STAR*ICU study published: Barrier precautions not effective

It's only one study. Everybody take a deep breath. OK, exhale.

You might have already heard about this study and you might even know the results.  Someday, someone might discuss how this study was designed, and why the investigators decided to ship all of the microbiology specimens to NIH for processing resulting in a 5-day test turn-around time.  Someday, someone might explain why this study took 4 years to publish and the saga behind its eventual publication in the NEJM.  Someday, someone might even discuss how the difficulties completing this study might be hindering NIAID from funding other infection prevention clinical studies.  Someday, someone.

What can I say about the study?  Barrier precautions (ie. gloves or gowns/gloves) are ineffective in halting the transmission of MRSA and VRE in ICU settings.

Methods: The cluster-randomized trial (ie a largish quasi-experimental study but with a cool fancy name - see my "Random note" below) was completed in 2006 with the intervention lasting 6 months from March to August 2006. There were 10 intervention ICUs and 8 control ICUs.

Random note: There were 18 ICUs in this study, so it's somewhat like an 18-person RCT.  With such small numbers you can't expect that all measured and unmeasured confounders to be randomly distributed between the intervention and control ICUs. Thus, this is more like a large QE study than a standard RCT and needs to be analyzed as a QE study using multivariable regression controlling for known sources of confounding. Don't believe me? Check out Table 2 to see how different the intervention and control arms were in regards to topical and systemic antimicrobial exposure. You would not typically expect these "significant" differences in a large RCT (or large cluster-RCT).

Microbiology: Nasal swabs for MRSA surveillance cultures and stool or perianal swabs for VRE surveillance cultures were obtained from all patients within 2 days after their admission to the ICU, weekly thereafter, and within 2 days before or after their discharge from the ICU. Swabs were shipped overnight, 6 days a week, to the NIH. The mean number of days from obtaining surveillance cultures to reporting of results was 5.2 days.  I would have liked to see this reported in median days and I would also have liked this number to be reported from time of admission and not time from obtaining the culture since 2 days could pass between admission and obtaining the culture.

Planned Intervention: Known colonized or infected patients were placed on contact precautions. All other patients were placed on universal gloving from the time of admission until their discharge or until the results of surveillance cultures results returned. If surveillance cultures were positive, patients were upgraded to contact precautions (gowns/gloves) and if they were negative, they were downgraded to standard precautions.

Actual intervention as implemented: In the intervention ICUs, 92% of the ICU-days were spent under barrier precautions (51% contact precautions and 43% universal gloving) while in the control ICUs, 38% of ICU-days were spent under contact precautions.  Thus, indepedent of what anyone says, this study is about whether increasing barrier precautions from 38% to 92% reduces transmission. Also, 4 times as many patients in the intervention group were exposed to a topical antimicrobial (e.g. mupirocin), 12% vs 3.2%. Now, some will say that there wasn't 100% compliance with these interventions. I agree, this is not an efficacy trial.  As Ebb and I said in our JAMA commentary yesterday, cluster-randomized trials are real-world effectiveness trials in the domain of infection prevention.

Compliance: Overall, 47% of contacts in the intervention arm occurred with clean gloves and exit hand hygiene compliance vs 25% in the control ICUs. Compliance with contact precautions was relatively good in the intervention ICUs: gloves 82% and gowns 77%. Hand-hygiene compliance was also higher in the intervention vs. control ICUs (69% vs 59%)

MRSA or VRE colonization or infection: The mean incidence of MRSA or VRE per 1000 patient days at risk was actually higher in the intervention arm than the control arm (40.4 vs 35.6, p=0.35) but this was not statistically significant.

My thoughts:  How can this study not find a benefit when so many others have? Since most of the previous studies were uncontrolled quasi-experimental studies and we know that uncontrolled QE studies can over-estimate the measure of effect, it is possible that barrier precautions don't work.  It is also possible that other factors need to be included in any MDRO prevention program including attention to environmental cleaning and far higher compliance with the hand hygiene and contact precautions. However, the compliance rates reported in this study are not abnormally low (at least at the mean/median). Finally, perhaps decolonization is needed to achieve the results (at least for MRSA) that we've seen in other studies.

