COVID-19 Can Have Airborne Transmission but You Don't Need to Run for an N95

This is a guest post by Jorge Salinas, MD, Hospital Epidemiologist at the University of Iowa Hospitals & Clinics. 

There is virtually no doubt that SARS-CoV2 is transmitted by droplets and contact. However, the debate continues about whether SARS-CoV2 can be transmitted through the air, in what epidemiologists call “airborne transmission.” As with most biologic processes, unfortunately this is not a dichotomy. Many (too many) factors play a role.

Population density matters. As people breathe, speak, sneeze, or cough we all produce many particles that have a continuum of sizes. These particles are unfortunately called too many names in the literature and the lay press (e.g., droplets, aerosols). Viruses and biologic processes don’t read textbooks. These particles can be large (what healthcare epidemiologists call “droplets”), medium size (no fancy name for them), and small (these are called “aerosols” by some but “droplet nuclei” by others). If we are near only one infectious person, the number of small particles (aerosols) expelled may not be enough to meaningfully contribute to infection. But if we are exposed to many infectious people at once, the number of small particles can increase. In such instances, airborne transmission in addition to contact and droplet transmission can play a role in outbreaks.

Patient characteristics are also tremendously important. Some may extrapolate that COVID is not as contagious or rule out the possibility of airborne transmission because of a paucity of hospital outbreaks, even if not following airborne precautions. If we follow the natural history of COVID, we now know that a person is possibly infectious 48 hours before symptom onset. Most people do not require hospitalization, and those that require hospitalization may be in later stages of the disease. We are learning daily that COVID, the disease caused by SARS-CoV2, is likely a continuum. Initially, the disease is predominantly caused by direct injury of the virus to tissues, but as days go by some patients will have immunologic or para-infectious syndromes that may require hospitalization. By the time a patient with COVID requires hospitalization, their infectiousness has likely decreased. It is now clearly recognized that presence of viral RNA does not equal risk of transmission in many cases.

The setting is also very important. How big is the space where the infectious person and their potential contact are located. If outdoors, the risk is tremendously decreased as air flows freely greatly decreasing the possibility of breathing “the same air.” Indoors, the number of air exchanges is very important: the more air exchanges, the lesser the likelihood of spread. Fortunately, most hospitals have already implemented an increased number of air exchanges likely decreasing the possibility of airborne transmission of pathogens in hospitals.

If airborne transmission plays a role in SARS-CoV-2 transmission, I believe it is predominantly in the early stages of the disease, in the viral phase. That may explain why most healthcare outbreaks have occurred in nursing homes and long-term care facilities. Not only because of potential infection prevention deficits but because patients are already in the facility when they become infectious. They are at the peak of infectiousness when in the facility. Hospitals on the other hand, will usually admit patients days or even weeks after the beginning of the infectious period, likely attenuating the risk of transmission in hospitals.

Recognizing that SARS-coV2 can also spread via small particles should not lead to panic. It should lead us to modify our behaviors in the community by avoiding crowded indoor settings, using universal source control with face coverings, and maintaining physical distance.

Modified from CDC.

In healthcare facilities, we need to continue educating stakeholders about the hierarchy of infection controls. Administrative and engineering controls are by far the most important measures. Decreasing population density, protocols for early identification and isolation of potentially infectious cases, especially those early in the disease course, and increased air exchanges are likely the most important measures. Personal protective equipment is also important. However, a debate only centered on whether respirators or medical masks are needed can distract us from the bigger challenges of administrative and engineering controls.

Reducing population density in healthcare facilities (patient census and personnel) can lead to increased safety but has a tremendous impact on population health (less capacity to take care of patients) and potential economic implications if healthcare personnel numbers are decreased. Engineering controls are also costly but fortunately most hospital design standards already address increased air exchanges compared to regular buildings and homes.

This pandemic has been challenging for all. COVID-19 keeps me humble as what I thought I knew yesterday may not be true today. Let’s all remain humble and nimble as we respond to COVID-19 in the community and in healthcare facilities.

Airborne vs Droplet: Turbulent Gas Clouds of Opinion!

There’s much about the COVID-19 pandemic that is unprecedented, at least in my lifetime. One aspect is very familiar, though: arguments about the primary mode(s) of transmission of a newly emerging respiratory virus.

