More VRSA

Earlier this week, Eli posted on the first case of VRSA in Europe. Today, a posting on ProMed reports on the first VRSA case in Latin America. This is also the first time VRSA has been isolated from the blood; all previous strains were isolated from wounds. The patient was a 35 year old man from Sao Paulo, Brazil with diabetes and Sezary Syndrome. His bloodstream infection was controlled with daptomycin but he died 3 weeks after VRSA was isolated. The vanA gene was detected in the VRSA strain as well as from an Enterococcus faecalis strain isolated from the same patient.

Graphic:  Wikipedia

Epidemiologic activists

There's an excellent article in this morning's New York Times on the quest by the Cochrane group to determine the efficacy of Tamiflu, which is part of a bigger story on how pharmaceutical companies selectively release data regarding their products. It demonstrates how epidemiology can involve more than just data analysis and how political activism is sometimes required to find the data to answer basic questions.

Photo: Dr. Tom Jefferson by Chris Warde-Jones for the New York Times.

Top Infection Control Papers - ICPIC 2013 Edition

Andreas Widmer and I had the honor of presenting the "Best" Papers lectures at ICPIC this year. In case we spoke too quickly or you couldn't make it to Geneva this year, we have have posted the slides below. We wish we could have included many more papers since the quality of infection prevention research has increase immensely over the past decade (e.g. Huang's REDUCE MRSA study and Bonten's MOSAR trial).

And now for something completely different...

I posted back in October about some “microtargeting” of the chronic Lyme disease vote in Virginia, and in the comment section I referenced a short New Yorker blog post by Michael Specter. In a recent interview on NPR, Mr. Specter noted that he got “about 207 million pieces of hate mail” after that post, such an astonishing response that he convinced his editors that he should do a longer piece on the topic. 

That piece, “Lyme Wars”, is in this week’s New Yorker and is well worth a read.

More dirty laundry......

A new study in the American Journal of Infection Control by Dr. Silvia Munoz-Price and her team at the University of Miami provides additional insights on laundering of clothing worn in the clinical setting. In a convenience sample of 160 physicians and medical students, the Miami team found that white coats were laundered on average every 12.4 days, while scrubs were laundered every 1.7 days. I found it a little surprising that for scrubs the frequency wasn't closer to 1.0, but that's tremendously better than 12 days! For both coats and scrubs, faculty laundered their attire more often than housestaff or students. Interestingly, the major reasons given for wearing white coats were: (1) ego (makes me looks and feel like a doctor, 29%), and (2) storage needs (25%). Neither is a good reason.

Late last year, the same team published a study that found that white coats were more commonly contaminated with pathogens than were scrubs in the ICU setting. Moreover, if the hands were contaminated with a pathogen, white coats were more commonly contaminated than were scrubs. And all of the HCWs with negative hand cultures were dressed in scrubs.

Both studies were relatively small and performed in a single (though very large) medical center. Nonetheless, there is a body of evidence accumulating that clothing contamination in the clinical setting is a real phenomenon and probably should no longer be ignored by infection prevention programs. So I was delighted a few days ago to see that West Virginia University Hospitals is considering banning ties and white coats.

Photo:  Dr. Munoz-Price (far right), in scrubs!

VRSA - First Case in Europe

Lost among the attention given to MERS in the recent NEJM and the H7N9 papers published in the Lancet today is a report of the first vancomycin-resistant S. aureus case in Europe. 

The case was in a 74yo in Portugal with diabetes on dialysis. She had prior pseudomonal and MRSA diabetic foot infections treated with vancomycin. This May she had VRSA detected in pus from a toe amputation wound with MIC for vancomycin of >256 μg/mL and MIC of 24μg/mL for teicoplanin. VRE and P. aeruginosa were also cultured. The VRSA strain was sequence type ST105, SCCmec type II, and had both the mecA and vanA genes (from her VRE). This VRSA was resistant to erythromycin, clindamycin, gentamicin, and ciprofloxacin, and susceptible to co-trimoxazole, tetracycline, tygecycline, linezolid, daptomycin, quinupristin/dalfopristin, fusidic acid, cloramphenicol, rifampicin, and mupirocin.

