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.


  1. In our 8 ICUs (140 ICU beds, 43,000 patient days) we had 0 MRSA CLABSIs in 2012. We do no screening for MRSA, except in our NICU. All adult patients are bathed with chlorhexidine daily. MRSA colonized neonates are treated with mupirocin.

  2. Bravo Marc. I have a question, following up on comments by Dan at a recent conference. What is the risk and issue with increased CHG resistance, especially with gram negatives?? We are seriously considering increasing our use of CHG for bathing, but I don't want to create more problems than we solve....

  3. My problem with this study was the lack of anything that looks like a control for the "decolonization." The patients in the group without decolonization didn't even necessarily get washed up daily with a terry cloth washcloth and Ivory soap. When I went to the NEJM article and downloaded the massive protocol and reviewed it I had to laugh.

    Two groups get washed daily with CHG wipes and the other gets "whatever." The groups that get washed have better outcomes in terms of infections. This is a great landmark scientific finding. Not.

    I was an inpatient (not in ICU) for 20 days post-op earlier this year (mostly due to ileus) and even ended up with a central line so that I wouldn't slowly starve... Every 2 days I would get about 6 washcloths and 2-3 towels from the nurses and spend about 45 minutes at the bathroom sink shampooing my hair and washing myself with soap (antimicrobial, but I don't think it had CHG - I unwisely left my Hibiclens at home) - literally from top to bottom and discarding washcloths along the way. And giving myself a clean shave so that I didn't look like a hobo. (My rule/advice #1 for inpatients: don't look like a hobo.) If I don't think anyone would have said anything about washing unless I started to stink. I had an 8 inch incision on my abdomen and guess what? It got infected, even though I had the pre-op CHG sponging at home the night before the operation... the infection wasn't diagnosed/evident until after I got home. Maybe they should have given me CHG wipes to use as an inpatient and to take home. I don't know. But this study basically says to me it's good to wash people everyday with an antimicrobial product when they are in an ICU. And I think to myself. OK, as opposed to what - not washing ICU patients every day? There was no distinction made between those who were "decolonized" with CHG wipes and those who were merely washed with washcloths and soap. SO I don't think this prove much, unless I misread something, which is possible.

  4. Zero in a year really is great! But Mike, that sounds like group 4 unless you use mup. Again, CHG bathing to prevent BSI? No objection. But that's not case closed. And just a clarification, 12% came in 2010-2011. By 2012 it was 14%.

  5. Neldridge that's an interesting study point. Most places I am familiar with have standard protocols but the frequency can be unit or patient specific. What is used (soap, Chg, or cloths) are also highly variable. It sounds like your experience was less optimal than I'm used to dealing with and that's not good. HCAHPS aside a clean patient is at least a happier one if not a safer one.

  6. The title of our editorial, "Case Closed," refers to active detection and isolation (no decolonization; group 1 in Huang's paper), which is the strategy that was touted for many years as the only way to control MRSA.

  7. At least we're now in a good situation rather than a bad situation. We have multiple studies that have "worked" to reduce MRSA, for example the VA program and the new one in Huang et al. And people are arguing over what's best. This is better than having nothing that works and being depressed about it.

    Before the VA program many people basically were resigned to widespread MRSA throughout hospitals and were saying it was too late to do much of about it because the bug was too well entrenched in our society in and out of hospitals. That point of view has been blown up.

    Full disclosure. I worked on the VA program although I had no role in its design or strategy, which was based on what worked in the Pittsburgh VA Medical Center and included things like "positive deviance" and an extraordinary involvement of the environment of care (cleaning) staff in addition to the usual suspects like docs and nurses. This is also what was rolled out to the VA hospitals, although it's not always mentioned. I can tell you first-hand it wasn't just talk. At conferences and meetings, logistics (purchasing) and cleaning people were literally in the same room for long periods of time listening to and being listened to by senior administrators and docs. How often does one see that? I probably remember it because it was so unusual...

    In defense of the hospital I was at - it was clear that I was in good enough shape to wash myself and maybe that's why no one ever said anything to me about it, or at least I don't remember anyone saying anything to me about it. ICU patients there may have been being washed regularly with or without a protocol. I have no idea about that.

  8. Thanks to all, we love an active comments section. Perhaps we can all agree that legislative mandates for specific approaches to HAI prevention are a bad idea. HAI threats vary by region and institution, and they evolve—so prevention approaches can’t be “one size fits all” and must also evolve (hopefully informed by good evidence).

