Monday, April 30, 2012

The end of post-op prophylactic antibiotics?

One of the best approaches we have for dealing with in-hospital antimicrobial resistance is stewardship - using antibiotics only when the patient is most likely to benefit. It's been known for a long time that there is little benefit in extending prophylactic antibiotics beyond the end of surgery, yet this practice still persists. Imamura et al. just published an RCT in Lancet ID that examined the possible benefits of extending prophylaxis in patients with gastric cancer undergoing distal gastrectomy for cure.

The trial was an open-label, stratified (by ASA score) randomized trial in seven hospitals. All patients were assigned (1:1) to receive cefazolin 1g before incision and every 3 hours. Those in the extended prophylaxis group received 1g at closure and twice daily for two  postoperative days.  Using CDC definitions, infection control staff monitored for SSI while in hospital and surgeons monitored post-discharge for 30 days.

In the intention-to-treat analysis, 176 patients received standard prophylaxis and 179 received extended prophylaxis.  Randomization appeared adequate with similar operative times and estimated blood loss in each arm; however, 4 patients in the extended prophylaxis arm received transfusions versus none in the standard arm.  I've pasted Table 2 above, so you can see the results broken down into superfical and deep SSI.  Twice as many patients in the extended arm developed an SSI (RR 0.51 95% CI 0.22-1.16), but this was not statistically significant. Caveats: open-label study and SSI not monitored by independent researchers after discharge.

The authors and the accompanying editorial (both behind a paywall) each conclude that extended prophylaxis is not recommended. Although it is likely true, as Hedrick and Sawyer state in their editorial, that "the study is unlikely to have a major impact in the USA and other countries where the maximum duration of perioperative antibiotics is limited to 24 h and is carefully monitored and regulated."

Sunday, April 29, 2012

New and improved!

Eli, Dan and I thought it was time for a blog makeover. We're now in our fourth year, have posted over 1,000 pieces, and readership continues to expand. So today we've introduced a new look and some cool new features:

  • At the bottom of each post, you'll note a string of colorful icons that allow you to share the post with your friends in several different ways. Clicking the first icon (the green one) enables you to share the post in multiple applications simultaneously. So next time you see a post that resonates with you, hit the button!
  • In the sidebar, you'll find Featured Posts. Here each of us will choose one of our recent posts that we think you shouldn't miss.
  • Also in the sidebar further down, you'll find another new feature, Presentations. Here you can view lectures that we and others have recently given that may be useful to you.
There are now several ways to follow us. If you're a regular Facebook user, by clicking "like" in the sidebar, each new post that we write will automatically show up on your wall. If you're a Twitterite, each post can be twittered to you by following eliowa. If you're averse to those, new posts can be emailed to you (see sidebar), or fed to your Google reader. So, one way or another, keep following, and send us your comments!

Graphic:  Totally Serial

Saturday, April 28, 2012

Detecting antibiotic resistance is hard!

Eli linked me to this recent Nature commentary on the limitations of current screening tests for certain antibiotic resistant gram-negatives (those that carry carbapenemases). Because the resistance mechanisms for gram-negative bacteria are so complex and varied, resistance detection in the clinical microbiology laboratory has become a huge challenge. Furthermore, even if tests perform well to detect a specific single mechanism of resistance, what about bugs that use combinations of mechanisms? Consider how complicated it turned out to be to refine molecular methods for that comparatively simple organism, MRSA....emergence of empty cassette variants that result in false positives, divergent mecA genes that result in false negatives, and on and on we will go.  Multiply that complexity by a thousand fold for gram-negatives.

What this means is that every clinical microbiology laboratory needs a smart, well-trained clinical microbiologist--to optimize testing strategies, to understand the limitations of currently available methods, and to anticipate and detect problems with shiny new methods.  As the authors of the Nature commentary point out, too many hospitals are trying to cut costs in their microbiology laboratories, including being unwilling to staff them appropriately.  I was asked to talk at SHEA on molecular testing and infection prevention, and covered some of these issues (see below).
SHEA 2012 Diekema

Friday, April 27, 2012

An Iowa City Non-Virtual Chat Room

Mike dropped by Iowa City today to give a talk on C. difficile for the 14th Annual Update in Infectious Diseases at UI. Dan is the Course Director.  The talks were all excellent.  Next year, you guys have to swing by.  Next up tonight is the Great Plains Emerging Infectious Diseases Conference put on by the UI College of Public Health and directed by Tara Smith.

photo credit: Carl Lebuhn, MD

Wednesday, April 25, 2012

Alcohol hand rub prevents rhinovirus infection (despite the authors’ claims) and it can get you really pissed!

