Pathogens & People: Flesh-eating bacteria one tough cookie

By EDWARD McSWEEGAN, For The Capital
Published June 01, 2008

There are occasional outbreaks of "flesh-eating" bacteria in the U.S. and elsewhere, and such outbreaks always attract intense media attention. A number of bacteria can cause a flesh-eating syndrome known as necrotizing fasciitis. Two of these bacteria are well known to readers. Staph is one. This bug is currently making the rounds in health clubs, schools and hospitals as MRSA. The other is strep, which is best known as the cause of strep throats. Strep, or Group A Streptococcus pyogenes, is a bacterium that could be described by the old recruiting slogan, "An Army of One." With an array of powerful enzymes and destructive toxins, GAS can cause a variety of illnesses, including strep throat, toxic shock, rheumatic fever, pneumonia, impetigo and NF. Jim Henson, the creator of the Muppets, died from a highly pathogenic strain of GAS back in 1990. The Centers for Disease Control and Prevention estimates there are about 10,000 annual cases of invasive GAS in the U.S. About six or seven percent of such cases are NF and one quarter of those NF patients will die. Not even early and aggressive treatment can always save a patient suffering from necrotizing fasciitis. Last month, the Tahoe Daily Tribune published a story about a 34-year-old woman named Tanya Gludau. She cut her finger with a kitchen knife. The small cut became infected with GAS and the highly invasive bacteria quickly spread from finger to hand to arm to chest. In order to save her life, surgeons cut away massive amounts of infected skin and tissue. The woman emerged from an induced six-week coma to find that most of her right upper body was gone. (The

woman, and the newspaper, should be commended for their mutual courage in publishing a photograph of the damage inflicted by strep and scalpel. It is a startling image that conveys the horror of NF in a way the newspaper's long article and my own few words cannot.) How does this microbial ''Army of One'' do some much damage so quickly? As with any good army, this one is equipped with a huge array of clever weapons designed to produce ''shock and awe.'' Literally. Enzymes are released to digest connective tissue, allowing the bacteria to quickly spread. Other enzymes kill the patient's white cells, break up red blood cells and degrade DNA. But the worst weapons are toxins called Streptococcal Pyrogenic Exotoxins. There are seven known pyrogenic toxins produced by different strains of GAS: A, B, C, F, G, H and J, which was recently discovered by Pat Schlievert at the University of Minnesota. In addition to being toxic and producing a skin rash characteristic of scarlet fever, they are also ''superantigens.'' Most microbial components or ''antigens'' provoke limited and highly specific immune responses. But superantigens are like skeleton keys, unlocking all of the gates that normally regulate immune responses to infection and disease. Once all of those gates are unlocked, there is a rapid proliferation of immune white cells (T-cells) and a sudden release of massive amounts of immune regulators called cytokines. The resulting "cytokine storm" often leads to shock and organ failure. Patients with NF and streptococcal toxic shock may have fatality rates as high as 67 percent. The high death rate likely is due to an unfortunate combination of invasive, toxigenic strains of strep and certain genetic patterns that make some patients highly susceptible to superantigens. Bad genes meet bad bugs with bad toxins. NF infections demand rapid medical attention. Standard practice has been to aggressively remove any dead or infected tissues, and amputate hopelessly damaged limbs. Penicillin is given to kill the multiplying bacteria, and clindamycin - another antibiotic - is given to shut off toxin production. Still, it's

not always enough. Patients die, and survivors can be left horribly disfigured and disabled. Lately, some infectious disease experts have been advocating an alternative approach that relies on more conservative surgery, and immune therapy with intravenous immunoglobulin. High doses of IVIG antibodies are thought to suppress the extreme inflammatory reactions caused by superantigens, and bind to the invading bacteria. Don Low at the University of Toronto has done a few studies using IVIG on patients with life-threatening GAS infections. He wrote at the conclusion of one small study, "The fact that seven patients with severe group A streptococcal soft tissue infections survived with this approach definitely warrants further studies … on the use of IVIG in these severe infections." Not surprisingly, there is serious debate among physicians about the merits of delayed surgery and IVIG versus traditional surgical approaches. Remembering Tanya Gludau and the other cases before her, however, I would rather take my chances with Don Low's limited data than the awful certainty of a surgeon's scalpel.

Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He works on and writes about infectious disease issues. He may be contacted at emcsweegan@nasw.org.