SENTRY at 20: So many bugs!

The SENTRY Antimicrobial Surveillance Program was begun at the University of Iowa in 1997, moving a few years later to JMI Laboratories (also in Iowa!). Since inception, it’s been an industry-funded platform that performs central laboratory testing of clinical isolates of bacteria and fungi from centers around the world. The isolate submission process has been consistent over time, involving submission of organisms from consecutive episodes of infection at specified body sites (more information here and in the many publications that have come from SENTRY). 

So SENTRY has been operating for >20 years, and there are hundreds of thousands of isolates characterized. The major trends are reported in an OFID supplement and in recent publications in JAC and AAC. The supplement articles and the AAC report on trends in 20 years of bloodstream infection (BSI) isolates are open access—take a look if interested! 

I’ll focus briefly just on the AAC report (which I first-authored, so that’s shameless self-promotion right there)—two major points, each of which confirms on a large scale what regional surveillance programs have reported:

• S. aureus and E. coli dominate the BSI landscape—together account for >40% of all episodes reported to SENTRY. Continued focus on prevention, detection and treatment of these two bad actors is critical, and IMO should include vaccine approaches, despite the disappointments to date.
• There’s an interesting divergence in proportion of BSI caused by important resistance phenotypes among Gram-positives (MRSA, VRE, DRE, etc.) versus Gram-negatives (ESBL, CRE) over the second decade of surveillance (2005-2016). The Gram-positive resistance phenotypes are stable-to-declining, whereas Gram-negative phenotypes steadily increase (as proportion of BSI episodes) over the entire surveillance period.

The decline in MRSA as a proportion of all SA BSI is particularly striking, occurring as it does at the same time worldwide (and at all body sites, both healthcare- and community-onset, as more detail in the OFID report of all SENTRY S. aureus confirms). As Eli and I discussed in this JAMA editorial almost 10 years ago*, this is not easily explained by hospital-based infection control interventions. The waxing and waning of epidemic clones of MRSA is more likely to be informative. There is so much we still don’t understand about an organism (S. aureus) that lives in relative harmony with 20-30% of the human population when it isn’t causing horrendous, difficult-to-treat infections.

Finally, the scope and number of isolates collected by SENTRY and similar programs represent an underutilized public health resource. Regulatory requirements for drug development and approval mandate surveillance for AMR. Better partnerships between public health authorities and the industry sponsors of such surveillance programs could enhance surveillance and response, particularly in the genomic era when ready access to large isolate collections can be so powerful. Some of this is already happening, but more could be done.

*still behind a paywall after 10 years?  What gives?

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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Upon Further Review: Reexamining the Illinois MRSA Active Surveillance Mandate

“Thinking without the positing of categories and concepts in general would be as impossible as breathing in a vacuum” – Albert Einstein (1949)

A couple weeks ago, Scott highlighted a study in CID by Lin et al. that sought to estimate the benefits of the 2007 Illinois state-wide mandate of MRSA active surveillance cultures in ICU settings. The post was titled “Good Intentions Does not Always Mean Good Policy” and concluded “There may be many reasons the hospitals in Illinois overall are seeing an estimated 30% decrease in their hospital-onset MRSA BSI (as most states are) since the 2010 NHSN baseline, but admission screening isn’t one of them.” 

I would like to list several reasons why I think we should reconsider the study authors’ conclusions. And if you skip to the end, you will read why I think this study might make more valid conclusions about the lack of benefits of CHG bathing.

Let’s start with validity from Shadish (2001) et al: “We use the term validity to refer to the proximate truth of an inference. When we say something is valid, we make a judgement about the extent to which relevant evidence supports that inference as being true of correct.” Cook and Campbell (1979) outlined four components of validity: statistical conclusion validity, internal validity, construct validity and external validity. I’ve written about their validity typology here, if you’re interested. 

Now let’s review the Illinois study methods. They included data from 25 ICUs and completed eight, one-day point prevalence surveys AFTER the mandate was initiated (twice annually 2008-2011 and annually in 2012 and 2013). There was no concurrent control group.

Thus, this quasi-experimental study design has very low internal validity. It has no measurement before the intervention (sometimes called historical controls) and no concurrent controls. Shadish labeled this design as a “one-group post-test only design” and summarized its limitations with “this design is rarely useful.”

The Illinois study also lacks statistical validity, since it is underpowered to detect a benefit of active surveillance. Shadish lists low statistical power as the first threat to statistical validity since “the experiment may incorrectly conclude that the relationship between treatment and outcome is not significant.” Since the Illinois study is a negative one – claiming active surveillance for MRSA didn’t work, power is particularly important. If you jump ahead to my ICAAC abstract, you will begin to see why the study is likely very underpowered. Point prevalence is very insensitive to changes in acquisition or transmission, so you would need very large studies to see a benefit.

