The landscape of MRSA in America's largest healthcare system: Acquisition carries a 1-4% chance of infection in the following year!

Note to readers: This is another guest post by esteemed FOTB (friend of the blog) Dr. Daniel Morgan. Soon I'll give him the keys, in the hopes he'll post more frequently!

One of the most informative articles I’ve read in 2018 on healthcare-epidemiology has largely sailed under the radar. This article summarizes the numbers for MRSA across the US Department of Veterans Affairs (VA). In the VA we perform active surveillance testing on admission and discharge to acute and long term care centers. A wealth of data is collected reflecting community and academic settings across all regions of the country. The reporting of extensive numbers without a single message probably made this study less eye-grabbing. The excellent team of data-savvy researchers at the Salt Lake City VA/University of Utah have done extensive cleaning and validating to come up with outcomes for almost 1 million first admissions from 2008-2015. Yes, 1 million patients who had MRSA surveillance tests on admission and discharge. They then followed them for a year post discharge to look for infection. Some may quibble that “acquisition” isn’t using whole genome sequencing but no past study comes close to having this much data. Congrats to Rich Nelson, Mike Rubin and colleagues! People should be dissecting these numbers for much guidance on MRSA. (And Mike, sorry to Lance Peterson you by reinterpreting your own data…but at least I didn’t title this “Mike Rubin’s team shows MRSA surveillance and isolation are of low value!”) 

A few nuts and bolts:

I will focus on non-ICU admissions for ease of numbers, but ICU conclusions are almost identical. There were 902,354 total patients admitted to non-intensive care units. 

• 7.3% (65,783 patients) were MRSA + on admission 
• Fewer than 1% (0.81%, 7,342 patients) acquired MRSA (negative on admission, positive on discharge)

They defined infection a few different ways: 

• Definite infection: MRSA + culture from sterile site—blood, CSF etc. 
• Likely infection: All Definite infections & patients on anti-MRSA antibiotics within 5 days culture 
• Possible infection: Any positive MRSA culture from any site (reflecting colonization and infection) 

Some conclusions: 

Acquisition of MRSA carries a small risk of developing infection. In contrast to past articles, across a broad population, this is true even within a year of admission. For non-ICU admissions, acquisition of MRSA carried a 1%-4% risk of definite or likely infections within a year. (7% risk of possible infection) (even if discharged from an ICU the numbers are only 2.5-8.6% develop infections or colonization) 

Previous studies have reported an absolute risk > 30%! Studies were often in a single tertiary care center, displaying how little those hospitals reflect the general population. This means THE BENEFITS OF PREVENTING ACQUISITION OF MRSA ARE SMALL. (Infections, however are important) 

I know Eli and other friends may disagree, but we need to focus on infections. Preventing those is the metric that matters. >95% of patients wouldn’t even know they acquired MRSA (as they never would have had an infection). 

The vast majority of MRSA infections occur in people who were MRSA + at admission, not those who acquire MRSA. This paper estimates that fewer than 10% of definite or likely MRSA infections occur in those who acquire MRSA during the admission. Let’s focus our efforts to prevent most MRSA infections. Contact precautions don’t help people who are already colonized. They instead require infection prevention efforts like device insertion bundles, chlorhexidine, and avoiding antibiotics. 

The official conclusion of their paper--that acquiring MRSA poses greater risk than being colonized on admission--is true, but the effect is small: ~1% absolute difference. 

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A shock to the system

Back in April of 2011, in a blog post about the VA MRSA Initiative, I wrote:

“It seems that HAIs are falling across the VA system, probably as a result of an important culture change, and improved application of so-called "horizontal" approaches to infection prevention. Bravo to the VA!”

Of course, in addition to praising the VA, I called into question the one “vertical” component of the MRSA initiative (MRSA screening/isolation) based upon the dramatic reductions in VRE and C. difficile that accompanied the intervention, and the evidence that very little of the reported MRSA reduction could have been due to reduced MRSA transmission.

