Conserving PPE in the COVID-19 Era

Photo by Ashkan Forouzani on Unsplash

In my 25 years as a hospital epidemiologist, this week was the hardest yet. Last Sunday, we learned of 3 COVID-19 cases in the Iowa City area. As of today, there are 14--that we know of. Because testing is still quite limited, these 14 patients likely represent just the tip of the iceberg. As all of this unfolds, it is like watching a train wreck in slow motion. And looking at the situations in Northern Italy and Seattle, we see that what lies ahead for us is quite scary.

One of the things I have focused on this week is personal protective equipment (PPE). It seems clear that, sooner or later, most hospitals will be in trouble. The PPE supply chain is deeply rooted in China and those factories have closed. That coupled with the just-in-time inventory concept has put all of us in a tough spot. For those of you not yet in the thick of this, I will offer some thoughts that may be of use to you.

Here is my practical strategy:

1. Know your inventory. Have your supply chain folks produce a tabular report of all PPE products used in your institution. In this table, ask them to also include the numbers of each item used in an average week so that you know your baseline utilization.
2. Develop an inventory target that includes projected usage and duration. We decided to set our critical target at 300% of normal usage for 12 weeks duration. This can be calculated from your baseline utilization for each item. On the table, any item's total inventory that is less than 300% normal usage over 12 weeks is coded red. Yellow is set at 12-16 weeks at 300% normal usage, and green is set at >16 weeks at 300% normal usage. We review the PPE inventory table daily at our Hospital Incident Command System meeting. The color coding of the table allows quick interpretation of inventory levels.
3. Critically evaluate your current usage and limit usage of PPE. Remember that we are not in normal times. Once you see how far away your current inventory is from your target inventory, you will rapidly begin to think of things that can conserve PPE. Here are several:
• If you use contact precautions for patients colonized with VRE or MRSA, PLEASE STOP! At best, the utility of this practice is questionable. Ask yourself this question: would you rather have PPE to care for a VRE colonized patient today, or that PPE for a COVID patient 6 weeks from now. 
• If you use contact precautions to isolate patients infected with VRE or MRSA, consider stopping. Numerous hospitals have done that with no ill effect. Ask yourself the same question as in the previous bullet.
• We made the decision this week that for non-COVID contact precautions we would stop the use of gowns, but continue gloves, and stress hand hygiene and bare below the elbows (to minimize clothing contamination).
• Begin re-using items such as face shields (after disinfection) and N95 masks.
• Stop annual N95 fit-testing to avoid the use of masks in the fit testing process.
• Limit the number of visitors.
• For patients in isolation precautions, avoid taking the entire rounding team into the patient room. 
• Limit care of the COVID patient to one nurse and one physician.
4. Send your supply chain staff on a scavenger hunt throughout the hospital to identify PPE that can be reclaimed. There are hoarders out there! In addition, secure your inventory to avoid theft.
5. Dispense PPE to individual hospital/clinic units in smaller increments.
6. Investigate alternative products. For example, we have a supply of old cloth surgical gowns that could be used as isolation gowns if needed. 

I'm sure others have ideas that we have not thought of. If so, please place them in the comment section. 

To my colleagues in the infection prevention community: This is hard. We are tired. And it's only the beginning. But our work is more important than ever. Stay strong! 

Namaste.

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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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.

De-implementation and Noninferiority in Infection Control Studies

De-implementation or "stopping practices that lack supporting evidence" is a popular topic in infection control circles. In fact, just yesterday I read a discussion where the authors suggested we no longer need to practice hand hygiene after removing gloves when caring for patients with CDI. I guess there aren't randomized trials - you can't be serious!

Which brings me to a recent review in the NEJM by Laura Mauri and Ralph D'Agostino titled "Challenges in the Design and Interpretation of Noninferiority Trials."  This review is very well written - perhaps required reading for epidemiology students well written. In infection control, it is important to recognize that most de-implementation studies are really non-inferiority trials. For example, when we discontinue contact precautions, we are really suggesting that "stopping contact precautions" is non-inferior to continuing contact precautions in preventing MDRO transmission - of course ignoring that compliance with contact precautions is probably so poor that they are basically the same intervention!