I’ll admit that a statewide study has strong external validity – that is generalizability. 

But let’s focus on construct validity. Construct validity - what Einstein was hinting at in the quote above - describes whether a study measures what it claims to be measuring. For example, if a study claims that active surveillance for MRSA and isolation doesn’t prevent MRSA transmission, that study better measure MRSA transmission. 

Let’s pause here. Now some might say, we don’t care about transmission, we just care about MRSA prevalence or MRSA infections or MRSA CLABSI (or even deaths in Avengers movies). Yet, active surveillance for MRSA doesn’t work like that – it prevents transmission between patients. 

But what if measuring MRSA point prevalence was good enough at detecting MRSA transmission? Thought experiment: what if we found PCN allergy alerts in the EMR annoying and so we eliminated them? To see if this was safe, we then checked to see if anyone was having a PCN allergic reaction every St Patrick’s Day for the next 5 years. Good enough, right? Probably not. Why would we be comfortable saying yearly point prevalence is an adequate way of measuring the benefits of MRSA transmission? I don’t think we should and here’s why:

Back in 2002 I presented an abstract at ICAAC titled: “Point Prevalence and Clinical Culture Positivity of Vancomycin Resistant Enterococci are Poor Estimates of Infection Control Intervention Impact.” This study was based on the VRE model that we eventually published in CID (2004). Anyway, we modeled VRE transmission in the ICU under a condition where active surveillance compliance on admission increased from 60% to 100% and I assumed that isolation prevented 71% of transmissions. This is a math model, so we know that the intervention worked– but could we detect it? The answer was yes but only if we used admission/discharge screening cultures.  If we used point prevalence, like the Illinois study, we would falsely claim that the intervention didn’t work 54% of the time. However, if we used admission/discharge cultures, we would correctly determine that the intervention worked 96% of the time. Here is our conclusion:

“Point prevalence or clinical culture positivity often failed to detect a benefit due to stochastic fluctuations in prevalence and high prevalence of VRE in patients entering the ICU. Studies to assess the benefits of active surveillance for VRE should measure new incident cases. Relying on point prevalence or clinical culture positivity to assess the benefits of infection control interventions may underestimate the magnitude of their benefit and may be responsible for a persistent bias against the broader institution of active surveillance. The benefits of active surveillance and other infection control interventions are probably underestimated.”  

Not bad for 16 years ago – replace VRE with MRSA and you can see why the study by Lin et al cannot be used to evaluate the benefits of active surveillance. Our conclusion was partially driven, as we said, by high rates of VRE colonization on admission. What did Lin et al say about their study: “we assessed MRSA prevalence in a region where MRSA is widely endemic both in the community and within healthcare facilities.” Thus, the MRSA situation in Illinois fits closely with what we modeled.

In conclusion – the study by Lin et al should not be used to claim active surveillance was ineffective in Illinois or elsewhere. When drawing inferences, it is important to remember all four components of validity described by Cook and Campbell 40 years ago. We still need to figure out why MRSA has declined by 30% in Illinois and elsewhere. I do wonder why we are so quick to claim CLABSI bundles, CHG bathing (see below) or other interventions have been driving these MRSA reductions and not active surveillance. If I had to guess, it’s something yellow and not the data.

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Side note: In this same study, the number of hospitals using CHG bathing in their ICUs went from 5 (20%) to 17 (68%). It appears the authors could use these same data and methods to show that CHG doesn’t prevent MRSA in ICUs settings. Interestingly since CHG bathing works at the level of transmission and also on individual patients’ decolonization, point prevalence data would have higher construct validity for evaluating CHG. The study might even be better powered to detect a benefit of CHG.

Good Intentions Does not Always Mean Good Policy

How often do negative studies influence our behavior, or better yet our policies? For those of you that are familiar with the work I have published, you know that I published a lot of material focused on MRSA; emerging resistance, community-emergence, burden of disease, attributable cost, risk factors, and on.  I was in a position at CDC to access and synthesize a lot of data, with a goal of putting the problem in perspective and ideally affect policy. Well intended as it was, I remember very clearly in mid-2007 when policy got way ahead of the science. Two independent (but related) events occurred on October 16-17, 2007 that led to several years of a watershed of policy developments. Although I give a huge amount of credit to the very passionate and important patient advocates and consumers that built momentum for the policies – but with hindsight the policy inertia was really overcome when a senior student at Staunton River High School died on October 16 from MRSA sepsis—MRSA he acquired in the community. The press linked that death to Dr. Elizabeth Bancroft’s editorial that same week stating “…more people die of MRSA in the U.S. than of AIDS” published on October 17. Many of us see much of the public reporting and mandatory reporting policies have opened up real pathways for additional hospital resources to invest in HAI prevention. However all of us should recognize some policies of that era are likely in place that really should be re-examined. 