A bundled intervention to decrease surgical site infections: A Video Abstract

Last week we discussed a recent BMJ meta-analysis of SSI prevention intervention studies in cardiac and orthopedic surgery. Who better to tell you about the important results than the authors themselves. Loreen Herwaldt and Marin Schweizer offer their thoughts. Enjoy!

The In(patients) and Out(patients) of Antimicrobial Stewardship

I've been lucky enough to attend the 4th World HAI Forum on Antimicrobial Resistance this week in Annecy. This morning's excellent session on antimicrobial stewardship was chaired by Stephan Harbarth and Herman Goossens and brought to light many barriers to the wider adoption of stewardship by non-ID physicians. For one, the accuracy and economics of rapid diagnostics and algorithms were identified as a major barrier. In particular the negative predictive value, which would allow primary care physicians to stop (or not start) antibiotics, was suggested as a key target.

Another, brought forth by Kent Sepkowitz, was that the whole enterprise of "stewardship" lacks a main outcome measure or at least has transitioned from Decreasing Antimicrobial Resistance, to decreasing costs, shortening length of stay, educating the next generation of clinicians, and finally easing workload for ID specialists and trainees. He suggested that presenting stewardship as a patient safety issue with a primary target of drug resistance rates in key indicator organisms will bring greater rewards. Tom Gottlieb responded that the burden should be on the others to prove that stewardship doesn't work since antibiotics are such a limited resource. Bob Wachter implied that a key "bias" against stewardship in the US is that compared to the patient safety movement, which targets the individual patient as the beneficiary, stewardship benefits "others." Loreen Herwaldt said that a microbiome outcome could provide an individually-focused patient safety target.

Of course, I can't even begin to transcribe and communicate all of the excellent points made by the attendees. Fortunately, two interesting studies were published in the past 2 weeks that examined the impact of stewardship interventions in the outpatient and inpatient settings.

The first study by Jeffrey Gerber and colleagues in JAMA described an outpatient cluster-randomized trial in 18 pediatric practices. They examined prescriptions for acute respiratory infections 20 months before and 12 months after the intervention, which included one 1-hour on-site clinician education session followed by 1 year of personalized, quarterly audit and feedback of prescribing. Prescription of broad-spectrum antibiotics decreased by 6.7% more in the intervention practices compared to usual practice clinics, while off-guideline prescribing decreased by 10.7% more for pneumonia and 14% more for sinusitis. Evidence supporting the public health benefits (i.e. reduced resistance) of this intervention are not described in the paper.  In fact, the word "resistance" appears only once in the entire article.

The second study by Greg Filice and colleagues at the Minneapolis VA examined the impact of an inpatient computer decision support system for antimicrobials on appropriateness of antimicrobial prescriptions in a retrospective cohort. The system was associated with a higher level of appropriate prescribing, 44% vs 33%. However, the most interesting finding was that the most important factor influencing prescribing was the accuracy of the initial diagnosis.  If the diagnosis was correct, prescribing was appropriate 62% of the time compared to only 11% when the diagnosis was incorrect or uncertain. Thus, unless we can help clinicians with their diagnostic accuracy, we will have a limited impact on antibiotic prescribing.

ok, back to the meeting for me...

Take a 3 minute break to watch this video....

Hat tip: Susan Peloquin

A pleasant surprise....

Yesterday, the FDA quietly posted an announcement regarding the requirement for submitting an investigational new drug (IND) application by physicians who perform fecal transplantation. In part, it says:

Some health care providers have stated that applying IND requirements will make FMT unavailable and have suggested that an alternative regulatory approach is needed to ensure the widespread availability of FMT for individuals with C. difficile infection unresponsive to standard therapies. 

