Lead study author answers key questions
A recently published MRSA study showing a universal decolonization approach is more effective than active detection and isolation (ADI) has prompted critical questions from proponents of ADI.1We asked lead author Susan Huang, MD, to respond to some of the issues raised, and she provided the following answers via email to Hospital Infection Control & Prevention.
While ADI proponents cite more than 200 studies support their approach, they say the decolonization research is a single study that should not be the basis for changing practice.
Huang: "A large clinical trial such as the REDUCE MRSA Trial can only occur after a foundation of pioneering studies that suggest benefit. There have been several pioneering single center and small multi-center studies suggesting a benefit from universal ICU decolonization that allowed this trial to occur. In conjunction with the other two cluster-randomized ICU trials2,3 published earlier this year — that compared decolonization to screening and isolation and showed reductions in all-cause bloodstream infections, MRSA burden, and MRSA transmission — the evidence for a universal decolonization approach is substantial and mounting."
Barry Farr, MD, professor emeritus at the University of Virginia in Charlottesville, an early adopter and one of the pioneer proponents of ADI, cited the following issues in comments posted on the MRSA Survivors Network website.
"One problem with the study was the universal decolonization was started at the time of admission, but in the two study groups using ADI, nothing was done to control spread on the first day after admission. In contrast, if ADI was being used to control MRSA properly and it was known that > 10% of new admissions were MRSA-colonized (as in the baseline data of this study), presumptive isolation would have been used pending screening results. Failure to do this biased the study in favor of the universal decolonization arm. Moreover, the study doesn’t say exactly when the admission’ screening was performed for the two ADI groups. If the screening got done on average in the middle of the first day after admission and took a full day for results to return, that would mean that half of a patient’s ICU admission could be over before any control measures were begun (the median ICU stay in the study was three days). This is a big problem."
Huang: "The ability of the universal decolonization protocol to begin immediately upon ICU admission is a benefit of that intervention strategy. Current screening methods, which commonly use chromogenic agar, require a delay in test results of approximately one day. In the case of the REDUCE MRSA trial, nares samples were taken upon ICU admission and resulted the next day. This one-day delay is reflective of the experience of this strategy when used in US hospitals and is not a flaw in study design nor does it constitute bias. If an immediate point-of-care test for MRSA were to become available, it would provide an alternative strategy that could be tested in a different trial. Of note, recent results from a cluster randomized trial suggest that the advancement in application of contact precautions due to use of same-day PCR vs next-day chromogenic agar testing did not reduce MRSA transmission or infection. Finally, it is not routine in US hospitals to apply presumptive universal isolation when a threshold of >10% of MRSA carriers is reached."
William Jarvis, MD, a former CDC hospital outbreak investigator who is now an infection control consultant, questioned the study’s lack of information on compliance with infection control measures like hand hygiene and isolation measures in the various research arms.
Huang: "We did not monitor compliance with other gold standard infection prevention practices. However, we note that the structure of the trial to compare each hospital’s intervention period to its own baseline helps to account for differences in measured and unmeasured activities across hospitals. In addition, we were vigilant to ensure that new campaigns and quality improvement activities that would conflict with the trial were not pursued. Finally, as mentioned in the paper, HCA continued its "Aim for Zero" campaign throughout all its hospitals which was to ensure adherence to national guidelines for infection prevention."
Jarvis also observed that "the decrease in CLA-BSIs is mostly skin commensal. Other pathogens gram negative rods, MRSA, fungi etc. — did not decrease."
Huang: "The study showed a decrease due to all bloodstream pathogens. The study was not powered to evaluate individual pathogens, thus those assessments were not tested. It is worth noting that the decrease in bloodstream infections appears proportional to their usual distribution in hospitalized patients. Meaning, it is not surprising that the greatest decrease is seen in gram positives since these are known to be much more common than gram negatives or fungal pathogens. In addition, the primary analysis assessed only time to first bloodstream infection. The evaluation of time to first gram-negative infection, for example, has not yet been pursued. We note that the study was not sufficiently powered to detect a reduction in MRSA bacteremia, but that the reduction in the point estimate is similar to what was seen for the reduction in overall bacteremia.
Martin Evans, MD, an infectious disease physician at the University of Kentucky in Lexington, raised a question about mupirocin resistance, noting that it was not addressed in detail in the decolonization article but was an important issue in another study co-authored by Huang. In that study the authors stated that "Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%."4
Huang: "As for resistance, we certainly need to be vigilant and there may be certain hospitals and nursing home settings where mupirocin resistance is already high enough to prevent universal benefit. In those scenarios, weighing the meaningfulness of the proportion of patients who could benefit will be important. Unfortunately, most facilities do not know what proportion of their MRSA strains are mupirocin resistant so this has been a moot discussion outside of research efforts. Our research efforts suggest relatively low (0-15%) rates outside of some nursing homes, but I am certain the real distribution includes the full range. Alternative agents are also available that are active against mupirocin resistant strains. It is important to assess the clinical condition of the patient and the protection mupirocin can afford. Certainly the ICU is a high risk place which should garner our highest attention with respect to the prevention of bloodstream diseases."
- Huang SS, Septimus E, Kleinman K, et al. For the CDC Prevention Epicenters Program and the AHRQ DECIDE Network and Healthcare-Associated Infections Program. Targeted versus Universal Decolonization to Prevent ICU Infection. N Engl J Med 2013; 368:2255-2265.
- Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection N Engl J Med 2013 Feb 7;368(6):533-42.
- Milstone AM, Elward A, Song, et al. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: A multicentre, cluster-randomised, crossover trial. Lancet 2013;381:1099-1106.
- McDanelav JS, Murphy CR, Diekema, DJ, et al. Chlorhexidine and Mupirocin Susceptibilities of Methicillin-Resistant Staphylococcus aureus from Colonized Nursing Home Residents Antimicrob Agents Chemother 2013;57:552-558