One of these is the Illinois 210 ILCS 83/ legislation requiring all patients admitted to intensive care units be screened for MRSA by nasal active surveillance testing (AST). Lin and colleges just published a negative study with a lot of important findings. To many, the findings will not be a surprise (CID May 15 2018, pp 1535-1539)

• Lin worked with 51 intensive care units at 25 hospitals over 5 years starting within months of enactment of this mandate to evaluate any changes in ICU MRSA prevalence through periodic point prevalence surveys performed by trained study staff during the time of this mandate. The study was a quasi-experimental time series evaluation but without a real before observation group and no control group. However, I believe that any impact would have been additive over time – the first year would have been a sort of wash in period for an intervention as broad in participation as this.  They sampled 3909 patients having the power to even detect an absolute difference in carriage as small as a 1.9% change in prevalence (eg, 10% vs 8.1%) – but they detected none. No change in prevalence of MRSA on these patients. 
  

• Compliance was high overall (93%), admission prevalence was comparable to other studies (9.7%), and overall, at any given survey of known positive patients and unknown, 11.1% were positive in any given month, in any given year of this study.  Sure, time to placement of contact precautions lagged from test turnaround time or from time to test result to actual placement of precautions, but most notably the mandated testing was only 84% sensitive compared to best testing methods  employed by the study investigators. This is the real world after all.

• While these ICUs have invested time, effort, and money into these admission swabbing and targeted placement of contact precautions, the prevalence of MRSA carriage has not budged in these intensive care unit patients.

There may be many reasons the hospitals in Illinois overall are seeing an estimated 30% decrease in their hospital-onset MRSA BSI (as most states are) since the 2010 NHSN baseline, but admission screening isn’t one of them. Maybe its CLABSI prevention, or that uptake of the percentage of study patients receiving CHG baths. However, this study suggests it was not the mandated AST for all ICU patients admitted to the ICU. These patients are bringing their MRSA in with them, let’s free up staff time to prevent the infections.

I know there are many major federal policies we all can be passionate about changing or starting, these are crazy days. But when the scientific evidence is so strong illustrating that a very well-intended policy regarding use of nursing and infection control resources does not have the intended impact – change it. Nursing care can better be spent caring for patients, practicing best infection control for all patients in these intensive care units. 

Even NFL Stars LOVE Contact Precautions

What do we love most of all on this blog? Yup - contact precautions. Humor!

Well, I do have respect for the utility of gloves in preventing HAIs and MDRO transmission- but I've never been sure of gowns. It's just that they are pretty annoying to don and doff and little evidence supports any additional benefit above wearing just gloves. I mean, if Rob Gronkowski from the almost champion New England Patriots can't even put on a gown correctly, what chance do we mere mortals have, seriously. Maybe that's the reason why the benefits of gowns and gloves for preventing MRSA and VRE are so hard to estimate?

There are many other reasons why the benefits of contact precautions for endemic MDRO are so hard to quantify, of course. In this week's JAMA, Mike Rubin, Matt Samore and Anthony Harris have written a very nice Viewpoint acknowledging the limitations in the current literature.  In addition, they point out why studying infection prevention interventions is so tricky and suggest a path forward. They should be commended for their thoughtfulness and honesty - something those of us (including me) who support other policies with even weaker evidence bases should remember. If Gronk is having trouble with contact precautions, it's OK if some of the rest of us do too.

When prevention success stagnates? Treat the patient!

Prevention is paramount – I do believe this, and I know that is so much of what healthcare epidemiologist strive for; however we often become very myopic and focus exclusively on “modifiable risk factors.” It is refreshing to read a nicely done epidemiologic study to illustrate what an impact the infectious disease community can have by improving the way we approach patient treatment. When reading the recent article in JAMA IM by Michihiko Goto and colleagues I was expecting a nice ecologic study showing an impressionistic picture of how improved treatment processes correlate with improved MRSA bacteremia mortality - but our VA colleagues working with big data have painted more of a realistic 

Le Déjeuner sur l’herbe Painting 

by Édouard Manet, 

1863 Musée d’Orsay, Paris

Google Arts & Culture

than an impressionistic picture. Using the VA database, capturing deaths occurring during both the inpatient stay and the post-discharge period, they quantify improved survival at the patient level is driven by improved processes of care for S. aureus bloodstream infection (Association of Evidence-Based Care Processes With Mortality in Staphylococcus aureus Bacteremia at Veterans Health Administration Hospitals, 2003-2014 JAMA IM).