Much of the problem stems from our need to divide transmission modes into simple categories in order to apply prevention measures effectively. When someone calls the infection prevention program to ask about precautions recommended for virus X on the respiratory viral panel, it's not helpful to begin the conversation by saying, 

“well, you know, droplet and airborne transmission is not really a dichotomy, it’s more like a continuum, and there are a lot of factors at play—can we talk in more detail about the patient’s condition, what procedures they might be undergoing, and whether they might break out in song during routine patient care activities?”

One recent review you may find useful was published in Current Opinions in Infectious Diseases in August of 2019 by Shiu, Leung and Cowling (talk about great timing…). A very important point made in this piece is that viral nucleic acids and (less often) viable virus can be found in air samples--including from healthcare environments--for influenza, RSV, adenovirus, rhinovirus, and other coronaviruses. So reports about airborne SARS-CoV-2 (which will keep coming out in both pre-print and peer-reviewed literature) are not surprising. Nor do they answer the most important practical question about SARS-CoV-2 transmission:

Is airborne transmission a major mode of COVID-19 spread in community and in routine (i.e. no aerosol-generating procedure (AGP)) clinical settings?

My view is that we should consider the epidemiology of COVID-19 thus far in the pandemic, to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens, or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, VZV and M. tuberculosis). We could compare, for example, attack rates in various settings (household, healthcare, public), and the infamous R0 (expected ‘average’ number of secondary cases from a single infected individual in a susceptible population).

For COVID I’ll point to two careful contact investigations—this one of the over 400 close contacts of the first 10 travel-related COVID-19 cases in the US, and this study from Guangzhou, China, which was ten-fold larger (4950 close contacts to confirmed cases). The US study examined symptomatic secondary attack rates, and the study in China did serial RT-PCR on all contacts in addition to monitoring for symptoms. The findings are remarkably similar: highest attack rates are among household contacts (10.5% in US, 10.2% in Guangzhou), with extremely low rates of transmission among healthcare or community contacts (zero in US study, 1% among healthcare contacts and 0.1% among public transport contacts in Guangzhou). As for the R0, which of course varies as a population begins prevention approaches, the best estimate in my opinion is the tragic natural experiment performed on the unfortunate passengers of the Diamond Princess: during the early stage of the outbreak the R0 was 2.3.

For measles, the R0 is 12-18 and the secondary household attack rates are >= 90%. 

For VZV, the R0 is ~10 and the secondary household attack rate is 85%.

For TB, the R0 for smear-positive untreated TB is up to 10 (per year) and the secondary household attack rate has been reported to be >50%.

Based upon the above, I’m confident that SARS-CoV-2 transmission is similar to that of other respiratory viruses we are used to encountering—for which experience suggests droplet + contact spread to be the primary route of transmission. The trick is determining under what conditions a higher-risk aerosol might be produced (i.e. what is our list of AGPs? See here and here, if you dare!).

Does this mean that every respiratory droplet falls to the ground immediately and within 6 feet of a coughing patient? No. Dr. Lydia Bourouiba has an excellent piece in JAMA about the role of “turbulent gas clouds” in allowing droplets to travel further, and to remain in the air longer, than our traditional “droplet-airborne” dichotomy considers. In my view, this kind of droplet + "gas cloud" production mostly contributes to the extensive surface contamination that results in the highest risk of transmission being among close household contacts.

Practical Strategies for Physicians to Avoid COVID-19 Infection at Work

The physician workforce is one of the most valuable resources of any hospital, and in the midst of the COVID-19 outbreak we need to do everything possible to ensure that physicians stay healthy. Like other hospital epidemiologists, I spend a lot of time thinking about practical ways to reduce the risk of infection. So to that end, I want to offer some suggestions for reducing your risk of acquiring COVID-19 at work.

