WHO - New Antibiotics Needed

Yesterday, WHO published a list of bacteria that are highly resistant and pose the greatest threat to human health. The list was created "to guide and promote research and development of new antibiotics" as part of an overall strategy to address the global antimicrobial resistance problem. I suspect this strategy also includes mention for resources targeting infection prevention and antimicrobial stewardship.

The creation of the list was a collaborative effort led by Prof Evelina Tacconelli and her colleagues in the ID Division at the University of Tübingen. They utilized decision-analytic techniques and many criteria including: "how deadly the infections they cause are; whether their treatment requires long hospital stays; how frequently they are resistant to existing antibiotics when people in communities catch them; how easily they spread between animals, from animals to humans, and from person to person; whether they can be prevented (e.g. through good hygiene and vaccination); how many treatment options remain; and whether new antibiotics to treat them are already in the R&D pipeline." 

Nature has a nice discussion of this effort and places it into context with other existing initiatives. The "money" quote comes from Michael Gilmore: “The bottom line is that the economic model (for antibiotic development) doesn’t work.”

Is hospital design making us sicker - Wait for the RCT?

• Confirmation bias – looking for evidence to support a pre-conceived opinion, rather than looking for information to prove oneself wrong. 

We've written often about cognitive biases and how they influence medical decision making. How else can we explain one colleague demanding RCT evidence before supporting influenza vaccine mandates for healthcare workers while at the same time ignoring the lack of RCT evidence when pushing bare below the elbows?  And what about another colleague calmly supporting influenza vaccine mandates yet slamming bare below the elbows while wearing his professional white coat and demanding cluster randomized trials? Confirmation bias anyone? (note: both of those colleagues have been me at various points in my blogging "career")

We've also written often about hospital design and how it might be changed to improve infection control. On this subject there was a nice editorial in the NYT a few days ago by Dhruv Khullar that linked poor hospital design to excess healthcare associated infections, falls and noise impairing sleep. I've included his paragraph on HAI below.

"It’s no secret that hospital-acquired infections are an enormous contributor to illness and death, affecting up to 30 percent of intensive care unit patients. But housing patients together very likely exacerbates the problem. Research suggests that private rooms can reduce the risk of both airborne infections and those transmitted by touching contaminated surfaces. One study reported that transitioning from shared to private rooms decreased bacterial infections by half and reduced how long patients were hospitalized by 10 percent. Other work suggests that the increased cost of single-occupancy rooms is more than offset by the money saved because of fewer infections. Installing easier-to-clean surfaces, well-positioned sinks and high-quality air filters can further reduce infection rates."

If you click on the links like I did, you'll notice one links to a 2008 JAMA editorial, another to a single hospital, uncontrolled quasi-experimental (before-after) study, another to a cost-analysis based on data from a single ICU, and the last to a 2008 non-analytic literature review. Given how expensive it is to convert hospital space from double (or more) to single hospital rooms and how scant the evidence appears to be, I suggest we consider the opportunity costs of these recommendations. If we won't spend any money on robust hand hygiene compliance programs, why should we support these huge architectural changes? Shouldn't we have more studies that examine bathroom location, copper surfaces, room proximity to nursing stations, lighting, alert systems, etc etc, before we rebuild hospitals that we'll be stuck with for the next 30 years?

Take the case of the beautiful Rush University Hospital that opened in 2012 (image above). I drove by it 3 weeks ago and to my (not) surprise, it was no longer gleaming white but more of a zebra-striped white/grey/black from air pollution. The hospital, I assume, is now stuck with years of cleaning expenses after a marketing/architectural leader no doubt suggested "white=clean=hospital" and will have less money in their infection control budgets. Did someone study white buildings in industrial cities?

Why do we fight over cheap reversible policy changes and not over expensive irreversible changes to our hospitals? I'd much rather support bare below the elbows or even influenza vaccine mandates - programs that can be reversed if additional trial data becomes available - than these hugely expensive, irreversible architectural changes. I'm holding out for better randomized trial data.

image source: TERRA

In Memoriam: Standing on the Shoulders of Giants

In the past two months, we’ve lost two prominent healthcare epidemiologists, Drs. Walter J. Hierholzer, Jr. and Barry M. Farr. Each served a term as president of SHEA, and each mentored many other influential epidemiologists who carry on their work.