I have been pushing for transitioning efforts to prevent S. aureus (more specifically MRSA) bacteremia to the post-discharge setting, worried that the recent reductions observed among hospital-onset MRSA BSI are not being realized in the post-acute care setting. We’re getting stuck; in fact we have been stuck for a while at preventing community-associated MRSA BSI (See figure). 

Goto and colleagues provide some clarity to preventing deaths related to MRSA BSI (and S. aureus BSI overall) even during periods of prevention stagnation such as we may be in currently. Of note, the incidences of healthcare-associated and hospital-onset MRSA BSI decreased in VHA hospitals between 2003 and 2014, whereas the incidence of CA bacteremia was stable. This is identical to trends illustrated nationally using CDC's EIP data, suggesting the VA analysis may be reflective of what is going on nationally.

Goto utilized the national Veterans Health Administration (VHA) health care system to first determine how to best risk adjust mortality; and then determine the independent effect of each of three pillars of guideline directed processes of care for managing S. aureus bacteremia (SAB): (1) appropriate antibiotic therapy, (2) echocardiography, and (3) consultation with ID specialists. They report lower risk-adjusted mortality among patients with SAB when they received (1), (2), or (3), and there was a nice dose-response relationship between the number of care processes and mortality. They estimate “57.3% of the decrease in risk-adjusted mortality among patients with SAB between 2003 and 2014 could be attributed to increased use of these evidence-based care processes.”

Their paper also sheds some light on the importance of capturing post-discharge data when quantifying mortality related to processes or infections related to the hospital setting!. Risk-adjusted mortality decreased from 23.5% in 2003 to 18.2% in 2014, regardless of MRSA, MSSA, and place of acquisition (Figure).

From Supplemental Figures, Goto et. al.

I was caught by the discrepancy between these mortality rates and the mortality reported by the CDCs Emerging Infections Program invasive MRSA Surveillance, reported around 12%. The latter is limited to in-hospital or 30 day mortality, whichever comes first. Recent data at IDWeek by one Emerging Infection Program site identified another 30% of deaths among patients with MRSA BSI occurred post-discharge. The Goto paper captures these deaths, making their conclusions more realistic. In addition, their risk adjustment for mortality included over 13 comorbidities, timing of infection, and susceptibility. They did an outstanding job of trying to evaluate the relative importance of each care process while accounting for changes/absence/presence of these underlying predictors of mortality (both inpatient and post-discharge). They even did a sensitivity analysis to account for early deaths, before these care processes could occur. Furthermore, the impact of receiving the care processes was similar regardless if the SAB was hospital-onset or community-onset!

The bottom line – following evidence base care processes does save lives. Their analysis support their conclusion that “there is a need for continued implementation of quality improvement initiatives to increase the adoption of these evidence-based care processes for patients with SAB.” Let’s be bold and call these what they are: performance measures! Here we have a potential metric (proportion of SAB receiving said care process), that are closely linked to improved survival, and can be captured electronically in an objective manner (at least in the VA!) improving the reliability of these metrics across facilities. I was glad to find through a google search that IDSA recently (December 2016) urged CMS to move in this direction -- although the details of the status of this proposed measure (#407) are not clear to me.

While we anticipate novel therapeutics for MRSA BSI including immunotherapy adjuvants or vaccines to become available in the not to distant future; quality improvement efforts in the evidence-based processes of care for SAB now will likely improve our patient’s outcome. I hope we can turn our attention here soon -- and have hospitals rewarded for doing so.

Contact Precautions for Endemic MRSA and VRE

by Andreas Voss and Eli Perencevich

This response to the recent JAMA Viewpoint by Morgan, Wenzel and Bearman is cross-posted on the “Reflections” and “Controversies” blogs. Both blogs were recently ranked "top 10" ID blogs by this recent ICHE study, so we might as well collaborate ;)

During the recent ICPIC 2017 and a pre-meeting think tank, the sense and non-sense of RCTs looking at various infection control measures was a major point of discussion during many sessions. Data from well-designed quasi-experimental studies, epidemiological evidence and logic seems to vanish whenever a new RCT is published, even if the results are not applicable to situations that are non-endemic, have higher or lower compliance with the preventive measures in question, or whether the intended measures were actually applied within the intended patient group. Some studies seem to assume that the transmission during the first days of admission are of no consequence. Others assume that given endemicity and a high patient load, the intended measures such as single-room isolation can’t be applied, even if a patient was randomized to receive those measures.