• Personal infection prevention: I strongly recommend that everyone in clinical areas follow bare below the elbows. This means that there should be nothing on your forearms, including wrist jewelry and wrist watches. This prevents contamination of sleeves and allows you to perform good hand hygiene. Hospital-laundered scrubs, doffed before going home, is optimal. We want to minimize clothing contamination, so I recommend not wearing white coats, cover jackets, or fleece jackets. Neckties are problematic because they frequently touch the patient/patient surroundings and are rarely cleaned. If you feel the need to wear a necktie, tuck it into your shirt. If you wear a long sleeve shirt, roll up the sleeves. Perform hand hygiene like never before (at least before and after every patient contact), and remember to wipe down your stethoscope after each use. Lastly, avoid touching your face.

• Work rooms: Physician work rooms are often small, so we need to think about how to achieve social distancing in these small spaces. One way to do this is to bring your laptop to work and do your documentation in another site to reduce the number of people in the work room. Also, it’s important to declutter these rooms so that housekeeping can come in to clean all the surfaces. It’s very difficult for them to do this when there is clutter everywhere. You should also wipe down your workspace before you use it. Avoid shared foods in work spaces.


• Conservation of personal protective equipment: Supplies of PPE are tight because many of these products are manufactured in China and factories are closed. This means we really need to conserve these items so that we can safely care for COVID patients for what may be an extended duration. At my hospital, we have modified contact precautions for non-COVID patients to not include gowns, since gowns are particularly in short supply. We continue to wear gloves for patients in contact precautions. If you anticipate a splash or spray, wear a gown for any patient. One way to think about this is to ask yourself: would I rather have this gown to care for a C diff patient today, or this gown to care for a COVID patient 6 weeks from now? I think this question puts the issue into perspective. Face masks and face shields marketed for medical use are in short supply, so consider purchasing a face shield from a hardware store. Here is an example of one. This particular model completely covers your face even laterally, and I think provides good protection and is comfortable. If you are a physician in an area such as urgent care or the emergency department, where there are many patients with respiratory symptoms, I would consider wearing the shield the entire shift. Avoid touching the shield, and wipe it down after use. To reduce supplies used, reduce the number of persons entering the patient room to the minimum necessary.


• Workflow: Again, we need to think about social distancing. In teaching hospitals, we tend to travel in packs, and this needs to stop. Consider asynchronous rounding (attending rounds with each intern separately) to avoid congregating in the hallways on rounds. You might also consider batching your duties to the degree that you can and doing more of your documentation at home. Avoid elevators.


• What to do if you become ill: The most important thing is to not come to work if you have fever or new onset respiratory symptoms. If you begin to feel sick at work, remove yourself from patient care as soon as possible. If you don’t have a thermometer (I didn’t have one until a few days ago), please get one, so that you can check your temp at home should you feel febrile. You might also consider purchasing a pulse oximeter to keep at home for self-monitoring in case you become ill.

Please take care of yourself during this difficult time. Patients need us, so let’s do everything we can to stay healthy!

Mike Edmond

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. 

-->

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. 

Will Antimicrobial Stewardship be the Next Target for De-implementation?

First, an honest confession, Mike's tweet had nothing to do with antimicrobial stewardship, but rather contact precautions. But his point is just as valid when discussing antimicrobial stewardship and there will come a time when forces will align to question the benefits and costs of stewardship programs since now and in the future they will lack the "necessary" cluster-randomized trial evidence supporting their existence.

There is a longer discussion to be had here sometime in the future, when I'm not writing a Center grant renewal, but the key question is what we consider "high-level" evidence. For most de-implementation supporters and indeed most infection control and stewardship guideline authors, high-level evidence is synonymous with individual or cluster-randomized trials. They simply cannot accept non-randomized, quasi-experimental designs as evidence. It is gotten to the point that the recent CDI Guidelines completely excluded quasi-expermintal designs from their level of evidence figure, despite the fact that one of the original Grade Criteria papers lists QE studies in its table and allows them to be ranked higher than RCTs, if certain criteria are met.

OK.  So why am I rambling on about level of evidence and misapplying a tweet from 2 weeks ago? There was a new systematic review just published in AJIC by Leandro Bertollo and colleagues that asked the question: "Are antimicrobial stewardship programs effective strategies for preventing antibiotic resistance?" To answer this question they reviewed all studies published between from January 2012 to January 2017 and followed the standard PRISMA statement recommendations for reporting their findings.