In the contact precautions example, we would be testing whether stopping contact precautions "is not worse than the control (continuing contact precautions) by an acceptably small amount, with a given degree of confidence." The null hypothesis would be that discontinuing contact precautions leads to higher transmission of MDRO (i.e. is worse) and rejection of the null hypothesis is used to support the claim that discontinuing CP is noninferior. Here I suggest you stare at Figure 1 for a bit (probably easier to read in the paper with the description of each condition, but I have included it below anyway)

Further discussion about the design and analysis of these trials is way beyond the scope of a humble blog post; however, the authors include nice descriptions of methods for deriving noninferiority margins, the "constancy assumption" and statistical analysis approaches. But their 6th and 7th components of noninferiority trials are worth mentioning from an infection control standpoint:

6) Adequate ascertainment of outcomes: The authors write that "incomplete or inaccurate ascertainment of outcomes, as a result of loss to follow-up, treatment crossover or nonadherence, or outcomes that are difficult to measure or subjective, may cause the treatments being compared to falsely appear similar."  I would suggest that studies that seek to de-implement contact precautions that do not include admission/discharge surveillance cultures seeking to detect transmission events fail this criteria.

7) Issues with "Intention-to-Treat" in noninferiority designs: In a superiority studies (typical RCTs), intention-to-treat analysis, where anyone who receives the treatment is included even if they get one dose, is the gold standard. The authors write: "In a noninferiority study, however, if some patients did not receive the full course of the assigned treatment, an intention-to-treat analysis may produce a bias toward a false positive conclusion of noninferiority by narrowing the difference between the treatments. In some instances, a per-protocol analysis, which excludes patients who did not meet the inclusion criteria or did not receive the randomized, per-protocol assignment, may be preferable in a noninferiority trial. However, a per-protocol analysis may include fewer participants and introduce postrandomization bias. In general, both the intention-to-treat and per-protocol data sets are important. We suggest analyzing both sets and examining the results for consistency."

Just some things to think about as we read the coming wave of de-implementation studies in infection control including diagnostic stewardship.

Universal gloving (+/-gowning) is a horizontal intervention

Years ago, Wenzel and Edmond described horizontal vs vertical infection control interventions. Horizontal interventions were defined as those where "all infections at any site are reduced" and vertical interventions were where "only specific organisms are targeted." It always seemed to me that universal gloving and universal gowning/gloving interventions were horizontal interventions, just like hand hygiene.

Thus, why is it that when we analyze and make a case against the universal gowns and gloves intervention (or trial) we only include MRSA outcomes? Put another way, why was it designed and critiqued as a vertical intervention and not a horizontal intervention? Shouldn't we also explore potential reductions in MSSA, GNR, MDR-GNR and CDI?  Of course, a critique of this approach would be that the BUGG study didn't look at pathogens beyond MRSA and VRE (yet), so we can't.  My response is then we shouldn't do studies of horizontal interventions unless they are properly funded to collect data on all pathogens possibly reduced through the intervention. These studies should also have high construct validity including tracking of post-discharge infections. Look what happens when hand hygiene's impact is limited to just healthcare-associated S. aureus bacteremia.

If we complete underpowered and underfunded studies with poor construct validity, they might come back to haunt us. And they could harm our field - infection control. More importantly, they might even harm our patients.

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.

The burden of contact precautions

A perspective published in JAMA today (free full text here) takes another whack at contact precautions. In this piece, Dan Morgan, Dick Wenzel, and Gonzalo Bearman nicely lay out the arguments against the use of contact precautions for endemic MRSA and VRE.

One thing this paper did was to stimulate me to think about using the gloved/gowned encounter as the unit of analysis rather than the number of days of isolation, or the number of patients impacted. Doing so highlights the burden for healthcare workers. To that end, I looked at the data cited in the perspective and did some calculations.

In the paper, they note that universal gowns and gloves in the BUGG Study resulted in a decrease of 1 acquisition of MRSA for every 336 patient-days of the intervention. There were 4 room entries per hour (96/day) in the BUGG Study in the intervention arm. They also note that 19% of S. aureus acquisitions represent transmission events when analyzed by whole genome sequencing. And 1 in 3 patients who acquire MRSA will become infected.