Walt spent almost a decade at our institution, the University of Iowa, and started a tradition of strength in infection prevention that exists to this day. Here is an excerpt from his obituary: 

Dr. Walter J. Hierholzer Jr., 82, Professor Emeritus of Internal Medicine and Public Health at Yale University of School of Medicine and resident of Guilford, CT, passed away on January 21, 2017. Born in Midland, MI to Walter and Florence (Rodammer) Hierholzer, he is remembered by his family and friends for his intelligence, warm sense of humor, and staunch support of the Democratic Party.

Dr. Hierholzer attended Albion College and the Yale School of Medicine with subsequent training in epidemiology at the University of Minnesota. He met his wife Bente while studying as a Fulbright scholar at the Biological Institute of the Carlsberg Foundation in Copenhagen, Denmark. As an Assistant Professor of Epidemiology and Internal Medicine at the Yale School of Public Health (1972-76), he made several trips to the Amazon to study the impact of infectious diseases on native Brazilian tribal populations. From 1976-85, Dr. Hierholzer was an Associate Professor of Infectious Diseases and Preventive Medicine at the University of Iowa and Director of Hospital Epidemiology Program overseeing statewide hospital epidemiology education. From 1985 until his retirement in 1999, he was a Professor of Medicine and Epidemiology at Yale and the Hospital Epidemiologist at Yale New Haven Hospital. 

Barry was hospital epidemiologist at the University of Virginia when I was a medical resident, and his impact on our field has been substantial. A passionate advocate of active detection and isolation (ADI) for prevention of MRSA and VRE transmission, Barry often sparred with us during the early months of this blog (which encouraged us to continue blogging, since it was evidence that somebody important was reading what we wrote!). Although we disagreed with his conclusions about ADI, there is no doubt that his strong advocacy sparked spirited debate and drew increased attention to healthcare-associated MRSA (HA-MRSA) infection in particular. Increased focus on this pathogen almost certainly played a role in the successful reduction in HA-MRSA that we’ve seen over the past decade. Here is an excerpt from a tribute to him written by Mitch Rosner and Bill Petri:

It is with great sadness that I report that Dr. Barry Farr, emeritus Professor of Medicine, passed away today. Dr. Farr received his medical degree from Washington University in St. Louis and a Master of Science degree in epidemiology from the London School of Hygiene and Tropical Medicine. He trained in internal medicine and infectious diseases at the University of Virginia. He spent the rest of his career on the faculty of the University of Virginia School of Medicine where he retired as the William S. Jordan Jr., Professor of Medicine and Epidemiology at the age of 52 due to physical disability from multiple sclerosis. Hospital Epidemiologist at UVA for 18 years and Chairman of the Master of Science Program in Epidemiology for 11 years, he mentored 18 postdoctoral fellows in research. He also was President of the Society for Healthcare Epidemiology of America, and Editor of the SHEA scientific journal Infection Control and Hospital Epidemiology. He co-authored 167 medical publications, 137 scientific abstracts for national scientific meetings, and co-edited two books entitled Catheter Related Infections. He was a leading authority on MRSA infections and his work in this field continues to inform clinical practice. 

In the past few years, Barry was a tireless advocate for patients with multiple sclerosis and he published an important book to help guide patients in avoiding complications due to the disease. For those of us fortunate to have known Barry, he was a tremendous mentor, a deep thinker with a questioning mind and a pioneer in quality improvement. We will greatly miss him and our thoughts and prayers are with his family.

Hand Hygiene and The Power of Labbit

Yesterday, Mike wrote about "The Power of Habit" and taught us that "40% of our daily activities occur without any active decision making" and suggested that "the trick...is for us to figure out how to get hand hygiene and stethoscope wipedown established as habits."  Of course, this all sounds reasonable. Besides hand hygiene, wouldn't it be great if we could get primary care doctors to stop prescribing antibiotics? Surely, poor stewardship is also a habit.

I used to believe, as Mike does, that infection prevention was a matter of education and re-education until good practice becomes habit. But after years of watching us fail to improve antibiotic prescribing and increase hand-hygiene compliance, I no longer believe in the magical thinking surrounding education and habits. First, there is minimal evidence that we can encourage folks to develop better habits - such as hand hygiene compliance. Take for example this recent systematic review on hand hygiene trials by Kingston et al. The authors reviewed studies published since 2009 and reported a baseline hand hygiene compliance of only 34.1% with a mean improvement to 57%. Some folks may look at this data and become excited about a 23% compliance improvement!!  But a realist would look at the data and realize that these trials couldn't have been the first time the healthcare workers in the intervention hospitals were exposed to hand hygiene interventions - their baseline compliance of 34% was after numerous rounds of "habit-forming" educational training.

