State of Antibacterial Resistance in the Union

President Obama delivered his State of the Union address last night. The event is always an interesting spectacle. I enjoy seeing who stands, sits and claps during specific parts of the speech. Several sections really piqued my interest and I've pasted them below. I suspect this is the first time a President has used drug-resistant bacteria in such a high-profile speech. Perhaps this is an important milestone or tipping-point. One can hope.

"Listen, China and Europe aren't standing on the sidelines; and neither -- neither should we. We know that the nation that goes all-in on innovation today will own the global economy tomorrow. This is an edge America cannot surrender. Federally-funded research helped lead to the ideas and inventions behind Google and smartphones. And that's why Congress should undo the damage done by last year's cuts to basic research so we can unleash the next great American discovery. (Cheers, applause.)"

"There are entire industries to be built based on vaccines that stay ahead of drug-resistant bacteria or paper-thin material that's stronger than steel. And let's pass a patent reform bill that allows our businesses to stay focused on innovation, not costly and needless litigation."

Reference: Washington Post's full-text of President Obama's SOTU address

Contact networks and infection prevention

Most pathogen transmission in healthcare facilities occurs via close contact, whether between healthcare personnel (HCP) or between HCP and patients. It is common sense that when it comes to transmission risk, all HCP are not equal. Consider the ICU nurse assigned to two patients during his shift, rarely venturing away from these two bedsides, versus the ID fellow or the respiratory therapist who contacts many patients across several units. Yet many models of disease transmission either don’t take contact network epidemiology into account, or don’t have sufficient data to understand the properties of HCP contact networks.

Our colleague Phil Polgreen and his collaborators in Iowa’s computational epidemiology group have constructed HCP contact networks using electronic medical record logins, validated the data using wireless sensors in our MICU, and applied the data to model the impact of various strategies to vaccination that focus on random application versus applying the intervention to HCP based upon degree (number) of contacts or distance (mobility) in the hospital. The figure below, from their recently published PLoS One paper, demonstrates the impact in a particular contact network (a) of vaccinating randomly (b), versus based upon degree (c) or distance (d).

This work has important implications for infection prevention practice. Imagine a year in which influenza vaccination is in short supply—see below for the impact on the disease attack rates in hypothetical scenarios where vaccination is based upon degree of contacts or mobility (distance) versus random allocation, in a sparse (a) or dense (b) contact network.

There's got to be a better way...

There are reports from across the country regarding severe influenza in young people. In addition to mechanical ventilation, many are requiring ECMO. Given the severity of illness and the presence of multiple organ dysfunction, relying on an oral antiviral for influenza therapy seems unwise. However, at this point, the only option for intravenous therapy is IV zanamivir, which is not approved by the FDA, but available on a compassionate use basis.

I recently had the misfortune of experiencing the compassionate use process. During my last stint on the Infectious Diseases consult service we were crazy busy, and on a Friday morning, with my fellow in clinic and unavailable, and with eight new consults to see, I was asked to see a patient on ECMO for severe influenza. I did a quick Google search to see how I could obtain IV zanamivir and learned that I needed to contact the drug manufacturer, the FDA and my IRB. I soon learned there were numerous forms to complete, almost all of which required me to record the same information over and over. From start to finish it took approximately 4 hours and the best word to describe the situation was kafkaesque. Some of the forms had pages of instructions, and after reading these instructions I still had no idea as to how to complete them. I finally called the FDA and said, "Just tell me which boxes to check." Is there anyone who thinks that physicians have 4 hours to spend filling out forms to get one patient one drug? I made the mistake of including the patient's initials on one form and the drug company called me to say that they would have to destroy the document and I would need to re-do it and re-send. Maybe I'm just a simpleton, but couldn't there be a website where information is entered once and then routed to the appropriate agencies? I'm sure we could leverage the technology to include the patient initials on the FDA's but not the company's forms. Over the ensuing weeks, I have spent several additional hours submitting more documents to the FDA, the drug company and the IRB. All of this makes me wonder how many patients don't receive treatment with potentially lifesaving drugs because the process is so painful, duplicative, time intensive and byzantine.

At dinner a few nights ago, my wife (also a physician) and I were lamenting about how much each of our days is filled with activities that don't add value to the care of patients. Every time I watch "House MD" I am immediately struck by what the physicians in the hospital are doing. They are either interacting with patients or discussing cases with each other. Those activities are the joy of medicine. But it seems that with every passing year, we do less true patient care as we heap on more nonvalue added activities. Unfortunately, twenty-five years into this career, I frequently find myself thinking, I didn't sign up for this!  

