Infectious-disease expert Stuart H. Cohen is not the type to lie awake at night worrying about potential medical nightmares. But that doesn't stop him from occasionally running "what-if?" scenarios in his mind.
Take the news last fall that nearly 19,000 people died in the United States in 2005 after being infected with a virulent drug-resistant bacterium – more than the number of people who died in the U.S. that year from AIDS. Cohen was hardly surprised, as the threat posed by methicillin-resistant Staphylococcus aureus, or MRSA, has been known for some time.
But the Centers for Disease Control and Prevention study reinforced one of Cohen's "what-if?" scenarios: As bad as these aggressive, antibiotic-resistant strains of staph are, even worse strains could be around the corner as they could become more drug-resistant.
"It's not my expectation that such strains will develop," Cohen says, "but if they somehow surface, it would definitely be a bad thing."
Cohen and other UC Davis researchers found further evidence that IV drug use is a significant risk factor for MRSA infection, at least in the Sacramento area. In a paper to be published in March, they also suggested that IV drug use could account, at least in part, for the increasing prevalence of MRSA in the urban community.
Flip side of success
Cohen, director of UC Davis Medical Center's infection control program since 1986, said hospitals have been a breeding ground for MRSA since shortly after the antibiotic methicillin was introduced into clinical practice in the 1960s.
In part, Cohen said, MRSA is the flip side of success. As medical technology has improved over the years and the number of immuno-compromised hospital patients has soared, the population at risk has increased.
"The technology in critical-care medicine has improved so that patients can be supported through horrendous illnesses," he says. "Groups that would have potentially died before – HIV patients, bonemarrow transplant patients, cancer chemotherapy patients – are now being kept alive a lot longer."
This population is fertile ground for infection with resistant bacteria, Cohen says.
Skin infections like MRSA are problematic because of the widespread use of IV lines and catheters and surgical procedures that break the skin.
The heavy use of antimicrobial medicines inside hospitals has done the most to shape the resistant strain of staph known as hospital-associated MRSA (HA-MRSA).
"This is Darwinism," Cohen explains. "If you live in a pool of antibiotics, you have to develop some strategy to be resistant or you die. It's in hospitals where the intensity of antimicrobial usage is highest, and so the [staph] organism has developed resistant genes."
Because antibiotics save lives, abandoning them is not an option. Cohen says a potential solution is to shorten the duration of antibiotic treatment.
"You can be aggressive up front and then turn it down. If the course of therapy is five days instead of two weeks, you're reducing the grams of antibiotics that are administered without withholding treatment."
Because the percentage of people on antibiotics in the community is far lower than inside a hospital, the type of MRSA seen outside the hospital is more treatable. Yet, ironically, community-associated MRSA (CA-MRSA) is, in fact, more virulent.
The strain is believed to get its potency from a protein known as the Panton-Valentine leucocidin (PVL) gene, which has been associated with the destruction of white blood cells and tissue. It is from PVL that CA-MRSA derives its characteristic signature of pus and blackened skin. Because spider bites leave a similar mark, CA-MRSA is often initially misdiagnosed.
Because of that, and because of the messiness of what Cohen termed the "PVL virulence factor," CA-MRSA is more easily transferred among groups of people than the hospital variety. That helps explain a worrisome trend, one identified in a 2006 study co-authored by Cohen that appeared in the Journal of Clinical Microbiology – the community strain that first cropped up in injection-drug users is spreading into hospitals.
Survival of the stronger
"We assume [CA-MRSA] has some kind of competitive advantage over other MRSA strains," Cohen explains. "Whether it grows faster, whatever Darwinian leg up it has, it appears to be a more fit strain than the hospital strain."
Five years ago, Cohen says, approximately 60 to 70 percent of MRSA cultures were of the hospital variety. Today, the situation is reversed.
"When cultures are sent to the microbiology laboratory, for every 100 isolates, 60 to 70 are from CA-MRSA compared to 30 to 40 that are from HA-MRSA. What this means," Cohen says, "is that CA-MRSA is spreading. In some hospitals, it's becoming the predominant hospital strain. It's a keeper strain."
Hien Nguyen, medical director of UC Davis' Acute Infections Management service, which provides intravenous antibiotic treatment on an outpatient basis, says he has been surprised at the number of people coming in with MRSA.
"We knew about MRSA, but I don't think anyone appreciated the full extent of it when we started the clinic."
Nguyen says the volume of MRSA cases has increased steadily since the clinic opened more than two years ago. He says that all of the cases seen at the clinic have been due to the community strain.
But is that strain acquiring the resistance to antibiotics that HA-MRSA has built up over the past few decades?
In the Journal of Clinical Microbiology paper, Cohen and his fellow authors wrote that CA-MRSA has probably adopted multiresistant genes from the hospital strains.
"We've seen a slight increase in the resistance patterns in the community strains, but not at the level of the hospital strains," Cohen says.
One of the worries Cohen harbors is that the two strains could end up in the same individual.
"If a patient has both these organisms, there could be a promiscuous swapping of genetic material," Cohen says. "It is not inconceivable that the resistance genes in the hospital strains of MRSA could be transmitted" to the community strains.
The result would be a new strain possessing CA-MRSA's "virulence factors plus multiple genes for antibiotic resistance," Cohen says.
Cohen emphasizes he is not saying that the creation of what would essentially be a super staph germ is likely, only that it's possible. Nevertheless, as Cohen wrote in his 2006 study, "The face of MRSA has changed."