Infection Prevention Summer Reading

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

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

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

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

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

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

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

Hand Hygiene Interventions: A Network Meta-Analysis

Summer is in full blaze (especially for those in Rome, France and the western US), so we don't have much time for long posts. However, I had to point you to an excellent study in the BMJ (open access) by Luangasanatip et al. that utilized a systematic review and network meta-analysis to determine the comparative effectiveness of the WHO 2005 hand hygiene campaign and other interventions. The WHO-5 Campaign (not to be confused with the WHO 5 Moments) recommended a multimodal strategy consisting of five components: system change, training and education, observation and feedback, reminders in the hospital and a hospital safety climate.

The authors completed a systematic review of interventions from 2009-2014 and used prior reviews to identify other studies. A strength of the analysis was that they looked beyond randomized trials and included high quality quasi-experimental studies including non-randomised trials, controlled before-after trials, and interrupted time series studies. They then completed a network meta-analysis which suggested that the WHO-2005 campaign was effective and compliance could be improved if other interventions were added including goal setting, reward incentives and accountability.

For those interested in reading more about network meta-analysis, I suggest you read John Cornell's editorial and the PRISMA Extension Statement in this past June's Annals. Briefly, it allows direct and indirect comparisons of interventions. For example, if two interventions are not directly compared they can still be compared if they were both directly compared to a third intervention (see Figure 1 above - Treatment D vs Treatment B or C through their direct comparison to Treatment A). Additionally if there is a closed-loop of studied interventions, additional information can be gained from indirect comparisons even if direct comparisons also exist. For example, in Figure 1 above, we can learn about Treatment A vs Treatment B from their direct comparison but also indirectly through Treatment C.

I encourage you to read the full study and the editorial by Matthew Muller. Very nice to see that the BMJ published this important study. And for those in the southern hemisphere, enjoy your cool weather...these summers seem to be getting worse and worse.

Ebola - Some Hope for Control in West Africa

Ebola, as we all know, is out of control. As an example, every time I turn on the TV there is Dan or Mike or Dan staring back at me. Eventually, we will calm down in the US and begin to focus our attention on the critical outbreak in West Africa. My prediction is that this will happen sometime soon after November 4th (Election Tuesday). In the meantime, there is some possibly, maybe, hopefully good news out of West Africa in today's NYT. As of a few days ago, fewer than half of the 649 available treatment beds in Liberia were occupied. Of course this could be good or bad, but I'm holding out for good.

There was also some potentially good news in a report published in the Annals yesterday. Dan Yamin et al. analyzed a stochastic model of Ebola transmission populated with parameters from a 2000-2001 Uganda outbreak and the current outbreak in Montserrado County Liberia. The authors used the model to determine the number of secondary cases infected by survivors or non-survivors and also evaluated the effect of isolating/hospitalizing patients. I have included the key figures from the paper below. In Figure 1a, they estimate the Ro stratified by whether the index case was a survivor or non-survivor. For the whole cohort, the Ro was 1.73. However, the difference between non-survivors and survivors is striking. It appears that non-survivors infect four times as many people as survivors (2.36 vs 0.66). This may explain why the two Dallas nurses were infected after being exposed to a non-survivor while no secondary cases have yet occurred in other US hospitals, where everyone else (so far) survived.

Figure 1a

In Figure 1c, the authors provide an estimate of the average number of secondary cases per day of symptomatic disease. You can see that there is very little transmission in the community at day 1 and it remains very low for survivors but jumps up after day 2 for non-survivors. This implies that waiting for symptom development is a scientifically valid strategy for preventing community transmission of Ebola even in Africa. (We expect these numbers to be far lower in the US where our communities are less crowded and we are fortunate to have toilets, indoor plumbing and clean water.)

Figure 1c

Finally, in Figure 2 the authors evaluated at what time point non-survivors (very sick individuals) must be actively isolated to prevent community transmission. They estimate that if 75% of the non-surviving cases are detected and isolated by day 4 this results in a 74% chance of disease elimination and if 100% are detected and isolated by day 4 then there is a 94% chance of disease elimination. Currently, the authors report that the average time from disease onset to hospitalization in Liberia is 5 days, so there is some room for improvement. However, I suspect that the current expanded efforts could achieve 4 days. When I put the results of this Annals paper together with the NY Times report of empty beds, it suggests that there is available capacity to hospitalize and isolate patients within 4 days of symptom onset and it might even suggest that current efforts are already working. I'm certainly hoping this is the case.

Oh, and if isolating patients 4 days after symptom onset works in West Africa, it means WE DON'T NEED TO QUARANTINE ASYMPTOMATIC FOLKS IN THE US. So please stop it...and sorry for shouting.