Thanks to Michi Goto and colleagues, we now have even more evidence that the MRSA Initiative coincided with a fundamental shift in infection prevention in the VA healthcare system. Their recently published CID paper adds hospital-onset Gram-negative bacteremia to the list of HAIs that saw significant reductions after the MRSA Initiative was implemented (see graph above). I will outsource most of the rest of this blog post to Maryn McKenna and Marc Bonten, please read their excellent analyses.

Marc ends his blog post by observing that “we still don’t know how” the VA achieved these HAI reductions—in particular, we don’t know the relative importance of the most expensive, resource-intensive aspect of the program (MRSA screening). As someone who served as a VA hospital epidemiologist during the implementation of the initiative, I’ll give my completely unsupported, data-free opinion: the MRSA screening was both unnecessary and essential to the VA’s success. 

Unnecessary because the HAI reductions, as Marc’s group demonstrated, were not achieved via the prevention of bacterial transmission that MRSA screening/isolation seeks to achieve. 

Essential because it served as a “shock to the system” within the VA. The complexity of implementing any universal screening and isolation program requires multidisciplinary buy-in, major investments in laboratory and infection prevention resources (in the VA system, funding for molecular detection and funding of a new “MRSA coordinator” position, essentially an extra infection preventionist). It’s this kind of system-wide investment that can change the culture, moving basic infection control practice higher on everyone’s priority list. 

We should be very surprised if any complicated, resource-intensive, universal screening intervention (including, now, universal C. difficile screening) doesn't move the needle in a quasi-experimental (before-after) study design.  We also shouldn't be surprised when that same intervention fails to impress in cluster-randomized trials, as we've seen with MRSA screening in STAR*ICU, REDUCE MRSA, MOSAR, etc.

Here we go again: Active detection and isolation, C. difficile edition

An interesting study in JAMA Internal Medicine, likely to generate a lot of discussion, addresses the use of “active detection and isolation” (ADI) for control of C. difficile disease. This quasi-experimental, single-center study employed PCR screening (tcdB detection) of all patients admitted through the emergency department (patients admitted from other locations were excluded, as were “short stay” patients), and those that were found to carry toxigenic C. difficile were admitted into a kind of “quasi-isolation”—gloves were used, but not gowns or private rooms. So all-in-all, a very pragmatic (and somewhat idiosyncratic) intervention. Healthcare-associated C. difficile disease rates declined after the intervention, which students of prior quasi-experimental studies of ADI for MRSA and VRE will find unsurprising. 

At this point, I will outsource my blog post to Jon Otter and Martin Kiernan at the Reflections IPC blog. Go on, head over there for an excellent pro-con post about this study, and vote on the question posed at the end of the post. Then come back here to read my only additional observation…..I can wait (spoiler alert: I agreed with Jon).

OK, you’re back: the only thing I have to add to Jon and Martin’s excellent post is this: we’ve been here before. Recall the persuasive quasi-experimental studies (many single-center, some multicenter) of MRSA and/or VRE ADI published over the course of a couple decades. When better designed studies were eventually performed and published (e.g. STAR*ICU, REDUCE-MRSA, MOSAR, this one by Harbarth and colleagues that doesn't have a catchy acronym)—you know, studies that included concurrent control groups (control groups are for losers!), it became evident that ADI wasn’t the key to MRSA or VRE control. I think we’re headed down that road again, this time with C. difficile. Who’s going to step up and organize the multicenter, cluster-randomized trial we need to do now? Or perhaps better to ask: who is going to pay for it?

It's time to kill MRSA exceptionalism

For nearly two decades, we've lived in a delusional state where many in the field of infection prevention somehow believed that MRSA was so much worse than MSSA that it needed to be treated in a special way. We needed to find all those who are colonized and isolate them (aka search and destroy). We needed to wrap ourselves in plastic before entering their room. We needed to destroy any unused disposable products that remained in the room at the time of hospital discharge. We needed to terminally clean the room in a special way. And on and on and on.... All because MRSA was special. We didn't need to do any of those special things for plain old MSSA.

Some of us have been baffled by this magical thinking from the start. After all, MRSA and MSSA are transmitted in exactly the same ways. We're even more baffled after we see the evidence that in the endemic setting search and destroy doesn't work and contact precautions don't work either. And can anyone honestly say that MSSA invasive infections are benign?

