Move over London, here comes Flint

Epidemiologists are drawn to London for its role in the etiological tale or origins of their field. It's hard to discount the importance of John Snow's investigation of the Broad Street cholera outbreak of 1854 and its role in advancing public health. Even when looking at the simple case-control study, many are first taught about the methodology using Doll and Hill's famous 1947 study linking smoking and lung cancer, which was completed in London hospitals.

Digging even deeper, we see that the initial case-control study was thought to be Janet Lane-Claypon's report comparing 500 women with and 500 women without breast cancer admitted to London and Glasgow hospitals published in 1926. However, as in many historical investigations, claims of "firsts" in epidemiology are often overturned upon further review. And while London will always have a special place in epidemiologists' hearts, it turns out that another city needs to be recognized; a city we often ignore...

For those of you not familiar with US or automotive history, Flint Michigan is best known as the birthplace of General Motors and like many industrial midwest towns, it has fallen on hard times. Beside GM, it is also the birthplace of Sandra Bernhard, Bob Eubanks, Michael Moore, Grand Funk Railroad, Glen Rice and, apparently, the Case-Control Study.

In a paper published in the December issue of the American Journal of Epidemiology, Alfredo Morabia uncovered an old case-control study by George Ramsey buried in a 1925 issue of the American Journal of Hygiene. In July 1924, there were 41 cases of Scarlet Fever; a high rate in the summer. A dairy inspector soon learned of an employee at an ice cream plant who had continued to work even after he developed a sore throat and rash (presenteeism!!). However, an investigation of the case patients with scarlet fever did not identify a specific risk factor, including ingestion of ice cream from a single dairy. Then the investigation was "supplemented" by histories taken from 117 controls, who did not have scarlet fever. The questioning revealed very few differences between cases and controls except that cases with scarlet fever were much more like to frequently eat ice cream (60%) compared to controls without scarlet fever (24%). When the investigators looked specifically where cases bought their ice cream, they identified a specific factory as the culprit (see Figure below).  It turned out that Factory A was where the sick worker had worked! Further testing revealed hemolytic streptococcus in ice cream samples from Factory A.

The Discussion section of this recent paper points out that most of the advancements in epidemiological methods occurred in cancer and heart disease. Apparently, there was not another case-control study used in infectious disease epidemiology until 1940. What is amazing is that it appears the Dr. Ramsey and the Michigan Department of Health hit upon the case-control design all by themselves. The paper concludes: "Flint, Michigan, the cradle of General Motors and of recognized labor unions in the United States, appears to have also been a birthplace of case-control studies."  Merry Christmas Flint - hold your heads up high!

image source: missourireview.com

Administrative data for HAI surveillance: fuhgeddaboudit!

There's a new paper in Clinical Infectious Diseases by Eli and company that is the definitive treatise on the use of administrative claims data for healthcare associated infection surveillance. I have never been a fan of using coded data for this purpose for two reasons: (1) it shifts the important work of surveillance from trained infection preventionists to medical records abstractors who are not trained in surveillance methodology and who are limited by their ability to only review notes written by physicians; and (2) while it's a quick, cheap and dirty method, as Eli's group proves, it's wildly inaccurate. The poor performance of coded data should really be not too surprising since these codes were developed for billing purposes not epidemiologic surveillance.

The authors performed a systematic review of the literature and found 19 papers for analysis. In each paper coded data was compared to either microbiologic data (C. difficile and MRSA) or manual chart review using standardized case definitions (SSI, VAP, CAUTI, CLABSI). Meta-analysis was performed when enough studies were available. Results are summarized in the table below.

As can be seen in the table, specificity of coded data is generally good to excellent, while sensitivity ranges from bad to horrible. I should mention there is a brand new study looking at CLABSI in the American Journal of Medical Quality, which found a sensitivity of 33% and specificity of 99%.

Perhaps the forthcoming ICD-10 will help, but the fundamental issue of only reviewing physician notes will remain. More sophisticated methods utilizing computerized algorithms for analyzing electronic medical records for case detection will probably be the ultimate solution.

JAMA Infectious Diseases Theme Issue: Deadline April 15, 2014

Just in time for the holidays, Santa has left a gift for ID folks under the tree. I'm not talking about the recent action by FDA to ask the livestock industry to stop using antibiotics for growth promotion, nor am I talking about the FDA's proposed rule to "require manufacturers to provide more substantial data to demonstrate the safety and effectiveness of antibacterial soaps (that contain triclosan or triclocarban)."  While I'm very excited about those developments, I'm pretty sure Santa doesn't work at the FDA.

What I am attempting to highlight is JAMA's ID theme issue planned for October 2014. I offer a few select quotes from the call for papers written by Preeti Malani and Michael Berkwits:

"Ironically, while advances in public health have been driven historically by management of infections, the body of evidence that guides contemporary practice in infectious diseases remains relatively limited."

"Clinical trials rarely can fill a journal issue, and important clinical questions far exceed the number of trials that can be planned, so we invite authors to submit research with other designs and approaches."

"Studies that present new information relevant to optimizing treatment strategies and prevention efforts, and those that enhance the understanding of quality-of-life and economic consequences of infection are also of interest."

Let's hope this theme issue has some new science in the fields of infection prevention, antibacterial resistance and stewardship. Deadline April 15th!

Congratulations, Mike!

Our Health Richmond magazine unveiled their inaugural “Best Bedside Manner” awards this month, and we are not surprised that Mike won first place in the Infectious Diseases category! Mike may or may not wish to comment on whether this recognition will be factored into his compensation plan. Most academic clinician compensation plans reward procedures and inpatient care, and punish ambulatory care providers who spend any sane amount of time with their patients. Let’s hope that whatever healthcare system we eventually settle upon will help restore some balance.

Congrats, Mike!  Every clinician should read (and live by) the quote that accompanies your award announcement.

2013 Studies in Memoriam - A Tribute to Studies Almost Lost

Each year the Academy Awards honors those actors and directors who've died in the prior year. It's one of my favorite tributes. Recently, I found myself with a stack of unread journals about four feet high and one of my routines is to clean my office before the start of each year. Thus, I am catching up on what studies I missed or failed to mention when they were first published. This post is a tribute to those studies that have "almost" died in my journal pile...happy holiday reading...