We do know that Morgan, Wenzel and Bearman are very well aware of the fine differences, but we fear that their cited research along with editorials like their viewpoint will be misinterpreted by many within the infection control community and those adjacent to infection control, such as the nurses, clinicians from other specialties, administrators, guideline makers, and legislators.

Our question would be, how many more RCTs do we need to slice and dice needed infection control measures? We believe that for as long as one can surmise an acceptable level of endemicity, deduce an allowable lack of compliance with the intended infection control measure, as well as justify the impossibility of applying the intended measures to all assigned patients, any infection control measure can be proven “unnecessary” in an RCT (or a poorly designed quasi-experimental study), and later on, in a Cochrane review. Is this what we need?

Let’s be clear about one thing. We believe that good studies in our subspecialty are needed and that evidence should be stronger than opinions. At a time when costs are critically important we need to know what to invest in. Infection control therefore needs to be effective and cost-efficient. Still we can’t help but feel that at present the “scientific pendulum” is swinging in the wrong direction.

At present, MRSA and VRE are endemic in many countries, ESBL is everywhere, and we are at a decisive moment before the same is true for CRE. Consequently, now more than ever, it is of up-most importance that we acknowledge the limitations of the existing RCTs as well as include all other available evidence in our evaluation of infection control measures. If we are forced to ignore strong epidemiological evidence supporting transmission in healthcare settings and methods for halting the spread of MDR-pathogens while waiting for the perfect study, are we really providing the safest care for our patients?

Chattin' 'bout contact precautions: Endemic?

It's been a quiet week out here on the edge of the prairie. Temperatures plunged into the 40s at night and the cooler breezes have been amazing - a nice change from the mid-90's in Geneva last week. I'd like to publicly thank SAS for losing my luggage for 4 days and especially the folks who still talked to me during the meeting. Four days in the same pants - reminds me of a doctor's white coat!

One of the topics that came up at ICPIC and on twitter after the various contact precautions posts and JAMA viewpoints was whether a pathogen's prevalence is an important criteria to use when deciding between types or levels of infection control interventions to implement. Put another way, should we treat common, ie endemic pathogens like MRSA, differently than outbreak or novel pathogens like CRE?

Of course, the first difficulty with answering this question is that endemicity is local, like politics. For example, MRSA is only endemic in certain parts of the US (we have little at the Iowa City VA vs the Baltimore VA) and MRSA remains rare in the Netherlands. Clostridium difficile is common everywhere, except that when we visited Vietnam last year, we heard that it is less common in SE Asia. So, we can agree that it would be difficult to write national guidelines or mandates for specific pathogens if endemicity is an important parameter.

Another question I have is how can we define an endemic threshold?  If we were concerned about MRSA, is it the proportion of clinical S. aureus isolates with mecA? Or would the threshold be set around some level of admission prevalence - say 10%? This might depend on the pathogen and such factors as the colonization to infection ratio.

Finally, I do wonder if using endemic thresholds for deciding whether to relax infection control interventions runs counter to the risk of transmission in our ICUs and wards. One of the most important risk factors in acquiring a pathogen, say VRE, is the colonization pressure (proportion of other patients colonized with the bacteria) on the unit. Doesn't it then follow that as a pathogen becomes "more" endemic, however defined, that the individual risk to the "negative" patient increases. We can agree that it is harder to eliminate a pathogen as it becomes more prevalent or endemic. Yet, elimination isn't the only or even primary goal of infection prevention - it is to protect the individual patients and populations in our hospitals. Usually, endemicity is beyond our control, as there are many outside factors that can impede our efforts. But I don't think we should use endemic thresholds in our decision making.

Of course, we still need to ask basic questions like does the intervention work? Is it cost effective? And to bring this back to contact precautions, I see little evidence that contact precautions are more effective in CRE or CDI control vs MRSA. I also don't see that mortality rates are much higher in those pathogens where we agree to use contact precautions routinely (e.g. CRE) and where there is debate (e.g. MRSA). So there must be other factors driving the decision making, like availability of effective antibiotics, but I don't think endemic thresholds should be one of them.

Killing contact precautions one study at a time

Dan Uslan's group at UCLA has just published a new paper in Infection Control and Hospital Epidemiology on the elimination of contact precautions for MRSA and VRE at their health system (2 hospitals).

They looked at the rate of positive clinical cultures for MRSA and VRE one year before and after contact precautions were stopped on July 1, 2014. Importantly, at around the same time they expanded daily chlorhexidine bathing from ICU patients to all inpatients.