Results: They identified and extracted data from 26 studies, of which 22 were single-center and four were multicenter studies. Study designs are listed in Table 2, below, with the special note that none of the before/after studies included a contemporaneous, unexposed control group. A major concern that the authors identified was that in 7 of the 26 studies (30%), there was evidence that infection control interventions were implemented at the same time as the stewardship intervention and that the majority (57%) of the stewardship studies that reported positive results were confounded by simultaneous implementation of new infection control practices. High fives for hand hygiene.

Their conclusion: "There is no solid evidence that ASPs are effective in reducing antibiotic resistance in hospital settings. There are still few studies analyzing this matter, most of them with inappropriate study designs. We uphold the need for more studies with appropriate study designs and standardized ASP interventions targeting common microorganism-antibiotic pairs."

The need for more studies. Sounds like the siren call for de-implementation to me. Sure, we can wait around a decade or four for some magical $20 million cluster-randomized study that swabs all patients on admission/discharge, completes a full microbiome analysis and tracks patients for a year post discharge for resistant infections. Or, we can expand our ideas around what "high-level" evidence means and fund well-designed and controlled quasi-experimental studies and also consider strong epidemiological evidence, such as exposure to antibiotics leads to colonization with resistant pathogens. We can be logical. Yeah, not gonna happen. But at least you were warned.

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.

Unwarping the playing field

Easing comfortably into my role as a "blogger," I've realized how easy it is to adopt a few key platform issues that tend to drive one a bit mad.  This blog isn't so fond of CAUTI, contact precautions, or devices that blow moist, warm particles over sterile fields (but then again, who is?).  We love diagnostic stewardship, influenza vaccination (um, mostly), and fecal transplantation.

Add advocating for better risk-adjustment of publically-reported HAI performance to my list.  A few months ago, I blogged about this issue and poor reporting validation by CMS -- now some excellent papers on improving risk adjustment have emerged, both from many FOB (friends of the blog) with senior authorship by Anthony Harris and his group at Maryland.  One focuses on SSI and one on CLABSI.  Their methodology is very similar and has some key features:

• They used comorbid conditions that are components of the Charlson and Elixhauser comorbidity indices
• These conditions were captured by diagnostic discharge coding that are currently routinely collected and submitted to CMS, limiting the data collection burden 
• They used conditions identified using Delphi consensus methodology from a survey of ID and infection prevention experts, providing some clinical credibility to the process

The authors examined the model performance and assessed changes in hospital rankings when compared to the traditional NHSN models. For SSI, a model containing procedure type, patient age, race, smoking history, diabetes, liver disease, obesity, renal failure and malnutrition showed good discrimination, and 86% of hospitals changed ranks within the cohort when the risk-adjusted model was used -- with 4 hospitals changing by >10 ranking spots.  For CLABSIs within the ICU, a model using coagulopathy, paralysis, renal failure, malnutrition and age showed improved predictability when compared to the NHSN ICU model, and 45% of hospitals changed ranking.  The authors note the clear limitations, including some of the challenges with using coded data, but these papers are important advances in the area of publically-reported HAI data.

You can read some of my more detailed thoughts in the accompanying editorial for the CLABSI paper (shameless plug).  At a time when there are many consequences for a hospital's performance on these surveillance metrics (e.g. last year my hospital received a draft quality incentive contract from a private insurer that required our large, tertiary care center to have ZERO of the Big 6 reported HAIs, to the tune of several million dollars in incentives), leveling the playing field to adjust for those factors that lead to HAIs that are beyond the control of the hospital is essential.  Thankfully, the CDC and HICPAC have recently chartered a new NHSN work group (disclaimer: Hilary and I serve on this group) and the issue of improved risk adjustment seems to be a major emphasis - fingers crossed that the field will start to level soon.

And what about antimicrobial scrubs?

Ascot: a neckband with wide pointed wings, traditionally made of pale grey patterned silk

The role that environmental transmission plays in the spread of important pathogens is increasingly recognized. One of the major mechanisms by which pathogens are thought to spread is via contaminated healthcare worker clothing. A major reason that gowns are included in contact precaution is that they are felt to interrupt the transmission from patient/environment to HCW attire. An old (2010) study that Dan Morgan completed found that gowns became contaminated 11% of the time when caring for patients with MDR-Acinetobacter and 5% of the time when caring for patients with MDR-Pseudomonas. A repeat (2012) study found that gowns became contaminated during 4% of HCW visits caring of MRSA+ patients, 5% for VRE, 2% for MDR-Pseudomonas and 13% for MDR-Aceintobacter.