1) I'm particularly embarrassed that we haven't yet mentioned this review written by Dan. He and Michael Pfaller published a review in the June 1 CID on the promise of rapid microbiological detection of MDRO for infection prevention. Sections cover MRSA, VRE and MDR-GNR. What I really like about this review is that it covers the barriers to successful implementation of rapid detection including the "post-analytic" turn-around time and the current dearth of data supporting the clinical utility for many of these approaches. A must read. (NOTE: Currently the CID website is down, I will update with a direct link to the paper once they are back online)

2) Bevin Cohen from Elaine Larson's group at Columbia published a retrospective cohort study in JGIM investigating gender differences in BSI and SSI risk.  The study included three years (2006-2008) of data from a single center. Odds of these HAI were between 15 to 22% lower in women.

3) John Hollingsworth. Sanjay Saint and colleagues from the University of Michigan published a systematic review and meta-analysis of non-infectious complications of indwelling urethral catheters in Annals this past fall. After identifying and reviewing 37 studies they found that minor complications were quite common. For example, urinary leakage ranged from 10.6% in short-term catheterized patients to 52% in those with long-term catheterization. Serious complications were also quite common. If CAUTI isn't reason enough to remove a urinary catheter, these non-infectious complications should be!

4) And to follow up on the urinary catheter removal theme, there was a meta-analysis published in BMJ that quantified the benefits of antibiotic prophylaxis after urinary catheter removal. When analyzing seven controlled studies (5 from surgical patients), they found antibiotic prophylaxis was associated with an absolute risk reduction of 5.8% for UTI and a risk ratio of 0.45. I suspect there are trade-offs in increased antimicrobial resistance that should be assessed before this is more widely adopted.

Credit: James Taylor at the 2010 Academy Awards - one of my favorite tunes

Does the white coat make the doctor?

There's a new piece in The Atlantic entitled The Psychology of Lululemon (free full text here). I probably would not have read that article but for the fact that I was in Lululemon just a few days ago buying my wife some yoga clothes for Christmas. This turned out to be an interesting read. The premise of the piece is that athletic clothing makes people want to work out--that in some way, clothes have power over the wearer. Of course, I began to think about the implications of the white coat for doctors, particularly because I remembered a survey we did a few years ago where some physicians mentioned that wearing a white coat made them feel more confident. I must admit that at the time I thought that was fairly absurd.

The Atlantic article cites a study from the Journal of Experimental Social Psychology, which I reviewed. Turns out, Eli blogged on this paper last year, so I won't belabor all the details. In a nutshell, investigators at Northwestern University set up a series of experiments in which subjects performed cognitive tasks that measured selective or sustained attention. In one trial some subjects wore white coats and some didn't; interestingly, those who did performed better by a factor of two. In another experiment, all the subjects wore white coats but some were told they were wearing a doctor's coat, while others were told they were wearing a painter's coat. The doctor's coat group scored significantly better. The results led the investigators to coin the term enclothed cognition, which they defined as the systematic influence that clothes have on the wearer's psychological processes.

Rehashing this paper made me stop and wonder whether after being white-coat free for the past five years I should put that dirty old thing back on. It is true that I know some very smart physicians who are never to be seen without their white coats. On the other hand, I also know some white-coated doctors, probably just as many, that I hope to never meet on the other end of a stethoscope. Maybe I'm just too grounded in reality. As much as I wish that if I ensconced myself in Under Armour my athletic abilities would surge, there's not enough magical thinking on earth to tear me from the bitter reality that my skinny, scrawny body would not perform any differently.

While I'll have to bow to science and come to grips with the concept of enclothed cognition, I still believe that keeping patients from contact with contaminated coat sleeves trumps whatever small intellectual edge the white coat might provide. As the psychologists have shown, it's all in your head. So here's my recommendation: as you enter your next patient's room, bare below the elbows in your freshly laundered scrubs, stop for a split second and imagine yourself sporting a shiny white coat in all of its radiant splendor with a Superman logo blazing above the chest pocket. Then strut confidently into that room, and bedazzle the patient with your diagnostic brilliance.  

Great news for patients with C. difficile

At this point in time, I've performed about 50 fecal transplants. I find these procedures to be both a blessing and a curse. They are amazingly effective for patients with recurrent C. difficile. Many of my patients have had chronic diarrhea for months, and are unable to leave their homes. So imagine how incredible it is for them to be cured within 24 hours of a fecal transplant. I have heard over and over, "you have given me back my life." And I have to admit it's a blessing for me, too. Rarely in medicine do we see such rapid and dramatic cures. What's not to like about this? How could it be a curse?

Well, as we have blogged before, the logistics of fecal transplantation are difficult and there are a number of barriers. While most patients don't have difficulty finding a donor (usually a family member), some elderly patients don't have a donor. Cost is also a barrier. Donor testing is not covered by insurance, so the out-of-pocket cost is up to $1500. For poor patients, this is quite a problem, and I've had patients whose family members all chipped in to pay for donor testing. Then the donor has to "perform" at a specified date and time (and sometimes they can't).

The transplant I did yesterday was fairly typical. I went to the clinic to pick up the donor specimen and ran it to the lab (10-15 minute round trip), where our laboratory technician began the dirty work of homogenizing the stool sample in a blender and filtering it. While she was doing that, I ran back to the clinic, got the informed consent, inserted the NG tube and sent the patient to X-ray for confirmation of tube placement. The queue in x-ray can be up to 45 minutes. While the patient was in X-ray, I ran back to the lab, picked up the prepared specimen and returned to clinic. When the patient returned, I injected the NG tube with the fecal slurry, flushed the tube with some water, then removed the tube. On most days, all of this takes 2-3 hours of my time. If insurance pays us, we collect less than $75. During the same time period, my colleagues will generate charges that are roughly 6-9 fold higher than mine. Since most of us now work in an RVU-based compensation model, it should be apparent why so few physicians do this work. But I can't not do it, even though it reduces my salary. I feel morally compelled to help these patients who are so desperate, particularly when I know that the odds are very high that I can cure them with a simple procedure.