Comparing the pre- and post-intervention periods in this quasi-experimental study, here are the key findings:

• There was no difference in the rate of clinical cultures for MRSA or VRE.
• There was no difference in C. difficile infection rates (a nonequivalent dependent variable).
• There was no difference in MRSA colonization rates (active surveillance cultures were performed on high-risk patients).
• An annual cost savings of $730,000 in isolation gowns, and $5 million in nursing time associated with donning personal protective equipment was demonstrated.

Now one could argue that the benefit of contact precautions was replaced by the beneficial effect of chlorhexidine bathing. That doesn't bother me. I'd gladly trade 24 hours of gowns, gloves and confinement to a small space for a 5-minute wipedown with chlorhexidine. 

This is the fourth paper that shows a consistent finding of no increase in MDRO infections after contact precautions are stopped. The others can be found here, here, and here. And there are two more studies in abstract form. It seems to me that we simply don't need contact precautions for MRSA and VRE given newer developments in infection prevention (chlorhexidine bathing, better compliance with hand hygiene, private patient rooms, and enhanced environmental disinfection). Hopefully, the addition of this new study will convince other hospitals that the world doesn't end when contact precautions are retired.

Photo:  Dan Uslan MD, UCLA

Infection Prevention Summer Reading

With apologizes to our colleagues in the Southern Hemisphere, many of us are traveling a bit this summer and are looking for good things to read. At the top of my reading list is Ed Yong's new book, "I Contain Multitudes: The Microbes Within Us and a Grander View of Life." The book by the highly regarded UK science journalist (The Atlantic, National Geographic) digs into the relationship between microbes and animals. Unfortunately, the book won't appear until August 9th, so you'll have to be a bit patient and find something else to read.

In the meantime, I've listed five recently published journal articles/studies that will hopefully tide you over until "I Contain Multitudes" appears at your bookstore.

1) A Flawed Revision of the Common Rule (Joffe and Magnus, Annals 19 July 2016). The Common Rule is the regulatory framework that guides human subjects research, think IRB. Last September, 16 federal agencies released a Notice of Proposed Rulemaking outlining proposed changes to the Common Rule. There are several potentially important changes that could negatively impact infection prevention and stewardship studies. First, the Notice seeks to redefine all research on biospecimens, including de-identified specimens, as human subject research requiring "broad consent" before storing the specimens. The discussion didn't mentioned microbiology specimens specifically, but this requirement is concerning. Second, the Notice would only exclude QI research from review if it analyzed proven interventions and limited study endpoints to utilization outcomes (e.g. cost). However, QI projects such as quasi-experimental studies of the impact of CLABSI checklists on BSI rates or mortality WOULD require IRB review and potentially individual informed consent. (Yikes!)  My sense is this could drastically curtail important research in MDRO prevention and most infection control research. Stay tuned.

2) Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea (Park GE et al. Annals, 19 July 2016). From May to July 2015, 186 confirmed cases of MERS-CoV occurred in S. Korea. The authors provide an in-depth description of a 92-person outbreak in a single tertiary-care hospital in Seoul. Interestingly, 82 of the cases occurred after exposure to a single secondary patient cared for in their emergency department. All cases were identified through contact tracing and monitoring of exposed patients and healthcare workers and all in-hospital transmission was secondary to three patients with pneumonia and productive cough. The description of events was very sobering.

3) Colonization With Methicillin-resistant Staphylococcus aureus and Risk for Infection Among Asymptomatic Athletes: A Systematic Review and Meta-analysis (Karanika S et al, CID 15 July 2016). The results of this study suggest that you shouldn't be an athlete (6% MRSA colonization rate), especially a wrestler (22% MRSA colonization rate). Additionally, the authors reported that colonization increases the risk of subsequent skin and soft tissue infection 7 times. If only it were safer to lay around on the beach this summer.

4) Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies (Cummings KJ et al. Annals 5 July 2016). Authors from the CDC, Texas Health Presbyterian Hospital in Dallas and other other institutions describe the massive infection prevention response that followed the infection of two MICU nurses who cared for the index patient from Liberia. The responses included protocols for specimen handling, managing medical waste and standardized PPE with education and monitoring. Nothing particularly novel in 2016, but the article certainly highlights the massive efforts and costs associated with the N=1 response that was required because of a chronically underfunded public health and infection prevention infrastructure.