Another criticism that we've heard and will hear again is that the turn-around time for the microbiology was too-long.  This is mostly a red herring.  Since we have little evidence that gowns add much to gloves, and 92% of contacts in the intervention arm occurred with gloves, this study had FAR better glove compliance than we would expect with any typical ADI program in the real world.  The use of universal gloves in the pre-result period in the intervention arm really saved this study and, thus, it provides VERY useful information and should not be discounted. A quicker test turn-around would not have magically led to reduced transmission. Sorry.

Again, this is one study and it shouldn't be the last.  AHRQ is funding some very important MRSA (and VRE) prevention trials that many of us are involved with and I hope the publication of this paper won't discourage AHRQ (or NIH or CDC or VA) from funding these large and important studies.

What this study really tells us is that we can't fall back on legislative mandates in MDRO prevention and we must continue to search for the right combination of interventions along with developing better implementation strategies. Don't stop with the STAR*ICU study. Let this be the beginning.


Huskins W.C. et al. NEJM April 14, 2011

VRE Forever!

Without despair we will share
And the joys of caring will not be replaced
What has been must never end
And with the strength we have won't be erased
When the truths of love are planted firm, they won't be hard to find
And the words of love I speak to you will echo in my mind

I believe when I fall in love with you
It will be forever
I believe when I fall in love this time
It will be forever

Stevie Wonder  -  I Believe (When I Fall in Love It Will Be Forever), 1972

One of the most consistent obstacles to halting the spread of MDROs in hospitals is the ability for the organisms to persist in the environment.  Nosocomial outbreak pathogens such as MDR-Acinetobacter baumannii have been shown to persist for up to a year in vitro. Vancomycin-resistant Enterococcus faecium (VREFm) has been shown to persist for up to 4 months.  Now a new letter to the editor in the March issue of Journal of Hospital Infection suggests that we may have underestimated VREFm.

Researchers at the University Medical Centre Utrecht took an outbreak CC17 VREFm strain and a non-outbreak but concurrently isolated non-CC17 VREFm strain recovered during a year 2000 outbreak and placed 1ml at 10^9 cfu/ml of each strain in 104 bottles to dry. They then tested for recovery weekly and then quarterly.  I have pasted the survival curve below.  Survival for both strains was gradual to 10^4 at 9 months and 10^2 during the next 30 months.  Out to week 170-194 between 1-7 colonies were detected. Thus, these strains survived almost 4 years!!!

Certainly gives you something to think about.  Just another reason to love the enterococcus and Stevie Wonder - the pride of Saginaw, Michigan.

Reference: Wagenvoort et al, JHI March 2011

More Chlorhexidine Love

Just in time for Valentine’s Day, another study extols the benefits of the compound we all love, chlorhexidine (CHG). We’ve posted before about the many uses of CHG, including its use as “source control” (bathing patients to reduce bacterial burden, to decrease both transmission and infection risk). The data on source control have to this point been from ICU settings (and, to be fair, not all the data suggest effectiveness, and concerns regarding CHG resistance are valid).

Now, the Rhode Island group has examined the impact of CHG bathing on general wards as well. Using a quasi-experimental study design, the investigators performed daily soap and water bathing of all patients on four general medical wards for one year, and then used daily CHG bathing for the next year (13 months, actually). The composite rate of MRSA and VRE healthcare associated infections (HAIs) was reduced by 64% during the intervention period. Interestingly, nearly the entire difference in infection rates was accounted for by UTIs (10 in the pre- vs. 2 in the post-intervention period). Nosocomial bloodstream infection rates were exactly the same pre and post (5 MRSA and 1 VRE BSI during each time period). Clostridium difficile incidence was unchanged over the time course of the study, serving as a nonequivalent dependent variable (to assess for confounders that might be associated with a general decline in HAI rates).

Given the quasi-experimental design, small size (few HAI events), lack of a concurrent control group, etc., these data require confirmation from a larger controlled trial. I also think the study would be more persuasive if the effect was seen across all body sites, rather than UTI alone. Enough of this unromantic nitpicking—go out and buy your valentine a big bottle of CHG!