Yesterday I stumbled on OpenBiome's website and as I explored it I was nearly euphoric. OpenBiome is a non-profit started by four students (a molecular biology PhD candidate, an MBA candidate, an MPA candidate, and an MD/MBA candidate) at Harvard, MIT and Princeton. The company provides processed, frozen human stool from donors that have been carefully selected and screened for multiple infectious diseases at least twice, at a cost that's 1/6 the price of me testing one donor, and 5 to 14-fold cheaper than the drugs that these patients have taken without success. And OpenBiome's goal is to reduce the price even more as they scale up their operation. I had a long conversation today with James Burgess from OpenBiome. He knew so much about C. diff that I assumed he was the medical student, but he's actually the MBA student. He was excited to tell me about their work and I was incredibly impressed. They have covered all the bases, including banking serum from donors for future testing should a patient develop an unusual infection.

So Kudos to OpenBiome! Many patients will benefit from their ingenuity and generosity. And they'll make my job a whole lot easier.

Resistance versus Virulence

The conventional wisdom is that bacteria pay a “fitness cost” as they accumulate antibiotic resistances, a phenomenon I discussed in a short post last year. More resistant, but less fit, and (one hopes) less virulent. Thus some of the most problematic multi-drug resistant organisms (MDROs), such as Acinetobacter, cause disease almost exclusively in the most vulnerable patients—those bugs simply aren’t virulent enough to wreak their havoc in the healthy. When an MDRO does emerge as a major community scourge, as was the case with community-associated MRSA, it’s big news.

So I was surprised (not pleasantly) to read this report in PNAS about Pseudomonas aeruginosa strains that refused to adhere to convention. Using a mouse model and well-characterized P. aeruginosa mutants, the investigators found that strains with mutations in a gene encoding a particular outer membrane protein (one that provides an entry channel for carbapenem antibiotics) were more virulent—more likely to disseminate from the mouse GI tract, and more resistant to in vitro killing by acidic conditions or human serum. Now mice are not men, and a murine gut colonization model isn’t necessarily predictive of an organism’s ability to cause infection at various human body sites. Still, it is nerve-wracking to know that our carbapenem use might produce P. aeruginosa strains that are not only more resistant, but also more virulent! As the title of the accompanying editorial points out, it is indeed a “worst case scenario”.

Scanning EM of P. aeruginosa from the Public Health Image Library

A Urinary Catheter's Perspective

Martin Kiernan, Infection Prevention Consultant at Southport and Ormskirk NHS Trust in the North-West of England, penned the Catheter's Lament while on the train to the IPS conference this year. It was the last slide of his EM Cottrell Lecture, "The Life and Times of the Urinary Catheter." Graphics courtesy of Clinidirect. Thanks to both for sharing.

A specialty in decline?

It was “match day” today for the internal medicine subspecialties. For some fields, there are far more applicants than training positions. Thus hundreds of would-be gastroenterologists and cardiologists find themselves out in the cold, unable to pursue their chosen profession. Not so for infectious diseases (ID). This year marks a new record for unfilled ID programs (54), with many training programs unable to fill a single training spot in the match. Given current trends, we are approaching a situation in which half of all programs will have unfilled positions. As funds for graduate medical education become increasingly scarce, some of these programs will likely reduce the number of training positions they offer, or shut down altogether. 

There are several explanations for this trend, including reimbursement of ID specialists (train longer to make less!), the educational debt burden of trainees, the rise of the hospitalist, and reductions in research funding for academic careers. I have no easy answers, but it is urgent that we address this slow motion train wreck. Multiple drug resistant bacteria already far outnumber the contingent of ID doctors, and that situation is bound to get worse over the next several decades. Some things to work on: (1) perform studies to demonstrate the value provided by the ID specialist, (2) advocate for increased funding for ID research and training, and (3) provide role models who demonstrate that ID is an incredibly interesting and rewarding career!

Word of the day: crapsule

There's a great article in The Atlantic on fecal transplants for C. difficile infection (free full text here). What I like about this piece is that it describes the very real barriers to fecal transplantation without any sugar coating. It also highlights the work of Dr. Bruce Hirsch, an infectious disease doctor who crafts capsules with fecal bacteria (or "crapsules" as he calls them) so that patients can be transplanted without an NG tube or colonoscopy.

Photo:  Salon.com

The beginning of the end for...CHG??

Chlorhexidine. We love it, we just can't get enough of it, we are up to our neck in it and we cheer for it. Basically it's the greatest. But some of us have been concerned that the widespread use of CHG would lead to resistance, particularly in Acinetobacter.

There is a new report in PNAS by investigators in Australia and the UK that looked at gene expression in A. baumannii after chlorhexidine exposure. The most highly up-regulated genes were those encoding the RND efflux system AdeAB. Importantly, the investigators also identified a gene encoding a previously uncharacterized membrane protein, AceI, which they determined to be an active CHG efflux protein capable of transporting CHG out of the cell. This novel AceI was said to be a member of the PCE family of efflux systems.

And to give you a sense of the ubiquity and potential importance of these systems in Gram-negative bacteria, I offer this quote from the authors:

"The primary features of the A. baumannii chlorhexidine resistance response, i.e., up-regulation of genes encoding RND and PCE family efflux systems, are conserved in other γ-proteobacteria, as well as β-proteobacteria. Given the phylogenetic distance of these organisms, this similarity of regulatory responses to a compound that has only been synthesized since the early 20th century is intriguing. RND efflux systems are well recognized for their broad protective functions in Gram-negative bacteria and it is not unusual for these systems to constitute part of a general stress response and to mediate resistance to foreign compounds, particularly amphipathic antimicrobials such as chlorhexidine. However, the involvement of the PCE family proteins in seemingly specific resistance to chlorhexidine is unexpected. It is likely that the physiological function(s) of this transporter family were originally unrelated to chlorhexidine resistance and that these proteins provide a fortuitous intrinsic resistance capacity."

h/t Ayush Kumar and Dan Ricciuto

image source: wikipedia

Six dangerous words

There's an interesting essay in JAMA this week entitled EBM's Six Dangerous Words. In it, Scott Braithwaite argues that physicians should banish the phrase "there is no evidence to suggest that..." He gives as an example: there is no evidence to suggest that looking both ways before crossing a street compared to not looking both ways reduces pedestrian fatalities. While that's technically true, as he puts it, such statements presume "a definition of evidence that requires formal hypothesis testing in an adequately powered study." It makes objective certainty the be-all and end-all, and "is ambiguous while seeming precise." I have heard hospital epidemiologists state that there is no evidence to suggest that white coats can transmit infections in the healthcare setting. Ok, but sometimes the common sense of the average Joe trumps the best the medical literature has to offer. Or so it should...