A new multicenter study of invasive S. aureus infections in hospitalized infants published in JAMA Pediatrics should drive another nail in the coffin of MRSA exceptionalism (free full text here). Nearly 4,000 infected babies were studied and outcomes were compared between MSSA and MRSA infections. MSSA infections were nearly three times more common. Although there was no difference in mortality rates between the two groups, twice as many babies died of MSSA infections.

We need to quit chasing pathogen-based approaches (vertical strategies) to infection prevention and focus on horizontal strategies that reduce infections from all pathogens (e.g., hand hygiene, stethoscope disinfection, bare below the elbows, chlorhexidine bathing). Because all pathogens are important. I often joke that I've never had a patient tell me that they don't want a MRSA infection, but they'll take an MSSA. And that is definitive proof that patients figured out that MRSA exceptionalism was a bad idea long before most hospital epidemiologists.

Photo:  CDC.

MRSA search & destroy: It's time to surrender

Over the past five years, we've blogged many times about active detection and isolation for MRSA (ADI, aka "search and destroy"), focusing on our doubts about its effectiveness and the stupidity of legislative mandates for this practice. Nonetheless, there remain some diehard believers. A new perspective piece in The Lancet takes another stab at analyzing the available evidence in order to guide practice. The authors focus on the large studies with the strongest designs. In a nutshell, they conclude that these studies demonstrate that ADI is either not effective or only effective as part of a bundle of interventions (i.e., combined with hand hygiene and/or MRSA decolonization). And in the case of bundles, is ADI an effective component? One study that specifically addressed this question found that ADI did not further reduce MRSA rates when added to optimizing hand hygiene compliance and chlorhexidine bathing. To provide further context the authors point out a number changes that have occurred since ADI was first touted as the best thing since sliced bread:  MRSA rates have decreased, new drugs to treat MRSA have been released, and other multidrug-resistant organisms have emerged. And then the unintended adverse consequences (fewer doctor and nurse visits, safety issues, patient dissatisfaction, anger and depression) need to be considered. The authors wisely point out that "isolation is the prototypical punishment in all societies."

This perspective piece is well reasoned and nicely summarizes a very complex topic in three pages. It should be required reading for everyone on both sides of this debate.

Photo: Paul Martinka, New York Post

Another burden for MRSA patients

We've blogged many times on the adverse unintended consequences of active surveillance for MRSA. A new study in the American Journal of Infection Control documents yet another setback for patients colonized with MRSA. Susan Huang's group studied admission practices at 13 nursing homes in California. Patients colonized with MRSA were nearly 3-fold more likely to be denied admission than those without MRSA colonization. Active detection and isolation for multidrug-resistant pathogens is one of the only interventions in medicine where the benefit accrues to patients who don't bear the burden of the intervention. And the more we study this, the bigger we find that burden to be.

Photo: FoxBusiness.com

Search and destroy is so last century...

A few weeks ago, Dick Wenzel and I responded to a letter in the New England Journal of Medicine regarding our editorial on Susan Huang's paper on targeted vs universal MRSA decolonization. We have long argued that active detection and isolation (AKA search-and-destroy, a vertical strategy) wasn't a necessary or particularly wise approach. A letter refuted this. In our response, we stated:

The key question remains: given an optimally functioning horizontal program (i.e., near perfect compliance with hand hygiene and chlorhexidine bathing), what is the incremental benefit of a superimposed vertical strategy?

Voila! A new study in Lancet Infectious Diseases by Marc Bonten et al addresses our question. In this 3-year study in 13 European ICUs, involving over 8,500 patients, there was a baseline data collection phase (6 months), followed by a hygiene improvement phase (hand hygiene campaign + universal chlorhexidine bathing for 6 months), followed by cluster randomization to a rapid screening group + contact precautions for carriers or a conventional screening group + contact precautions for carriers. Both screening groups used chromogenic agar to detect MRSA, VRE and ESBL; the rapid screening group also used PCR testing for MRSA and VRE. Primary endpoints were the acquisition of MRSA, VRE or MDR-GNR.