Doing the math, we find that in order to prevent 1 MRSA infection in the ICU setting using universal gowns and gloves requires 514,449 "protected" (gowned/gloved) encounters. Now using contact precautions for patients with targeted pathogens only (as opposed to universally) would greatly reduce the burden of the intervention, but even if  it were reduced by a factor of 10, or even 20, the burden would remain extraordinarily high.

When you combine high burden with questionable effectiveness and the current focus on alternative interventions (like hand hygiene and chlorhexidine bathing), it's not surprising that contact precautions is increasingly viewed as a decrepit concept.

It's not about you. Really. Well, most of you

After my posts discussing construct validity and other issues with studies attempting to understand the effect of eliminating contact precautions, several folks expressed concern that I was specifically talking about their proposed study, published study, abstract or hospital.  Well, I can assure you that none of my recent posts are about your studies or hospitals. Well, expect one, but not the one you might be thinking about.

While it's true that there have been many notable back and forth discussions about contact precautions on this blog from its initiation, I greatly respect Dan’s and Mike’s right to implement infection control in their hospital, their way. For example, we might even agree that contact precautions reduce transmission of MRSA by a certain amount; however, they might decide that MRSA is rare enough in their hospital that contact precautions are not locally cost-effective. I might even agree. Others colleagues have been concerned that I’m commenting on their specific study including ones presented yesterday at ICPIC. Yet, I never attended the session where several studies of ESBL control methods were presented. Unfortunately, jet-lag prevented me from making the earliest session, so I can’t claim specific knowledge or concerns about those studies.

However, I will share what prompted my recent posts (and hopefully a few more). A few weeks ago I had the opportunity to hear about a planned study that will examine the effect of discontinuing contact precautions. This planned study is large, includes a diverse set of hospitals and has a randomized design. However, the study only plans to discontinue contact precautions in non-ICU settings and only track clinical cultures. So, in my opinion, the study has strong generalizability, good internal validity but very poor construct validity.

During the discussion of the planned study, I mentioned this issue. The PI on the study was very quick to say that sure, it's not a perfect study but isn’t some information better than nothing? Of course the PI knows that it is hard for other scientists to say no to that question. We all like data. However, in this case the answer is a resounding no. Any large study will have economic and other impacts. For example, one opportunity cost of funding a large study with poor construct validity is not funding another study that could have a stronger design. Additionally, if you aren’t measuring the outcome properly, how can you tell if your intervention is harming patients? This is a human subjects issue, potentially. So, hopefully they will add methods that can measure colonization on discharge or better yet track post-discharge infections.

There you have it. You can be assured that I wasn’t thinking about your study or hospital. Of course, I can’t promise the same in the future.

Construct Validity and Infection Control Nihilism

As describe by Cook and Campbell (1979) there are four components of validity: internal validity, external validity, statistical conclusion validity and construct validity. Internal validity relates to whether there is a causal relationship between an exposure (e.g. contact precautions) and an outcome (MRSA infections) that is free of bias. Randomization is thought to improve internal validity through reduction in confounding associated with unmeasured factors. External validity describes the generalizability of the findings to other populations (quasi-experimental studies typically have higher generalizability vs RCTs). Statistical validity is concerned with covariation between exposure and outcome and strength of the association (e.g. Type 1 and Type II error). All types of studies can have high or low statistical validity – it is independent of study design.

Finally, construct validity describes whether a test measures what it claims to be measuring. For example, if you claim a person is ESBL negative, is she actually free of ESBL colonization or infection and will not develop an ESBL infection in the future. As you can see, without high construct validity, all the other components of validity are unimportant. If your study design or microbiological method is unable to detect ESBL properly, it is irrelevant if you’ve completed a cluster-RCT or whether your p-value is significant. Thus, validity theory defines construct validity as the primary concern, subsuming all other types of validity evidence.

Which brings me to studies claiming contact precautions don’t prevent MRSA, ESBL or VRE. Let’s think about MRSA. If an MRSA negative patient is admitted to a hospital with a 4 day length of stay. On average (normal distribution) that patient would be expected to acquire MRSA at the end of day 2. Thus, they would have to go from acquisition to infection over the next two days prior to discharge for most studies to prove she didn’t acquire MRSA. Would two days even be long enough for her to have a positive nasal swab? So, how sensitive are surveillance cultures or clinical cultures at detecting this event. I’d suggest not sensitive at all. Thus, to have strong construct validity in any study looking at the benefits of eliminating contact precautions, the study would have to track patients for a prolonged period of time (months) and in particular look at infections that manifest during subsequent admissions including those to long term care facilities.

