Retractions - One now, perhaps more in the future

We've written before about article retractions and why high-profile journals like NEJM might have the highest retraction indices (figure). Yet, retractions in infection prevention are very infrequent. In fact, the one major retraction we mentioned during 7 years of blogging was not strictly a retraction, but a re-analysis of N-95 vs surgical masks.

Which brings us to a rare retraction in infection prevention, namely this 2014 AJIC study looking at zero fluid displacement intravenous needless connector and CLABSI prevention. As reported this week in Retraction Watch, the study was initially questioned because of a failure to report conflicts of interest but has now been fully retracted by AJIC since an investigation found problems with the "consistency of the statistics over various study periods as well as the methods by which study sites were chosen." Fortunately, since this study was published less than 2-years ago and only cited once, this retractions won't be particularly damaging to the field.

However, with the recent announcement that NIH is providing an additional $100 million for antimicrobial resistance (AMR) along with increases in CDC and industry funding, there are now resources to fund high-impact studies that will appear in high-impact journals. And as if those pressures are not enough, the US Government has been tasked to reduce C. difficile infection by 50%, CRE by 60% and MRSA by 50% by 2020 compared to 2011. With the unprecedented increase in funding combined with difficult to achieve targets, there will be unbelievable pressure to cut corners in study design and analysis and over-promise or over-promote results. This all represents a potential recipe for disaster if our field isn't careful. On the bright side, societies like SHEA have very strict conflict of interest reporting, so we have some checks in place to identify conflicts and bias. Of course, this won't be enough. Be careful out there.

FS for CS - When The Public Helped Fight Tuberculosis

This past weekend, there were lots of public tributes for Ol' Blue Eyes, as Frank Sinatra would have been 100 years old.  Given the season and limited public health funding for tuberculosis research and programs, I wanted us to remember a time when the public was directly involved in an infectious disease (i.e. TB) fight. The Christmas Seals were first issued in 1907 to fight tuberculosis, but are now used more broadly to fund respiratory disease research. Maybe it's time to bring back campaigns to fight underfunded infectious disease research programs? MDRO Seals? Happy Christmas everyone.

$1.2 billion Requested for Antibiotic Resistance!

You don't tug on superman's cape
You don't spit into the wind
You don't pull the mask off the old lone ranger
And you don't mess around with Jim

-Jim Croce

Most days, controlling the spread of antibiotic-resistant bacteria in hospitals feels like fighting with one hand tied behind our backs, or spitting into the wind or...  For example, we have very little control over whether patients are colonized or infected with antibiotic resistant bacteria on admission. It's not like we can move a hospital from the high-prevalence East Coast to the low prevalence Upper Midwest. And once resistant bacteria become endemic in our region/hospitals, we have few reliable evidence-based interventions to prevent patient-to-patient transmission.

So, it's with some trepidation that I began reading the President's proposal to provide extra funds to tackle antibacterial resistance. Would there be any funds for infection prevention? When discussing past initiatives, we've remarked on how little attention is given to infection control programs and research. This time, however, things are looking better.

Here's how the $1.2 billion will be distributed under the current plan:

• $650 million to the NIH and the Biomedical Advanced Research and Development Authority to expand development of antibacterial drugs and diagnostics
• $280 million for CDC-led efforts to curb overprescribing of antibiotics and track outbreaks of drug-resistant infections
• $47 million would go to FDA to evaluate new drugs and monitor livestock antibiotics use
• $77 million to USDA to help develop alternatives to the antibiotics used in farm animals
• $75 million to DoD and $85 million to VHA to focus on reducing antibiotic-resistent infections in health care settings 

This is a well thought-out list and is very close to how I would wish to distribute the resources. I would perhaps request a bit more for CDC to study HAI prevention interventions in addition to stewardship efforts; however, this extra-funding, while long overdue, is on target. I'm also encouraged that the President is asking for increased funds and not reducing other critical research in infectious diseases like HIV, TB and malaria. Let's just hope Congress can approve this request and it's renewed annually. It will be nice to get back to work preventing HAI - this time with two hands and a mask to keep the spit off our faces.