5) A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection (Khanna S et al. J Infect Dis 15 July 2016). The authors describe an alternative method to fecal transplants that could potentially avoid donor screening among other barriers. They tested SER-109, which is encapsulated spores captured from healthy human donor stool that was treated with ethanol to eliminate pathogens, for the prevention of recurrent CDI. The cohort of patients had to have had >3 CDI cases in the prior 12 months and a clinical response to antibiotic therapy for their current CDI episode immediately prior to dosing of SER-109. The 15 patients in cohort 1 received high-dose capsules (15 on day 0 and 15 on day 1) and 15 patients in cohort 2 received lower dose capsules on a single day. Overall, 87% achieved the endpoint of no CDI at 8 weeks. If you're interested in reading more, there is an excellent accompanying editorial.

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.

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.

ECCMID 2015 - "Best Of" Infection Control Literature (Part 1)

Every year it seems that one of us at the University of Iowa is roped into giving one of these "Best of Infection Control" talks at an annual conference. This year it seems that almost all of us have been asked and for some inexplicable reason, we all said yes! I was the lucky one to kick off the 2015 season with this talk I gave last week at ECCMID in Copenhagen. I covered S. aureus, MRSA, VRE, VRSA, surgical site infections and hand hygiene. I look forward to Mike's talk at SHEA. Loren Herwaldt's talk at ICPIC and Dan's talk at IDWeek. On Iowa.

Screening, Decolonization and Environmental Decontamination for MRSA in Nursing Homes Doesn't Work

Just in the past couple of weeks, we've written about pneumonia prevention bundles, MDRO prevention bundles, and spread of S. aureus - all in nursing homes.  It's like no one cares about acute care facilities any more! (humor) There is now more great data for those charged with managing infection control in nursing homes.

Cristina Bellini and colleagues from Lausanne University Hospital in Switzerland just published the results of cluster-randomized trial of an MRSA prevention bundle in 104 nursing homes (53 intervention, 51 control) in the April ICHE. All residents in intervention and control nursing homes (NH), who gave consent, were screened for MRSA carriage at study entry and 12 months thereafter on a single day in each NH. Newly admitted or readmitted residents were screened when admitted to the NH. Screening included nasal, groin and ulcer swabs along with urine cultures if residents had an indwelling catheter. In the intervention NHs MRSA colonized residents underwent decolonization along with environmental decontamination.

The primary decolonization bundle included 5 days of nasal mupirocin, 5 days of CHG oral rinse twice per day, 5 days of CHG showers including CHG shampoo on day 1 and 5. Environmental disinfection included daily clothing changes for 5 days, new linens on day 1 and day 5, and daily bed/table/phone/remote/wheelchair/walker disinfection with 70% alcohol. A lot of steps.

Unfortunately, the MRSA decolonization and decontamination bundle was not successful. The baseline prevalence of MRSA was 8.9% in both groups. The rate declined in intervention units to 5.8% in the intervention unit and 6.6% on the control units after 12 months (p=0.66) Full stratified results are in Table 3 below, and as you can see, no matter how they analyzed the intervention, the MRSA bundle intervention did not reduce MRSA prevalence compared to controls. This was despite the fact that the participation rate was 87%.

A limitation of this study was that they only measured prevalence and not individual level acquisition of MRSA. It is possible that by measuring prevalence they missed detecting benefits of the intervention related to reduced patient-to-patient transmission of MRSA. In any case, as I said last week about the study in CID, congratulations to the authors and journal (this time ICHE) for publishing this important negative study.

MDRO Prevention Bundle in Nursing Homes: A Randomized Trial

In keeping with our long-term care theme (more on this later in the week), there is a new trial published in JAMA Internal Medicine by Lona Mody and colleagues at the University of Michigan. The team completed a cluster-randomized trial of a bundled intervention to prevent MDROs in nursing homes. Specifically, residents with indwelling urinary catheters, feeding tubes or both in 6 nursing homes were randomized to a targeted infection program (TIP) bundle that included (1) preemptive barrier precautions; (2) active surveillance for MDROs (baseline, day 15 and monthly at nares, oropharynx, feeding tube, supra-pubic catheter, groin, peri-rectal, and wound sites) and infections, with data feedback; and (3) NH staff education on key infection prevention practices, including minimum criteria for initiating antibiotics, and hand hygiene promotion. Inclusion required a signed inform consent. Six other nursing homes served as controls.

The outcomes assessed were quite broad. The primary outcome was "overall MDRO prevalence density rate, defined as each participant’s total number of MDRO-positive anatomic sites across all MDROs per visit averaged over the duration of his or her participation." This would result in residents "with persistent MDRO colonization (having) a higher prevalence than someone with intermittent or no colonization" and residents colonized at more sites (up to seven were tested) having a higher prevalence. Secondary outcomes included new MDRO acquisition and device-associated HAI both with 1000 device-day denominators.