So, before we can make claims about the benefits or lack of benefits of infection control interventions we need to design studies with high construct validity. I would suggest that our ability to respond to current MDR-bacterial pandemics will foremost depend on us designing studies with strong construct validity. Pathogens will continue to harm our patients until we identify methods to halt their spread. The current trend towards infection control nihilism that is manifesting with those eliminating contact precautions based on studies with poor construct validity and typically very poor statistical validity (underpowered) is harming our patients – often after they are discharged from our facilities.

Questions for Contact Precautions Eliminators

Over the past eight years, I've been the lone supporter of contact precautions on the blog. Of course, Tom and Hilary haven't publicly committed either way, at least on this blog. And to clarify my position, I'm greatly in favor of more studies examining the role of isolation strategies and how/where to best implement them. For example, do we need gowns or would gloves alone suffice? And should we isolate uncolonized patients instead of colonized patients since we're most interested in preventing transmission from contaminated healthcare worker to uncolonized patients? This latter question is why I currently favor exploring the benefits of universal gloving strategies. But of course, there is a growing number of studies that explore the discontinuation of contact precautions, which have led to places like Iowa eliminating contact precautions for MRSA/VRE colonized or infected patients. So with that in mind, I have a few questions for folks who are in favor of eliminating contact precautions. Specifically, I want to understand the who/what/when/where/why behind their recommendations.


Question #1: Are hospitals no longer a source for MDRO-bacterial acquisition? Do acute care hospitals or subpopulation (ICUs, hemodialysis) remain sites for patient-to-patient transmission or have we completely eliminated transmission in these settings?

Question #2: If transmission has been eliminated, how would we know? Are you aware of data that proves patients who are uncolonized on admission remain uncolonized by the time of discharge? Does your hospital do discharge surveillance cultures for sentinel organisms like MRSA, CRE?

Question #3: If you don't do surveillance culturing on discharge, do you follow patients post discharge to make sure they don't develop an MDRO infection at a subsequent point? Do patients no longer develop MDRO infections linked to a prior hospital stay suggesting that all transmission is now occurring in the community setting?

Question #4: If transmission in acute-care settings has been eliminated, how has that happened? Is it that hand hygiene compliance of 34 to 57% is enough to halt all transmission? Is it that the environment is so sparkling clean these days that clinicians can't even pick up bad bacteria on their hands?

Question #5: Perhaps you agree that hospitals (or ICUs) are still engines powering the emergence of MDRO in human populations and your hospital might even be a source for patient acquisition. Is it that you think hands are not a source of transmission and contact precautions just don't work? Do you feel similarly about hand hygiene - does hand hygiene not reduce transmission? Since we know that when caring for patients that healthcare workers gloves/gowns become contaminated 8-39% of the time, where do these bacteria go? Do they just disappear?

Question #6: Finally, even if transmission is occurring via the hands of healthcare workers maybe you're convinced it's not your problem? If you can't see the benefits directly in your hospital, it's not important. Tragedy of the commons? - meh. Perhaps, it's up to me to detect all MRSA colonized patients in my clinic or on admission to my hospital and decolonize them?

Putting contact precautions in their place

Last September, I had the honor to attend the Infection Prevention Society's Infection Prevention 2016 conference in Harrogate, England. During the conference, I was fortunate to meet Professor Graham Ayliffe and give the annual Ayliffe Lecture on the Science Behind Hand Hygiene and I also got to meet and discuss infection control with many of the dedicated members of the Society. Attending the IPS conference was a great way to learn how infection control interventions are implemented in other countries.

In particular, I greatly enjoyed meeting and debating! Dr. Fidelma Fitzpatrick of The Royal College of Surgeons in Ireland and Beaumont Hospital in Dublin. I was charged with debating For contact precautions and Fidelma was charged with Against. At the end of the debate, we realized that there was much common ground in our understanding of where and when to implement contact precautions for MDRO prevention. In particular, we realized that the underlying context in which contact precautions are implemented, de-implemented or studied is critical. And by context, we mean things like availability of single rooms or the baseline (poor) hand hygiene compliance in your hospital. With that in mind, Fidelma and I just published what we learned in a JHI opinion piece called Putting contact precautions in their place. In addition to highlighting the very poor evidence supporting de-implemention of contact precautions, we concluded:

"Where we implement or de-implement CPs will depend on how we frame the literature findings and our local institutional infrastructure, epidemiology, specific MDRO rates, patient factors, and institutional culture along with the local staffing and laboratory capabilities."

