MERS in S. Korea and Infection Control

I've been thinking about this all week, and came to the conclusion that I don't have much of a take on the latest outbreak. Surprising, I know, given how we are the number one "therapeutically abrasive blog"* on the interweb. With that said, I want to counter a meme I've seen emerging.

In Nature News today there was an article and a quote from David Heymann, chair of Public Health England, that I found a bit concerning. He said, “The focus on South Korea would be better directed towards Saudi Arabia.” It appears to me that the article and he are suggesting that it's more important to study episodic animal-to-human transmission than to focus on human-to-human infection control. I think this is a poor choice (or perhaps a poor choice of words) for a number of reasons. First, it is unlikely that prevention activities in Asia compete for research dollars with epidemiological investigations in the Middle East - we can and should do both! Second, in the case of MERS, CDC has estimated that more than 90% of cases could be linked to health care exposures. So, if we care about preventing incident human cases, public health authorities must still focus on understanding and halting nosocomial transmission. Finally, in a recent article in Time, the CDC's Tom Frieden said “Hospitals can become amplification points...It’s the case in measles, it’s the case for drug-resistant tuberculosis, it’s the case for MERS and SARS and Ebola. That’s where sick people go and that’s where vulnerable people are. It really emphasizes the importance of good infection control in the health care system.”

And if I can extend what Dr. Frieden said - we don't actually know how to achieve good infection control for MERS and the other pathogens he mentioned. If only we invested in studies to understand how to best implement PPE in these settings. One could imagine improved PPE technology, refined PPE donning and doffing algorithms and enhanced environmental cleaning as potential targets for future studies examining optimal protection from MERS. Not coincidentally, many of these are the same targets that Mike, Dan and I mentioned in our Ebola+PPE editorial several years months ago. If we invest in infection prevention technology and implementation research, our health care system will be safer regardless of the pathogen du jour.

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For those interested in reading more about infection control for MERS, I suggest a recent review by Westyn Branch-Elliman, Connie Savor Price, Alison McGeer and Trish Perl in the March 2015 ICHE. ICHE has graciously made the review "free access" for the month, so download the PDF now. Of note, this group has first hand experience with MERS infection control in Saudi Arabia. Additionally, CID just published an invited review on MERS for clinicians that is also free access. Finally, for a recent update on the S. Korean outbreak I suggest this excellent article by Julia Belluz in Vox.

*I found "therapeutically abrasive" quite funny and think it could be very useful in preventing C. difficile. 

Numbers Matter: Why counting only resistant bacteria ultimately harms our patients

You've seen the numbers. The CDC estimates that 23,000 deaths are caused by antibiotic resistant pathogens annually and as many as 14,000 of these deaths are linked to C. difficile. Every time I look at those numbers, they make me incredibly sad. First, they include all C. difficile deaths and not just those attributed to fluoroquinolone-resistant C. difficile, for example. This tends to incorrectly overweight the importance of C. difficile relative to other pathogens. Second, and you've heard me rant about this before, they only count deaths caused by the small proportion of bacterial pathogens that happen to be resistant, as narrowly-defined. This would tend to diminish the importance of bacterial pathogens compared to other causes of death (e.g. accidents). But I'm getting ahead of myself.

The numbers I'm about to throw at you are very rough estimates. I'm using these estimates to illustrate a point and hope that others will eventually provide more accurate estimates. If you think I need to correct a specific number, let me know in the comments, and I'll do my best to make the change - but I'm not promising. 

Let's take S. aureus as an example. The CDC estimates that 80,000 infections and 11,000 deaths are attributed to MRSA each year. In 2005, they also estimated that MRSA was associated with 18,650 deaths, but I'll be conservative and stick with 11,000. Per this 2013 NHSN report, the proportion of S. aureus that were MRSA ranged from 43.8% (SSI) to 58.7% for CAUTI. I'll use the lower proportion (44%) since this allows for some mortality secondary to more community (less MRSA) infections. However, I suspect most patients that die from S. aureus infection will ultimately be hospitalized. For simplicity, I will also assume that MRSA is twice as lethal as MSSA (AKA penicillin-resistant S. aureus).

Taking the above numbers, if there were 80,000 MRSA infections, we would expect 102,648 MSSA infections. If the mortality rate for MRSA was 13.75% (11,000/80,000) then MSSA's mortality rate would be half of that or 6.875%. So there would be 7057 deaths from MSSA. If you add that to the 11,000 you get 18,057 deaths due to S. aureus. We can quibble about numbers, but I suspect that 7,000 deaths caused by MSSA, passes the so-called giggle test.

Thus, if we used the CDC rankings to fund research and prevention activities, we would rank C. difficile at the top of the report. However, if we used my ranking system, S. aureus (MSSA+MRSA) ranks ahead of CDI. Since most interventions to prevent MRSA deaths would also work against MSSA (vaccines, new antibiotics) shouldn't both types be included in burden of disease estimates? The imbalance gets worse when you look at Gram-negative infections. Do we really only care if grandma dies of the 2-12% of E. coli or Klebsiella that are resistant to carbapenems? Do we really only count the 610 deaths from CRE and 1700 from ESBL? Clearly it would be better if we counted all deaths from E. coli and Klebsiella and projected a future where almost all strains would be ESBL or CRE.  This would allow us to make better decisions regarding current and future research priorities and prevention efforts.

I suspect if the S. aureus mortality estimate jumps from 11,000 to 18,000 when counting MSSA, it's not a stretch to imagine that deaths from bacterial infections would approach 100,000 in the US. If we count attributable mortality appropriately, deaths from bacterial infections would be a top 10 cause of death in the US. Top 10 means more money for research and prevention. Let's get these numbers right - grandma is counting on us.