More on CLABSI validation

A new study in the American Journal of Infection Control looks at validation of publicly reported CLABSI (central line associated bloodstream infection) data in New York. To my knowledge, New York has done the most work on validation, so it's worth taking a look at this paper. The authors analyzed CLABSI data from 2007 through 2010. By year, the sensitivity of reported data varied from 68% to 74%, and for the entire time period was 71%. Of concern, there appeared to be no improvement over time, and for 2010 sensitivity for medical ICUs was only 46%. Specificity ranged from 90 to 99%. So, about 30% of CLABSIs are not reported in a state that has focused on validity. It makes you wonder how bad validity may be in states that have done little work on this. It's interesting that consumer advocacy groups don't seem to be too concerned about the validity issue, and to some degree neither do payers. A consumer advocate once told me, "Just give us all the data. We don't care if it's correct." Caveat emptor!

Graphic: WhyWeSuffer.com

Now here's something to be thankful for...

Personalize funny videos and birthday eCards at JibJab!

Vaccines! This week's New England Journal of Medicine has a study from the University of Pittsburgh that analyzed 125 years of weekly surveillance reports for infectious diseases, and today's New York Times has an article about the study. By analyzing time periods before and after introduction of vaccines, the investigators were able to estimate that in the last decade 99% of cases of childhood diseases have been prevented. Quick, someone please call Jenny McCarthy!

Turkey Links

We at the Ye Olde Humble Controversies Blog (YOHCB) wish you a safe and happy Thanksgiving. We have lots to be thankful for including the many tireless state and federal partners in infection prevention, fantastic infection preventionists, colleagues across many clinical disciplines and our readership. Thank you!

While you are out and about or gathered around a turkey or television, you might want to browse these studies/posts which we haven't covered yet. Just promise that you won't read any while driving, OK?

Links:

1) Stephan Harbarth's group has published in BMJ Open a surgical patient sub-study under MOSAR comparing the impact of (1) enhanced hand hygiene promotion (2) universal MRSA screening and decolonization  or (3) risk-factor based, targeted MRSA screening and enhanced hand hygiene in 10 hospitals encompassing 33 surgical wards. This quasi-experimental study found that neither intervention alone reduced monthly MRSA clinical culture rates. However, the combined intervention (3) was associated with a 12% reduction in monthly clinical cultures.

2) The CDDEP Blog has a new post by Stan Deresinksi covering Antibiotic Stewardship Programs and Education. Stanford's antimicrobial stewardship program has just posted an online course covering appropriate antimicrobial use.

3) Think Like an Anthropologist (HBR). Even though this is a business-oriented article, I think its points are generalizable to health-related administrative data. Key portion of the article: "efforts are typically driven by econometricians, computer scientists, and IT technicians—the people who are expert in database management. They understand digital information, but they don’t always understand how to get from information to meaning. So they boil the data down to percentages, treating random comments (and pictures of people with foil on their legs) as noise. But if you want meaning, you have to think like an anthropologist."

4) Marin Schweizer and colleagues from CDDEP recently published an study in ARIC looking at whether clinicians prescribed antibiotics based on national MRSA or local MRSA data. Clinicians appeared to prescribe linezolid and clindamycin based on national MRSA data but not local data suggesting that providing better local antibiogram data might help with outpatient antimicrobial stewardship efforts.

5) There's a really nice paper in Pediatrics that explores the importance of clustering of unvaccinated patients in the recent California pertussis epidemic. It appears that non-medical exemptions may be contributing significantly to the spread of pertussis. h/t Melissa W

6) There's a new study in PLoS Medicine that recalculated the mortality associated with pandemic 2009 H1N1. This study found mortality to be ten times prior low estimates but in line with a typical influenza season. NPR covered the study. h/t Jonathan Eisen

7) The physician at the center of a Las Vegas clinic Hepatitis C outbreak received a life sentence. h/t Daniel Sexton

8) Finally, we have nothing to worry about. The dragonfly's nano-tech black silicon will eliminate those nasty bacteria. It'll even kill spores.  h/t Judy Stone

Turkey: Best recipe (h/t MO Wright)

Photo Credit: Bob Evans

CRE decolonization: Can we? Should we?

There's a new paper in American Journal of Infection Control which poses an interesting question: can CRE (carbapenem-resistant Enterobacteriaceae) be eradicated from the gut? Given the increasing problems with these organisms, decolonization could play an important role in their control.

This study was performed at a large tertiary care hospital in Israel where active surveillance is performed on admission and weekly in targeted populations. Unfortunately the design of the study makes it difficult to interpret. There were 4 study arms: treatment with oral gentamicin, treatment with oral colistin, treatment with oral gentamicin + oral colistin, or no treatment. In part, the susceptibility of the colonizing strain dictated the study arm (e.g., patients with a colistin-resistant, gentamicin-susceptible strain were treated with gentamicin, unless they did not consent to treatment, in which case they were assigned to the control group). If the patient's isolate was susceptible to both drugs, they were randomized to either drug or to combination therapy. Treatment was given for 60 days or until eradication (defined as 3 consecutive negative rectal cultures with PCR performed on the 3rd negative sample), whichever came first. In the end, 26 patients received gentamicin alone, 16 colistin alone, 8 received both, and 102 were untreated. Eradication occurred in 42% for gentamicin, 50% for colistin and 37% for combined treatment. Only 7% of the untreated patients spontaneously decolonized.

What conclusions can we draw?

1. Spontaneous decolonization is a rare event.
2. It appears that some patients (one-half or less) can potentially be decolonized or at least suppressed while on treatment. Of note, 2 patients in the gentamicin arm, 4 in the colistin arm, and 2 in the combo arm relapsed. It would be interesting to know whether patients who had CRE eradicated remained culture negative for the long-term (e.g., 3 months or 6 months after treatment). 
3. Given that colistin remains one of the most important drugs for treatment of these infections, it worries me that widespread use of this drug for decolonization could result in resistance. Indeed, colistin resistance was reported in 1 of 16 treated patients, and 6 of 26 patients in the gentamicin arm developed gentamicin resistance.

In the end, how do we use the data from this study? I suppose if I practiced in a hospital with high rates of CRE colonization, I would be tempted to try decolonization for very high risk patients (e.g., neutropenic leukemic patients). I would favor use of gentamicin if the isolate were susceptible. But it would make me very nervous.