Graphic: Drawception.com

SHEA: Obsessed, and proudly so

The SHEA guidance on healthcare personnel (HCP) attire is now available (free!), and is already drawing media attention. I particularly enjoyed the NBC News description of SHEA as “the group obsessed with stopping infections in hospitals and health care settings”. Obsessed? Miriam-Webster describes obsession as “a state in which someone thinks about something constantly or frequently, especially in a way that is not normal”*. And it got me thinking that this may be behind some of the general resistance to any guidance about HCP attire. What is this group doing, suggesting what I should wear (or not wear) in the hospital, and how often I should wash my garments? They must be obsessed or something. Show me the data, weirdos!

Therein lies the rub with HCP attire, as with so many other infection prevention practices. There may be biological plausibility that clothing plays a role in pathogen transmission, there may be evidence for pathogen contamination of HCP attire, and there may be a favorable balance of benefit versus harm in implementing changes in practice (such as a bare-below-the-elbows (BBE) approach). But we still lack that direct link between HCP attire and HAI risk. Thus the SHEA guidance ends with a laundry list (pun intended) of research priorities for HCP attire:

· Determine the role played by healthcare personnel (HCP) attire in the horizontal transmission of nosocomial pathogens and its impact on the burden of HAIs.
· Evaluate the impact of antimicrobial fabrics on the bacterial burden of HCP attire, horizontal transmission of pathogens, and HAIs. Concomitantly, a cost-benefit analysis should be conducted to determine the financial merit of this approach.
· Establish the effect of a bare-below-the-elbows (BBE) policy on both the horizontal transmission of nosocomial pathogens and the incidence of HAIs.
· Explore the behavioral determinants of laundering practices among HCP regarding different apparel and examine potential interventions to decrease barriers and improve compliance with laundering.
· Examine the impact of not wearing white coats on patients’ and colleagues’ perceptions of professionalism on the basis of HCP variables (e.g., gender, age).
· Evaluate the impact of compliance with hand hygiene and standard precautions on contamination of HCP apparel.

Now try to imagine the logistics, and costs, associated with a study large enough to demonstrate the incremental contribution of HCP attire to HAI infection risk, or the impact of BBE on HAI incidence. Knowing how long we will be waiting for such evidence, what do you plan to do in your hospital?

* I prefer the Urban Dictionary definition of obsessed: “just a word the lazy use to describe the dedicated”

Graphic credit to Ben Tremblay.

Patient - Wash Thy Own Hands!

There has been increasing attention over the past decade in engaging patients in patient safety. In infection control this trend has manifest through efforts to have patients monitor and encourage hand hygiene compliance among health care workers. In a related trend, there is also increased interest in patients washing their own hands in a framework called "patient-centered hand hygiene." My understanding of this approach is that having patients clean their own hands could potentially increase their engagement in infection control initiatives including encouraging health care workers to practice hand hygiene. This approach might also have the additional benefit in decreasing the organism burden on patients' hands and interrupting direct or indirect transmission of MDROs in healthcare settings.

It is with this background that Kundrapu and colleagues at CWRU and the Cleveland VA completed a randomized trial of soap and water versus alcohol hand rub in reducing C. difficile spore burden on patients' hands. Forty-four infected or colonized patients were included in the study. Hand cultures were positive in 32% of patients with CDI and 38% of colonized patients prior to hand hygiene. As you can see from the figure below, soap and water significantly reduce the proportion of positive cultures and mean CFUs, while alcohol hand rub did not. Interestingly, around 10% of patients still had C. difficile recovered after washing with soap and water. Seems like a trial is in order to determine the role of patient hands in transmission and whether cleaner patient hands reduces the incidence of CDI and other MDROs in hospital settings. One major limitation is that this intervention could not be implemented in settings where the need is the greatest, namely ICUs, since most patients would be too sick to wash their hands.

Bacteriophages and the spread of antimicrobial resistance

One component of the human microbiome which is garnering more attention lately is the “phageome” or “virome”, that portion of our microbial ecosystem comprised of viruses (phages) that infect and replicate within bacteria. A recent Nature paper demonstrated that antibiotic treatment of mice resulted in an expansion of phages bearing antibiotic resistance genes that could then spread back to wild-type bacteria and confer resistance. In this month’s issue of Antimicrobial Agents and Chemotherapy, a group from Spain examined the phage DNA in fecal samples of 80 healthy adults. Almost 80% of the samples revealed one or more of the six genes they sought (genes encoding two beta-lactamases (TEM and CTX-M), methicillin resistance (mecA), high-level aminoglycoside resistance (armA) and quinolone resistance (qnrA and qnrS). 

Phages survive well in the environment, probably better than do their bacterial hosts. In addition, they aren’t detected using culture methods designed to find resistant bacteria. They almost certainly play a key role in the transmission of antimicrobial resistance genes.

Using NHSN C. difficile Infection Rates? Mind your denominator!

Over here in the US hinterland we're completing a systematic review of MDRO outcomes for CDC in cooperation with investigators in Salt Lake City. At the moment we're tackling C. difficile and are busily pouring through the literature. We've come across many good studies, such as an ICHE paper from early 2013 by Gase and colleagues from the New York State Dept. of Health that compared NY State CDI surveillance to NHSN in 30 hospitals. The authors noted an 80% agreement between the methods and thus recommended that NY State adopt the NHSN LabID method because of ease of implementation.