The agency acknowledges these concerns and intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products. Informed consent should include at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks. 

FDA intends to exercise this discretion while the agency develops appropriate policies for the study and use of FMT products under IND. The agency intends to issue guidance reflecting the agency’s intention to exercise enforcement discretion.

During this time FDA strongly encourages compliance with the IND regulations, and stands ready to work with sponsors who are interested in conducting clinical trials.

I've read this a couple of times, and I'm not sure exactly what this means. Can fecal transplantation now be performed without an IND as long as there is informed consent? It sounds as though further information is forthcoming. Nonetheless, it appears to be a step in the right direction. Kudos to the patients and their families for making their voices heard. Yesterday, one of my patients spoke about her experience here:

NBC12.com - Richmond, VA News

Am I an indicator of a decline in hygiene?

A few weeks ago I was seeing patients at a clinic in an affluent suburb. My first patient of the day was a professional woman. At the end of the encounter, she said: "Can I ask you a question?" I had no idea where this was going, sensing that this was probably not going to be a medical question, but said, "of course." She then proceeded to ask me how I liked my Toms, as she wanted to buy her husband a pair. I was in my typical summer clinic attire, which consists of a polo jersey, khakis, and Toms (no socks). Now I think Toms are great--they're comfortable, not made of leather (i.e., animal friendly), and for every pair sold a pair is given away to a child in need. But this post isn't really about Toms.

The Toms question from my patient was a great segue for me to ask the patient about doctor's clothing. I asked her what she thought about how I was dressed and her expectations of how physicians should dress. She said that she saw me walk into the clinic and knew I was her doctor because she had Googled me before the visit. She noted the way I was dressed and thought I would probably put a lab coat on (by the tone of her voice I could tell she didn't like the lab coat concept). She went on to tell me that my clothes made me "a real human" and it made her more comfortable in interacting with me. I suspect that some other patients may feel differently, but I carefully follow my patient satisfaction scores and must admit that if my clothes are problematic, it's not reflected in my scores. Patients don't really care how their doctor is dressed, as long as the doctor demonstrates empathy, communicates well, and ensures that the patient has access to him/her when they have a problem.

There's an essay in this week's BMJ by Dr. Stephanie Dancer, former editor of the Journal of Hospital Infection. It's entitled, Put your ties back on: scruffy doctors damage our reputation and indicate a decline in hygiene. In her poorly argued essay, which I think is sexist and borders on crazy talk, she attempts to link the bare-below-the-elbows concept to lower standards for infection prevention. She writes:

"No tie"--along with stubble, spitting, picking your nose, and gravity defying trousers--symbolize the real status of hygiene in today's society.

In one paragraph she discounts the role of clothing in infection prevention:

Given that bed linen and pajamas are habitually contaminated with their owners' personal microbial flora, the focus on transmission from what staff are wearing seems disproportionate and perhaps even irrelevant. 

This, of course, fails to distinguish between endogenous and exogenous pathogens. A paragraph later she chastises doctors for wearing the same clothes for several days as it "showers the environment with millions of skin organisms."  However, the vast majority of clinicians who wear white coats wear the same coat for days to weeks without laundering them.

I continue to believe that bare below the elbows is useful in infection prevention as it reduces clothing contamination and makes compliance with hand hygiene easier. And I wholeheartedly believe that doctors should appear neat and clean. But I'm still trying to determine biologic plausibility for how banning neck ties has led to nose picking... Maybe it's because neckties function as handkerchiefs!

Infection control rule #1: if you're sick, stay home.

A new study from the University of Pittsburgh Graduate School of Public Health uses epidemic modelling to determine the impact of reducing presenteeism on workplace transmission of influenza during a pandemic, such as the one we experienced with H1N1 in 2009.