Guest Post: IDSA’s Take on the Match Results

This is a special guest post by Dr. Stephen B. Calderwood, MD, FIDSA, President, Infectious Diseases Society of America (IDSA)

The first annual IDWeek Mentorship Lunch, IDWeek 2014    

The IDSA community is over 10,000 doctors strong, and we’re all concerned with the match results for this year. But the dumpster fire metaphor is only half right: Yes, it’s a crisis, but we aren’t shrinking from it. Everyone at IDSA is fighting for our specialty, and we need our whole community to join in. 

Compensation

HAI Controversies has talked before about this, and Mike Edmond put the blame squarely on the economics of being an ID doctor. The Society continually advocates for better compensation for ID services and how to value their input differently under health care reform. This past year, IDSA has pushed hard for ID specialists to be required for hospital stewardship programs. To help individual doctors with compensation, several IDSA veterans compiled The Value of the ID Specialist, a comprehensive study that documents how ID consultations result in better outcomes and lower costs.  And for IDSA members, we offer a Value Toolkit (login required), which collects presentations, videos, and documentation to help ID doctors make the case to their own employers, hospital administrators and health plan executives.

Funding for Research and Public Health

Funding cuts in research and public health affect all of us, not just ID specialists, and IDSA joined hundreds of other professional societies to Rally for Medical Research. In addition, our policy and government affairs team works tirelessly, advocating for more research funds for HHS agencies and encouraging the White House and Congress to commit more of the federal budget to infectious disease research and public health.

We actively encourage our members and the public to join these efforts. In three minutes, you can let your congressional representatives know that budget cuts hurt the infectious disease community, and ultimately the patients we serve. Of course, you can also contribute more directly: the IDSA Education and Research Foundation supports medical students and young investigators with fellowships, travel grants, and research funding to help recruit more people to our specialty and to help with their early career development.

Mentorship

Mike Edmond’s post led with a moving tribute to the mentor who inspired him to choose ID. IDSA is dedicated to expanding our mentorship efforts. In addition to our two Fellows’ meetings every year and our scholarships for medical students, we launched a new Mentorship Program at IDWeek 2014. Students, residents, and fellows were teamed up with seasoned ID professionals and explored the meeting together. We’re actively trying to expand our mentorship programs, and encourage our members to volunteer for these efforts.

Responding to the match is a community effort that will require a multi-pronged approach. We at IDSA are all thankful to have an active, involved, and passionate community of ID doctors in our Society who want to see the specialty thrive and expand; we welcome all thoughts individuals may have in better addressing this issue. We certainly want to ensure that we continue to attract the very brightest and committed individuals to our specialty. We’re committed to ensuring that the future workforce brings the clinical expertise and new knowledge needed to address the many problems we face, including the enormously important areas of antimicrobial resistance and stewardship, HIV, TB, emerging infectious diseases (such as Ebola!), and all the other key areas our specialty contributes to so uniquely on a daily basis.  

Ebola: What can we learn from an N of 1?

Most of us woke up to the very unsettling news that a health care worker had acquired Ebola during the care of the index patient in Dallas. Those following the blog know that we've been worried about just this type of event since July, when Mike provided an Ebola primer. Specifically, we've been worried about the complexity of the PPE required and how this could paradoxically increase risks to health care workers. We've also highlighted the massive WHO budget cuts, CDC cuts and Prevention and Public Health Fund cuts since at least 2012.

In addition to the national cuts, individual hospitals have seen reduced support for infection control programs just as more and more is being asked of them. It used to be that hospital epidemiologists and infection preventionists could do surveillance rounds on the wards and educate from-line staff. Now, many hospitals have barely enough staff to complete their surveillance and public reporting duties leaving many trapped at their desks analyzing data. There is zero excess capacity to educate clinical staff on basic infection prevention practices like contact precautions. At many hospitals there is no capacity to add additional training in Ebola PPE protocols. As Marc-Oliver Wright said to me once: "You can't fight and prepare for the maybe (insert scary virus) when the required was due yesterday." Yet many hospitals are managing by shifting staff away from MRSA, away from CLABSI and away from influenza, which leaves our patients vulnerable to these more likely threats. If this were the military, there would be claims about fighting with one hand behind our back. That's the case here - we are fighting a war against Ebola and we've got an un-gloved hand behind our back.