Overprotection Does Not Equal Protection: Ebola and Healthcare Worker Deaths

There is a disturbing, if not surprising, post in Bloomberg describing the horrible conditions that healthcare workers face when caring for patients with Ebola. In the current outbreak it is estimated that over 300 healthcare workers have been infected and 150 have died. It is clear that the systems designed to protect healthcare workers are failing. The central problem is that the temperatures inside the "Ebola Suits" can reach 115 degrees and can take a long time to safely remove. To begin to understand the problem, all you have to do is read this quote from Douglas Lyon:

“The first 15 minutes I was just hot...After that I was hot and had a wicked headache. Each breath in was a mix of a hint of cool relief and the feeling of suffocation. Each breath out was as warm and hot and humid as the rest of you.”

How long can you wear such a suit? How carefully will you remove such a suit? I suspect that it's hard to be deliberately slow when you're suffocating. On top of that, these suits are expensive. A facility caring for 70 patients is estimated to go through 200 sets of protective equipment per day at $77 each - $15,400. This is in countries where they can't normally afford to purchase alcohol hand rub, so hospitals distill it themselves from sugar cane or other sources.

The suffering and cost would be fine if bodysuits were both effective and necessary; however, this might not be the case. Our co-blogger Dan and colleagues wrote a wonderful opinion in the Annals last month that highlighted CDC recommendations: contact and droplet precautions - a fluid-impermeable gown, gloves, a surgical mask, and either goggles or a face shield along with shoe/leg coverings if the patient has “copious” secretions and N95 mask if they are undergoing an aerosol-generating procedure.

CDC does not recommend full-body HazMat suits.

Apart from asking you to read the paragraph below and suggesting that if we had better science around infection prevention, we'd have safer hospitals and less debate around things like HazMat suits, I would like to close with a quote from the Annals commentary: "Exceeding these recommendations may paradoxically increase risk. Introducing new and unfamiliar forms of personal protective equipment could lead to self-contamination during removal of such gear. Requiring HazMat suits and respirators will probably decrease the frequency of provider–patient contacts, inhibit providers' ability to examine patients, and curtail the use of diagnostic tests...Using extra gear inflates patients' and caregivers' anxiety levels, increases costs, and wastes valuable resources."

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Usually, when I'm frustrated about the lack of science around infection prevention, I end my post by requesting adequate research funding. What is entirely obvious is that we take infection prevention for granted. We know hand hygiene should be 100% and we have gloves, gowns, masks, bodysuits, yet we fund NO research on how to improve hand hygiene compliance, develop better gloves or design new bodysuits that clinicians can remove safely. We are now paying a price for this lack of attention. I hope that federal agencies or the Gates Foundation will fund infection prevention studies that determine ways to improve systems of prevention so that caring for patients with Ebola isn't life threatening and so we no longer transmit deadly pathogens in our hospitals.

To CDC or not CDC - That is the Ebola Question

It's been a busy couple weeks out here in infection control land. We had our SHEA 2015 planning committee meeting in DC. There's an exciting program planned - can't wait to share it with you. While I've been planning Ebola symposia for the May meeting in Orlando, Dan and Mike have been very busy discussing and implementing Ebola management plans. If you haven't had a chance to read their excellent posts, you can peruse them all here.

The debate over the CDC droplet+contact precautions guidance is strangely similar (in an opposite day kinda way) to discussions around N95 masks during the 2009 H1N1 outbreak. To remind yourself of the debate, you can read one of Dan's 2009 posts on the topic. What is almost ironic is a quote included in the post: "when did influenza become Ebola." What is actually ironic is that back in 2009/2010, CDC recommended "respiratory protection that is at least as protective as a fit-tested disposable N95 respirator for healthcare personnel who are in close contact with patients with suspected or confirmed 2009 H1N1 influenza." Yet now, CDC does not recommend N95s in most clinical situations for Ebola. And if you're keeping score, in 2009 CDC wanted "higher-level" protection and hospital epidemiologists wanted "lower-level", while in 2014 most hospital epidemiologists are implementing policies that extend way beyond CDCs recommendations.

All of that is by way of background to a thoughtful commentary in Annals of Internal Medicine by Michael Klompas, Daniel Diekema, Neil Fishman and Deborah Yokoe. The authors carefully review the data behind the CDC's current guidance and suggest that hospitals stick closely to the current recommendations. They claim that exceeding the CDC guidance could paradoxically increase health care worker risk and anxiety while also increasing cost and waste. They also suggest that exceeding "CDC's recommendations fans a culture of mistrust and cynicism about our nation's public health agency." The only thing I would add is that no matter what's included in your local Ebola management plans, don't forget the ice cream.

image source: The Onion