The investigators compared the status quo (72% of employees with paid sick days stay home with flu, while 52% of those without sick days do not) to three other scenarios: (1) all employees have access to paid sick days, (2) all also have access to 1 flu day, or (3) all also have access to 2 flu days. The concept here is that employees are specifically paid to stay home when ill with influenza.

The findings:

• Universal paid sick days resulted in a 6% reduction in workplace transmission (applied to Allegheny County, PA [population 1.2 million] that is equivalent to nearly 4,000 fewer infections).
• Adding 1 flu day resulted in a 25% decrease in workplace transmission (15,000 infections averted)
• Adding 2 flu days resulted in a 39% decrease in workplace transmission (26,000 infections averted)

Bottom line:  Efforts to reduce presenteeism (a horizontal infection prevention strategy) can have significant impact. 

Implication:  If we're really serious about reducing infections transmitted to patients in hospitals from staff, we must start thinking about how to reduce presenteeism. And that's a lot harder than firing healthcare workers who refuse to take their flu shot. 

Photo:  Man by Virgil Cantini, 1965, bronze and steel sculpture on Parran Hall at the University of Pittsburgh Graduate School of Public Health.

Save your mupirocin for SSI prevention in cardiac and orthopedic surgery

As our guest blogger, Marc-Oliver Wright, posted last week, widespread use of mupirocin was associated with 400% increase in mupirocin resistance at his hospital. Many are very concerned about widespread and non-selective use of mupirocin as a result of the REDUCE MRSA trial, particularly since the incremental benefit of mupirocin added to CHG is not known. Based on prior studies, it is possible that many of the benefits seen were due to CHG and not necessarily mupirocin.

With that in mind, why should we care about mupirocin resistance? Well, there are instances were mupirocin has more established benefits in the literature and one is in surgical site infection prevention. The issue with most infection prevention intervention studies is that most outcomes like SSIs are rare (fortunately) and research budgets are small, which leads to numerous underpowered quasi-experimental studies. The problem with this type of literature base is that it can lead to unnecessary controversy with clinicians cherry-picking study results to support their specific hypothesis.

To make use of such a literature base and scientifically determine the benefits of nasal decolonization (and other interventions), Marin Schweizer and Loreen Herwaldt at the University of Iowa completed a meta-analysis of SSI prevention intervention studies in cardiac and orthopedic surgery, which was published today in the BMJ (free open access). (COI note: I'm a co-author on the paper and was an independent reviewer/data abstracter) After screening 1423 articles published between 1995 and 2012, they identified 39 studies of moderate to high quality. 17 studies assessed the benefits of nasal decolonization (16 mupirocin and 1 nasal CHG), 15 studied glycopeptide prophylaxis and seven examined the bundle: screening+nasal decolonization+vancomycin). The pooled effects were quite impressive.

Nasal decolonization was associated with a 61% reduction in S. aureus SSIs, a 70% reduction in MRSA SSIs and a 50% reduction in MSSA SSIs. Glycopeptide prophylaxis was associated with a 60% reduction in MRSA SSIs while the full bundle was associated with a significant reduction in S. aureus, MRSA, MSSA and Gram-positive SSIs. I have pasted the table below (click to magnify), but since the full article is open access, you can also read the full article at BMJ.

This meta-analysis guided the implementation of an ongoing trial funded by AHRQ, so more data are coming soon. But what to make of this paper in the context of the recent REDUCE MRSA trial?  I myself am concerned that widespread mupirocin use in all ICU patients will select for resistant S. aureus isolates and render this highly-effective SSI bundle ineffective in short order. It will be sad to watch this example of the 'tragedy of the commons' play out in real time, as I suspect we will. And we will only have ourselves to blame. The data is right before our eyes.

ICPIC 2013 - 25-28 June 2013 - Geneva

ICPIC 2013 by HUG

I really enjoyed speaking at and attending the 1st International Conference on Prevention & Infection Control (ICPIC) in 2011. It was great opportunity to share the best science and best practices with colleagues from around the world. I hope to see many of you there in 2013.