So what are the lesson's from Dallas?

First, PPE is not 100% effective with current technology and training protocols. If health care workers auto-contaminate their hands when removing gloves 11% of the time when they caring for VRE colonized patients and 4.5% of the time when caring for patients with Acinetobacter, there is little room for error in PPE removal and hand hygiene when caring for patients infected with Ebola, particularly near the end of their disease course.

Second, the focus of Ebola preparedness in the US has to be 100% directed towards hospitals, initially the ICU settings. It's a simple fact that patients aren't infectious until after they develop symptoms and they are highly infectious once they are in shock in the ICU. Each and every hospital must walk through PPE donning and doffing and plans for Ebola patient care. They must train a cohort of doctors, nurses and environmental services staff now. Practice, Practice, Practice. Once the ICU staff are trained, the net should be widened to include the emergency department and other clinical settings. Work backwards from the highest risk settings where patients are most infectious (e.g. ICU) to the least.

Third, we need to demand funding for infection control in our hospitals. Double the number of infection preventionists and make sure each hospital has an Infectious Disease trained physician responsible for ensuring that all infection prevention protocols are followed. If we aren't even prepared for Ebola, how will we ever be prepared for a far more infectious avian influenza or MERS?

Fourth and finally, we must increase national funding for infection prevention. We must develop new PPE technologies and new methods to improve compliance and education. Right now we are using ancient technology - gloves, gowns, masks. We must also fund local and regional public health departments, as well as CDC, WHO and the PHEP, whose funding has been cut if half since 2006 (see below). We might get lucky with Ebola in the US (sadly it continues to get worse in Africa), but I doubt we'll be so lucky with the next virus.

***And for reading beyond the events of today, I suggest reading Judy Stone's excellent post on the problems with politics and public health mixing. She's covered many of the same topics that I've mentioned but with a broader scope.

...at least she didn't die of MRSA

For the past six months our group at Iowa has been collaborating with colleagues at the University of Utah on a project for CDC. We are tasked with measuring the burden of MDRO using systematic reviews to inform economic models that will project MDRO incidence and attributable cost over the next 20 years. We are studying pathogens like C. difficile, VRE, MRSA, ESBL-GNR and CRE. It's a tall order, but we expect that CDC and others will use these estimates to guide funding for research and prevention efforts. Since bacterial pathogen research is so widely underfunded compared to their burden of disease, these new estimates can only help.

But, it has occurred to me that the planned approach of estimating the burden of disease using pathogens typically categorized as MDRO, such as CRE and MRSA will result in serious underestimates of the bacterial pathogen burden and lead to perpetuating the chronic underfunding of our research and prevention efforts. A simple way of demonstrating the impact of neglecting susceptible bacteria is to focus on S. aureus. One widely cited estimate of yearly MRSA mortality burden is 18,650 in-hospital deaths. Ignoring secular trends and community deaths, while assuming 50% of S. aureus infections in the US are MRSA (and thus 50% are MSSA), we might estimate that S. aureus kills 37,300 people annual in the US. This would place S. aureus (one bacteria!) ahead of traffic deaths and rank it as the #11 cause of death in the US (see table below). Imagine if we included "susceptible" (and resistant) bacteria like E coli, Klebsiella and Streptococcus in a total bacterial burden estimate!

For those that will argue that we have effective antibiotics for MSSA, so that it's unimportant, I offer several counterpoints. First, people die of "susceptible" bacteria (18,650 MSSA!) and we don't fund HIV research based on mortality burden for only protease inhibitor resistant strains. Second, even strains we call susceptible are actually resistant to numerous classes of antibiotics - most MSSA is actually PRSA and try treating enterococcus with a cephalosporin. Third, by ignoring susceptible strain burden, we underinvest in strategies that could treat or prevent all infections, not just arbitrarily defined resistant ones. For example, S. aureus vaccines could prevent both MSSA and MRSA infections. If NIH (or CDC or ECDC) uses only MRSA burden to guide funding of S. aureus vaccine research, they would underfund by 50%.