This morning, two kind folks independently pointed me to new reports on the efficacy of alcohol hand rub.  The first report in CID by Ronald Turner et al. describes a randomized trial of the efficacy of 62% ethanol hand rub for the prevention of rhinovirus infection.  In the study, 116 volunteers were randomized to the active hand rub group and asked to apply the hand rub after each hand washing episode and also every three hours for 9 weeks. Apparently, there is data showing ethanol hand rub prevents rhinovirus for up to 4 hours. The 96 unblinded controls were asked to practice their usual hand hygiene routine. All enrolled kept a diary of symptoms, had weekly nasal lavage for PCR and two additional nasal lavages if they developed cold symptoms.

The results of the study were somewhat surprising, especially if you just read the abstract and focus on the highlighted p-values.  The authors conclude that "hand disinfection did not reduce rhinovirus infection or rhinovirus-related common cold illnesses."  When you look more closely, only 39% of treated subject developed a confirmed infection versus 49% of untreated. Sure, the p=0.3, but this is just because the study is underpowered. Oh, and reported common cold illnesses were lower in the hand disinfection arm (56% vs 72%, p=0.01). And then read their conclusion - a bit of an over-reach: "the results of our study call into question commonly held assumptions about the route of spread of rhinovirus infection..."  Wow. Do one underpowered study - not blinded, cherry pick the results and then claim rhinovirus might not be spread via hands?

h/t Charlesnika Evans 

The second report highlights the efficacy of hand rub in getting kids wasted.  The report by Jane Weaver (with Today Show video) describes how 16 LA teens have been treated for intoxication after guzzling 120-proof alcohol hand rub.  Some might even be distilling it first.  Very ingenious.

h/t Mark Vander Weg

Tuesday, April 24, 2012

If you're criticizing methods, your methods better be strong

This morning I innocently set out to review a new study in ARIC that looks at methodological issues in C. difficile outcomes studies assessing the association between infection and excess hospital stay.  The authors make a very important point in the paper: "The studies did not collect data concerning the time of onset of CDI; therefore, it is not possible to exclude the possibility of reverse causality, in which longer lengths of hospitalisation may have increased the risk of CDI." They then go on to discuss time-dependent bias and recommend the use of multi-state models...we've made this point before.

What caused me the emotional anguish was their Table 1 that lists the 16 studies included in the review. In column two, three of the studies are listed as retrospective case-control studies...what??!!  How can you do a case-control study with an outcome being hospital length of stay?  I'm pretty sure you can't, at least not easily.

You see, a case-control study requires identifying an outcome and looking back for risk-factors associated with the outcome. For example, you could look at 50 people that died (and 100 that didn't die) and see how many had CDI, to determine if CDI was a risk-factor for death.  For length of stay, I can't even make up a good way to do a case-control study.  Would you find patients who stay >14 days and compare them to patients that stay <14 days? The three studies listed MUST have been cohort studies, so why did the authors of the ARIC paper seeking to teach us about proper methods for outcomes studies list them as case-control studies? Perhaps they pasted them from the individual studies' methods sections?

Just to confirm this, I looked at all three papers: (Ananthakrishnan (2008), Bajaj (2010), Pepin 2005).