With so much contamination and a desire to rid the world of unnecessary gown use, investigators have been exploring the benefits of antimicrobial textiles, such as scrubs. If these novel scrubs could reduce contamination, maybe we could drop the dreaded gown and go with universal gloves for contact precautions?

Which brings us to a ASCOT study by Deverick Anderson and colleagues funded by the CDC Prevention Epicenters Program. ASCOT: Antimicrobial Scrub Contamination and Transmission. The investigators examined the benefits of two different antimicrobial scrubs (Scrub 1: silver-alloy and Scrub 2: organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion) vs standard poly-cotton surgical scrubs in a 3-arm RCT during 3-consecutive 12-hour ICU nursing shifts. The primary outcome was change in total contamination on the nurses scrubs as sum of CFUs. Of note, all MDRO colonized patients in the study were placed on contact precautions and HCW placed gowns over their scrubs and wore gloves while caring for those patients.

The study collected many cultures: 2919 from the environment and 2185 from the HCW clothing. 41 nurses were randomized but one was excluded for a total of 40 nurses caring for 102 patients during 167 encounters. Their primary finding was the scrub type had no effect on HCW clothing contamination (p=0.70) There is a lot to unpack in this study and it warrants a careful read - a lot of data! but I've included Table 3 below with the contamination before/after each shift. Overall, the median CFU increase was 61.5 (interquartile range [IQR], −3.0 to 191.0) in the control arm, 73.0 (IQR, −107.0 to 194.0) in the Scrub 1 arm, and 54.5 (IQR, −60.0 to 215.0) in the Scrub 2 arm.

There were acquisition events during 39 (33%) of the shifts with 20 (17%) environmental acquisitions and 19 (16%) acquisitions on HCW attire. Looking at the 19 HCW attire acquisition events, 12 (63%) were confirmed: 7 from the patient, 3 from environmental contamination, and 2 from the patient/environment.

Overall, the authors reported that there were no benefits from either antimicrobial scrub. However, there was significant transmission from patient or environment to HCW attire.  Back to the drawing board on antimicrobial scrubs?  Maybe. I would like to see the study repeated in a hospital where contact precautions are not used to see if benefits might exist in settings where gowns are not worn when caring for MDRO+ patients. With this much acquisition of nurses' clothing, it's going to be hard to ditch gowns, unfortunately.

Oh, and I love the ASCOT name. Brilliant.

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?

When will the p-value finally die?

Over the past 7 years!, I've written about my concerns regarding the misuse of p-values, which I've dubbed "death by p-value." First and foremost, no one really understands what a p-value means and perhaps more importantly, a singular focus on a p-value threshold detracts from important concepts such as effect measures (e.g. hazard ratios) or the continuous nature of confidence intervals.

Recently, I've seen an increasing number of calls to hasten the death of the p-value from folks such as Ken Rothman (you might have read one of his books?) and Miguel Hernan. Professor Hernan has a request on twitter saying "statistical significance must go" where he is asking for examples of outrageous misuses of p-values. He's also suggested that "if your journal still uses 'statistical significance' in 2017, retire your statistical consultant."

Below, I've posted a letter to the editor by Professor Rothman and colleagues that he recently circulated. It has a nice brief example of how p-values are frequently misused. The key sentence, I believe, is this one: "given the expected bias toward a null result that comes from non-adherence coupled with an intent-to-treat analysis, the interpretation of the authors and editorialists is perplexing." I'll ask, are there situations such as studies of contact precautions or hand hygiene interventions where they would be analyzed using an intent-to-treat analysis and non-adherence levels might be high?

I'll leave you with this video on p-values from Carl Bergstrom at University of Washington. He and Jevin West have a course and planned book titled "Calling Bullshit: in the age of big data," which has been well received. And to connect this to MDRO, Carl is the author of a 2004 PNAS paper "Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals", which is a nice example of how math models can improve our understanding of antimicrobial stewardship interventions. It's still worth reading.