Methicillin-resistant Staphylococcus aureus (MRSA) continues to develop resistance to a range of therapies, according an update on the epidemic at the 48th ICAAC/IDSA 46th Annual Meeting in October. In other developments updated at the session, Panton-Valentine leukocidin does not appear to be the primary virulence factor.
With nearly 100,000 invasive infections and 19,000 deaths each year, MRSA is “the epidemic of our time,” said Robert Daum, MD, of the
University of Chicago Medical Center.
Community-associated (CA) MRSA, particularly the USA300 strain, has become the leading cause of emergency department visits for skin and soft tissue infections (SSTI) in most of the
United States, and the rise of USA300 coincides with a sharp increase in SSTI hospitalizations, according to the Centers for Disease Control and Prevention’s Rachel Gorwitz, MD, MPH. The increasing incidence of MRSA community-acquired pneumonia is also becoming a serious concern. While most invasive MRSA infections are associated with health care, onset of infection predominantly occurs in the community, Dr. Gorwitz said.
The presence of Panton-Valentine leukocidin (PVL) is associated with epidemic MRSA strains and is a known virulence factor. However, Frank DeLeo, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID), presented data suggesting PVL is not the primary virulence factor. Instead, a group of proteins called phenol-soluble modulin-like peptides (PSM), not PVL, appeared to promote severe SSTIs, pneumonia, and neutrophil lysis in animal models.
The primary management for CA-MRSA SSTIs is incision and drainage (I&D), Dr. Daum said. He noted that although most respondents to a recently published survey said they would add anti-MRSA antibiotics, there is very limited data on the efficacy of antibiotics for these infections. An NIAID-sponsored study is underway to provide some of the missing data. (IDSA urged NIAID to undertake a study like this one.)
Clindamycin is one of the top choices for empiric therapy of SSTIs, but reports of clindamycin-resistant MRSA are increasing. Some strains carry the erm gene that confers resistance to erythromycin and—sometimes—clindamycin. To assess clindamycin susceptibility, Dr. Daum strongly recommended performing a “D test,” which determines whether clindamycin resistance can be turned on. A positive D test generally—but not always—indicates clindamycin resistance. Before changing therapy, Dr. Daum advised, “Go to the patient’s bedside and see if they are already cured.”
For MRSA pneumonia, vancomycin remains the mainstay of treatment, Dr. Daum said. But vancomycin has poor bacteriocidal activity, does not penetrate tissues well, and resistance is increasing. There are a few options beyond vancomycin, but all have serious shortcomings. Daptomycin is perhaps the next-best option, but elevates creatine phosphokinase levels. Linezolid has problems with hematologic toxicity, neuropathies, and lactic acidosis, especially with prolonged use. Daptomycin and tigecycline are not recommended for pediatric cases. There are reports of resistance to all these drugs. Drugs in clinical development all have serious shortcomings as well.
“I believe we need a Staphylococcus aureus vaccine,” Dr. Daum concluded. “I think the attack rate is high enough, and the antibiotic resistance problem demands it.”
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