Thus, we need to be honest with ourselves and acknowledge that difficult system changes are needed to improve practice. For hand hygiene, for example, we need shelves outside rooms so nurses can rest things they're carrying while cleaning their hands. For clinicians we need rapid diagnostics and health information systems to inform antibiotic prescribing. Any talk of habits suggests that change can occur at an individual healthcare worker or prescriber level. And any suggestion that this is an individual healthcare worker problem will necessarily lead to learned helplessness and blame, neither of which will be productive.

In the end, we're going to need to move past our focus on "habit" and its flipside, blame. Let's work towards system change and innovation that directly address the barriers to hand hygiene compliance and proper antibiotic prescribing. You might have another name for it, but I'm gonna call it The Power of Labbit.

Labbit image source: Kidrobot Blog

The power of habit

Over the past few years, I have focused on wiping my stethoscope down with an antiseptic wipe after I examine each patient. Initially, a problem was that I couldn't always find the wipes. We've focused on getting them available throughout the medical center so that's rarely a problem anymore.

While on the ID consult service last week, I walked out of a patient's room, and wiped down my stethescope. Halfway through that action, I realized that I had not used my stethoscope on the patient. I was thrilled! The stethoscope wipedown had become a habit, since I demonstrated a key characteristic of habits: automaticity. I didn't think about it. I walked out of the patient room and my cue (crossing the threshold of the room) prompted me to automatically sanitize my stethoscope. Just like sitting down in the seat of a car prompts me to latch my seatbelt.

If you haven't read The Power of Habit by Charles Duhigg, I highly recommend it. From the book I learned that 40% of our daily activities occur without any active decision making. These activities are habits. The trick, of course, is for us to figure out how to get hand hygiene and stethoscope wipedown established as habits. We need more psychologists working with us in infection prevention since the field is increasingly dependent on influencing the behaviors of healthcare workers.

When a dead horse is your only horse...

I’d like to thank Tom Talbot and Hilary Babcock, two of the authors of SHEA’s position paper on mandatory influenza vaccination of healthcare workers, for their response to my recent post on why I think this policy is misguided. Hilary and Tom are excellent hospital epidemiologists that I respect. Nonetheless, on this issue, I remain unconvinced by their arguments.

They point out that that I mischaracterized SHEA’s position being based on four nursing home cluster randomized trials, when in fact the position paper has 63 references. There are, indeed, 63 references, the majority of which do not address the impact of vaccinating healthcare workers on patients. In fact, most of the references lay out the biologic plausibility that vaccinating healthcare workers should have an impact on patients, as well as other issues, such as the impact of mandatory programs on vaccine rates. The biologic plausibility arugment is very nicely laid out in their blog post, and I agree with it completely. So, I’ll be more precise: SHEA’s best evidence for their policy is contained in the four cRCTs.

Tom and Hilary go on to cite newer studies that they believe support SHEA’s position, one of which is a cluster randomized trial from the Netherlands. I was not familiar with this paper so I reviewed it. In this trial, 6 hospitals were randomized—3 had an intervention to increase vaccination rates in HCWs and 3 did not. Significantly higher vaccination rates were demonstrated in the intervention hospitals. The patient outcomes were divided into adult and pediatric patients and the outcomes reported for patients were influenza and/or pneumonia and pneumonia. Influenza was not an outcome. Thus, the influenza rates cannot be determined. If the two outcomes are mutually exclusive, then the influenza rate is actually higher in the intervention hospitals (though not likely significantly so). For children, there was no difference between the intervention and control hospitals. And interestingly, the intervention hospitals had significantly higher HCW absenteeism rates, a metric Hilary and Tom argue as important for demonstrating the effect of employee vaccination. Thus, I don’t think this paper in any way supports mandatory vaccination.

Despite the studies published in the seven years since the SHEA position paper was published, there remains an irrefutable fact: there is no high level evidence demonstrating that vaccinating healthcare workers reduces influenza in hospitalized patients. I agree with Hilary and Tom that the four nursing home studies are a dead horse. Unfortunately, however, that dead horse is their only horse.