Photo: Klebsiella pneumoniae, CDC

One way of Getting to Zero

Favorite quote: "I can disagree with gravity but it doesn't mean that it no longer applies to me."

 

Wipe it down!

There's a short paper in American Journal of Infection Control that looks at stethoscope contamination. The authors cultured 112 stethoscopes; 48 (43%) were found to have pathogens on the diaphragms. Of the 50 pathogens isolated, 3 were gram-negative rods, 4 were E. faecalis, and 43 were S. aureus. Of the S. aureus isolates, 18 were MRSA. Despite the fact that stethoscope contamination is common, I see little effort in the infection prevention community to address this. So here's another reminder to wipe down that stethoscope!

Photo: KREM.com

Re-designing rooms and re-engineering care to reduce infections

There's an article in the Wall Street Journal on the hospital room of the future. It notes elements of architectural and product design that can reduce the transmission of infection. Take a look at the graphic above. You'll note, for example, that on entering the patient room the sink lights up in red to remind healthcare workers to wash their hands. There are a number of other examples of using design to reduce infection in the graphic. One not specifically designed for infection prevention that may still be useful in preventing infection is the large video monitor on the footwall of the room. Let's say I'm a consultant and I have influenza. I could still interact with the patient without being physically present, not feel guilty about staying home, and not risk transmitting influenza to the patient. Obviously I could not perform all the elements of a physical exam, but not all follow-up visits require an exam, though I have heard rumors that some doctors perform perfunctory exams for billing purposes only. Moreover, does every consultant and medical student need to exam the patient every day? Think of how many contaminated stethoscopes and dirty white coats are touching patients every day with the majority of those interactions adding no value to the care of the patient. Perhaps one physician could examine the patient and the rest skype in.

I've been thinking lately that we really need to carefully exam all the things we do in hospitals and then engineer out the opportunities for transmission of infection. I was reminded of this by a paper in Transactions on Healthcare Systems Engineering, which examines something as simple as how ICU nurses cover patients for each other while on breaks. This paper points out that by providing a structured coverage arrangement the number of unique persons interacting with any given patient are significantly reduced, which potentially reduces transmission of infection. I bet there are many such  examples where re-engineering patient care could reduce the potential for infection transmission.

Graphic:  Wall Street Journal

European Antibiotic Awareness Day: Why Not Go Global?

A conversation between Dr Angela Huttner* and Professor Herman Goossens**

*Infection Control Program and WHO Collaborating Center on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
**Laboratory of Medical Microbiology, University Hospital Antwerp, Belgium.

Prof. Herman Goossens is Chair of the European Antibiotic Awareness Day Technical Advisory Committee. 

Angela Huttner: There has been some discussion about why there is a “European Antibiotic Awareness Day” (EAAD) and not simply a Global Antibiotic Awareness Day. Those in favor of a “global” day have a good point. There is a lot of work being done the world over to counter the spread of resistance, and at the same time this resistance is everyone’s problem the world over. 

Herman Goossens: It might be helpful to explain a bit about the history of EAAD and how it all started. I discussed the idea of an antibiotic awareness day for the first time during a meeting in late 2006 with Zsuzsanna Jakab, director of the European Centre for Disease Prevention and Control (ECDC) at the time. Zsuzsanna liked the idea and gave it her full support. We discussed whether we should start at the European level or immediately expand its scope to the rest of the world. Zsuzsanna felt that we should start in the European Union, with the support of ECDC, and if successful, expand later to the rest of the world, with the support of World Health Organization (WHO). Needless to say that without her support back in 2006, the EAAD would never have reached its success of today.

AH: And yet today it remains European in name and fact.

HG: In February 2007, two months after my meeting with Zsuzsanna, our Minister of Social Affairs in Belgium, Rudy Demotte, traveled to the US to meet with the Secretary of Health and Human Services, Michael Levitt, and members of the Commission of Health, chaired by Ted Kennedy at that time. I had prepared a note for him to appeal for a “World Antibiotic Resistance Day” supported by ECDC and the US Centers for Disease Control and Prevention (CDC). It appears that, at that time, there was little stateside interest to join this European initiative. Since then, however, the situation has changed a lot. The US and other countries have joined and perhaps it is indeed time for a global initiative.

AH: So now we have the US CDC’s “Get Smart About Antibiotics Week” and Australia’s “Antibiotic Awareness Week” in addition to EAAD. Similarly, there are active initiatives in Canada, Mexico and several other countries worldwide. These disparate movements seem to display all too clearly the recurring and problematic theme in the global spread of resistance: a great deal of effort is being made in many corners of the world, but coordinated action among all players is lacking.

HG: Of course it would make sense to merge all of these movements into one stronger one, especially since resistance is truly a global challenge. I fully support this idea. But the EAAD is very successful because of the enormous support and leadership of the ECDC. We would need similar leadership and support for a world event. The obvious partner would indeed be WHO, as suggested by Zsuzsanna back in 2006. I would hope that WHO could show comparable leadership—the kind required by such a huge public health crisis. If not, in my opinion, this initiative will fail. My conclusion is: a Global Antibiotic Awareness Day … or even Week -who knows?-… is a great idea, but it needs leadership, careful planning, coordination, and massive support to be successful.

Note: Today, November 18th is European Antibiotic Awareness Day. This special guest post came together quickly after a few emails and other e-discussions. Special thanks to Didier Pittet for making the connections and targeting this for posting on our blog.

For more information see:
1) The EAAD website

2) Special Commentary at the ARIC Journal: Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum by Angela Huttner, Didier Pittet and co-authors

3) Special Editorial at ARIC: Controlling antimicrobial resistance: Interfering in the process of natural selection by Johan Mouton

Antibiotic Resistance - A Global Problem

Today, The Lancet Infectious Diseases Commission on Antibiotic Resistance led by Otto Cars from the Swedish Institute for Communicable Disease Control has published "Antibiotic resistance—the need for global solutions." The stated goal of this 42-page tour-de-force is to "explore why antibiotic resistance has become such a problem worldwide, and, most importantly, propose solutions to avert the impending crisis."  The Commission is broken down into nine parts with each group of authors responsible for their individual sections. I've pasted the table of contents to the right (click to enlarge). The document discusses antimicrobial use in humans and animals including stewardship, improved diagnostics (hopefully Dan will comment on part 3), novel therapeutics and antibacterial drug discovery.

The Commission is accompanied by 7 commentaries from the global community, which are each worth a read. All articles are free to access once you set up a username and password.