The study showed:

• Hand hygiene increased from 52% in phase 1, to 69% in phase 2, and 77% in phase 3.
• Chlorhexidine bathing was 0% in phase 1, and 100% in phases 2 and 3.
• Improved hand hygiene + chlorhexidine bathing (phase 2) resulted in a significant decrease in MRSA acquisition, with no change for VRE or MDR-GNR.
• Neither search-and-destroy strategy resulted in any further reduction for any of the targeted pathogens.
• There was no change in the prevalence of chlorhexidine resistance genes in MRSA isolates in phase 1 vs. phase 3 (13% vs 14%).

So we now have another study demonstrating the lack of need for active detection and isolation to control multidrug resistant pathogens. Will the search-and-destroyers finally pack it up and go home?

Photo:  Jeff Swensen, New York Times

REDUCE MRSA: Readers weigh in!

In my short post about this study last week, I promised that I’d follow up with the most likely criticisms we’ll be reading in future letters-to-the-editor. My post was going to focus on concerns about emerging resistance to topical agents, the lack of impact on MRSA bacteremia, and the outsized influence of skin commensals on the outcomes (see my post on the chlorhexidine bathing studies).

Fortunately, our readers have done this work for me. Below I’ve excerpted a comment we received today:

"We applaud investigators for their hard work in completing a high quality study. However, it has limitations and recommendations are overreaching.

--The intervention

Mupiricin/Chlorhexidine for all patients is very aggressive. Would chlorhexidine alone work in a similar fashion? (resistance is a real concern, especially for mupiricin, and if these agents become inactive they can't be used on high risk patients) We don't really know, but there will be calls to vastly increase antimicrobial exposure to mupiricin based on a study with a mixed intervention that prevented relatively few MRSA clinical cultures even over 74 ICUs I.E. A LOT OF PATIENTS WILL RECEIVE MUPIRICIN FOR A VERY SMALL ABSOLUTE DECREASE IN POSITIVE MRSA CLINICAL CULTURES!

--Outcomes

Bacteremia rates were elevated in the intervention arm during baseline period (6.1 vs. 4.8 or 4.2). Overall bacteremia rate was nearly 50% higher in ICUs that were randomized to the intervention! The intervention itself brought bacteremia rates down to what they already were in other ICUs.

The effect on bacteremia was mostly skin commensals such as coagulase negative Staphylococcus. As in Climo et al, this is probably the least important organism and may relate to decreasing contamination rates. We think this point is also important in the Climo paper, chlorhexidine bathing only had an effect on VRE acquisition and not MRSA acquisition and only had an effect on coagulase negative Staphylococci and candida bacteremia.

MRSA Clinical Cultures are a mixed group of colonization/infections that vary depending on sites. Is MRSA in the sputum the same as MRSA in a deep surgical wound? Or urine culture? or superficial wound culture? Did the frequency of culturing change during the intervention. Given data was obtained from a datapull, all of these questions could be answered which would help interpretation of this trial.

Although the trial is being hailed as a nail in the coffin of active surveillance culturing for MRSA, there are potential harms with over interpretation of the trial. If we begin using mupiricin and chlorhexidine on all ICU patients nationwide, as our European colleagues have suggested will occur, we may eventually have as many problems from the study as early studies of ASC. We also think that one cluster randomized trial should not change practice in such a sweeping manner.

From a more cautious perspective, this trial and Climo et al support that chlorhexidine bathing likely has a benefit on infections in the ICU. It isn't a huge effect and it is predominantly on markers that aren't as important (MRSA clinical cultures and coagulase negative Staphylocci AND CANDIDA (and VRE for Climo)). However, it should be considered by hospital ICUs with problems in these infections.

We should be worried that ASC may be finished only to be replaced by an equally problematic mandate (that more than swabbing every patient is actually treating every patient)."

We will also soon feature a guest blogger from a healthcare system with a long history of using active surveillance for MRSA control.  He also has quite a lot to say about REDUCE MRSA. We welcome all of our readers to weigh in, please feel free to do so in our comments section! The name of this blog begins with the word "controversies", after all.... 

REDUCE MRSA by getting horizontal

The results of this large cluster-randomized trial of different MRSA prevention strategies are now out in the New England Journal of Medicine, and are being widely (and mostly accurately) reported in all the major media outlets. Those who have followed this blog for any length of time know that we are not surprised at the results. Here’s just a sample of what we’ve written on the topics of active surveillance and the difference between horizontal and vertical infection control strategies.