Everyone has opinions about infection prevention interventions biased by their own experiences and perceptions, and I’m glad that Tom and Hilary pointed out one of mine—bare below the elbows. As I write this post while on service, I’m, you guessed it, bare below the elbows! There’s clearly biologic plausibility that clothing can transmit pathogens to patients, but there is no evidence that following a bare below the elbows approach to patient care lowers infection rates, and in every talk I give on this topic I make that very clear. I would never argue that HCWs wearing white coats should be fired; otherwise, Tom and Hilary would have to be fired (based on their photos). And unfortunately, they missed the entire point of my post. I’m not arguing against vaccination of HCWs. My point is that you can’t mandate an intervention (and in this case threaten a person’s livelihood) when the intervention is not supported by high level evidence. In other words, you can’t mandate on opinion, but that’s exactly what SHEA did. Expectations for compliance with an intervention must be correlated with the strength of the evidence. 

SHEA made a huge mistake when they published this position. And seven years later, there’s still no published evidence that can bail it out. It was wrong seven years ago, and it’s still wrong. Healthcare workers in the US deserve better, especially from a professional society that prides itself on using science to guide practice.

Reporting bias: Missing the point of HCP influenza vaccine mandates

We invited our good friends Hilary Babcock and Tom Talbot, distinguished epidemiologists and co-authors on the SHEA statement regarding mandatory influenza vaccination of healthcare personnel (HCP), to respond to our previous posts on this topic.  Thanks, Tom and Hilary!

Disclaimer: This commentary solely represents the opinions of the authors and does not represent an official statement from SHEA

Nothing seems to ignite the fires of the Controversies blog like a few key infection prevention topics: CAUTI as an HAI metric, bare below the elbows, and the topic of a recent blog post, mandatory HCP influenza vaccination and the SHEA 2010 Position Paper. As authors on the 2005 and 2010 SHEA papers, we provide a different perspective on the issue.

A key misconception of opponents of mandatory influenza vaccination programs is the claim that the 4 cluster RCTs referenced in the recent post are the only evidence underpinning the position of SHEA (and the numerous other professional societies also endorsing such policies). The 2005 SHEA paper has 100 references while the 2010 paper has 63, a majority of which are peer-reviewed publications in the medical literature. The 4 RCTs noted are far from the only “papers on which SHEA based its recommendation,” as Dr. Edmond states and the De Serres paper implies.

These studies are not perfect by a long shot and the challenges of accurately studying the impact of HCP vaccination on patient outcomes have been nicely highlighted in analyses of these trials, of which there are several – the De Serres paper highlighted in the blog, a CDC analysis that came to different conclusions (and surprisingly was never featured as a blog post), and three separate Cochrane analyses (are there not enough topics out there for them to review??). We also encourage readers to closely review the detailed editorial that accompanied the De Serres paper for an excellent response to the many assumptions in their analysis. If only other infection prevention proposals were scrutinized as heavily as these 4 studies (cough, cough, we’re looking at you bare below the elbows . . . ). Of note, the limitations of these 4 trials were noted in the 2010 SHEA paper, which also cites the first Cochrane analysis in that discussion (despite claims to the counter).

What is missed in the arguments against mandatory programs (including the recent blog post) is the biologic rationale and additional supporting evidence for this strategy as part of a comprehensive infection prevention program. We refer readers to the 2005 and 2010 papers for more detail but summarize briefly here:

