By Abby S. Van Voorhees, MD, October 01, 2013
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Susan S. Huang, MD, MPH about her recent New England Journal of Medicine article, “Targeted versus Universal Decolonization to Prevent ICU Infection.”
Dr. Van Voorhees: How much of a problem are methicillin-resistant Staphylococcus aureus (MRSA) infections in the hospital setting? What kinds of infections are these patients at increased risk for?
Dr. Huang: MRSA is still producing substantial problems, both from cases that are acquired in the community and come into the hospital setting and from hospital-associated infections. Even though the nation has made great strides in reducing hospital-associated infections, the CDC’s most recent data, from January of this year, suggest that Staph aureus, as the combination of MRSA and MSSA, is still the number one health care-associated infection pathogen. Staph aureus is a virulent bacterium which can affect almost all organ systems and is still a major pathogen to be contended with.
The types of infections that come from the community are usually skin and soft-tissue infections, but can also include superimposed pneumonia after influenza, for example. In the hospital, the most common things relate to hospital-acquired pneumonia, bloodstream infections, and skin and wound infections, including surgical-site infections. What’s most important is that the people who acquire MRSA, either as a carrier or those who become infected ,usually have a high-risk profile. They usually have serious comorbidities, wounds or other loss of intact skin, or devices which put them at greater risk and they commonly have multiple outpatient or inpatient visits for medical care.
The other thing that I should mention is that MRSA infections that occur in the hospital and the post-discharge setting can be quite serious; in general, about a quarter of them involve the bloodstream. [pagebreak]
Dr. Van Voorhees: Are there patient populations who are considered high risk?
Dr. Huang: The risk factors most commonly noted in the literature are diabetes, hemodialysis, wound and skin disorders including eczema or other chronic skin conditions that provide a portal of entry, those who have active cancer or are immunosuppressed, and patients with HIV or AIDS. There are other groups that are also at risk, but those are the most common and persistent risk factors in the literature.
Dr. Van Voorhees: Up until your study how did ICUs typically handle the risk of MRSA infections?
Dr. Huang: In general, a hospital’s main arsenal of prevention is to use contact precautions. Many ICUs screen patients upon admission by swabbing their noses for MRSA since the nose is the main reservoir for MRSA. Carriers are then placed into single rooms with gown and glove precautions. This means we are largely focused on preventing spread from someone who already has MRSA, whether it’s an infecting or colonizing pathogen, to someone who doesn’t. I think that’s part of the issue as we look at the U.S. where the prevalence of MRSA continues to rise. Around 8 percent of people who come to the hospital have MRSA; this is a high proportion of people who are carriers, and carriers are predisposed to infection. In recent years, a very strong interest has emerged to do something for the 8-10 percent of hospitalized patients who already have MRSA. That percentage is often even higher in the ICU and in places like nursing homes. If we can get MRSA off the body, off the skin, and out of the noses, we can prevent infection. The strategy, arising in the past decade, is to decolonize using special soaps and nasal ointments to eliminate the carrier state. That’s the thrust of this study and of others that led up to it which enabled us to do a big randomized controlled trial.
Dr. Van Voorhees: What does decolonization of patients entail? Has it been shown to reduce the risk of MRSA acquisition?
Dr. Huang: The most common regimen for decolonizing a patient with MRSA consists of five to seven days of daily bathing or showering with chlorhexidine, which is an OTC antiseptic combined with twice daily prescription mupirocin ointment to the front of both nostrils for five days. This regimen has been demonstrated to be effective in removing MRSA from the body and preventing MRSA infections. In the REDUCE MRSA Trial, it has been shown to effectively reduce MRSA burden and all-cause bloodstream infection. Other studies have found a benefit in reducing all-cause bloodstream infections with chlorhexidine alone, but there are data to suggest that it may not be as effective for MRSA as the combination with mupirocin since the nose is the primary reservoir of MRSA. [pagebreak]
Dr. Van Voorhees: Tell us about your study. What did you find?
Dr. Huang: Our study was a three-arm, cluster-randomized trial; we randomized the hospitals, not individual people. Each participating hospital was assigned a specific campaign and all of the adult ICUs in that hospital did the same thing.
The first arm screened the noses of patients who came into the ICU for MRSA. This practice is common in many hospitals and legislated by several states. Those that had a positive screen, a positive clinical culture, or a history of MRSA were placed into contact precautions as is consistent with CDC guidance for hospitals.
The second arm not only screened and isolated patients, but also actively decolonized MRSA carriers with a five-day regimen of mupirocin twice a day and daily no-rinse cloth baths of 2 percent chlorhexidine.