Oh, and check out the excellent iOS app: here and Android app: here

Perry Mason and REDUCE MRSA: Another "Case of the Positive Negative"

This guest post is by Marc-Oliver Wright, MT(ASCP), MS, CIC
 from NorthShore University HealthSystem
 in Evanston, IL 

"We need Perry Mason. Someone to put you in place." – Ozzy Osbourne

This week’s articles in the NEJM (Huang et al. “Targeted versus Universal Decolonization to Prevent ICU Infection”) and accompanying editorial (Edmond and Wenzel “Screening Inpatients for MRSA-Case Closed”) left me reminiscing of classic TV courtroom dramas where the well intentioned and sophisticated district attorney has finished presenting his/her case but Perry Mason has just cleared his throat and Matlock is still shining his ankle boots.


For those of you who missed it, Huang and colleagues randomized 74 intensive care units (ICUs) at 43 Hospital Corporation of America hospitals to one of 3 interventions among 2 cohorts.

1. Cohort one: States with mandatory MRSA screening (n=5)
     a. MRSA screening and isolation for ICU admissions (3)
     b. MRSA screening, isolation and decolonization for ICU admissions (2)
2. Cohort two: States without mandatory MRSA screening (38)
     a. MRSA screening and isolation for ICU admissions (13)
     b. MRSA screening, isolation and decolonization for ICU admissions (12)
     c. No screening, decolonization for all ICU admissions (13)

Decolonization included 5 days of intranasal mupirocin therapy and daily baths with chlorhexidine gluconate (CHG) for the duration of their stay in the ICU.

Adjusted hazard ratios for clinical cultures of MRSA with both decolonization strategies netted confidence intervals that were less than 1.0. Ditto for bloodstream infections with any pathogen (not just MRSA). When the authors selected out bloodstream infections caused by MRSA the findings were not significant. In the pairwise analysis universal decolonization attained statistical significance over screening/isolation/decolonization in the unadjusted analysis for bloodstream infection due to any pathogen. The authors conclude that universal decolonization is superior to either targeted decolonization or screening and isolation without decolonization.

This was a large, rather well designed, certainly well coordinated evaluation of multiple ICUs across the country. But the case is far from closed.

Defense exhibit one: Follow the blood. This article further affirms an already well conducted study by some of the same authors that demonstrated CHG bathing of ICU patients reduced bloodstream infections in ICU patients (Arch Intern Med. 2007;167:2073-9, ICHE 2009;30:959-63). There’s ample biological plausibility for this and in general, the horizontal (as opposed to vertical one MDRO at a time) approach is more logical. However, this effect in all likelihood has nothing to do with mupirocin, which has never been independently associated with a reduction in bloodstream infections. CHG reduces all-pathogen bloodstream infections in ICU patients: no objection your honor.

Defense exhibit two: An eyewitness-I see you. MRSA infections are not restricted by the boundaries of the unit. An APCHE score is not a pre-requisite to acquiring an MDRO. According to the evidence, ICU patients are at higher risk for MRSA infection, but many of prior studies were conducted in large academic medical centers where and when the case mix was different from today. Arguably, it’s operationally easier to limit intervention and research studies by geography.

Illinois was the first state to succumb to MRSA screening legislation; the legislation which reads that such screening will be performed on patients in “all intensive care units, and other at-risk patients identified by the hospital.” We, in the Land of Lincoln, have all, by design, implemented the former, but the latter is a hodge podge ranging from denial (only ICU patients are high-risk) to the assumed, evidentiary but not all-encompassing (patients from LTC are high-risk) to the near complete (70+ variable model built decision support module embedded in the EMR). The VA as well as my own organization deployed MRSA prevention strategies in ICU as well as non-ICU settings.