You get my point, but I will leave you with my final reason for recommending inclusion of "susceptible" strains when measuring burden of disease for bacterial pathogens. Imagine if your aunt is very sick with an MSSA prosthetic hip infection in the ICU. And then imagine if the doctor comes to inform your family that she is very sad that your aunt has passed away, but adds... "at least it wasn't MRSA." Does that make you feel any better?

beer image: source

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

When did "CDC Funding" become an oxymoron?

A proposed $664-million cut in congressional funding may be in store for the CDC in FY2013. There appears to be some attempt to backfill the cuts with support from other sources including the Prevention and Public Health Fund.

Per a recent Nature-News article, the cuts would impact the CDC core budget and impact grants to "local, county and state public-health departments to monitor infectious diseases or track food-borne outbreaks." If these cuts stand, the CDC budget will have fallen by 20% since 2010.

Just last week, Trish Perl circulated an email query asking what key concerns we have in infection prevention over the next 2-3 years. Many were concerned about increased work demands for public reporting and mandates. Mike and Dan had several other concerns they will hopefully share with us in future posts. My main concern was the loss of the CDCs voice in the fight against antibiotic resistant bacteria as their funding is slowly cut. I guess it will be quickly and not slowly.

Source: Meredith Wadman in Nature 483, 19 (01 March 2012) doi:10.1038/483019a

Call me when your disease kills more than HIV….

HIV has become the standard against which all infectious public health threats are now measured. First with MRSA, now with hepatitis C virus (HCV), the media are abuzz with the news that another infection kills more people than HIV does. There are many reasons for this meme, perhaps the most instructive is that the resources put into research and prevention efforts for HIV are astronomical compared with those for many other infectious disease threats (a point Eli has made clearly). This investment has paid off, too, in the form of steadily falling HIV-associated mortality rates in developed nations. I look forward to the day when shark attacks, or “events of undetermined intent”, kill more people than HIV. Check out Table 2 in this document to see if your disease-of-interest kills more than HIV.

Maybe if we invested as much in research and prevention of multiple-drug resistant bacterial infections and other healthcare-associated infections, we’d see similar success.

Silver lining in rising MDR-N. gonorrhoeae?

We've written about poor funding for MDR-bacterial prevention studies and antimicrobial discovery. In fact, our NIH funding paper with Dan Kwon and Marin Schweizer looking at NIAID support for ESCKAPE-pathogen studies was just published in ARIC. It's a major problem, as there has been almost no governmental or private funding for antibacterial discovery in decades. Don't even get me started on funding for infection prevention studies. Only 4 good studies on hand-hygiene improvement since the 1950's, seriously?

With that background, I read with interest Gail Bolan's (CDC) editorial in this past week's NEJM.  In it she sounds the alarm for resistance in gonococcus based on a recent 17-fold rise in 3rd-generation cephalosporin resistance (cefixime) from 0.1% to 1.7% with higher rates in Western states. (See graph above) This rise in cephalosporin resistance follows sulfa resistance in the 1940s, PCN and TCN resistance in the 1980s, and fluoroquinolone resistance by 2007.

An interesting fact shared in the article is that when resistance to a particular drug class reaches 5%, the CDC's Gonococcal Isolate Surveillance Project(GISP) changes treatment recommendations to a new class of antibiotics. Sadly, only third-generation cephalosporins are left. I wonder if this class switch at 5% is contributing to the rise in resistance?  That question will remain unanswered - no funding. Also, imagine having a 5% threshold in hospitalized patients.  We would have run out of choices years ago!

So what is the silver lining in all of this?  I have a suspicion that politicians and others might be motivated by an STD with an annual incidence of 600,000 in the US. I'm not saying that politicians are at higher risk for STDs, no judging, but STDs put many people at risk, so there will be pressure to respond to this.  The silver lining is that antibacterials designed or discovered that are effective in treating GC will likely have efficacy for other MDR-bacteria, such as Acinetobacter. 

Thus, when Bolan and colleagues suggest that "the immediate priority is replenishing the drug pipeline to treat gonococcal infections," I have hope that people will listen.  There are few grassroots organizations fighting for antibiotic discovery, but there may be soon.  I hope so; our hospitalized patients are counting on it.