Another reason to wear a wide-brimmed hat to the beach

Attacking seagulls Dewey Beach, Delaware 2007

These days, with everyone worried about skin cancer, one shouldn't go to the beach without plenty of sun screen and one of those wide-brimmed floppy hats that protects your cabeza. Now you have another reason to look totally awesome at the beach - VRE protection.  That's right.  Researchers collected 57 faecal samples of Seagulls (Larus cachinnans) of Berlengas Natural Reserve in Portugal.  Using a combined proteomic and genomic approach they found that 95% of the gulls had detectable Enterococcus isolates with 50% being E. faecium and 10% E. faecalis with the remainder being other species. Around 10% had vanA containing VRE (Four E. faecium and two E. durans). Other resistance genes were detected including tet(M) and erm(B).

Of course finding VRE in other species isn't the true discovery here as the authors state they've identified proteins involved in both antibiotic resistance and the stress response in vanA-containing enterococci. They also suggest that their results may reflect the expression of a few membrane proteins involved in resistance which could be targets for the development of novel antibiotics.  I can't comment much on that, but I am going to wear my large-brimmed hat to the beach.

Radhouani et al. Proteome Science 2010.

New glycopeptide resistance gene cluster (VanM) found in E. faecium

Originally recovered in 2006 from a Shanghai patient with an intra-abdominal infection, the new Enterococcus faecium was highly resistant to Vancomycin(MIC, >256 µg/ml) and teicoplanin (MIC, 96 µg/ml).  The novel vanM cluster shares a similar DNA sequence to vanA, but is arranged more like vanD. At least the VanM, like VanA, confers glycopeptide resistance by the inducible synthesis of precursor ending in D-Ala-D-Lac. One less thing to learn. So now we have to remember vanA, vanB, vanC, vanD, vanE, vanG, vanL and vanM. The enterococcus sure has been busy making new VREs.

November 2010 AAC article Xu X., et al.

Gloves and gowns are not enough...

Back at Maryland, we had a surgeon who always asked for evidence that hand hygiene was necessary if he wears gloves. We gave him some evidence, but like many clinicians, he wanted data from his own institution. I guess everyone is the exception. Like good soldiers, we proceeded to collect that data. We gathered a great team over the years - Graham Snyder, Stephen Liang, Catherine Smith, Hannah Day and others to approach healthcare workers (HCW) before they entered patient rooms and collect cultures on their hands before entry and gowns/gloves after exiting the room.

The initial study from this work was published by Graham Snyder et al in ICHE 2008. He reported that MRSA was detectable on 19% of gowns/gloves of HCW after exiting an MRSA+ patients room, while that result for VRE was 9%.

The latest report from this group published in this month's ICHE by Dan Morgan et al, provides somewhat more humbling data. HCW had MDR-acinetobacter on their gloves 36% of the time after entering a colonized/infected patient's room. Wow. But the truly humbling finding was that after removing their gloves, 4.5% of the HCW still had it on their hands. Thus, while gloves reduce contamination of hands by around 85% per contact, to achieve true infection prevention, HCW must wash their hands after they remove there gloves.

I have posted Table 2 from the paper, which shows the likelihood of HCW contamination that would occur at various levels of compliance with contact precautions and hand hygiene. Even with 90% compliance with both wearing gloves and hand hygiene, almost 1% (0.8%) of contacts would be expected to contaminate the HCW hand and place them at risk for contaminating other patients and the environment. Multiply that 1% (or higher if lower compliance exists) by the number of HCW that enter the patients room in a day and you have an estimate of the daily transmission of MDR-AB. This sort of data highlights the Achilles heal of active detection and isolation strategies. No matter how much effort and money go into rapid detection of MDR organisms, without 100% compliance to gowns and hand hygiene, the effort is wasted. We have shared this data with our favorite surgeon. The description of how that went must wait for another study, or at least another day.

Graham Snyder 2008 ICHE paper (here)
Dan Morgan July 2010 ICHE paper (here)

Guidelines and conflict of interest

Annals of Internal Medicine has a new paper that caught my eye-- The Vexing Problem of Guidelines and Conflict of Interest: A Potential Solution. As you read it, think about how this applies to SHEA's Guideline for Preventing Nosocomial Transmission of MRSA and VRE.