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    Infections are getting more serious

    Community-acquired MRSA appears to be on the rise

    San Diego - The incidence of community-acquired methicillin-resistant staphyloccocus aureus (CA-MRSA) infections rapidly increased in 2003, and the infections appear to be getting more serious, according to Dennis L. Stevens, M.D., Ph.D.

    "It's a big deal and it's only become known that it's a big deal in the last six months," said Dr. Stevens, Chief of the Infectious Diseases Section of the Veterans Affairs Medical Center in Boise, Idaho. He described the growing problem at the annual meeting of the Infectious Diseases Society of America (IDSA).

    There are no comprehensive statistics on CA-MRSA infections, but reports from around the world give cause for concern. Out of 450 infectious diseases consultants who responded to a survey by the IDSA Emerging Infections Network, 84 percent reported encountering a CA-MRSA infection during 2003, says Larry Strausbaugh, MD, an epidemiologist at the Portland Veterans Affairs Medical Center who coordinated the survey. "We were surprised," says Dr. Strausbaugh. Collectively, the respondents estimated that they had seen almost 4,000 cases during the year.

    Nosocomial MRSA has also become steadily more common in the past 10 years as strains have evolved resistance to the most commonly prescribed drugs, including vancomycin, the treatment of preference.

    Most outbreaks are still in hospital settings. In recent years, however, infections have broken out in otherwise healthy populations. According to the U.S. Centers for Disease Control and Prevention, these include children, injecting drug-users, aboriginals in Canada, New Zealand and Australia, Native Americans in the United States, incarcerated persons, and homosexual males. In recent years, four children have died from CA-MRSA infections in the Midwestern United States, Dr. Stevens said.

    Among the most surprising have been outbreaks among athletes, according to CDC reports. In separate incidents in the fall of 2000 in Pennsylvania and the fall of 2002 in Los Angeles, college football players developed MRSA infections. Nine were hospitalized in the two outbreaks. Investigators theorized that the bacteria spread through the sharing of such items as unwashed bath towels, balms and lubricants and entered the skin through areas of trauma from turf burns and shaving.

    In January 2003, two infections were reported among Indiana high school wrestlers. Neither was hospitalized.

    More puzzling, MRSA infections cropped up in February 2003 at a Colorado fencing club and in club members' households. Three patients were hospitalized. Although none of the patients reported sharing clothing, masks or weapons, such sharing was common among the club members. In addition, the patients did share a sensor wire used under clothing to detect touches. They reported areas of chafing from their fencing clothes that may have given the bacterium points of entry.

    One reason for the surge in community infections might be that a new gene for methicillin resistance has appeared. "What we're seeing is an emergence in skin and soft tissue infections of this unique strain of MRSA," said Dan Jernigan, MD, Chief of the Epidemiology Section for the Division of Health Care Quality and Promotion in the National Center for Infections Diseases. "On top of that, the bacterium has acquired a gene that makes it more likely to cause pus disease in a boil or abscess that, when it drains, is good at sharing the infection."

    The gene for methicillin resistance most often found in CA-MRSA appears to be different than genes usually seen in hospital-acquired MRSA. It is smaller than these genes and some researchers believe that this makes it easier to transfer.

    "Up until probably six months ago, you had to do some intensive epidemiological sleuthing to call it community-acquired rather than hospital-acquired," said Dr. Stevens. Now the genetic markers help to set the two types of infection apart.

    Not only are community infections more widespread, they could also be more severe. Some research has shown a toxic shock syndrome toxin-1 and staphylococcal enterotoxin to be twice as prevalent in MRSA strains as compared with methicillin sensitive S. aureus strains. There have been reports from Japan of increased toxic shock syndrome caused by MRSA. Furthermore, investigators have found a gene for the Panton-Valentine leukocidin in 96 percent of community-acquired MRSA. The gene, associated with primary skin infections and occasionally necrotizing pneumonia, hasn't been found at all in hospital-acquired MRSA, said Dr. Stevens.

    The upsurge of MRSA infections is particularly threatening because third generation cephalosporins are ineffective against it. And the recent emergence of S. aureus with intermediate resistance to glycopeptides and heteroresistant MRSA suggests that full glycopeptide resistance may soon arrive, limiting the effectiveness of vancomycin, said Dr. Stevens.

    Physicians should be on the lookout for five risk factors, said Dr. Jernigan: frequent skin-to-skin contact, compromised skin integrity, contaminated surfaces and shared items, crowding, and cleanliness.

    Physicians who believe they have encountered MRSA should begin by culturing for the disease in order to be sure of selecting the right antibiotic, says Dr. Jernigan. Though vancomycin is the treatment of choice for hospital-acquired MRSA, other antibiotics are still effective against many strains of CA-MRSA, including trimethoprim/sulfamethoxazole and tetracycline. Also, whenever indicated, physicians should treat CA-MRSA infections by incision and drainage.

    Fortunately, as MRSA develops resistance to older antibiotics, a new class of antibiotics is proving effective, said Dr. Stevens. In April 2000, linezolid (Zyvox) became the first drug in more than 40 years approved by the U.S. Food and Drug Administration to treat MRSA infections. An oxazolidinone, linezolid works by a novel mechanism of action; it binds to the 23S ribosomal RNA of the 50S subunit on the bacterial ribosome to prevent the initiation phase of protein synthesis, stopping the bacterium from multiplying.

    In a randomized, open-label trial reported in the June 2002 issue of Clinical Infectious Diseases, linezolid appeared as effective as vancomycin against hospital MRSA infections. Dr. Stevens, the principal investigator, said dermatologists should consider using vancomycin, linezolid, daptomycin (Cubicin) or quinupristin/dalfopristin (Synercid) when treating patients with skin and soft tissue infections who are systemically ill or have aggressive infection. Once the patient is better and sensitivities are available some older antibiotics like tetracycline and trimethoprim/sulfamethoxazole may be effective.

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