I can keep this post short, because Mike Edmond and Dick Wenzel have already done my work for me in their excellent accompanying editorial (no subscription required!). I’d mostly like to congratulate and thank Susan Huang (pictured) and her excellent group of collaborators from HCA and CDC for making this very important contribution to the infection prevention literature, a contribution that should have a major impact on prevention practices.

But is it really “case-closed” on universal MRSA active surveillance, as the title of Mike and Dick’s editorial suggests? Every study that has questioned the effectiveness of MRSA screening has been followed by a barrage of letters-to-the-editor questioning the findings, and I suspect that this study will be no different. Later this week I will predict the contents of these future letters with uncanny accuracy. Stay tuned….

How strong is our first line of detection?

I feel like I should expand on this recent post about why relying upon prompt laboratory detection of CRE carriers is unlikely to help contain spread (aside from during local outbreak responses). Why shouldn’t screening be a pillar of our prevention efforts, particularly given the inspiring stories of local and regional CRE control that utilized screening to detect carriers? Leaving aside the question of how important screening was among multiple simultaneous interventions, these two reports are from academic tertiary care centers with robust on-site laboratory support and external funding to provide financial support for state-of-the-art screening approaches (such as rapid PCR detection of KPC producers).

The sad fact is that this level of clinical microbiology laboratory support is far from the norm. The trend over the past two decades has been toward consolidation and outsourcing of laboratory services, and reducing local resources available for diagnostic microbiology labs. I spoke about this trend, and some of the consequences, at the 5th Decennial conference a few years ago (you can view the slide set here). In the decade that has passed since we noted frequent errors in testing and reporting of blood culture results in a sample of 14 hospital laboratories, I doubt that much has improved. Yes, there are CAP proficiency surveys, but for several reasons these are not good indicators of actual laboratory performance. And while outsourcing microbiology to a regional lab may make short-term financial and technical sense for some hospitals, it also removes lab support further from the front line of patient care and infection prevention, prolongs turnaround times, and comes with a host of pre- and post-analytic problems.

If current fiscal and political trends continue, with additional cuts to public health infrastructure and CDC’s budget, it is difficult to imagine that we can do much in the short term to shore up our surveillance capabilities to respond to the CRE threat.

Meanwhile, thank goodness we’re spending almost $500 million to stockpile a ridiculous amount of a new drug to treat smallpox. I wonder how we might expand our national CRE surveillance and response if each of our state public health departments could focus $10 million on the effort. My head hurts.

Keeping "CRE" out

Last week was officially “CRE” (carbapenem-resistant Enterobacteriaceae) week, and I encourage anyone who hasn’t done so to read Eli’s excellent posts about the entirely predictable emergence and spread of these bad bugs. Before this crisis disappears down the media memory hole, it is worth mentioning one additional line of defense against CRE that is not up to the challenge: our clinical microbiology laboratories. This is particularly concerning when the new recommendations made by the CDC in response to CRE require additional laboratory support: (1) confirmatory testing and determination of the carbapenem resistance mechanism for CRE, and (2) rectal screening cultures of all patients admitted to U.S. hospitals who were hospitalized outside the U.S. in the prior 6 months.

The CDC provides a phenotypic method for CRE screening, and there are several other published methods (including commercial screening agars), but these approaches don’t provide clinically relevant turnaround times, nor do they tell us which mechanism is at work (e.g. KPC, NDM, VIM, IMP, etc.). Some referral centers use home-brew PCR tests for the most common carbapenemase in the U.S. (KPC), and there are commercial assays being developed that utilize real-time multiplex PCR to detect several enzymes at once, but these tests aren’t available to most labs. So if your hospital lab does find a bug that looks like a possible CRE (after 24-72 hours!), it can perform the Hodge Test (which isn’t great for emerging carbapenemases), send the bug out to a reference lab….and wait for the result.

I completely understand why the CDC has recommended new screening questions + rectal swabbing as part of CRE response. However, trying to keep these organisms from entering our hospitals and long-term care facilities using screening questions and rectal swabs is like depending upon a poorly built levee to hold back floodwaters. 

