Scoring against MRSA—studies shed light on what works

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Anne Paxton

August 2014—A race for prevention may lack the drama of a race for the cure. But to fight methicillin-resistant Staphylococcus aureus and other multidrug- resistant organisms, hospitals really have no choice. A disease with a higher number of annual U.S. deaths than for salmonella, tuberculosis, influenza, and HIV put together, MRSA can only be tamed with prevention.

Despite the fact that U.S. guidelines for the past 10 years have not considered active screening as essential, in 2012, 59 percent of hospitals were screening for MRSA. The question is: Which strategies do the best job of forestalling the infection and spread of organisms like MRSA that are difficult, if not impossible, to treat?

“Traditionally, very few randomized trials have been funded on MRSA strategies,” says Anthony Harris, MD, MPH, medical director of infection control at the University of Maryland Medical Center and professor at the University of Maryland School of Medicine. “But in the last half decade, we’re fortunate that the Agency for Healthcare Research and Quality, the National Institutes of Health, and the CDC have sponsored some trials.”
Results from two large-scale randomized clinical trials published in the past 14 months are shedding light on what works in MRSA prevention. Both the REDUCE MRSA trial of universal decolonization (Randomized Evaluation of Decolonization vs. Universal Clearance to Eliminate MRSA) and the BUGG trial (Benefits of Universal Gowning and Gloving) will inevitably change the role of the clinical microbiology laboratory as hospitals absorb the trials’ lessons and adjust their MRSA protocols.

The timing is appropriate for a number of reasons—but especially because studies giving better guidance on best practices are coming out just as the Centers for Medicare and Medicaid Services is about to raise the stakes significantly. The agency will start cutting Medicare payments to hospitals whose hospital-acquired condition rates, including infections, are out of line. From Oct. 1, 2014 through Sept. 30, 2015, hospitals getting the penalty will lose one percent of each Medicare payment.

Of those hospital-acquired conditions, MRSA may be the one with the highest profile. But a major issue in MRSA prevention is whether efforts should be directed at individual pathogens, or at people who are highly susceptible to multiple pathogens. The REDUCE MRSA study, published in June 2013, specifically addresses this question by looking at intensive-care unit patients as being especially vulnerable to infection. (Huang SS, et al. N Engl J Med. 2013: 368:2255–2265).

Dr. Platt

REDUCE MRSA involved 75,000 people who were in hospital ICUs that were randomized to one of the three evaluated regimens. “It is the largest study of its type that has ever been conducted,” says principal investigator Richard Platt, MD, MSC, professor and chair of the Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute.

The study demonstrated a substantial improvement in its primary outcome, which was clinical isolates of MRSA associated with universal decolonization, and a substantial reduction in one of its major secondary aims, which was all-cause bacteremia. “The results were quantitatively impressive in terms of the magnitude of reduction in disease burden, and we think they will have substantial value in guiding clinical practice,” Dr. Platt says.

Participating hospital ICUs were assigned to three regimens tested in REDUCE MRSA. In arm one, all admissions were screened for MRSA and isolated if the screen or the history were positive, which is the baseline practice currently at most U.S. hospitals. Arm two was targeted decolonization, meaning the screen-and-isolate policy plus decolonization by mupirocin and daily chlorhexidine baths for five days. Arm three was universal decolonization, with no screening: All patients were decolonized, and isolation was ordered if a positive clinical isolate was reported.

When the study was completed, “It was pretty clear that both of the other intervention arms were better than arm one, the surveillance culture/isolation-if-positive protocol,” Dr. Platt says. But the study found that the third arm, universal decolonization, was preferable. “It was both better and easier. It was less costly to implement and yielded a better result.”

When they set out, the researchers did not know what the results of their study would be, but he finds the results plausible. “The technique of doing the surveillance cultures and isolation if positive means that under the best of circumstances, it’s a day or two before you know the person is positive and you begin isolation. That assumes the surveillance mechanism is 100 percent sensitive, which it may not be.”

“So it might miss some people who are actually positive. That’s a reason that the regimen would reduce the amount of spread from patient to patient in the ICU. But in addition, the decolonization regimen reduces the level of bacterial colonization that a person has, so that might reduce the chance of the patient becoming sick with his or her own flora.”

It’s important to note, Dr. Platt says, that REDUCE MRSA was a “pragmatic embedded” trial, meaning it was implemented in the hospital sites in the way it would normally be used in hospitals employing their regular clinical teams, not on-site research staff.

Several studies, he says, have had results consistent with the idea that universal decolonization is beneficial, and many hospitals are evaluating adoption of the protocol. However, the fact that so many states require hospitals to do surveillance cultures to prevent MRSA is a potential problem.