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