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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New evidence supports high-dose influenza vaccines

People older than 65 years are at particularly high risk for influenza-related medical complications including hospitalizations and death. In 2009, the FDA approved a trivalent inactivated vaccine with four-times the hemagglutinin antigen per strain, which was thought to improve immune response in seniors.

Background data has largely supported high-dose vaccination among seniors. In a multicenter, randomized controlled trial of high vs standard dose vaccine that included almost 32,000 patients during 2011/12 and 2012/13, 1.4% of high-dose and 1.9% standard-dose patients had an influenza-confirmed influenza-like illness, resulting in a relative efficacy of 24%. Adverse events were slightly, but significantly lower in the high-dose group but 3 high-dose recipients had serious vaccine-related events (which all resolved) vs none in the standard-dose group. A very large Medicare study during 2012/13 and 2013/14 reported similar benefits but only during 2012/13 when H3N2 was more common. Perhaps it is difficult to measure a benefit during more mild, H1N1 seasons? There have been other studies supporting the effectiveness and cost-effectiveness (at least during the 2011/12 and 2012/13 H3N2 seasons) of high-dose vaccine.

One of the larger groups of seniors in the US are patients in the Veterans Health Administration (VHA) system, so it makes sense to measure the benefits of high-dose vaccine using the VHA integrated EMR. In the June 1st JID, authors reported results of a large (industry-funded) retrospective cohort study completed using data from the 2015/16 influenza season (an H1N1 year) that included seniors with at least one inpatient or outpatient visit during the prior year (2014/15). The primary outcome was any hospitalization for pneumonia or influenza. The study used a number of nice methods to adjust for confounding including matching on baseline characteristics and the Care Assessment Need (CAN) score, that is a proxy for frailty. They also adjusted for residual confounding using the prior event rate ratio (PERR) method, which you can read more about here. Basically, PERR adjusts for outcome rates in the baseline period (before vaccination) by dividing the relative rate post-vaccination by the relative rate pre-vaccination (in the baseline period).

The final cohort (before matching) included 104,965 standard-dose and 125,776 high-dose recipients during the 2015/16  influenza season. The matched cohort had 49,091 standard-dose and 24,682  high-dose patients. Using the unmatched and matched cohorts, and using the PERR method with each, the relative vaccine effectiveness of high-dose influenza vaccine was 23% and 25%, respectively. This suggests that high-dose vaccine was effective in preventing influenza or pneumonia-associated hospitalizations among VHA patients.

These results are encouraging since they were from a more mild H1N1 season. Even more encouraging, the authors plan to automate the data extraction process and report vaccine effectiveness within 3 months of the end of each influenza season. But one note of caution, having a high-dose vaccine that is 25% more effective isn't a huge improvement, since influenza vaccines in general aren't very effective. So high-dose influenza vaccine is a small step in the right direction - but more research and new influenza vaccines are needed.

A Research Agenda for MDRO Prevention

Of course, I don't need to explain the clinical importance of multi-drug resistant bacterial pathogens to readers of this blog. I probably don't need to remind you that "more research is needed" either - that's why we have controversies! But, I should probably point you to five papers recently published in ICHE that outline the future research agenda for MDRO prevention in the US Veterans Health Administration (the VA).

For our non-US readers, the VHA is the largest integrated healthcare system in the United States with over 130 acute care facilities, 1000 outpatient clinics, numerous long-term care facilities and 9 million enrolled patients. The VA has been a leader in medical and health services research for decades and has been well-ahead of the curve in application of interventions to prevent MDRO including its MRSA prevention bundle and antibiotic stewardship initiative.

To continue the VA's success in MDRO prevention and link future research questions to the greatest clinical need, we invited a multidisciplinary group with 37 participants to Iowa City in September 2016. The aim of the panel was to outline the VHA's research agenda for MDRO prevention. Dan Livorsi describes the process we used to identify the domains and research questions in an introductory editorial. The outlined research agenda was broad in scope and included efficacy, effectiveness and implementation questions. In addition, many of these questions are broadly applicable to study in non-VA and non-US hospitals. We are all more alike than different.

Research questions fell into four domains:

1. Transmission dynamics: Resistant pathogens are spread via human hands and environmental surfaces. Disrupting this transmission is essential to controlling MDROs.

2. Antimicrobial stewardship: Strategies to reduce and improve the use of antimicrobials will slow the emergence of resistant pathogens.

3. Microbiome: There may be ways to manipulate or augment the human microbiome to eradicate or prevent colonization with resistant pathogens.

4. Special populations: Strategies need to be tailored to patient populations with distinct underlying conditions and in nontraditional care settings.

All 5 papers are open access. Thanks ICHE!  And thank you to the brilliant group of VA investigators, clinicians and operational partners who traveled to Iowa City and contributed to this effort. We all hope it's helpful.

More good news about MRSA. This time from VA.