Jon Otter at the Reflections blog had a nice overview of our debate. He concluded:

"It was a slightly odd set-up in that Fidelma was arguing against contact precautions from a hospital that uses them, and Eli was arguing for contact precautions from a hospital that doesn’t! But I got a sense that the debaters were putting across genuine views, and not talking to a side of the debate they didn’t subscribe to. My conclusion: contact precautions make sense and fulfil the logical idea of ‘disease segregation’. The studies that seem to show stopping them makes no difference are probably explained to a large degree by the fact that they’re not done right in the first place! It was interesting that all agreed that you should apply contact precautions for the ‘really bad bugs’ (like CPE and C. difficile diarrhoea), so what is the logical difference between these and other organisms?"

Post debate, the attendees were charged with voting Against or For the motion supporting contact precautions with their feet. A fun idea!

Wherein I reveal the top 3 approaches for preventing C. difficile disease!

1. Antibiotic stewardship

2. Antibiotic stewardship

3. Antibiotic stewardship

I’ve listed these in order of importance. Supporting evidence is accumulating, including three recent papers that I found very interesting:

Dingle, et al. Lancet Infect Dis 2017. This observational study from Oxfordshire, UK combined overall CDI rates, antibiotic use data, and whole genome sequencing to determine whether declining CDI rates were more likely driven by reduced antibiotic use or by transmission prevention efforts. The results are nicely summarized in Figure 2 from their manuscript (see below). It’s extremely cool to see how the big reduction in fluoroquinolone (FQ) use from 2005-2007 was followed by the near-extinction of FQ-resistant isolates. The disappearance of these FQ-R genotypes accounted for the entirety of the significant CDI reduction seen in Oxfordshire. If infection prevention approaches were a major driver of the CDI reduction, one would’ve expected to see at least some reduction in the non-FQ-R genotypes. Equally interesting: as FQ use crept up, rates of FQ-R CDI didn't follow, possibly due to eradication of these genotypes from asymptomatically colonized, or due to the still-lower usage (or usage in different populations). Anyway, there’s a lot of great detail in this report, so read it yourself, but the results support the centrality of stewardship to CDI prevention. LATE ADDENDUM: See this post by Marc Bonten and this Wellcome Open Research article for important caveats to the above "simple interpretation" of this study.

Anderson, et al. Lancet 2017. I’m kind of embarrassed that we haven’t weighed in on this one yet, since the Benefits of Enhanced Terminal Room (BETR) Disinfection study is definitely “BETR” than most infection prevention studies. It’s a cluster-randomized, multicenter, crossover study that compares standard disinfection to bleach, UV-C, and bleach + UV-C for terminal room disinfection after occupancy by patients with MRSA, VRE, multiple-drug resistant Acinetobacter, or CDI. The outcome is acquisition of colonization or infection with the index organism by the subsequent room occupant. One reason I haven’t blogged about the study yet is that I really don’t know what to make of it. It’s a great study, but some of the results are confusing or counterintuitive, and don't make me want to rush out and buy more UV robots (full disclosure: we have a whole army of them at our hospital already, all of which were purchased prior to the results of this study). For rational takes on the entirety of the study I’ll outsource to our colleagues Jon Otter and Marc Bonten at Reflections IPC. As for the C. difficile results (see below for per-protocol results from Table 3 of the manuscript), UV-C didn’t reduce CDI risk beyond that of standard bleach disinfection. For the purposes of this blog post, I’m going to concur with the authors’ contention that “the environment might not play as large a role in C. difficile transmission as previously suspected” (or at least not as large a role when you’ve already cleaned said environment with bleach). It’s all about the antibiotic stewardship, baby!