Pepin: from the Methods  - "We compared mortality and total length of hospital stay among inpatients in whom nosocomial CDAD developed and among control subjects without CDAD."  This is a cohort study - exposed and unexposed to CDAD, looking forward to outcomes.  Just because they incorrectly use the word control, doesn't make this a case-control study. (Strike 1)

Ananthakrishnan: "Our primary case group (C difficile–IBD group) included patients who had a primary diagnosis of C difficile colitis and a secondary diagnosis of either Chrohn's Disease (CD) or Ulcerative Colitis (UC). Patients admitted to hospital with a primary diagnosis of CD or UC without a diagnosis of C. difficile colitis formed one of our comparison groups (IBD group)." Another cohort study - defined by the exposure to C. difficile and not by the outcome. (Strike 2)

Bajaj: "Among the cohort of hospitalized patients with any diagnosis of cirrhosis, co-existing diagnosis of C. difficile was associated with significantly greater in-hospital mortality."(Strike 3)

The error of incorrectly describing cohort studies as case-control studies is very common - enough to be a pandemic.  The journal CID is one of the worst offenders. One of my favorite examples is this recent VAP treatment cohort study described as a case-control study in the title!  When I've mentioned the problem to CID editors, they suggest I write a letter.  You can't write letters for each issue.

OK: Cohort - exposed/unexposed look forward in time to the outcome. Case-control - find outcomes and look back for exposures. Got it?  EOR

Sunday, April 22, 2012

CDC "shameful and unethical"???

I'm heading to Delaware in a few weeks to speak at an Infectious Diseases symposium. My assignment is to talk about myths and controversies in infection prevention. It's a juicy topic, and one that I find fascinating. So once again I'll be speaking on "Getting to Zero," a myth so big it rivals the Tooth Fairy. We've blogged about it many times, with Eli recently attributing the death of Facts to be partly due to this big lie.

There are a couple of interesting recent developments on the GTZ front. First, one of the biggest promoters of the concept, APIC, appears to have expunged it from its website. Good thing I made screenshots of the old website for posterity's sake! Secondly, Paul Levy, a former hospital administrator, who writes the blog Not Running a Hospital, devoted a posting to GTZ yesterday. The title of the post is "Unethical and Shameful Behavior at the CDC." He blasts CDC and its director, Tom Frieden, for the use of the standardized infection ratio (a "meaningless methodology"), risk adjustment (he questions why medical school affiliation should impact infection rates), and the use of benchmarks (since zero is the goal). Unethical and shameful? Really?

The concept of Getting to Zero HAIs is at least 5 years old, and I find it amazing that I have yet to meet an infectious diseases physician (you know, those people that every day actually take care of patients with infections) who believes that HAI rates can be reduced to zero. Those of us in the reality-based community understand that when you immunosuppress patients as profoundly as we do, and use ever more invasive devices for ever longer durations of time, believing in Getting to Zero requires ingesting an awful lot of kool-aid. We certainly have to keep trying our best to reduce infections, but we also have to recognize that the advances in medicine are double-edged swords, and honesty requires that we acknowledge that infections will continue to occur despite our best efforts.

So kudos to APIC for moving on, and to CDC for the great work it does with not nearly enough resources. 

Graphic: Jeffrey Sumber

Friday, April 20, 2012

Did "Getting to Zero" contribute to the death of Facts?

The Chicago Tribune just published an obituary for "Facts, 360 B.C.-A.D. 2012", stating that it finally succumbed after years of fighting against the 24-7 cable news cycle and the internet. Apparently, the final straw was when "Florida Republican Rep. Allen West steadfastly declared that as many as 81 of his fellow members of the U.S. House of Representatives are communists."  I can see how that could do it; even enterococcal bacteremia can kill you if you're already close to dead (i.e. APACHE II score ~70). After first checking to make sure I wasn't reading the Onion or QFever, I realized that Facts probably did die, as I think it died in infection prevention several years ago.

We've written often about the problems with the "Getting to Zero" campaign or mindset. In one of this blog's very first posts, Mike wrote about how the false premise of Zero leads to a culture of blame. Dan has written about how APIC's "I Believe in Zero CLABSIs" campaign shows that it's "unwilling or unable to speak honestly about HAIs" and that "they will eventually lose credibility with their members who fight daily to prevent them."  There are other examples of post-factual truthiness in HAI prevention, including the claim that the only way to prevent MRSA is through a nasal PCR swab.

In closing, it's a sad day when an idea dating back to Aristotle has officially died.  At least those of us working in HAI prevention can take comfort in the idea that we've done our part through paving the way to a post-Factual "Getting to Zero" world.

