Bad Bug II—Community Acquired Methicillin Resistant Staphylococcus Aureus (CA-MRSA)
By John G. Bartlett, M.D., Johns Hopkins University School of Medicine, February 7, 2006
Community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) has become an epidemic problem of serious concern in the U.S. and much of the world. The 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which was held on December 16-19, 2005, in Washington D.C., featured 11 symposia and 120 abstracts on this topic. What follows is a brief review of the more recent data.
What is CA-MRSA?
Community-acquired methicillin resistant Staphylococcus aureus is largely synonymous with the CDC’s term “USA 300,” which refers to a family of related strains of S. aureus that were originally derived from ST8, a methicillin-sensitive strain. The epidemic strain of CA-MRSA in the U.S. is clonal. It produces the Panton-Valentine leukocidin (PVL)1 and has the type IV SCC mec element2 that confers methicillin-resistance. These properties are rare in the USA 100 and 200 family, which have historically accounted for most nosocomial infections. However, recent data shows that the USA 300 strains now account for an increasing portion of these infections as well. For example, a report from Emory indicated that the USA 300 genotype accounted for 39/116 (34%) of bacteremic isolates in 2004, including 20% of nosocomial MRSA bacteremias (Seybold U, et al. Emergence of community-associated methicillin-resistant S. aureus USA 300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis 2006;42:647). A study reported at ICAAC indicated that the USA 300 strains were actually the dominant isolates in nosocomial MRSA bacteremias at San Francisco General Hospital (Chambers HF. MRSA: The San Francisco experience. 45th ICAAC, Washington DC 16-17, 2005, Abstract 1324). These data indicate a blurring of the distinction between the USA 300 strains as “community-acquired” and USA 100/200 as “nosocomial” or “health-care associated.”
The current epidemic of CA-MRSA appears to be global, but is derived from different strains of S. aureus. For example, the epidemic strains in the Netherlands and Japan are derived from ST80 and ST5, respectively. Because clinical expression and treatment are similar across strains, such clonal distinctions may not be very important clinically.
The epidemic in outpatients is a result of crowding and poor hygiene, with outbreaks described in children, prison inmates, gay men, military recruits, football players, gymnasts, wrestlers, fencers, injection drug users and homeless persons. About 33% of the U.S. population harbors S. aureus in the nose, but less than 1% have nasal colonization with MRSA. In the words of one expert, it “seems to sting and run.” Nevertheless, some unfortunate patients are subject to multiple occurrences of furunculoisis.
In outpatients, the usual presentation is furuncles, often characterized by large collections of pus that require drainage. Necrotizing fasciitis, pyomyositis and necrotizing pneumonia have been described as well. Necrotizing pneumonia is usually a complication of influenza and often has a rampant course with shock and pulmonary cavities. Of great concern is the presence of CA-MRSA in hospitals, where it now may account for more than 50% of MRSA isolates in some institutions.
Clinical expression of the USA 300 genotype in nosocomial infections is similar to that of common nosocomial MRSA infections, such as line sepsis and surgical wound infections, rather than the types of infections typically noted for community-acquired infections. Thus, the characteristics of the infection caused by this organism tend to reflect the place of acquisition rather than strain-specific idiosyncrasies.
Infection control measures for CA-MRSA are the same as for regular MRSA. Early recognition of cases is important not only for optimal management of patients, but also for the prompt implementation of infection control measures such as covering wounds and maintaining fastidious hand hygiene. Good infection control practice is critical since there are few other examples of microbes for which the evidence of person-to-person transmission is as compelling as it is for CA-MRSA.
A characteristic feature of the USA 300 strains is resistance to all beta-lactam antibiotics; however, more than 90% of strains are sensitive to gentamicin, TMP-SMX, doxycycline, fluoroquinolones, clindamycin and rifampin.
Soft tissue abscesses require drainage, but usually do not require antibiotics; when they are necessary, TMP-SMX, doxycycline or clindamycin are usually recommended.
For serious infections, parenteral drugs that are universally active include vancomycin, linezolid, daptomycin and tigecycline. Some experts think the approach with necrotizing fasciitis or pulmonary necrosis should be similar to that taken with serious streptococcal infections, which gives preference to drugs that inhibit toxin production at subinhibitory concentrations, such as linezolid or clindamycin (Micek ST, et al. Pleuropulmonary complications of PVL positive CA-MRSA S. aureus. Chest 2005;128:2732). If clindamycin is to be used as the only drug, this selection should be based on demonstration of in vitro sensitivity to clindamycin, including lack of inducible resistance with the D test.
Historically, infection with strains of MRSA was acquired in hospitals and long-term health care facilities. In contrast, CA-MRSA infection is becoming more prevalent in a number of healthy populations without prior contact with health care institutions. This epidemic is yet another example of how old pathogens can emerge with greater virulence and spread broadly. Now, infectious diseases experts are beginning to voice concern that CA-MRSA may become an even larger problem if and when pandemic influenza materializes. Further surveillance for CA-MRSA is important to further delineate the extent of the problem and to develop preventive efforts.
For an excellent review of the subject, see: Weber JT. Community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2005;41:S269-S272.
PVL is a cytotoxin encoded by genes carried on a bacteriophage, which causes leukocyte destruction and tissue necrosis. This cytotoxin has been associated with necrotic lesions involving the skin and with severe necrotizing pneumonia.
MRSA isolates possess a penicillin-binding protein 2a that has reduced affinity for binding to â-lactam agents. This protein is encoded by the mec A gene, which is carried by a large mobile element referred to as staphylococcal chromosome cassette (SCC) mec. Five types of SCC mec genes have been identified, designated as I, II, III, IVa, and IVb. The sequence of SCC mec type IV lacks non–â-lactam antibiotic resistance determinants carried on this genetic element. It has been speculated that the SCC mec type IV element possesses greater mobility and a greater propensity toward transferring to S. aureus strains with diverse genetic backgrounds via plasmids or, possibly, bacteriophages [http://www.medscape.com/viewarticle/498770_5].