For the primary outcome, 27% of swabs were positive in the intervention NH residents while 33% were positive in the control NH residents. The adjusted rate ratio was significant 0.77 (0.62-0.94). This outcome seems largely driven by lower MRSA colonization in residents with urinary catheters, feeding tubes, or both and lower ceftazidime-resistant GNR colonization in residents with urinary catheters in the intervention NHs. However, rates of VRE were higher in the feeding tube requiring residents but this increase was not significant. (see Table 3) Interestingly, new MRSA acquisition rates were lower in the intervention NH residents (see Table 4, below) and first new CAUTI rates were also lower in the intervention NH residents, HR 0.54 (0.30-0.97).

Overall, an important study and one that should be read closely. Clearly this was a very difficult RCT to undertake, especially with informed consent, and the research team should be congratulated. The primary outcome of MDRO prevalence density rate is an interesting choice and the authors make a compelling argument for why they chose it. However, it is unclear if the interventions in the TIP bundle are major components in the causal pathway for limiting MDRO colonization density or reducing CAUTI. However, the lower MRSA acquisition rate in the intervention NHs is an important outcome and does fit with how we expect barrier precautions to work. Minor quibbles aside, this RCT should be discussed widely and many components of it are worth testing in other settings in future trials. 

Numbers Matter: Why counting only resistant bacteria ultimately harms our patients

You've seen the numbers. The CDC estimates that 23,000 deaths are caused by antibiotic resistant pathogens annually and as many as 14,000 of these deaths are linked to C. difficile. Every time I look at those numbers, they make me incredibly sad. First, they include all C. difficile deaths and not just those attributed to fluoroquinolone-resistant C. difficile, for example. This tends to incorrectly overweight the importance of C. difficile relative to other pathogens. Second, and you've heard me rant about this before, they only count deaths caused by the small proportion of bacterial pathogens that happen to be resistant, as narrowly-defined. This would tend to diminish the importance of bacterial pathogens compared to other causes of death (e.g. accidents). But I'm getting ahead of myself.

The numbers I'm about to throw at you are very rough estimates. I'm using these estimates to illustrate a point and hope that others will eventually provide more accurate estimates. If you think I need to correct a specific number, let me know in the comments, and I'll do my best to make the change - but I'm not promising. 

Let's take S. aureus as an example. The CDC estimates that 80,000 infections and 11,000 deaths are attributed to MRSA each year. In 2005, they also estimated that MRSA was associated with 18,650 deaths, but I'll be conservative and stick with 11,000. Per this 2013 NHSN report, the proportion of S. aureus that were MRSA ranged from 43.8% (SSI) to 58.7% for CAUTI. I'll use the lower proportion (44%) since this allows for some mortality secondary to more community (less MRSA) infections. However, I suspect most patients that die from S. aureus infection will ultimately be hospitalized. For simplicity, I will also assume that MRSA is twice as lethal as MSSA (AKA penicillin-resistant S. aureus).

Taking the above numbers, if there were 80,000 MRSA infections, we would expect 102,648 MSSA infections. If the mortality rate for MRSA was 13.75% (11,000/80,000) then MSSA's mortality rate would be half of that or 6.875%. So there would be 7057 deaths from MSSA. If you add that to the 11,000 you get 18,057 deaths due to S. aureus. We can quibble about numbers, but I suspect that 7,000 deaths caused by MSSA, passes the so-called giggle test.

Thus, if we used the CDC rankings to fund research and prevention activities, we would rank C. difficile at the top of the report. However, if we used my ranking system, S. aureus (MSSA+MRSA) ranks ahead of CDI. Since most interventions to prevent MRSA deaths would also work against MSSA (vaccines, new antibiotics) shouldn't both types be included in burden of disease estimates? The imbalance gets worse when you look at Gram-negative infections. Do we really only care if grandma dies of the 2-12% of E. coli or Klebsiella that are resistant to carbapenems? Do we really only count the 610 deaths from CRE and 1700 from ESBL? Clearly it would be better if we counted all deaths from E. coli and Klebsiella and projected a future where almost all strains would be ESBL or CRE.  This would allow us to make better decisions regarding current and future research priorities and prevention efforts.

I suspect if the S. aureus mortality estimate jumps from 11,000 to 18,000 when counting MSSA, it's not a stretch to imagine that deaths from bacterial infections would approach 100,000 in the US. If we count attributable mortality appropriately, deaths from bacterial infections would be a top 10 cause of death in the US. Top 10 means more money for research and prevention. Let's get these numbers right - grandma is counting on us.

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.

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