These documents are largely focused on antibacterial use and development, which are incredibly important global problems that will require collaborative responses at the local, national and international level.

But much like the recent Frontline documentary that, as Dan mentioned, did not have "enough discussion of the hard work of basic infection prevention," infection control is only briefly mentioned in the main document. (Section 2, page 7) You can get the sense of the Commission's approach with this quote: "From a resistance perspective, prevention reduces antibiotic use and the spread of resistant bacteria; however, prevention is not the main strategy to control resistance because antibiotic use also needs to be controlled."

Of course, "benchmarking (open comparison of health-care facilities) of frequencies of health-care-associated infections is useful." Yet public reporting is only useful as far as we have effective methods to prevent the reported infections.

Despite these minor quibbles, this is an incredibly timely and tremendously useful report. The authors and the Journal should be congratulated. Let's hope it moves the needle towards more recognition and funding for antimicrobial discovery, antibiotic stewardship, and perhaps... infection prevention?

Presenteeism makes the Sunday NY Times

As regular readers know, “presenteeism” (coming to work while sick and potentially infectious) is a frequent topic on this blog. It’s nice to see the issue getting wider attention, this weekend in the pages of the New York Times. Go ahead and read Danielle Ofri’s excellent piece on the topic, from which I’ve pasted a couple quotes below:

“This, of course, is ridiculous behavior on the part of medical professionals who would never recommend such nonsense to their patients. Medical workers with respiratory infections are contagious. Caregivers with gastrointestinal infections — as I had — can easily infect their patients. ….  

What we can do, however, is examine the existential qualms that doctors have about illness. From the beginning of medical school it is important to advance the idea that illness is a part of all of us — doctors and patients alike; that there is very little that separates us from our patients, other than the circumstance of the moment; and, for goodness’ sake, that we need to call in sick when we are sick.”

Searching for an Optimal Hand Hygiene Bundle

One of the things we frequently discuss is the central role that hand hygiene compliance plays in preventing the horizontal transmission of resistant bacterial pathogens. 16 "hand hygiene" posts so far in 2013. Hand hygiene compliance is consistently lower than we wish for and it's common that healthcare workers are blamed for poor compliance. I've often mentioned the 2011 Cochrane Review of "Interventions to Improve Hand Hygiene Compliance in Patient Care" and how only 4 papers made the cut, as it struck me that the inclusion criteria were too restrictive. We then wondered if expanding the number of studies included would offer any additional guidance for developing a standardized hand hygiene improvement program.

With the support of the VA National Center for Occupational Health and Infection Control (COHIC) and VA Office of Public Health, Marin Schweizer and our group at Iowa City have completed an extensive meta-analysis of interventions (and bundles) targeting hand hygiene compliance (just published in CID). The review included all studies published from 2000-2012; The year 2000 was selected since ABHR became more widely utilized around that time. 8148 articles were identified and 46 studies were reviewed and included with 1/3 from the US and 1/3 from Europe.

There were several important findings:

1) Only 46 studies from 45 populations have been completed in over a decade. For a critical intervention, this is an unacceptably low number of studies. Funding agencies (and folks that blame HCW for poor compliance) should take note.

2) Meta-analyses of single interventions could not be performed because there were too few studies. It's surprising that we are building bundles without examining individual components first.

3) Increasing the number of interventions included in a bundle was not associated with greater improvements in compliance. For example, bundles with only 1 or 2 interventions were associated with more than a 3-fold increase in hand hygiene compliance while bundles of 3-4 or >5 interventions were associated with a smaller 2-fold improvement in compliance.

4) Several bundles were frequently studied and deemed effective. One bundle that included education, reminders, feedback, administrative support, and access to alcohol-based hand rub was associated with improved hand hygiene compliance (pooled odds ratio [OR], 1.82, Group B below) and another bundle that included education, reminders, and feedback was also associated with improved compliance (pooled OR, 1.47 - Group A below). See the figure below.

More work to do!

Reference: Schweizer ML, Reisinger HS, Ohl M, Formanek MB, Blevins A, Ward MA, Perencevich EN. Clin Infect Dis; 2013.

Global Conspiracy to Hinder US MRSA Control Efforts Uncovered. US and Swiss Scientists Implicated

I was going to title this post "Making Shit Up" but then thought better of it. First of all, profanity can be offensive to some and for reasons that will hopefully become clear, there was a lot of crap written but some of it wasn't made up. It was just that it was twisted and some really great scientists and their science were denigrated. In addition, many scientists were mentioned in an unprofessional manner (first names?) and perhaps some points bordered on ad hominem. Thus, rather than limiting myself to name calling, which lies below ad hominem on Paul Graham's Hierarchy of Disagreement, I've decided to aim a little bit higher...so let me begin my counterargument.

First, please step away from this post and go read the 2-page commentary just published in AAC titled: "A Perspective on How the United States Fell behind Northern Europe in the Battle against Methicillin-Resistant Staphylococcus aureus."

Some thoughts. First, the authors suggest in their title that the US is falling behind Northern Europe in MRSA control. Little evidence is provided to support this claim other than that the proportion of S. aureus infections caused by MRSA is higher in the US. No mention is made of livestock-associated MRSA or MSSA or even MRSA related mortality. In addition, the authors focus on only one aspect as a possible cause for this difference between the US and Northern Europe - the US doesn't have legislatively mandated universal active detection and isolation (ADI).

The authors explain that everything would have been wonderful in the US if the 2003 SHEA guidelines recommending ADI were just followed. No mention was made of the fact that Northern Europe lies at the latitude of Anchorage Alaska and that environment might play a role. No mention was made of other potential differences that could influence the carriage rates of this human commensal. And when you read it closely, you realize the commentary authors aren't just upset that the US lacks mandatory ADI but conjure evidence that there's actually an anti-ADI conspiracy aimed at preventing legislative mandates. One supported by antisurveillance activists named Huang and Huskins, and mysterious JAMA Swiss folks, and Diekema and Climo and meddling yet unnamed kids like Weber and Edmond writing position statements and editorials closing cases.