Building on that study, Haley and colleagues also from the NY State Dept of Health completed an analysis of the sources of bias in NHSN "Hospital Onset" CDI rate calculations using data from 124 NY hospitals. Their findings were published in the January 2014 issue of ICHE and were accompanied by a nice editorial by two of my former Maryland colleagues Jessina McGregor and Anthony Harris. The NY authors looked at how auditing, including outside labs, age adjustment and exclusion of "patient days not at risk in the denominator" would improve the calculation of hospital-onset CDI rates. As you can see by the portion of Table 2 that I pasted below, most of the corrections had minimal impact on the average hospital-onset CDI rates.  However, "exclusion of patient-days not at risk" had a huge impact on the calculated HO-CDI rate. The correct rate after controlling for all factors was 11.6/10,000 patient days; however, excluding auditing or outside labs, or age adjustment had minimal impact, whereas not excluding patient days not at risk from the denominator led to a rate that was 45% lower (6.4/10,000 pt-days).

The reason that eliminating "patient-days not at risk" from the denominator had such a huge impact is that the CDC NHS definition excludes CDI cases that occur in the first three days from the numerator but does not exclude patient-stays less than three days from the denominator. For example, a patient that stays only two days would not be at risk from contributing a HO-CDI case to the numerator but contributes their patient-days to the denominator.

This has several important implications.  One, not removing the patient days not at risk results in reported CDI rates that were much lower than they actually are. This occurs since many if not most patients have stays that are shorter than 4 days.  Second, as the authors state, "HO-CDI rates at hospitals with shorter LOS are biased downward more than the rates at hospitals with longer LOS." It seems to me that this artificially hurts the rates at tertiary-care and academic medical centers more than it would smaller community hospitals. We always hear how academic hospitals are falling behind, but it may have something to do with how rates are calculated, especially if we are including the wrong patient-days in the denominator.  It seems like this would be an easy fix - hospitals could just exclude the first three days from their patient-day calculations.  I hope this happens.

Evidence-based infection prevention: A modest proposal

This is a special guest post by David Hartley, PhD who is a Research Associate Professor in the department of Microbiology and Immunology at the Georgetown University Medical Center.

I don't know if there are dedicated courses in schools of medicine and nursing in the US devoted specifically to hospital infection control and prevention, but if there are, I haven't found them. There are lots of training courses offered by trade societies, and many of these are great at conveying procedure, technique, and rationale, but I'm thinking about academic, didactic courses presenting a comprehensive picture of what is known, how it is known, and emerging ideas about infection control and prevention. Any science-based course should expose the learner to the continuum of theory, evidence, and practice. I think it could be done in a semester.

How best to approach such a course needs to be discussed and worked out, but one might, for example, begin with a survey of what we know about what people are commonly colonized and infected with, and how they got that way. This would entail examination of aerosol, alimentary, percutaneous, and other infectious pathways as appropriate, focusing upon important pathogens of concern in healthcare facilities. It could then go on to examine microbial life histories along each route of infection, and how common hospital practices act synergistically or antagonistically with each such route. Host response to infection would be important to cover, and a quantitative epidemiological component should also be included. To tie everything together, learners could undertake a final project assessing what current infection prevention practices are evidence-based and which aren't, and what evidence might be useful for better informing infection control practice. Such a course might be entitled Infection Control and Prevention: From Science to Practice. If done well, the course could help to train learners to think about infection within the context of a coherent, interconnected, evidence-based picture.

By and large, it seems like such an expansive, theoretical picture of hospital infection control and prevention is lacking at present. There are mathematical and computer models of varying complexity and realism that together have led to insights, though how to generalize and apply these is sometimes unclear to preventionists. There are also rules and guidelines, though some (many?) are not as well studied as one might expect (e.g., handwashing and contact precautions). There are increasing numbers of studies suggesting that this intervention works here and that intervention works there, but understanding how all this knowledge fits together to inform thinking and practice, in a truly robust way, remains elusive. A systems approach to both teaching and thinking about infection prevention may prepare the next generation of researchers and clinicians to think more holistically and progressively about infection in healthcare environments.

Another burden for MRSA patients

We've blogged many times on the adverse unintended consequences of active surveillance for MRSA. A new study in the American Journal of Infection Control documents yet another setback for patients colonized with MRSA. Susan Huang's group studied admission practices at 13 nursing homes in California. Patients colonized with MRSA were nearly 3-fold more likely to be denied admission than those without MRSA colonization. Active detection and isolation for multidrug-resistant pathogens is one of the only interventions in medicine where the benefit accrues to patients who don't bear the burden of the intervention. And the more we study this, the bigger we find that burden to be.

Photo: FoxBusiness.com