It's not often that good news about hospital-acquired infections (HAI) is reported in the media. When was the last time you read an article congratulating a hospital for having lower CLABSI rates or good hand hygiene compliance? It's even rarer to hear good news about VA Medical Centers. While the quality of care in VA often meets or exceeds that in the private sector, it's rarely reported, since high quality runs contrary to established memes.

That's what's unique about today's 'Opinionator' article in the NYTimes. It reports greater improvement in MRSA infections in VA vs non-VA hospitals. To those of us that study HAI and resistant bacteria, this isn't that surprising. Integrated, public (national) health care systems, like VA, have built in incentives to prevent infections since they see the direct benefits of reduced costs and better outcomes - incentives that aren't well-aligned in other hospitals. However, to most folks it is probably surprising that VA was an early adopter of a bundled approach to MRSA prevention and has set the bar for the rest of the country.

Dan and I are both quoted in the article, so I encourage you to read it. However, I'd also like to highlight one section:

"The V.A.’s achievement is even more remarkable because its patients are older and sicker than patients in other hospitals. (Most patients are Vietnam-era vets. None are healthy young women giving birth, a large patient group in most hospitals.) They are twice as likely to come to the hospital already testing positive for MRSA. The greater the percentage of people who have the bacteria, the harder it is to control its spread. Because their immune systems are weaker, V.A. patients are also more likely to go from testing positive to full infection."

The fact that VA patients are older, sicker and often poorer than other hospitalized patients is frequently missed in the wider discussion about quality measures. When you have all the cards stacked against you and you still deliver high-quality and safe care, it should be recognized. Nice when it is.

CREATE-ing an opportunity

I can’t count the number of times we’ve pined for increased funding of healthcare-associated infection prevention research. I’m happy to say that Eli is putting more “money where his mouth is” in this regard, having just received a $4.2 million, five year grant to investigate MRSA infection prevention approaches. This VA HSR&D grant was part of the “Collaborative Research to Enhance and Advance Transformation and Excellence (CREATE)” initiative. Much like the NIH PPG, the CREATE grants fund several (in this case four) major projects that are interrelated along a common theme.

So, a CREATE grant now creates a great opportunity for Eli and his colleagues to advance the science of MRSA prevention. Among the principal and co-investigators in this multicenter partnership are Heather Reisinger, Marin Schweizer, Mark Vander Weg (all in Iowa City), Mike Rubin (Salt Lake City), Luci Leykum (San Antonio) and Dan Morgan (Baltimore).

Congratulations—now, of course, the work begins!

Accentuate the negative

Dan has posted previously on how difficult it is for authors to get negative studies published.  Perhaps this is the real reason why the STAR*ICU study took 4+ years to make it to press.  I suspect that if the study was completed the exact same way that it was but found a benefit for barrier precautions, it would have appeared in press around 2009 or even earlier.  Just a guess.

Mike has posted at least twice on Ben Goldacre and his blog/book called Bad Science (part 1 and part 2).  Ben has a new post in the Guardian that discusses how medicine, academia and popular culture all favor positive, eye-catching and potentially spurious trial results and ignore important negative studies.  His discussion centers around a paper published last year that seemed to provide evidence of precognition - you know it before it actually happens.  That "positive" paper received tons of press, while a new negative study can't see the light of day.  I think this sort of bias plays a large role in infection prevention research - it is so much easier to publish a positive quasi-experimental study showing a benefit than a negative study.  This is why it was so great that after 4+ years of waiting the STAR*ICU study, which was a negative study, was published at the same time as the VA study, which showed a benefit.  This way, we could have a rational discussion with the positive/negative evidence receiving "almost" equal billing.

Ben Goldacre "Backwards step on looking into the future" Guardian 4/23/2011

Control groups are for losers

That’s what I learned from today’s New York Times editorial. In their review of the two NEJM studies we covered last week (here and here), they describe the VA study as “broader” (true, if by broader they mean larger) and “possibly more rigorous” (untrue). They also point out that “if other hospitals could replicate the effort, thousands of patients might be saved from needless infections”. The editorial board at the NY Times should know that hospitals across the country are already saving thousands as MRSA HAI rates drop nationwide! And many of these hospitals are saving lives without also stimulating the economy by doing universal MRSA screening. A bundle with multiple interventions, one of which is unproven and hugely resource intensive, doesn’t seem in keeping with the spirit of health care reform. And sadly, determining the proper role of the most expensive element in the VA's MRSA bundle requires studies that use something we epidermatologists like to call a “control group”.

Special Invited Veterans Day Post on MRSA

By Dan Morgan

For the Veterans Day post, it is worthwhile mentioning the role of the VA in advancing research on infection prevention. Despite some bureaucratic hurdles, the VA has supported some of the more creative work over the years and having one of the few fully electronic medical record systems, has the potential to implement a more sophisticated approach to infection prevention.