This brings me to: Defense exhibit three: A character witness. My organization’s strategy for the past 9 years has been a strategy most akin to Group 2 (screening, isolation and decolonization). Though we started in the ICU, we failed to see the kind of reduction we wanted (see defense exhibit 2) until we later expanded to universal screening. We used this experience to develop a robust multi-variable prediction model that was built as decision support system into our electronic medical record. This tool automatically calculates a MRSA risk score as patient data is entered and evolves within the record during the patient’s admission. When the risk score reaches a threshold the user is instructed to screen the patient. We used this to transition from universal screening to targeted screening in January 2012.

Ok. I am by no means an expert on MRSA. I am good with numbers though.

In the NEJM article, the best intervention for reducing MRSA clinical isolates is a rate of infection of 2.1 per 1,000 patient days. At NorthShore (and for comparison purposes, these measures are in our ICUs only) in the past 38 months, our unadjusted rate of MRSA infection is 0.3 per 1,000 patient days. Their best intervention netted an infection rate ratio versus my own ICUs of 7.0 (95%CI: 4.3-11.5, p=5.9 * 10-23).

Similarly, the NEJM article reported an overall, unadjusted rate of bloodstream infection from any pathogen of 3.6 per 1,000 patient days in the universal decolonization intervention arm. At NorthShore (and for comparison purposes, this is in our ICUs only) in the past 38 months, our unadjusted rate of bloodstream infection is 1.08 per 1,000 patient days. Their best intervention netted an infection rate ratio versus my own ICUs of 3.33 (95%CI: 2.54 -4.38, p=1.3 * 10-22).

I’m afraid I’ve only had 1 BSI due to MRSA in the past 38 months. My crude rate comes out as 0.018 per 1,000 patient days. If I understand Table 3 of the NEJM article correctly, the universal decolonization group experienced 48 BSIs with MRSA during the intervention and attributable ICU patient days of 101.603 for a rate of 0.47 per 1,000 patient days. This yields an infection rate ratio versus my own ICUs of 26.11 (95%CI: 4.53-150.45, p=3.1 * 10-8).

I am all too happy when a group of dedicated and brilliant people in hospital epidemiology find a new and improved way to prevent infection. And for this group, they did discover a new strategy for reducing their MRSA and bloodstream infections. I was not surprised to see that they have decided to implement the universal decolonization strategy across all HCA hospitals. But as long as their best rates are between 3 and 26 times higher than mine, I’ll be sticking with my own plan.

Defense exhibit four: If the antibiotic doesn’t fit you must acquit. Arguably, the single greatest concerning factor of this study that wasn’t addressed is the rise of mupirocin resistance. This exhibit, like the preceding, is rooted in personal experience. Until this year, our organization decolonized all MRSA-screen positive patients. During that 8 year endeavor our proportion of mupirocin resistant MRSA increased from about 3% to almost 12%. Nasal decolonization has been most convincingly demonstrated to reduce infection risk in the pre-surgical patient population and arguably only with select procedures. Our rise in resistant strains and the overwhelming desire to reserve this ammunition for the people that really need it (pre-surgical patients) gave rise to our decision to suspend mupirocin decolonization starting in 2013. We hope to see our resistance pattern return to baseline, though such a decline will likely be slow.

Justice may be blind, but we shouldn’t be to known potential adverse outcomes like antibiotic resistance.

Closing argument:  If none of the above convinced you that this case is far from closed at least consider this final argument. Living in Illinois, I am frightened awake at night with the sounds of what I imagine to be fingers typing on keyboards. The well-intentioned hands of a well-meaning lawmaker in our state or federal capital pounding out some new legislation in light of the latest and greatest publication on preventing some iteration of our nation’s bacterial scourges. Convinced that if they don’t do something those conniving hospital epidemiologists and infection preventionists won’t do anything to protect our nation’s sickest and frailest citizens. That all we’re here for is the big money check we get every week. By heaven, we must mandate! *shudder*

This paper, like all well designed and well-conducted studies deserves critical attention and consideration. Consider the methods they used and those they didn’t, the intervention processes they measured (CHG/mupirocin supply) and those they did not (isolation compliance), the settings in which the study was conducted (ICUs) and where it was not (everywhere else) and the outcomes they measured (MRSA and BSIs) and those they did not (antibiotic resistance). You must also compare their outcomes to your own performance. With such a wide variety of organizations the results may be generalizable despite HCA’s additional vertical strategies for MRSA that may have overlapped the study periods. How do your rates in your methods group compare those published here (1, 2, or 3?) versus the alternatives? Use this evidence as a tool for your ongoing risk assessment and make an educated decision before someone makes an uneducated one for you.