    Mommarazzi, I know the talk you are referring to, so let me outline my concern about CHG and gram-negative pathogens: keeping in mind that we have little idea how to interpret minimum inhibitory concentrations (MICs) for topical agents, it is clear from published reports that some gram-negatives (such as KPC-producing Klebsiella) have CHG MICs that are many-fold higher than the CHG MICs of staphylococci and enterococci. In addition, the bloodstream infection (BSI) results from comparative trials of CHG bathing have been underwhelming with respect to gram negatives (and S. aureus too, for that matter). It’s tremendous to be able to reduce HA-BSI--and I don’t want to disrespect the coagulase-negative staphylococci (CoNS)--but when almost all the reductions we see are among the CoNS I worry about what is going on (or not going on) with the more virulent pathogens.

    As CHG use increases, if overall BSI rates fall, MRSA/VRE transmission rates fall, but BSI and transmission rates for gram negatives don’t budge, that’s still a victory. The question is whether that will be all that happens, or if we’ll start to see a “squeeze the balloon” effect, where the niche inhabited by relatively less virulent skin colonizers will be taken over by resistant gram-negative pathogens. It’s hard to see exactly how that would happen without further emergence of CHG resistance—but if there are any lessons that infection prevention folks should have learned by now, they include: (1) unintended consequences happen, and (2) messin’ with the microbiome (even the cutaneous/mucosal microbiome) is a complicated and risky business.

    That’s enough hand-waving and rear-end smoke blowing. I still love CHG.

    1. Thank you, most helpful, and it was a great talk. Love those microbiomes! Since we are long-term care, and our residents would get only weekly exposure to the CHG, we are going to pilot on a random sample of units for the weekly shower, and see if it does anything to the rates of UTI or antibiotic use. We have used CHG on a quarterly basis as part of a large MRSA study, and have had no complaints of any skin dryness or any other complaints or side effects. Was glad to hear that the NEJM study only had about 7 complaints of any sort of side effects (dry skin mainly).

  9. Excellent blog Marc-Oliver, I really enjoyed reading it.

    Dan, Mommarazzi, I have written a blog post focused on this article and the potential for mupirocin resistance and reduced chlorhexidine susceptibility that you may find interesting:

    Clinically significant reduced susceptibility to chlorhexidine in S. aureus has been hard to define for a number of reasons (which mostly apply to Gram-negs too) (Otter et al. J Antimicrob Chemother. 2013;68:992-9):

    1. There is no generally agreed methodology for detecting reduced chlorhexidine susceptibility.
    2. Population MICs vary considerably making a meaningful breakpoint difficult to determine.
    3. Higher MICs displayed by some isolates (4–16 mg/L) are still well below the effective chlorhexidine concentration applied to skin (10000–40000 mg/L).
    4. Although genes encoding membrane efflux pumps have been identified in S. aureus, including qacA, these have an unclear relationship with reduced susceptibility.
    5. Other mechanisms of reduced susceptibility, such as decreased uptake of chlorhexidine, may confound the apparent effect of efflux pumps.
    Although many studies have reported on qacA carriage or reduced chlorhexidine susceptibility in S. aureus isolates, few have evaluated clinically relevant outcomes.

    Notwithstanding these limitations, it is clear that the implementation of chlorhexidine based decolonization drives an increase in the carriage of genes associated with reduced susceptibility to chlorhexidine, and this may be clinically relevant based on studies from London (Batra et al. Clin Infect Dis. 2010;50:210-7) and Geneva (Lee et al. Clin Infect Dis. 2011;52:1422-30). For example, a recent article from my research lab in London (Otter et al. J Antimicrob Chemother. 2013;68:992-9) found that the implementation of universal chlorhexidine-based decolonization was associated with the selection of qacA linked with a higher chlorhexidine MIC in one dominant endemic MRSA clone (CC22), but not another (CC30). The slower reduction in the CC22 MRSA bloodstream infection rate suggests that carriage of qacA confers a selective advantage.

    So, will the introduction of universal decolonization result in resistance to mupirocin and chlorhexidine? The answer for mupirocin is a resounding yes; the answer for chlorhexidine is currently not clear.

    1. Thank you for the references! Yes, I'm waiting for some sort of nasal disinfectant that is a highly effective decolonizer with 0 Health Hazard: Something that does not leave huge holes in the natural microbiome. Also waiting for that sporocidal surface cleaner/disinfectant with a 0 Health Hazard that does not make the place smell like a tossed salad. Wish I lived in Canada...

  10. Rereading these entries and some of the papers on MRSA reduction and related topics, I'm thinking that hospital epidemiologists and related folk are maybe suffering from some physics envy. Because in physics, clear hypotheses can be established and tested. With hospitals and squishy (made of meat) patients and providers not so much. They are full of crazy confounders and intangibles (even maybe Rumsfeld's "unknown unknowns") regarding the behaviors and practices of hundreds or thousands of healthcare providers, other staff, and patients. Nice summary of "physics envy" here:


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