A recent, high profile intervention in the VA is the MRSA Prevention Initiative. Mobilizing millions of dollars with a top down mandate, the VA has focused efforts on infection control, especially as it relates to MRSA. The majority of the intervention relates to improved hand hygiene and compliance with Standard and Contact Precautions and encourages involvement of local healthcare workers through positive deviance. More controversial was the mandate to perform active surveillance for MRSA, swabbing patients admitted to acute-care facilities almost ceaselessly (admission, transfer and discharge, obtaining > 90% compliance in many facilities). While no verdict has been reached on the effectiveness of active surveillance for MRSA, the VA, to its credit, has supported research into alternative approaches.

One of these alternative approaches was hatched by a mentor of mine known to this blog simply as Eli. Focusing on the known risk factors for MRSA as a means of identifying patients at high risk for carriage, he and I looked at simple rules that could predict patients who should be targeted for MRSA (and VRE) screening. In a closed system like the VA with a fully electronic medical record, these prediction rules could be automated. In the Baltimore VA, we examined possible prediction rules and found that documentation of antibiotic use within the past year identified 84% of the risk of MRSA transmission and 98% of the risk of VRE transmission. In other words, if the electronic medical record had documentation of antibiotic use, an order could have been automatically generated at time of admission for MRSA or VRE culturing. This testing would identify virtually all patients with VRE and most with MRSA while culturing half the patients currently subjected to swabbing. The full effect of such an approach needs investigation in other VA populations but is promising.

At a time when attention is turning towards generating solid data on sometimes intrusive infection control interventions, I’d like to salute the VA for taking the lead on supporting research that may help transform hospital epidemiology from expert opinion to a scientifically outcomes based field.

Morgan DJ et al. Infect Control Hosp Epidemiol. December 2010

Note: Special thanks to our guest blogger and author of the discussed ICHE paper, Dan Morgan. Dan is an assistant professor at the University of Maryland and currently supported by an AHRQ K-award to study the non-infectious consequences of contact isolation.

What happens in Vegas...

...stays in Vegas? Always a good catchphrase, although not necessarily a good movie. I do often wonder if we should adopt a slogan in infection prevention such as "What happens in the ICU, stays in the ICU," where the happens part is MRSA or MDR-Acinetobacter acquisition.

It looks like there is a move afoot in Nevada to mandate universal MRSA screening. Sheila Leslie, D-Reno, whose otherwise healthy cousin recently died from MRSA infection at a California hospital, is considering drafting a bill on the subject. A recently posted Las Vegas Sun piece focused on the MRSA surveillance mandate in the VA system and quoted from the usual and also unusual subjects in the never ending debate around MRSA control.

Some of the more interesting quotes from the article:

“You get paid and paid and paid for doing the wrong thing in medicine. You don’t get paid for keeping people well,” said Phillip Longman, author of “Best Care Anywhere: Why VA Health Care Is Better Than Yours.”

“I know the bundled approach works, but I don’t know which component of the bundle is the most essential component of success.” Dr. Rajiv Jain, who leads the VA’s MRSA prevention program.

It appears that Nevada will look to the VA's data and experience in MRSA control. What isn't clear is if states or hospitals or even local health systems should try to apply data from a federal system with >150 acute-care hospitals. I do welcome the VA publishing their results and hope we see some nice VA-based interrupted time series data analyzed soon. When it comes to the results of the VA's MRSA mandate, what happens in the VA shouldn't stay in the VA.

Las Vegas Sun Article

Keeping veterans safe

As we pause on Memorial Day to remember those who have died fighting our wars, it seems fitting to recognize the strides that Veterans Health Administration (VHA) hospitals have made in patient safety, including prevention of healthcare associated infections. Over the nine years I was hospital epidemiologist at the Iowa City VAMC, I became convinced that most U.S. hospitals could learn a lot from the VA system (beginning with their early implementation of an electronic medical record that remains superior to the one we have implemented in our university hospital). While I can nitpick about the way certain directives came down, overall I think the VHA has been ahead of the curve, which may also be a commentary on progress in the rest of our fragmented healthcare system.

The VHA is the largest integrated healthcare system in the United States. It can and should serve as a model for healthcare-associated infection prevention.

The VA colonoscopy problem...

Thanks to Mike for keeping up with the blog over the past few days—I’ve been out of commission for a several reasons, including an ill-advised decision to finally take the exam for certification by the American Board of Medical Microbiology. Now I’m leaving the country for a couple weeks, so it will be Mike’s blog until early July.

When I return, I may address the brewing political overreaction to the VA colonoscopy mess. I have some personal experience here, being the epidemiologist at one of the VA’s that underwent surprise site visits by the Office of Inspector General (here is the report). In the meantime, I’ll just highlight what I think is the best quote I’ve read on this so far, from Philip Alcabes, associate professor of urban public health at Hunter College in New York City:

“To claim that an extra threat of transmitting blood-borne viruses pertains to the VA's colonoscopy clinics seems like showmanship. Since it isn't clear that any patients were actually infected by this equipment, the situation doesn't seem to warrant special rhetoric. It would be better to try to separate the political controversy from the actual health problem here."