Dramatic advances in hand hygiene, environmental disinfection, and antimicrobial stewardship, on the other hand, would be the prevention equivalent of moving out of the floodplain to higher ground. Allow me to dream, please!

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

Revisiting the VA MRSA Initiative

Most of our readers know about the VA MRSA Initiative, the results of which were published in the NEJM at the same time as the STAR*ICU study results. These two studies were widely and mistakenly viewed as having contradictory results.

The tremendous success of the VA initiative (see here for my earlier summary of the results) was also mistakenly assumed to be primarily related to the most expensive aspect of the “bundled” initiative, universal active detection and isolation (ADI). This was despite the fact that transmission fell only by 17-21% while infection rates fell by over 60% in ICUs, and infection rates due to non-targeted bugs (VRE and C. difficile) were reduced even more dramatically than was MRSA. In other words, there was plenty in the original paper to suggest that ADI accounted for very little of the observed MRSA infection reduction, and that the bulk of that reduction was due instead to prevention of MRSA infection among those already colonized.

Well, we now have a mathematical model, by Gurieva, Bootsma and Bonten, that demonstrates this point quite clearly. I refer you to their paper and to my colleague Eli’s excellent commentary for details, but the bottom line: transmission prevention was likely responsible for no more than 6% of the reduction in MRSA infection rate. As you’d expect, the proportion of infection reduction due to transmission prevention is strongly correlated to the relative risk for MRSA infection among the newly colonized (via transmission) versus existing MRSA carriers. But as the figure below (from Gurieva paper) shows, even if one assumes a 10-fold higher daily risk for MRSA infection among newly colonized versus existing colonized, transmission prevention would still account for less than a quarter of the observed infection reduction

Chart of the day

The graph here shows the yearly number of publications found via a PubMed search using the terms "MRSA" and "active surveillance." What this means is open to interpretation, but I do sense that some of the fervor for this practice may be waning.

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!!!

Papers you should read, September 2011

We know. Postings have been light these past few weeks. Hey, we are getting ready for ICAAC and IDSA. So cut us some slack, already...(joking)

OK, in a matter of full disclosure, I have conflicts of interest with both of these papers, so following our standard practice of not critiquing papers where we have conflicts, I will leave the interpretation of each paper to you, our dear readers.

Click to enlarge: Frequency of non-prescription use of antimicrobials in the general population

Dan Morgan, who was our invited contributor on Veterans Day, has published a review of world-wide, non-prescription antimicrobial use in this months Lancet ID.  The review included 117 articles including 35 community surveys published between 1970 and 2009. I've pasted a summary figure above.

Co-blogger Dan has a paper coming out in ICHE (ahead of print) surveying IDSA's EIN Network of ID clinicians on their pre-op screening and decolonization practices for S. aureus. The survey included 488 respondents, who had knowledge of their hospital's pre-op screening. Overall, 60% screened for S. aureus with 47% screening for MRSA only and 13% for all S. aureus. Less than 20% screened extranasally. Screening method was led by PCR (36%) followed by standard culture (30%) and chromogenic agar (27%). Additionally, 52% decolonized with 31% decolonizing MRSA carriers, 8% decolonizing S. aureus carriers and 15% decolonized irrespective of colonization status. To find out more, you need to read the paper!

Why all the letters? STAR*ICU and VA studies agree!

Remember that April 2011 New England Journal of Medicine issue with results from two seemingly contradictory studies on MRSA control? Here was our take on both the VA and STAR*ICU studies, written the same week the studies were released. Apparently, some people chose to dust off their typewriters and comment the old-fashioned way. Those letters, and the authors’ responses, are now published. Aside from the last two letters, which make a good point about a flaw in the denominator of the VA study (the failure to remove patients not at risk for acquisition by virtue of already being colonized), all the letters start from the premise that these two studies have contradictory results.

As Charlie Huskins and his colleagues point out in their letter, this is a flawed premise. They point to Figure 3 of their paper to make this point—allow me to expand, since they were obviously working within some crazy word limit that bloggers are not bound by.