The defense rests.

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

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

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

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

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

REDUCE MRSA: Readers weigh in!

In my short post about this study last week, I promised that I’d follow up with the most likely criticisms we’ll be reading in future letters-to-the-editor. My post was going to focus on concerns about emerging resistance to topical agents, the lack of impact on MRSA bacteremia, and the outsized influence of skin commensals on the outcomes (see my post on the chlorhexidine bathing studies).

Fortunately, our readers have done this work for me. Below I’ve excerpted a comment we received today:

"We applaud investigators for their hard work in completing a high quality study. However, it has limitations and recommendations are overreaching.

--The intervention

Mupiricin/Chlorhexidine for all patients is very aggressive. Would chlorhexidine alone work in a similar fashion? (resistance is a real concern, especially for mupiricin, and if these agents become inactive they can't be used on high risk patients) We don't really know, but there will be calls to vastly increase antimicrobial exposure to mupiricin based on a study with a mixed intervention that prevented relatively few MRSA clinical cultures even over 74 ICUs I.E. A LOT OF PATIENTS WILL RECEIVE MUPIRICIN FOR A VERY SMALL ABSOLUTE DECREASE IN POSITIVE MRSA CLINICAL CULTURES!

--Outcomes

Bacteremia rates were elevated in the intervention arm during baseline period (6.1 vs. 4.8 or 4.2). Overall bacteremia rate was nearly 50% higher in ICUs that were randomized to the intervention! The intervention itself brought bacteremia rates down to what they already were in other ICUs.

The effect on bacteremia was mostly skin commensals such as coagulase negative Staphylococcus. As in Climo et al, this is probably the least important organism and may relate to decreasing contamination rates. We think this point is also important in the Climo paper, chlorhexidine bathing only had an effect on VRE acquisition and not MRSA acquisition and only had an effect on coagulase negative Staphylococci and candida bacteremia.

MRSA Clinical Cultures are a mixed group of colonization/infections that vary depending on sites. Is MRSA in the sputum the same as MRSA in a deep surgical wound? Or urine culture? or superficial wound culture? Did the frequency of culturing change during the intervention. Given data was obtained from a datapull, all of these questions could be answered which would help interpretation of this trial.

Although the trial is being hailed as a nail in the coffin of active surveillance culturing for MRSA, there are potential harms with over interpretation of the trial. If we begin using mupiricin and chlorhexidine on all ICU patients nationwide, as our European colleagues have suggested will occur, we may eventually have as many problems from the study as early studies of ASC. We also think that one cluster randomized trial should not change practice in such a sweeping manner.

From a more cautious perspective, this trial and Climo et al support that chlorhexidine bathing likely has a benefit on infections in the ICU. It isn't a huge effect and it is predominantly on markers that aren't as important (MRSA clinical cultures and coagulase negative Staphylocci AND CANDIDA (and VRE for Climo)). However, it should be considered by hospital ICUs with problems in these infections.

We should be worried that ASC may be finished only to be replaced by an equally problematic mandate (that more than swabbing every patient is actually treating every patient)."

We will also soon feature a guest blogger from a healthcare system with a long history of using active surveillance for MRSA control.  He also has quite a lot to say about REDUCE MRSA. We welcome all of our readers to weigh in, please feel free to do so in our comments section! The name of this blog begins with the word "controversies", after all....