According to Kavanagh et al. it all started with the 2006 HICPAC statement that suggested to consider ADI while requesting more evidence and the SHEA-APIC position paper in 2007 by Weber (and Huang and Huskins) that came out against legislative mandates for ADI. You see, according to Kavanagh and his colleagues, Huang and Huskins would later spend years writing grants and completing complicated and intentionally imperfect studies at a huge personal cost in a twisted antisurveillance plot! Even against these odds, the US Congress held a hearing to push through mandatory ADI but just then unnamed JAMA Swiss folks published a study finding universal ADI ineffective and Diekema and Climo agreed as much in their editorial. Even if we overlook the obvious conspiracy given the timing of the publications, how can these JAMA authors live with themselves suggesting high quality studies overwhelm prior uncontrolled quasi-experimental studies? - the nerve!

But it gets worse (or better)! The authors then highlight the VA MRSA study but suggest that the only reason it was published was that MRSA activists demanded it. And to further prove the conspiracy, they point out that this fantastic study was published in the very same issue of the NEJM as the Huskins STAR-ICU study finding no benefit of ADI. Yup - fact. They then mention limitations (however valid) of the STAR-ICU study while neglecting any potential limitations of the VA study. Very smooth.

The conspiracy theorists authors lose me a bit when they say the US demands surveillance for CRE and HIV and hepatitis C without evidence, and wonder why there's such a high bar for MRSA. It's just not fair!

Further evidence of a conspiracy is offered when they point out that two reviewers of an AHRQ systematic review were none other than the aforementioned Huskins and Diekema! And then it really gets strange. The authors point out that the AHRQ review gave more weight to the higher quality studies that were negative compared to poorly controlled studies that found a benefit. As I read this paragraph I almost become sad, as they basically lost the debate right there. They even mentioned hepatitis C screening again and plead that MRSA ADI evidence is maybe even probably hopefully better. Finally, the REDUCE-MRSA trial by Huang and the accompany editorial by Edmond were mentioned and criticized, you know, because.

They conclude with saying that this whole anti-ADI conspiracy has occurred with the sole purpose of avoiding legislative mandates. They correctly point out that the best way to avoid such mandates is to base clinical decisions on the best available evidence. Fortunately for our patients, that is exactly what we are doing now. We are using the best available evidence as produced by Huskins, Huang, Climo, Diekema, Edmond, Swiss folks like Harbarth and many other colleagues from our ever-growing, evidence-based field of infection control. You know, ADI may be indicated in some settings but not all settings and the way to determine where and when is through more high-quality studies. And there is no conspiracy.

Staphylococcus aureus continues to evolve: MRSA without mec edition

I just returned from a wonderful MRSA conference this past week where I enjoyed learning about how European countries are handling antimicrobial use in livestock and the emergence of potential human pathogens like livestock-associated MRSA. Perhaps I will post further thoughts on the conference later in the week.  However, I just saw this new report in JAC on a novel resistance mechanism in S. aureus, so first things first.

It is known that hyper beta-lactamase producing strains of S. aureus exist and that some strains have chromosomal mutations and resultant modified penicillin binding proteins. These strains can have phenotypic methicillin resistance while lacking the mecA (or mec C) gene. Thus, they can evade detection by genotypic methods and the underlying mechanisms can be missed by phenotypic methods, as Dan nicely described here.

There is now a report by Xiaoliang Ba and colleagues that describes four clinical S. aureus isolates that were found to be MRSA but lacked mec A or mec C. The strains were from clinical wound infections and deposited in the Scottish MRSA Reference Lab. They belonged to sequence types 1, 15 (two isolates) and 8. Three strains were resistant to oxacillin, cefoxitin and PCN by ETest and disc diffusion and the fourth isolate was at the oxacillin Etest breakpoint, while three were beta-lactamase producers. Whole genome sequencing confirmed that none contained a mec-like sequence and that beta-lactamase production was not mediating the resistance. Interestingly they found similar single amino acid substitutions across sequence types in PBP1, PBP2 and PBP3 suggesting independent evolution of the same trait (homoplasy).

The authors acknowledge that their targeted search of the genomes could have missed other possible mechanisms of resistance in these isolates. I would add that this was in four isolates out of an unreported denominator, so we don't know the magnitude of the clinical impact yet. What we can say is that our surveillance techniques had better keep up with S. aureus. Unfortunately, it seems to be just as good at evolving away from our prevention methods as it does our antibiotics.

Obligatory S. aureus image courtesy of wikipedia

Addendum: For further insight, scroll down to read Dan's comment on this study

HICPAC lays down the letter of the law

This week's Annals of Internal Medicine has a paper entitled "Public Reporting of Health Care–Associated Surveillance Data: Recommendations From the Healthcare Infection Control Practices Advisory Committee." It's a somewhat misleading title, as the paper isn't about public reporting, it's about what happens in hospitals before HAI data are publicly reported. The primary message is this: if a case meets criteria for HAI sensu stricto, it's an HAI, dammit! Don't go asking a doctor for her clinical opinion on whether it's an infection and then erasing that case from your line list if she says, "doesn't look like an infection to me."

I have mixed feelings about this. On the one hand, in order to allow for valid inter-facility comparisons of infection rates, everyone has to play by the same rules. I think we all get that. But it's incredibly frustrating to review a case that is clearly not an HAI, yet be forced to label it as such. And it's not an uncommon occurrence. Last week, my IPs brought me a case of a patient admitted with pneumonia and because the patient's condition worsened after admission, we were forced to label the case a possible VAP. This morning, an IP from another state emailed me a case of a patient who was admitted with an infected wound, went to the OR, and subsequently developed a surgical site infection, which had to be categorized as an HAI. The IP notes, "the same patient, without the surgery, would have a community acquired wound infection and would not be counted as an HAI."

Even more commonly, hospitals with large oncology populations see many cases of bloodstream infections with enteric flora in patients who just so happen to have a central line. While I give CDC credit for now allowing us to classify cases as mucosal barrier injury related bloodstream infections, it's of little value, as these infections are still publicly reported as CLABSIs. And to add insult to injury, those poor IPs in Pennsylvania have to send patients a letter telling them they suffered an HAI that wasn't an HAI.

All of these problems with post-ascertainment veto and adjudication are occurring because the stakes are high. Most of the time, this is done in good faith, I believe. There is a big push in hospitals to hold staff accountable for adverse events, and it really stings to have the finger pointed at you for an event that was not preventable, or maybe not even an event. It undermines the credibility of IPs and hospital epidemiologists with clinicians when you call a single positive VRE blood culture in a neutropenic leukemic patient a CLABSI. To mitigate that, I find myself appearing at committee meetings to explain that while this case technically meets the criteria for CLABSI, all evidence tells us this is an infection not related to the central line, and is in fact, not preventable. Some hospitals keep two sets of books--the official publicly reported set, and the internally "correct" set.