Addendum: Rex Huppke, the author of the Tribune obit, speaks about how and why he wrote "one of the best op-ed pieces ever."

the American Journalism Review's excellent take on the obit, can be found here.

Thursday, April 19, 2012

Manuscript Provenance: Why NEJM has a high retraction rate (and it's not a reason mentioned in the NYT)

A recent high-profile story in the NYT by Carl Zimmer discussed a surge in article retractions since 2000. Over the period 2000 to 2009, retractions have risen by 3300%. (see calcs below) The Time's article draws much of its data and discussion from a pair of editorials published by Ferric Fang and Arturo Casadevall covering "structural reforms" and "methodological and cultural reforms" and a recent news feature in Nature. I highly recommend the two calls for reform from Fang and Casadevall, which cover topics ranging from increased administrative burden to problems with grant review. However, it is hard to make a link from any of these problems and scientific error or misconduct without further research.

For example, much of the discussion falls into the category of "survival of the fittest" with scientists doing everything possible to publish in high-profile journals (e.g. NEJM), which then is supposed to lead to increased grant funding and wealth.  I'm not denying that this could be a factor in scientific fraud, but it's hard to imagine this would increase errors, directly. If you look at the NYT graphic (above), fraud is associated with a minority of all retractions. To provide evidence that a scientists desire for fame is driving the retraction epidemic, Fang and Casadevall, published another editorial that included an analysis linking impact factor of the journal to a retraction index. They found that the higher the impact factor, the higher rate of retraction with NEJM at the top.

Reasons given for the association include higher risk-taking by authors in papers submitted to high-ranking journals and that publications in high-impact journals may just be subject to greater scrutiny (e.g. via social media). These reasons are appealing, although I'm not sure there's a testable hypothesis among them. One testable "systemic aspect of the scientific publication process" that is likely to be associated with both journal rank and retraction (and more likely to be causal) is a manuscript's provenance.

Manuscript Provenance
In the art world, a painting's provenance refers to the chronology of ownership of a specific painting or work.  When I speak of a manuscript's provenance, I mean where it's been submitted and received peer review prior to publication.  As anyone who has submitted a manuscript knows, you almost always submit the paper to a higher-impact journal first and then if not reviewed or accepted, you aim a bit lower.  In fact, there is only one paper we've submitted out of >100, that's gone initially to a lower-ranked journal and then when rejected, was submitted and accepted by a higher-ranked journal.

Thus, manuscripts submitted and accepted at higher-ranked journals are more likely to have been reviewed only once, or received one round of peer review. Yes, I know that some papers go to JAMA then NEJM and some papers are submitted directly to a specialty journal and are reviewed once, but in general, papers published in higher-ranked journals have been through fewer rounds of peer review.  Unfortunately, these data are not easily available, but it's likely this hypothesis can be tested. Nevertheless, I think quantity of peer review is an important predictor of quality of the final product.  It is unlikely that more peer review could detect outright fraud, but most retractions aren't fraud related.

So before we blame the entire system for a few bad apples, there need to be more epidemiological studies as to why this is occurring.  My first suggestion is that we should consider manuscript provenance as a factor and my second suggestion is that journals should pay for peer review, so that it becomes a valued exercise.  Peer review service should also be considered for promotion. Sure the system could be improved in many ways, but it's a stretch from there to finding a causal pathway between a journal's impact factor and a higher retraction index. Oh, and this is all probably because of twitter anyway.

***Retraction Rate Calculation: Using rates of 3/year in 2000 to 180/year in 2009 from the NYT article and given that there's been a 64% increase in PubMed articles  (529,000 in 2000 to 866,000 articles in 2010), this represents an increase from 0.0006% to 0.02%, or a 3300% increase.

Tuesday, April 17, 2012

The Year in Infection Control: Almost Live from ECCMID 2012

Jan Kluytmans and Maria Luisa Moro were kind enough to share their presentation from ECCMID in London earlier this month.  What a great review - wish I was there. Enjoy! The Year in Infection Control

Monday, April 16, 2012

Loophole Found in FDA Antibiotic Restriction Rule

Last week, Dan posted on the new FDA rule requiring prescriptions for antibiotics in farm animals. This rule is potentially significant since 80% of antibiotics in the US are used in animals, as mentioned in the referenced NYT article. Now an astute reading by Tom Philpott at Mother Jones picks out a potential loophole in the new FDA rule. 

