CHICAGO, IL—The last decade has seen an explosion in drug-resistant infections, with the most common organism isolated in patients with methicillin-resistant Staphylococcus aureus. And while the general public and many physicians still consider MRSA to be a problem that falls solely into the realm of hospitals and other health care facilities, the infection poses significant problems for families and communities.

Researchers at the University of Chicago’s MRSA Research Center are currently looking at how MRSA spreads outside the hospital—what are the vectors of infection and what ways might that infection be slowed or stopped in its tracks.

A Community Problem

Staphylococcus aureus is an organism that has become well-adapted to its human host and able to colonize as many as 35% of humans asymptomatically, or turn on its host, causing a wide variety of infectious skin diseases and soft tissue infections. The methicillin-resistant version of the disease brings the added problem of antibacterial resistance. And after 10 years of study, researchers recognize that there are strains of MRSA circulating in the community that were never seen in a hospital.

“It’s become widely appreciated that there is an epidemic of community-associated disease that is represented and propagated by new strains that are not the strains that were ever circulating in the hospital,” explained Dr Robert Daum, principal investigator at the MRSA Research Center. “MRSA is really a community problem now. And if the public could be educated to that fact, it would be a major advance. But the public still thinks of it as a hospital infection or a health care associated infection, and that’s just not right.”

According to the Centers for Disease Control, there are an estimated 292,000 hospitalizations with a diagnosis of S aureus infection annually. Of these, approximately 126,000 are related to MRSA. Centers for Disease Control studies conducted at the early part of the decade showed that as many as 15% of MRSA strain patients infected were community-associated MRSA (CA-MRSA), but that as many as 75% of skin and tissue infections were caused by those strains.

“With the recognition of the community-based nature of the epicenter of the problem was the identification of brand new strains, the most prominent of which is called USA300, which is an S aureus strain [that] has a methicillin sensitive form as well,” explained Dr Daum. “We’ve been trying to develop a research agenda to cope with this shifted emphasis into the community and try to understand what the issues are that are allowing the strain to propagate, to spread in the community, to infect new kinds of populations, and understand how best to treat it.”

Household Contact Study

MRSA spreads rapidly within a family setting. If one family member is identified as infected, it is very likely that others in the family will soon become colonized as well. The MRSA Research Center is currently being funded by the National Institutes of Health to investigate how MRSA travels from person to person within a household in the hopes of better understanding the organism and how it spreads.

“Every day we see who has [a positive lab test for MRSA at the University of Chicago hospital]. We contact the patient by phone, who is almost always an ambulatory patient. We make a date, if they’re willing, to allow us to come to their house and culture every member of the family at multiple sites, and also selected inanimate objects that might have staph on them,” Dr Daum explained. “And we return to the house a total of three times over 6 months,andwe accumulate dataon whogot infectedin the house overthattime, and whoremainscolonized and whoisn’tcolonizedanymore.”

And colonization does frequently occur among members of the same household. But to know that an organism is contagious is not the same thing as knowing why it is contagious. “MRSA is a very contagious disease within households, but whether it’s for genetic reasons or environmental reasons, we don’t know,” Dr Daum noted. “It’s very important to try to understand what that means when we say it’s a contagious disease. Just how contagious? How commonly are these families colonized and infected with MRSA themselves?”

The Household Contact Study is still enrolling, and it will be several years before data from the study is available. But according to Dr Daum, patients and their families are usually very accommodating. “The general public, more and more, gets it now,” he declared. “That is to say, when you call people and tell them someone in their house has been identified with having MRSA and it’s contagious, and can we come out and help them stop the spread or understand the parameters of spread, people are willing to open their doors to us.”

MRSA in Jails

“One of the interesting things that’s happened with the MRSA epidemic, which began 10 years ago, is that there have been outbreaks of disease in populations that have never had outbreaks before. Sports teams are one example. Jail detainees are another. There have been outbreaks in jails scattered throughout the country,” Dr Daum explained.