Widmer, et al. Clin Infect Dis 2017. This is the laziest, least resource-intensive of these three studies, and also my favorite. What better way to determine whether an intervention to prevent transmission is effective than to just stop doing it and see what happens? [I’m now picturing Andreas Widmer leaning back on his office chair, feet on his desk, overseeing a decade of not placing CDI patients in contact isolation.]  I’m kidding, of course, in fact they did quite a lot of sampling of the contacts of these CDI patients (451 of them) to assess for transmission events. The upshot: only 2 (!) proven (and 4 probable) transmission events were documented using genome sequencing over the decade, and no outbreaks occurred. Of note, they did place those with “severe incontinence” in contact isolation (really, this is in the spirit of Standard Precautions), and all CDI patients were assigned a dedicated toilet. Oh, and they also had no active antibiotic stewardship during this time period, but report a >90% adherence to hand hygiene (paging Eli!). 

To sum up: three interesting studies, and the combined results lead me to conclude that, assuming I have a limited budget with which to reduce CDI, I’d be wise to invest most of it in active antibiotic stewardship.

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

Is it time to ditch CHG bathing in ICUs and get back to basic infection control?

We are at an interesting inflection point in infection control. On the one hand MRSA is in decline and VRE has flat or declining incidence in many national samples. Yet on the other, we have largely pulled back from what is considered traditional infection control practice. It is important for us to understand what may be driving the declines in MRSA (and to a lesser extent VRE) and on what shaky foundation these declines are actually resting.

The recent MRSA decline is due to multiple factors including the underlying epidemiology of the pathogen, host immunity and the emergence of effective antibiotics targeting MRSA that are not named vancomycin (e.g. linezolid, daptomycin, ceftaroline). These factors are intertwined. For example, recent CA-MRSA strains have susceptibility to many existing antibiotics (e.g. clindamycin, tmp-sulfa), which highlights the complexity of the underlying reasons for MRSA's decline. I should also mention the antibiotics CHG and mupirocin here too, but I'll get back to them in a bit.

During the past decade, we've also seen a decline in the importance of basic infection control. Many of you will disagree with this statement but let me explain. The cornerstone of infection control has always been hand hygiene compliance and yet very little "honest" attention is paid to it. There is now so much pressure to report hand hygiene compliance rates greater than 90% that we have hit the target without actually improving compliance. Over and over in studies at hospitals across the US where we've looked, hospitals are reporting compliance rates over 90% and it's actually 40-60%, when we look closely with independent observers. Why does this matter? Because when we believe it's 90%, we ignore it.

On top of our hand hygiene conundrum, contact precautions are no longer favored for MRSA prevention. A bit of history - the second ever post on this Blog back in 2009 was titled: "Why I hate Contact Precautions, vol. 1." So there's not much love here for ye olde CP. Which brings me to the point of this post (finally) - when we no longer have hand hygiene compliance, gowns and gloves and when the foundation of infection control is based on antibiotics like linezolid, CHG and mupirocin, what will we do when the foundation begins to crumble?  Will we even notice the crumbling or will we stick our heads in the sand and ignore it?

Many of the gains in infection control over the past decade have rested on the foundation of CHG bathing. Ignoring for now that CHG might select for Gram-negative pathogens that have fewer effective therapies, CHG use might also select for CHG resistance through efflux pumps coded by qacA/B, which has been associated with MRSA decolonization failures. Yet the long-term (and after a decade, we are getting longish) effects of daily CHG bathing are not well described.

Into this void, David Warren and colleagues just reported in ICHE 8-year trends in the epidemiology of MRSA strains after initiating daily CHG bathing in their SICU. A random sample of 504 MRSA isolates were selected for analysis (63/year). Among all isolates from 2005 (when CHG bathing was implemented) to 2012, 7.1% were qacA/B(+). Somewhat disconcerting was the rise of qacA/B from 6.2% (2005) to 16.9% in both 2009 and 2010. Also concerning was the finding that 25% of qacA/B(+) MRSA isolates were mupirocin resistant. Results stratified by timing of nasal swab collection are in the Figure above. In explaining this increase the authors noted: "qacA/B(+) isolates from 2009 and 2010 were more likely to have ≥1 hospital admissions in the prior year, suggesting a possibility of an expansion of qacA/B(+) MRSA at BJH during this time period, which resulted in qacA/B(+) patients in those years being exposed in prior admissions."

