Plagues and Peoples: Why MRSA hasn’t gone away

Scanning electron micrograph (SEM) depicts numerous clumps of methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA; Magnified 2381x. (Image: CDC)

Scanning electron micrograph (SEM) depicts numerous clumps of methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA; Magnified 2381x. (Image: CDC)

From August 26 to 29, 2014, the University of Chicago Medicine and Biological Sciences will host the 16th International Symposium on Staphylococci and Staphylococcal Infections (ISSSI). This is the second time this conference has been held in the United States in the last 28 years, and the first time in Chicago. The program, presented by leading experts from six continents, will cover “pathophysiology, omics, regulation, resistance, and therapeutic and prophylactic interventions.” Nearly 500 physicians, scientists and others from 31 countries have signed up. ScienceLife asked Robert S. Daum, MD, professor of pediatrics at the University and chair of the organizing committee for the conference: Why does this meeting have such global appeal?

ScienceLife: The most popular pathogen of the summer seems to be Ebola, not just in the news but also in the New England Journal of Medicine, which has published a series of articles on this virus over the last few months. Why have so many infectious disease specialists chosen to come so far to learn about Staphylococcus aureus?

Robert Daum: Ebola is new and exotic and lethal. But you need to remember that although this is the most extensive outbreak of that virus we have ever seen, and still growing, it is relatively rare. We know of about 2,500 cases and close to 1,500 deaths since the virus first emerged in West Africa in March. Compare that to 600,000 deaths a year from tuberculosis, around 300,000 from malaria, or 250,000 from seasonal influenza. Staph. infections are in that league.

DaumMRSA2In terms of the number of people infected, Staph. aureus is right up there, either number 1 or 2. It colonizes a high percentage of people. Almost everyone has had some sort of Staph. infection, probably several, a hangnail for instance. But it can be a lot worse than a hangnail.

Attendance levels for the conference are one indication that there is high interest. Anybody who is a health care provider of any sort should be curious, but our audience is mostly people oriented toward patients who get infections. The field is not going to rest until we have a Staph. vaccine.

SL: How does it rank as a pathogen among hospitalized patients?

RD: It’s a pathogen that spreads among hospitalized patients. For at least 20 years we’ve seen drug resistance become a community problem as well. Staphylococcus aureus is the most common organism isolated from patients. It is remarkably versatile, well adapted to living with humans. But it can also turn on its host and cause a wide variety of problems ranging from skin and soft-tissue infections to overwhelming sepsis with a rapid, downhill course.

Is the epidemic still raging or has it come under control?

Under control would be an exaggeration. At one point there was an exponential curve, going up. Nurses in emergency rooms were running from patient to patient. That hasn’t entirely gone away, but it has slowed. The emergency-room skin and soft-tissue problem has decreased by about 50 percent. We don’t know why.

How does this infection spread?

In hospitals it can spread easily, mostly by healthcare workers’ hands. That’s one of the many reasons why there is so much emphasis on hand hygiene. We’ve been studying MRSA in the community, where the household is the most important location of transmission. In households where there is a patient with MRSA, we see it spread and we see recurrence. Household fomite contamination, bacteria that persist on surfaces — doorknobs are a common example — is common. The bacteria also spread through direct person-to-person contact.

We’ve also found that when patients with a Staph. infection have been in a hospital room, there’s often still MRSA recoverable from fomites — even though the room has been thoroughly cleaned. We also know that patients who go into such a room have a slightly higher rate of MRSA infections. It’s not much higher, but it can be an issue. We need better drugs for this persistent pathogen.

DaumMRSA3Are there effective treatments for serious Staph. infections?

There were very good treatments, once, but that’s no longer so certain. In the late 1940s and ‘50s, penicillin was highly effective, but that has changed. The bacteria developed resistance. Then a second drug, methicillin, was developed, but methicillin-resistant strains of Staph aureus, what we now call MRSA, emerged as well. By the 1990s, MRSA was common in hospitals. In 1998, our group documented the emergence the community-acquired version, referred to as CA-MRSA, here in Chicago.

Many people still think of the hospital as the primary source of Staph. infections, where MRSA is spread. We’ve shown over and over again that that’s no longer the case. In fact, the community strains have been replacing the hospital-acquired strains, even in hospitals. After many years of dealing with a MRSA epidemic, first in hospitals and then in the community, more research is needed to understand the epidemiology and how the community strains evolved to cause severe disease.

Once someone has had a MRSA infection, do they develop immunity?

Sadly, no. Once you have an episode, the chances of having another episode remain very high. Michael David, MD, assistant professor of medicine at the University, has been enrolling patients who have recovered from with a Staph. infection in a study and following them for two years. About 50 percent have a recurrence.

It’s troubling when a patient who has recovered from one infection gets re-infected. It means people, or at least some people, don’t develop effective immunity. This may be part of why there is no MRSA vaccine. On the other hand, we are beginning to suspect there may be something immunologically different about people who get recurring infections. Researchers are starting to look carefully at their immune systems. How can we protect the people who are getting recurrent disease?

DaumMRSA4Has there been progress on making a vaccine?

The vaccine issue has been a problem. There are many antigens that are immunogenic, but none seem to be protective. We don’t know why. Several pharmaceutical companies have gone to the mat and tried to created vaccines in mice. They have found antigens that are immunogenic. But guess what. They don’t defend against infections. Some have focused on the capsule that encases the organism, a reasonable target. But the most problematic MRSA strain in this country, known as USA300, doesn’t make a capsule.

Big pharma has failed us here. At a meeting at the National Institutes of Health, one of them simply announced: “We have no idea how to make a MRSA vaccine.”

Is anyone from the pharmaceutical industry present at the conference?

Yes. Three companies are presenting in a special symposium: Cepheid on rapid diagnostics, Durata on their new antibiotic, Dalvavancin, and Clorox, on their favorite cleaning product.

What are the primary topics for the conference?

The meeting is focused on clinical issues. There are several big topics: immunology, molecular epidemiology, mechanisms of drug resistance and the creation of new antibiotics, as well as how to make a vaccine. The two keynote speakers will focus on how Staph. aureus interacts with the immune system and an overview of community–associated MRSA. There’s also a session on the use of antibiotics in livestock, with a focus on pigs. Most pigs on big industrial farms, as well as the people who handle them and their families, are colonized with MRSA.

DaumMRSA5Who else was involved in organizing the conference?

This was all pulled together by University of Chicago faculty. The team includes Olaf Schneewind, MD, PhD; Dominique Missiakas, PhD, from the Department of Microbiology; and Juliane Bubeck-Wardenburg, MD, PhD, and Susan Boyle-Vavra, PhD, from the Department of Pediatrics; plus a scientific committee including 19 experts from the U.S., Europe, Asia, and Australia. The next meeting, in 2016, will be in South Korea.

What is the University of Chicago presenting at ISSSI?

We’re presenting our vaccine work. This is pretty exciting. We’ve identified some antigens, good potential targets for a drug or a vaccine, including a signal transduction system, a global regulator called SAE. Christopher Montgomery, MD, assistant professor of pediatrics, presents this work: “Proteomic identification of saeRS-dependent targets critical for protective humoral immunity against Staphylococcus aureus SSTI.” That’s at 12:15 on Thursday. Do not miss it.

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