To address this, the MRSA Research Center is undertaking a CDC-funded study looking at ways to stop the spread of MRSA inside the Dallas County Jail. “Jails, unlike prisons, are high turnover facilities. That is to say, every 90 days the jail population turns over 90%,” Dr Daum said. “These are largely young African American men, and if you think about the 90% turnover, it means that they’re going in and out of the inner city communities and back and forth to the jail. And carrying their MRSA strains with them. MRSA is occurring at very high rates there.”

MRSA Research Center staff recently published a paper focusing on the Cook County Jail in Chicago, the largest jail in the United States, which showed MRSA is by far the commonest cause of skin infections among detainees and occurs at a very high rate. “We’re seeing the same thing in Dallas,” Dr Daum said. “And what we’re doing in Dallas is an intervention study. We randomize groups of detainees housed together in the jail, and we’ve randomized them either to wipe themselves with chlorhexidine cloths that were made special for us, or lotion cloths that lack chlorhexidine, or not wipe themselves at all.” The code on the study is set to be broken, with results expected within the next 6 months.

Embracing Prevention

But what happens when researchers come back with proven, evidence-based practices that can facilitate MRSA prevention in households, jails, and other places? How easily will people and institutions embrace them?

“I think the answer is going to depend on what the intervention is that we’re asking people to do,” Dr Daum said. “Depending on the complexity of it and the amount of stress the unit—the unit being a family or jail—feels at having MRSA in their environment. That’ll motivate them to carry out a plan or not. Without knowing what plan we’re asking people to execute, it’s kind of hard to speculate. If we come back and tell them they can stop the spread by doing “X” activity for a week, such as wiping down surfaces or taking an antibiotic or putting a topical antibiotic on their bodies, [I think] people are going to be highly motivated, because they fear this disease.”

Dr Daum also believes that officials in charge of jail populations are similarly motivated. “We have found in the jails, there are many people who have told us that they know that MRSA is a problem in jails, and when someone in one of these institutions gets a MRSA infection, they want that person out. When we set up the study in the Dallas County Jail, we did not include the guards in the study design, and many of the guards came up to us and said, ‘We need something too.’ My belief is that people are scared of this, and if we can identify the correct strategy for them to do, we’ll try and carry it out.”

However, if that intervention becomes more difficult, it might be a factor in families embracing the intervention. The role of inanimate objects and household pets in the spread of MRSA remains unknown, and treating pets as well as people might be necessary to fully stop the spread of the organism. “Getting people to put an antibiotic in their nostrils to decrease colonization is one kind of effort. Getting them to take their dog to the veterenarian if that becomes an important part of this equation becomes another,” Dr Daum admitted. “There are levels of inconvenience that will cause people to differ in terms of them being able to carry out decolonization programs.”

Deconstructing the Organism

The Center’s researchers are also looking at the problem from the inside out, examining what internal mechanisms make MRSA so infections and so resistant to antibiotics. Currently they are looking at the USA300 strains to discover what makes them so virulent. “We’ve understood that [making a strain of Staphparticularly virulent] probably is not a matter of acquiring new genes, but upregulating new genes that Staph currently already has, upregulating them so they’re overexpressed,” Dr Daum explained. “And by being overexpressed, they appear to be more virulent. Staphyloccocus has these amazing master gene control mechanisms called global regulators [that fire up and turn] on multiple genes all over the cell that are involved in expressing virulence. Now trying to figure out what the mechanism is of that hyperexpression.”

Dr Daum expects some results of that study within the next couple of months. “In addition to that, we’re working on a signal transduction system, which is a regulator in the cell wall of Staph strains that senses cell wall stress, so that anything that’s threatening the integrity of the Staphylococcal cell wall, this two-component signal transduction system reacts and fires up in reaction to cell wall stress,” Dr Daum said.

And antibiotics are a prime example of something that causes cell wall stress. When they encounter a MRSA cell, this system within the cell reacts strongly. “They turn it on like crazy,” Dr Daum declared. “So we’re trying to understand how the system works. We have some some knockouts of the genes in the two-component system and we’re understanding that the organism can’t seem to express antibiotic resistance in the knockout strains, which is very curious. And so we’re trying to understand how it is that resistance expression is blunted in these knockout strains.”

He added, “It’s a very contagious disease, and what the organism has in terms of its secrets and its ability to cause disease, we haven’t figured that out yet. But we’re working on it.”

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