So where do these findings leave us? Yes, more studies, larger studies, bigger and better studies - $6 million dollar man studies. But pending those dream-like studies, can we state at what level of CHG resistance we should ditch universal CHG bathing?  Are we compromising the effectiveness of CHG in preoperative settings like those supported by STOP-SSI? And when can we get back to basic infection control? To my knowledge hand hygiene and gowns/gloves don't drive resistance like CHG. Well, except resistance from my esteemed co-bloggers and colleagues. ¯\_(ツ)_/¯

Guest Post: Thinking about Contact Precautions

Anthony Harris, MD MPH

This is a guest post from Dr. Anthony Harris, Professor of Epidemiology and Public Health, University of Maryland School of Medicine.

I have a lot of admiration for this blog and in the spirit of academics, I would like to share my somewhat different interpretation of the contact precautions literature. I offer three points for your consideration:
 
1. Contact precautions do not lead to an increase in adverse events: 

Instead of the frequently cited small observational studies, I think it is most important to focus on the one randomized trial that evaluated adverse events associated with contact precautions (I acknowledge my bias in that it is the study I led). A randomized trial should most often trump observational studies especially since it's near impossible to control for confounding by indication, i.e. why was the patient placed on contact precautions. In fact, the latest analysis of our randomized trial data showed a trend towards decreased adverse events in the universal contact precaution arm. (See: Croft L et al. Clin Infect Dis. 2015 Aug 15;61(4):545-53). To quote from the Conclusion: "Concerns of adverse events resulting from universal glove and gown use were not supported." So we should be clear that other than the cost issues of gloves and gowns no high level study has shown any adverse events from contact precautions. Healthcare workers do go into the patient room less often when the patient is on contact precautions but this has not been shown to lead to an increase in adverse events. In my experience (and the data supports this), healthcare workers just bundle their activities and thus perform the same activities in the room with fewer visits.

2. Methodological problems in studies that have removed contact precautions: 

Studies that show no effect of removing contact precautions have serious methodological problems. The largest problem is that they are incredibly under-powered. The studies that show “no difference when you remove contact precautions” are too small to detect a difference and thus may falsely conclude that removing contact precautions is safe.

3. Need a better solution before removing the current standard of contact precautions: 

As much as I would love to stop wearing gloves and gowns, antibiotic-resistant bacteria are a continuing problem. They are not going away and other than MRSA, they are not decreasing. Until we have better solutions, I believe that we should not be abandoning contact precautions. This is particularly true in high risk settings such as the ICU. In the ICU where acquisition of an MDRO leads to infection 20-30% of the time during the index ICU admission, the stakes are too high not to prevent patient-to-patient transmission. I believe that the phase 0, phase 1 and phase 2 data on contact precautions are strong and the biologic plausibility that they prevent patient-to-patient transmission so strong that I don’t think we should abandon contact precautions based on underpowered "removal studies" and an adverse-event literature with few studies with strong internal validity. Of course there are certain settings and certain bacteria where removing contact precautions might make sense and these scenarios should be studied using large, sufficiently powered and methodologically sound trials.

Rethinking contact precautions

I'm working on a talk entitled "Rethinking Contact Precautions" for the Winter Course in Infectious Diseases. If you've never been to the Winter Course, it's a great conference in a casual setting with state-of-the-art lectures on a wide variety of ID topics. And there's lots of skiing. This year, we'll be at Big Sky, Montana, February 14-18.

This weekend, I ran across a brand new paper in Infection Control and Hospital Epidemiology on discontinuing contact precautions. This one comes from Roswell Park Cancer Center where active surveillance (weekly perianal cultures) for VRE was discontinued in March 2011. At the same time contact precautions for VRE infection and colonization were also discontinued. The investigators compared VRE bacteremia rates for the 3-year period before and the 3-year period after discontinuing active surveillance and contact precautions. The 6-year period of the study included over 1,300 patients with hematologic malignancies, bone marrow transplant and lymphoma. Over the study period there were no changes in antibiotic utilization, nurse-to-patient ratio, age, gender, underlying malignancies or length of stay. Importantly, via interrupted time series analysis, there was no significant change in the rate of VRE bacteremia (2.32 infections/1,000 patient days before vs. 1.87 after). This is the third published study (see the others here and here) and there are two more studies in abstract form all showing no change in infection rates after contact precautions were discontinued.