So while I agree with HICPAC in spirit, this paper only addresses a part of the problem. It ignores the fact that we need definitions with more specificity, and those definitions are needed now. The mucosal barrier injury infection definition has been validated, so let's use it for public reporting. Task IPs to send in descriptions of cases where the definitions are not working, catalog them, categorize them, and start fixing the definitions in a timely manner. Allow for relatively rapid tweaking of definitions instead of acting as if definitions are carved in stone and represent some absolute truth. While we will never be able to have perfect case definitions in the murky world of medicine, fixing the underlying problem to the degree that it can be fixed would decrease the drive for post-ascertainment veto and adjudication. Or how about embracing adjudication but have it occur at a central level? In a world of electronic communication it wouldn't be that difficult.

And one last thing: I think that any official statement from HICPAC should be in the public domain, not behind a journal paywall. Perhaps this paper is also posted somewhere on CDC's website, but I was not able to locate it, if it is indeed there.

Is hand hygiene prior to nonsterile gloving really necessary?

There's a new study in American Journal of Infection Control that I think is really important. The University of Maryland group performed a randomized controlled trial to evaluate the impact of hand hygiene prior to donning nonsterile gloves. The study involved 230 healthcare workers in 7 ICUs who were randomized to either perform hand hygiene with an alcohol-based handrub or perform no hand hygiene, prior to donning nonsterile gloves for contact precautions. Hands were cultured prior to randomization and after donning of gloves.

The key findings were as follows:

• There was no difference in baseline hand contamination between the 2 groups
• There was no difference in contamination of the gloved hand between the 2 groups
• A pathogen was detected on only 3 hands (1 MRSA in the hand hygiene group, and 2 MSSA in the no hand hygiene group)
• Importantly, hand hygiene prior to gloving added 31.5 secs to the gloving process. For the average ICU nurse caring for a patient in contact precautions, this adds up to 19 extra minutes per 12-hour shift.

Bottom line:  this study suggests that hand hygiene prior to gloving is a nonvalue-added activity.

Photo:  The Sound of Science

Not to beat a dead horse, but..........

Here's another paper on adverse events associated with contact precautions. In this study from two French ICUs, 1150 patients were followed for adverse events. Outcomes for patients in contact precautions for MDROs were compared to those who were not in contact precautions. Patients in contact precautions were 1.5-fold more likely to have hypoglycemia and hyperglycemia, 1.9-fold more likely to have anticoagulant prescribing errors, and 2.1-fold more likely to develop VAP due to an MDRO.

When I read the study results I couldn't understand why there could be a causal relationship between contact precautions and anticoagulant prescribing errors. However, the authors later tell us that in these ICUs the patient charts (which are not electronic) are kept in the patient rooms.

I don't think we can blame contact precautions on the higher risk of VAP due to an MDRO. There was no higher risk of VAP due to all pathogens in the contact precautions group. Since patients found to have MDROs would be transferred to contact precautions, it only makes sense that VAP due to MDRO would be more common in patients in contact precautions.

Photo: Massachusetts General Hospital

Let me hate on contact precautions some more

The very first post on this blog was written by Dan in March 2009. It was entitled, Why I Hate Contact Precautions, vol. 1. I'll let Dan and Eli speak for themselves about how they feel now, but I remain a hater.

Results from three new studies add fuel to my fire:

(1) In one hospital, patients in contact precautions were found to wait approximately 10 hours longer for CT scans than those who were not in contact precautions. This is a reminder that there are downstream adverse effects of contact precautions that impact quality of care that perhaps we haven't even thought about.

(2) Another paper (different journal, same authors as the first paper) was a retrospective cohort study of patient safety incidents before and after patients were placed in contact precautions. Medication errors were 1.5-fold higher under contact precautions, and patient injuries were over 3-fold higher.

(3) Dan Morgan and his colleagues at University of Maryland found that patients cared for under contact precautions were twice as likely to perceive that their care was poor. Specifically, they reported poor care coordination and lack of respect for their needs and preferences.

There's an old belief shared by bartenders that nothing good happens after 2 AM. In my line of work, nothing good happens after contact precautions.

Photo: Healthcare Purchasing News

Search and destroy is so last century...

A few weeks ago, Dick Wenzel and I responded to a letter in the New England Journal of Medicine regarding our editorial on Susan Huang's paper on targeted vs universal MRSA decolonization. We have long argued that active detection and isolation (AKA search-and-destroy, a vertical strategy) wasn't a necessary or particularly wise approach. A letter refuted this. In our response, we stated:

The key question remains: given an optimally functioning horizontal program (i.e., near perfect compliance with hand hygiene and chlorhexidine bathing), what is the incremental benefit of a superimposed vertical strategy?

Voila! A new study in Lancet Infectious Diseases by Marc Bonten et al addresses our question. In this 3-year study in 13 European ICUs, involving over 8,500 patients, there was a baseline data collection phase (6 months), followed by a hygiene improvement phase (hand hygiene campaign + universal chlorhexidine bathing for 6 months), followed by cluster randomization to a rapid screening group + contact precautions for carriers or a conventional screening group + contact precautions for carriers. Both screening groups used chromogenic agar to detect MRSA, VRE and ESBL; the rapid screening group also used PCR testing for MRSA and VRE. Primary endpoints were the acquisition of MRSA, VRE or MDR-GNR.

The study showed:

• Hand hygiene increased from 52% in phase 1, to 69% in phase 2, and 77% in phase 3.
• Chlorhexidine bathing was 0% in phase 1, and 100% in phases 2 and 3.
• Improved hand hygiene + chlorhexidine bathing (phase 2) resulted in a significant decrease in MRSA acquisition, with no change for VRE or MDR-GNR.
• Neither search-and-destroy strategy resulted in any further reduction for any of the targeted pathogens.
• There was no change in the prevalence of chlorhexidine resistance genes in MRSA isolates in phase 1 vs. phase 3 (13% vs 14%).

So we now have another study demonstrating the lack of need for active detection and isolation to control multidrug resistant pathogens. Will the search-and-destroyers finally pack it up and go home?

Photo:  Jeff Swensen, New York Times