MRSA is a superbug: caution advised.

Dr. Christopher J. Harrison might be a bit too casual in his outlook regarding methicillin-resistant Staphylococcus aureus ("In Fight Against MRSA, Panic Is Not a Practical Tool," Guest Editorial, January 2008, p. 14).

First, the two most disturbing aspects of MRSA are its resistance to many (and sometimes all) of the standard antibiotics and its production of molecules which puncture and injure the immune cells trying to contain the infection. Regarding the second point, Michael Otto, Ph.D., of the National Institute of Allergy and Infectious Diseases, has shown that community-associated MRSA (CA-MRSA) has a considerable amount of phenol-soluble modulin. This complex destroys neutrophils by forming pores on these white blood cells, greatly contributing to the organism's deadly potential. Although Dr. Harrison hates the terminology, this trait of MRSA does make it a "superbug" with "flesh-eating" potential.

Secondly, although many of the pharmaceutical giants are able to develop new antibiotics for these new strains of bacteria, costs are inhibitory. In 2000, a report in the Journal of Health Economics indicated a cost of more than $800 million to develop (and get approval for) a novel drug with a new molecular structure. That figure has been revised, to adjust for inflation, to $1.3 billion.

One must also add the probable legal costs, given the penchant by lawyers to initiate lawsuits, especially when dealing with virulent organisms.

As the government pays more of the cost for pharmaceuticals, including innovative drugs, this issue of development of new antibiotics is woven into many aspects of health care policy. As with most national health issues, there is not a quick solution to CA-MRSA.

Craig G. Burkhart, M.D.

Sylvania, Ohio

Dr. Harrison replies:

I thank Dr. Burkhart for his comments, and I would stress that my outlook toward MRSA is not casual. CA-MRSA has become an increasing problem in the office, clinic, and hospital.

A recent report defines a USA300 lineage for most isolates of this strain of CAMRSA that seems to have appeared approximately 10 years ago. It has acquired multiple antibiotic resistance genes and multiple virulence genes. My guest editorial mentioned some such factors: "Most S. aureus can 'eat flesh" using coagulase and other enzymes." Dr. Burkhart points out that phenol-soluble modulin (PSM) was reported by Dr. Otto's group to be a candidate factor for increased virulence, suggesting it to be more important than Panton-Valentine leukocidin (PVL). However, Dr. Otto himself, commenting on the same report, did not claim that that PSM was the single virulence gene that determines the outcome of community-acquired MRSA infections.

PSM is a pleiotropic factor with multiple effects. It has long been noted to be a factor in producing biofilm associated with Staphylococcus epidermidis, not a highly virulent or aggressive pathogen. Biofilm, however, reduces penetration of even effective antibiotics and provides an environment that allows staphylococci of any species to adhere well to foreign bodies or even to human tissue. When a pathogen combines PSM with antibiotic resistance and other virulence factors, it can be more difficult to treat, particularly late in invasive disease. So PSM's major impact may not relate only to the injury of the immune cells trying to contain the infection, as noted by Dr. Burkhart, but to other effects and their interaction with more than a dozen factors or enzymes which have accumulated in this MRSA strain. These include some that most clinicians may recognize, such as staphylococcus protein A (a super antigen), leukocidins, and coagulase itself. Most of these same virulence factors also occur in methicillin-susceptible S. aureus.

The USA300 CA-MRSA strain owes its potential for severe disease to a constellation of factors together with a universal resistance to current beta-lactams, macrolides, an increasing resistance to quinolones, and occasional although potentially increasing resistance to clindamycin. This combination can, in selected hosts or with delayed/inadequate therapy, lead to serious outcomes. However, the overwhelming majority of CAMRSA infections are mild and can be treated on an outpatient basis with trimethoprim-sulfamethoxazole or dindamycin. Most CA-MRSA strains are also susceptible to doxycycline and rifampin. Almost all are susceptible to linezolid and all have been susceptible to vancomycin.

We still need to be vigilant in detecting CA-MRSA in our patients and treat it appropriately before it produces severe outcomes. Our other role is to provide practical advice on measures to attempt prevention. Adding to the panic or recommending excessive interventions will not be useful.