support for infection control (everywhere, not just in Israel) and continued overuse of the antimicrobials we do have.

Reference: Schwaber MJ et al. CID April 2011

Note: Dan posted on the CDC Guidance for Carbapenem-Resistant Enterobacteriaceae a couple years ago.

VIM-producing carbapenem-resistant Klebsiella pneumoniae

CDC just released in MMWR a report of the first case of a Verona integron-encoded metallo-beta-lactamase (VIM) carbapenemase in an Enterobacteriaceae in the United States. The patient was initially hospitalized in Greece and then transferred to a US hospital.  CDC was notified in July and, fortunately, the screening of the 22 patients whose U.S. hospital stays overlapped with this patient were all negative. I would write more, but a nice post by Alex Kallen from the CDC puts this in the proper context.

Sept 24 MMWR article
Alex Kallen CDC post