Here is the quote from the NYT's article as I read it: "Michael Taylor, the F.D.A.’s deputy commissioner for food, predicted that the new restrictions would save lives because farmers would have to convince a veterinarian that their animals were either sick or at risk of getting a specific illness."


Here is the quote as Tom Philpott read it: "Michael Taylor, the F.D.A.’s deputy commissioner for food, predicted that the new restrictions would save lives because farmers would have to convince a veterinarian that their animals were either sick or at risk of getting a specific illness."

That does seem like a pretty big loophole.  If pediatricians used the "at risk" determination for prescribing antibiotics, I think my kids would have been on them 24-7. You can read his full interpretation over at Mother Jones. As Dan mentioned last week, only time will tell. Since Mike Taylor said "we’re confident that it will result in significant reductions in agricultural antibiotic use," we probably should wait a bit before all becoming vegetarians.

Wednesday, April 11, 2012

Good news, bad news, on the use of antibiotics in livestock

First the good news: the FDA is now requiring prescriptions for antibiotics used in livestock. Time will tell if this has any impact on the sheer tonnage of antimicrobials used in agriculture.

As for the bad news, I’m not confident that I can do justice to this publication about “feather meal” as an avenue for antibiotic re-entry into our food supply. Here is an excerpt from the abstract:

...Following poultry slaughter, feathers are converted by rendering into feather meal and sold as fertilizer and animal feed, thereby providing a potential pathway for reentry of drugs into the human food supply. We analyzed feather meal (n = 12 samples) for 59 pharmaceuticals and personal care products (PPCPs) using EPA method 1694 employing liquid chromatography tandem mass spectrometry (LC/MS/MS). All samples tested positive and six classes of antimicrobials were detected, with a range of two to ten antimicrobials per sample. Caffeine and acetaminophen were detected in 10 of 12 samples. A number of PPCPs were determined to be heat labile during laboratory simulation of the rendering process. Growth of wild-type E. coli in MacConkey agar was inhibited by sterilized feather meal (p = 0.01) and by the antimicrobial enrofloxacin (p < 0.0001) at levels found in feather meal. Growth of a drug-resistant E. coli strain was not inhibited by sterilized feather meal or enrofloxacin. This is the first study to detect antimicrobial residues in feather meal.
Two to ten antimicrobials per sample! Concentrations high enough to inhibit growth of wild-type E. coli! I’m going to outsource my outrage to Tara Smith, who has an excellent post on this.

Tuesday, April 10, 2012

JAMA's Hand Hygiene Ditty

Not sure how I missed Adam Posner's hand hygiene poem, but I did.  Truly sorry.  To make it up to you, I've pasted the poem below. We all have crosses to bear, although I'm not sure hand hygiene rises to that level. Of course, I am not JAMA nor am I Adam Posner. Truth.

Ode to Dry Hands

It always happens in the winter
    with constant washing my hands splinter.
Even if I use gel and lotion
    skin becomes sandpaper in motion.
Fissures open, the knuckles turn red
    a few times my hands even have bled.
How it stings me—such irritation!
    The stigmata of sanitation!
Yet, I still say as the water pours
    “Let me clean my hands, then I’ll shake yours.”
It is a soapy cross that I bear
    an important way to show I care.
For as a doctor I know this much
    first do no harm starts with the first touch.

h/t Mark Vander Weg

Saturday, April 7, 2012

Chlorhexidine: Just can't get enough!

There's a new paper in the American Journal of Medicine by Marisa Montecalvo's group on chlorhexidine bathing in ICUs. In this quasi-experimental study, 6 ICUs in 5 hospitals implemented daily bathing of adult ICU patients with chlorhexidine. The outcome of interest was central line associated bloodstream infections. Compared to the pre-intervention period, there was a nearly 60% reduction in CLABSIs. So here's another study that supports the utility of chlorhexidine bathing to reduce healthcare associated infections.