The third arm was the universal decolonization arm. We stopped screening, which saved those costs, and decolonized everyone. Everyone got a five-day regimen of mupirocin twice a day and daily no-rinse cloth baths of 2 percent chlorhexidine for as long as they were in the ICU. If they were only in the ICU three days they got both for three days. If they were in the ICU for three months, the mupirocin stopped after five days and the daily chlorhexidine baths continued.
What we found were two major outcomes. The first was a burden estimate, an estimate of any source of MRSA from a clinical culture that a doctor would send. We chose that as an outcome because since we were decolonizing, we didn’t want to see MRSA from any source, regardless of if it was an infecting strain or just a colonizing strain. We were able to show that the all-cause burden was reduced in the universal decolonization arm by 37 percent. Then we looked at bacteremia. We had two subsets, bacteremia due to MRSA, where we had a nice trend of reduction in the targeted decolonization group but it was not statistically significant we knew we were underpowered for that outcome. And in the other subset we looked at bloodstream infections from all pathogens and found that the middle arm, the targeted decolonization arm, was better than the routine arm, and the universal arm was better than both with a 44 percent reduction in bloodstream infections. [pagebreak]
Dr. Van Voorhees: What costs were associated with the universal decolonization arm?
Dr. Huang: In the trial, we used a 2 percent chlorhexidine cloth which currently has a single manufacturer in the U.S. We also used the trade version of mupirocin because it’s FDA-approved to clear MRSA. Nevertheless, hospitals may opt to use generic mupirocin or liquid chlorhexidine in basin baths. For chlorhexidine, the important consideration is whether the application is done properly. This should be possible with a basin bath, but more attention is needed to ensure proper dilution, skin application, and lack of rinsing. Studies are underway to see if skin concentrations following basin baths are similar to the 2 percent no-rinse cloth. If applied correctly by massaging CHG into the skin, it will bind skin proteins and protect against re-colonization of bacteria on the skin for 24 hours. So it works nicely given as a daily bath; you can protect patients every day. Cost will vary depending on the exact product used. Every hospital negotiates its own pricing. Chlorhexidine baths are approximately $6-7 per bath for the cloth, and much less if you use the liquid. It’s worth noting that liquid will lather much better with a mesh sponge. The mupirocin is between $30-40 for the entire five-day course if you use the branded version, or about $5-7 if you use the generic.
Dr. Van Voorhees: As dermatologists we’d be a little concerned that some of the patients might have found the chlorhexidine bathing harsh on the skin. Were rashes a problem in this study? [pagebreak]
Dr. Huang: We had 75,000 patients in total over the 18-month intervention period, divided across the three arms. That means about 25,000 people in the universal arm were receiving a 2 percent no-rinse chlorhexidine bath every day, plus a fraction who were MRSA-positive in the second arm. Thus, we treated between 27,000 and 30,000 people with chlorhexidine. All told, we had seven reports of adverse events, all very mild, all skin-related to the chlorhexidine, and all of them rapidly improved after cessation of product. Overall, this is a very low adverse event rate. In the literature, about 1 percent of patients have mild skin irritation, but this was far less in our study. The cloths we used have emollients in them which help keep the skin soft and prevent drying. Some data in the literature even suggest that chlorhexidine may be better for the skin than soap and water baths. However, if you use a higher percentage of chlorhexidine say a 4 percent no-rinse solution, you will get a higher level of irritation. Overall, 2 percent no-rinse and 4 percent with rinse has been very safe and well tolerated in many studies across thousands of patients.
Dermatologists may already be familiar with chlorhexidine because of its longstanding use for other medical indications. It is the gold standard for prepping the skin prior to placing a central line. Chlorhexidine plus alcohol is also considered a gold standard for skin preparation prior to surgery. Furthermore, the CDC recommends that people bathe or shower with chlorhexidine three times prior to arriving at the hospital for elective surgery. So in the past 15 years, hundreds of thousands of people have bathed with chlorhexidine for up to three days prior to surgery. That should be quite reassuring to dermatologists and other physicians who are concerned about tolerability and allergy. It’s also used often in oral care for periodontitis and gingivitis as a mouth rinse.
Dr. Van Voorhees: As caregivers primarily in the outpatient setting, dermatologists generally utilize mupirocin intranasally for patients with MRSA infections. Are there implications from your work for the patients that we see?
Dr. Huang: Yes and no. This particular trial was focused only on ICU patients and whether we were able to effect a change in post-discharge time is unknown. But we have a second trial, Project CLEAR, which is ongoing and is a post-discharge trial. Patients who are discharged with a culture positive for MRSA are randomized to education alone or education plus decolonization for MRSA. Hopefully that will have direct relevance to outpatient settings when results are known in two years.