1. HCP (like our patients) can become infected with influenza.
2. Persons infected with influenza may not present with classical ILI symptoms. This is often missed in criticisms of vaccine effectiveness. Babcock et al demonstrated how poorly the ILI definition captures hospitalized adults with laboratory-confirmed influenza. Thus studies that look just at vaccine impact on ILI will likely miss true influenza outcomes, while also capturing infections due to other viruses not covered by influenza vaccination. Since clinical testing is usually prompted by stereotypical ILI symptoms, lab-confirmed influenza outcomes are also likely under captured. In addition, since hospital length of stay is shorter and most facilities do not have post-discharge surveillance for influenza, the impact in acute care facilities is more challenging to assess than in long term care settings. 
3. Persons infected with influenza can shed virus even with minimal or no symptoms. While not to the same degree as a coughing, febrile person, the role of asymptomatic infection has been noted in numerous studies of households and experimental challenges. A 6-year study from Hong Kong of a cohort of 824 households with an identified 224 cases of secondary influenza infection examined the relationship between symptoms and viral shedding (as detected on nasal and throat swabs). Shedding was detected before onset of respiratory symptoms in influenza A-infected persons but peaked on the first 2 days of clinical illness, while influenza B shedding peaked up to 2 days prior to symptom onset. So relying on HCP to stay home when ill (which they don’t anyway, see below) will not protect patients. 
4. HCP work while ill. Sadly, this is a huge issue, as nicely noted in several posts on this blog. Studies consistently note ~75% of HCP with febrile ILI admit to working while ill, a startling yet unsurprising fact that does not capture those with atypical, mild, or even asymptomatic infection. We completely agree that this is a major infection prevention issue. The SHEA 2010 paper notes the importance of “restriction of ill HCP from working in the facility” as part of a “comprehensive infection control program” to prevent healthcare-associated influenza (and other respiratory infections). We definitely support a stronger stance on the infection risk of HCP working while ill and the various disincentives for staying at home (e.g. leave policies where sick days and vacations days are in one lump “bucket”). Perhaps we need a new chapter of the Compendium focused on the prevention of healthcare-associated respiratory infections?
5. HCP have contact with patients at higher risk for complications from influenza than the general public. The privilege of that close relationship carries an obligation to do all we can to protect those patients. 
6. Many patients won’t be adequately protected by receiving the vaccine themselves. Proponents of mandatory vaccination frequently note the moderate effectiveness of the vaccine, and we completely agree on the need for a better vaccine. The suboptimal effectiveness only emphasizes the need to optimize immunity among those who are more likely to respond in order to prevent transmission of influenza in healthcare settings (to protect the “herd”). Most HCP are healthy and therefore more likely to have a robust immune response to vaccine than already ill patients, many of whom are elderly and/or immunosuppressed. 
7. Most agree that HCP should be vaccinated against influenza, though they may disagree with a ‘mandate.’ Extensive literature now demonstrates that a mandate is the most effective way to increase HCP vaccination rates. If it is an outcome (HCP influenza vaccination) that we all support, should we not encourage its use through the most effective method for high vaccination rates? 

Fortunately, as more institutions have employed a mandatory program, new evidence that further supports the need for HCP immunization that was not available when we wrote the 2010 paper has emerged:

• Researchers at the Denver Health Medical Center reported a decrease in employee absences during the influenza season following implementation of their mandatory program when compared to prior seasons of similar influenza activity. 
• In an analysis of the province-wide vaccination with masking policy in British Columbia, researchers noted a significantly reduced rate of HCP absenteeism due to all-cause illness in vaccinated vs. unvaccinated HCP during the first season of the policy. 

Even more important than the impact on HCP illness is the impact on patient outcomes:

• MD Anderson Cancer Center implemented a mandatory vaccine with masking policy and examined the impact of increasing HCP influenza immunization over the course of 8 years. The proportion of influenza infections that were healthcare-associated among patients significantly decreased and was significantly associated with increased HCP vaccination rates. 
• A cluster randomized trial in the Netherlands of HCP at six medical centers, where the intervention arms offered vaccination to HCP vs. no vaccination at control facilities, noted a significantly lower rate of healthcare-associated influenza among internal medicine patients at the facilities with the higher rates of HCP influenza vaccination (3.9% vs. 9.7% of patients). 
• In a study encompassing 7 influenza seasons and over 62,000 hospitalized patients, a significant association was noted between increasing influenza vaccine coverage among HCP and decreasing healthcare-associated ILI among patients at an Italian acute care hospital.
• Finally, a nested case-control study in France noted a significant association between lower rates of laboratory-confirmed healthcare-associated influenza among patients and higher vaccination rates among HCP.

We don’t have time to go into the ethical arguments for HCP vaccination or the need to broaden these programs to include all recommended immunizations for HCP, but we close with a noteworthy pronouncement made by the Board of the National Patient Safety Foundation’s Lucian Leape Institute: there are two “must do’s” for HCP to ensure patient safety, hand washing and HCP influenza vaccination. 

Time to stop re-analyzing those 4 poor cluster RCTs – that horse has been beaten to death.

Brown and Yellow? I might have gone with Raw Umber and Maize