At my hospital, we like it so much that in addition to bathing ICU patients with chlorhexidine, we are now bathing ward patients who have devices with it, and we're expanding chlorhexidine pre-operative bathing to more types of surgical procedures.

Thursday, April 5, 2012

Revisiting the VA MRSA Initiative

Most of our readers know about the VA MRSA Initiative, the results of which were published in the NEJM at the same time as the STAR*ICU study results. These two studies were widely and mistakenly viewed as having contradictory results.

The tremendous success of the VA initiative (see here for my earlier summary of the results) was also mistakenly assumed to be primarily related to the most expensive aspect of the “bundled” initiative, universal active detection and isolation (ADI). This was despite the fact that transmission fell only by 17-21% while infection rates fell by over 60% in ICUs, and infection rates due to non-targeted bugs (VRE and C. difficile) were reduced even more dramatically than was MRSA. In other words, there was plenty in the original paper to suggest that ADI accounted for very little of the observed MRSA infection reduction, and that the bulk of that reduction was due instead to prevention of MRSA infection among those already colonized.

Well, we now have a mathematical model, by Gurieva, Bootsma and Bonten, that demonstrates this point quite clearly. I refer you to their paper and to my colleague Eli’s excellent commentary for details, but the bottom line: transmission prevention was likely responsible for no more than 6% of the reduction in MRSA infection rate. As you’d expect, the proportion of infection reduction due to transmission prevention is strongly correlated to the relative risk for MRSA infection among the newly colonized (via transmission) versus existing MRSA carriers. But as the figure below (from Gurieva paper) shows, even if one assumes a 10-fold higher daily risk for MRSA infection among newly colonized versus existing colonized, transmission prevention would still account for less than a quarter of the observed infection reduction

Wednesday, April 4, 2012

Why is the public health community losing to Jenny McCarthy?

There is word of a huge pertussis epidemic in the state of Washington. So far this year, there have been 640 reported cases through March compared to 94 cases during the same period in 2011. If my math is correct, that's a 649% increase, which is quite possibly more than even Apple's stock increased over the same period.* Per a report in the Seattle Times, if the trend continues, this would equal an outbreak not seen since the 1940's! The article also contains a telling anecdote describing a mother who passed pertussis to her one-month old infant, who turned blue and had to spend a week in the ICU and a month in the hospital.

This outbreak isn't limited to Washington. In 2010, whooping cough killed 10 infants and infected over 9,000 in California, which was the state's worst outbreak in 60 years.

Why is this happening?  I won't go into all of the reasons, as we've had plenty of posts on the topic over the years. I'll just refer you to Red Sox fan and PLoS co-founder Michael Eisen's tweet from yesterday. In an earlier tweet he mentioned that 34% of the parents in his daughter's school don't fully vaccinate their kids.  I agree that this is all Jenny McCarthy's fault and anyone who listens to her or gives her a voice.  It is clear that after years of neglect, the public health community is so weak that it can't even compete with Jenny 'Effin' McCarthy.

*By law, nothing is allowed a larger percent increase than Apple's stock.

Sunday, April 1, 2012

Reducing barriers to fecal microbiota transplant (FMT)

It is now conventional wisdom that FMT (a.k.a. “stool transplant”, “transfaunation”) is effective treatment for recurrent C. difficile disease. So why aren’t more being done? Many centers, including ours, have stumbled upon two barriers: the ick factor, and the logistics of patient-identified donor selection and screening. Not everyone can identify a willing donor, and there is no easy way to pay for the expensive set of screening lab tests performed on the donor.
So these two reports, which describe moving from patient-identified to universal volunteer donors, are welcome. One of the reports, out of the University of Minnesota, also examines the use of frozen, banked fecal material. In the absence of progress in replicating the fecal microbiome in culture, I think this is the best way to make FMT more universally available.
Don’t worry, I don’t think we’ll be staging “stool drives” in the future, like we do blood drives now. A single universal donor could provide all the stool required by a single center to treat multiple patients with C. difficile, and could be called back whenever the bank was running low (“Honey, it’s the clinic calling, they need more of your sh**”).
If you don’t have subscription access to the articles above, here is a short summary from the IDSA newsletter.

Image from