Our long and winding road

We issue frequent reminders on this blog about how little we really know about healthcare-associated infection (HAI) prevention, and have called many times for increased support for HAI research. We also enjoy pointing out well-designed studies that help advance the field. So I’m happy to direct you to SHEA’s just-released update on HAI prevention advances and roadmap for HAI research. From surveillance to prevention, implementation and dissemination, this review summarizes our progress-to-date and provides an exhaustive list of research priorities. So read it and get to work!

Antibiotic Discovery: Focusing on supply while ignoring demand is doomed to fail

There is an article in today's New York Times (above the fold on page one - see image) that brings the problem of antimicrobial resistance and antibacterial discovery to the public's attention. It's a very important issue and many of the points raised in the article are spot on. Just some things for you to think about when you read the article:

1) Health and Human Services is giving between $40 and $200 million to GlaxoSmithKline over the next 5 years for drug discovery. This amount approximates what NIH spends on all antimicrobial resistance research for ESCKAPE pathogens ($50 million annually).  It's surprising that this amount couldn't be targeted to NIH or CDC funding instead (or ever).

2) Frustratingly, there was not one mention of antibacterial stewardship or infection prevention. Back when I was studying economics under this guy at University of Michigan, I learned about price determination. In principle, the price for a good will tend to settle where demand equals supply. I think of antimicrobial resistance the same way - demand is the need for broad-spectrum antibiotics based on resistance levels in the community and supply is the availability of effective antibiotics to treat resistant infections. If we focus on the supply side by funding pharmaceutical companies, we may end up with more effective antibiotics, but the set point equilibrium with high levels of resistance will remain if we continue to ignore the demand side.  To fix the demand side we need equal investment in stewardship and infection prevention research and implementation. Give $200 million to prevention research and we might actually find ways to scientifically achieve hand hygiene compliance over 50% without just yelling at health care workers! Imagine that...pause...

What did grandma tell me when I was little? - "an ounce of prevention is worth a pound of cure." I think she was spot on and it's is probably why I became a hospital epidemiologist. Thanks grandma.

CREATE-ing an opportunity

I can’t count the number of times we’ve pined for increased funding of healthcare-associated infection prevention research. I’m happy to say that Eli is putting more “money where his mouth is” in this regard, having just received a $4.2 million, five year grant to investigate MRSA infection prevention approaches. This VA HSR&D grant was part of the “Collaborative Research to Enhance and Advance Transformation and Excellence (CREATE)” initiative. Much like the NIH PPG, the CREATE grants fund several (in this case four) major projects that are interrelated along a common theme.

So, a CREATE grant now creates a great opportunity for Eli and his colleagues to advance the science of MRSA prevention. Among the principal and co-investigators in this multicenter partnership are Heather Reisinger, Marin Schweizer, Mark Vander Weg (all in Iowa City), Mike Rubin (Salt Lake City), Luci Leykum (San Antonio) and Dan Morgan (Baltimore).

Congratulations—now, of course, the work begins!

Death of the Mid-Career Investigator

Now that we Iowans have failed to select a candidate in the GOP caucuses, we can turn our attention to other political pursuits.  There is an important article just released in PLoS ONE by Kristin Matthews and colleagues at Rice University that describes the aging of the biomedical-research community in the US and its potential impact. 

The authors report that the average age of an NIH investigator rose from 39 to 51 between 1980 and 2008, while the average age of a new (first time) investigator rose from 36 to 42 during the same period. They also make some interesting comparisons to the average age of Nobel Laureates to determine if the rising age barriers at NIH could impact future innovative ideas and research. They found that during the same period, 96 scientists won a Nobel Prize in medicine or chemistry for biomedical research at an average age during the awarded research of 41 and 78% completed their research before age 51. They suggest that scientists do great work early in their careers but now those early careers won't be funded.

They conclude that "if nothing is done to reverse the rising age of PIs and first-time grantees, the scientific community could lose a generation of researchers, leading to an unsustainable biomedical research infrastructure and a dearth of talent participating in NIH-funded projects in the near future." I think a similar problem exists in infectious diseases and infection prevention research.

A world filled with only postdocs  (source Matthews et al PloS ONE)

Thus, there appears to be little funding or opportunity in the early and particularly mid-career period. This results in many fine and well-trained investigators leaving biomedical research in their 40's and never returning. Sure, a few lucky people will survive this pyramid scheme, but there won't be enough senior investigators in 10-20 years to mentor the next generation.

I'm not sure what the solution is or even the exact problem.  Is it ageism in scientific review committees or the lack of tenure-track faculty positions at the University level?  I suspect both of those issues are intertwined.

Source: Matthews et al. PLoS ONE 12/28/2011

Top priorities for clinical effectiveness research

The Institute of Medicine has released a list of the top 100 priorities for clinical effectiveness research, which it defines as "the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care." Of the top 100 research priorities, 3 fell into the primary area of infectious diseases, 2 of which directly relate to healthcare epidemiology. Both of these were ranked among the top 25 most important priorities and are:

--To compare the effectiveness of various screening, prophylaxis, and treatment interventions in eradicating methicillin resistant Staphylococcus aureus (MRSA) in communities, institutions, and hospitals.

--To compare the effectiveness of strategies (e.g., bio-patches, reducing central line entry, chlorhexidine for all line entries, antibiotic impregnated catheters, treating all line entries via a sterile field) for reducing health care associated infections (HAI), including catheter-associated bloodstream infection, ventilator associated pneumonia, and surgical site infections, in children and adults.

The purpose of the IOM's project is to identify how to distribute $400 million in federal stimulus funds.