I also re-read Kathy Kirkland's thoughtful paper, Taking Off the Gloves: Toward a Less Dogmatic Approach to the Use of Contact Isolation (free full text here). Kathy was way ahead of the curve with her thinking on this topic. Below is a table from her paper that summarizes the likelihood of benefit for contact precautions:

As I thought more about where we are in infection prevention in 2016, it seems to me that contact precautions is a decrepit concept. When introduced 50 years ago, contact precautions made sense. At that time hand hygiene rates were abysmal, alcohol-based handrubs were not available, patients weren't bathed with chlorhexidine, there were few single-bed hospital rooms, and there was no enhanced technology for environmental disinfection.

Putting it all together, there's little evidence that contact precautions are effective in the non-outbreak setting, and we're learning that nothing bad happens when contact precautions are stopped. At the University of Iowa, we're focusing on hand hygiene, stethoscope wipe down and bare below the elbows. And the list of hospitals forgoing the plague doctor suit for MRSA and VRE grows ever longer.

And another reason to hate contact precautions...

There's a new paper in the Journal of Trauma and Acute Care Surgery that adds to the concern regarding the safety of contact precautions. This retrospective two-year study evaluated approximately 4,400 trauma patients and compared the incidence of venous thromboembolism [VTE] (as detected by active surveillance via duplex ultrasound) in patients who were isolated versus those who were not. I should note that there is an error in the title of the paper as isolated patients also included those on droplet and airborne precautions. However, in most hospitals contact precautions account for the vast majority of patients who are isolated, and even more so in the hospital studied since they performed active microbiologic surveillance for MRSA via PCR. VTE occurred in 17.7% of the isolated patients and 3.5% of the non-isolated patients. After controlling for a number of confounders, isolation remained an independent predictor of VTE (odds ratio 2.6, CI95 1.7-4.0).

Increasingly, hospitals are scaling back contact precautions for MRSA and VRE, and with good reason!

Lovin' Contact Precautions (this time in nursing homes)

Contact precautions get very little love on our humble blog. So little in fact, that I've taken it upon myself to be the resident contact precautions fanboy. Just today on rounds, I was waxing sentimental about the poor yellow gowns that protect us from horrible pathogens and how we unceremoniously toss them into the trash after wearing them - we never even say goodbye...but I digress

There is a new study in the September ICHE by Mary-Claire Roghmann and colleagues from the University of Maryland and University of Michigan that sought to estimate the transmission of MRSA from nursing home residents to healthcare workers' gowns and gloves based on clinical activity and resident characteristics (i.e. skin integrity or stool incontinence).  They aimed to determine if there were certain situations where wearing gowns/gloves would be most protective of HCW contamination (and thus reduce MRSA transmission).  The logic - if gowns and gloves are contaminated, the underlying hands would be contaminated if gloves/gowns weren't worn and since no one has ever gotten hand hygiene compliance near 90-100% anywhere, including nursing homes, then gowns/gloves result in cleaner hands and less MRSA transmission. I know, much more complicated than a cluster-RCT, but important data...but I digress again...

RESULTS! Overall, they enrolled 401 nursing home residents from 13 facilities including 113 (28%) who were MRSA colonized. 62% were nasally colonized, 9% were colonized at the perianal skin and 28% were colonized at both sites. There were 954 HCW interactions (median 7 per patient) with MRSA+ patients with a median duration of 6 minutes. Overall, gowns were contaminated after 14% of the interactions and gloves were contaminated 24% of the time. Gown/Glove isolates were identical (Spa type) to patient isolates 89% of the time. Overall, the contamination rate ranged from zero to 24% for gowns and 8 to 37% for gloves based on activity. So as far as hand contamination goes, there were no safe interactions and thus, we wouldn't expect activity-based precautions to be effective. (See figure below)  Significant predictors of glove/gown contamination included dressing, transferring, patient hygiene, changing linens and changing diapers.

As far as patient characteristics, stool incontinence did not modify gown/glove contamination with MRSA, but skin breakdown was associated with higher contamination when healthcare workers transferred the patient, changed their diapers and helped dress the patient.

My interpretation of the study is that if we want to limit the substantial transmission of MRSA in nursing homes, we better up our game. And that game should probably include gloves and perhaps gowns for most of the analyzed patient care activities. Unless we can get hand hygiene compliance up to 100%, we better just learn to love the glove.