Below you’ll find Figure 3 from the STAR*ICU study, which graphs the number of MRSA and VRE “events” (new colonization or infection) during an extended baseline period and the intervention period, in both control and intervention units:

No differences between control and intervention units, and no significant difference from the baseline rates, right? Hold on a minute!! It really isn’t fair to compare these data to the VA data, since the VA study doesn’t include a concurrent control group and doesn’t include sufficient baseline data with which to perform a proper segmented regression analysis. So now let’s take all of that extraneous stuff out (you know, all that tedious extended baseline data and the control arm data—get rid of it!!!). Now the graph looks like this:

The trend line is mine, and demonstrates that MRSA and VRE events dropped by about a third in the intervention units. Since this measure incorporates both transmission and infection metrics, you’d predict it would land smack in the middle of the VA estimates for reduction in MRSA transmission (17-21% reduction) and infection (62% reduction). And it does!

So please stop claiming that the VA study and the STAR*ICU study don’t agree—they do agree, if you just ignore the baseline and control arm data. And as we’ve already learned, control groups are for losers.

Rising plague, falling plague?

In a continuation of the EIN string I recently blogged about, a commenter discussed the success of an MRSA “search and destroy” program they implemented at their hospital. I thought the response by Brad Spellberg (ID doc extraordinaire, and author of “Rising Plague”) was right on target (and consistent with one of the points Eli and I tried to make in our JAMA editorial):

"With respect to the comment, “With this aggressive search and destroy program, we have had a drop in our MRSA rates for the past 4 years in a row with a marked decline in nosocomial transmissions”, I’d advise caution in interpretation.

I think many healthcare systems are seeing declines in MRSA rates nosocomially, including sites that haven’t done much different. Furthermore, we and others I’ve talked to have been seeing dramatic declines in community MRSA rates as well. Let’s not forget, we have no idea why MRSA emerged into the community, why USA300 took over, and where the related phage 80/81 strain went in 1961 and where it hid for nearly 40 years before re-emerging. Why should we be surprised that it has decided to move on now? Let us not underestimate the impact of changes in bacterial ecology that are not necessarily related to things we’ve done."

VA reduces HAIs! In other news, VA spends millions on MRSA screening

Jain and colleagues just published data from the VA healthcare system implementation of the "MRSA directive". For those who are still unaware, in 2007 the VA began mandating the IHI MRSA bundle system-wide, with MRSA screening (active detection and isolation, or "ADI") applied to all VA admissions. The results? From October 2007 until June 2010, the MRSA transmission rate decreased by 17% in ICUs and 21% in non-ICUs, and the incidence of healthcare associated MRSA infections in ICUs fell by 62%. Very impressive indeed.

But that's not the whole story. During the same time period, a subset of these VA hospitals also reported their rates of healthcare-associated VRE and C. difficile infections, and guess what? VRE HAIs fell by 100% in ICUs and 70% in non-ICUs, and C. difficile HAIs fell by 57% in non-ICUs. It seems that HAIs are falling across the VA system, probably as a result of an important culture change, and improved application of so-called "horizontal" approaches to infection prevention. Bravo to the VA!

Here's the problem: because the VA jumped right into universal ADI, utilizing the most expensive screening technology available, they've poured millions of dollars into one specific intervention (ADI), and we still have no idea if ADI had anything to do with their MRSA reductions. After all, MRSA HAI rates have been falling across the country, both inside and outside of ICUs, including in hospitals that do no ADI, or that do targeted ADI. And of course Mike's hospital, where no ADI is done, would scoff at a mere 60% rate of decrease, having reduced MRSA HAIs by almost 90% using horizontal approaches.

My conclusions? First, the VA is to be congratulated for demonstrating real and sustained progress in HAI prevention (disclaimer: I was a VA hospital epidemiologist for 10 years, including during the first 2 years of implementation of the MRSA directive). Second, VA policy makers should consider the possibility that universal MRSA screening is now doing more harm than good, if only because it costs millions of dollars annually that could be used to improve other infection prevention programs. By all means, continue the MRSA initiative. But consider relaxing the "universal" ADI directive to allow individual hospitals the latitude to tailor ADI practices to best address their current risk assessment.