Community Associated Methicillin-Resistant Staphylococcus Aureus: A Review

Michael J. Rybak, PharmD; Kerry L. LaPlante, PharmD

Disclosures

Pharmacotherapy. 2005;25(1):74-85. 

In This Article

Virulence Factors and Toxins

Staphylococcus aureus produces numerous unique toxins and virulence factors, such as the toxic shock syndrome toxin (TSST-1), enterotoxins, and exotoxins, that can inflict severe clinical syndromes, such as septic shock, necrotizing pneumonia, and complicated skin and soft tissue infections.[43] Highly diverse and unique virulence genes appear to be characteristics of CA-MRSA that clearly distinguish them from typical HA-MRSA strains. Genomic studies have shown that CA-MRSA strains carry a range of virulence genes that are distinct from those found in other S. aureus strains. A research group compared 32 CA-MRSA strains with respect to clonal relatedness and S. aureus superantigen toxins.[35] As expected, most isolates (81%) were susceptible to a wide variety of non-β-lactam antimicrobials. Thirty-one of the 32 CA-MRSA isolates were highly related as determined by PFGE and superantigen testing, and were genetically unrelated to HA-MRSA strains. The 31 related CA-MRSA isolates produced either staphylococcal enterotoxin B or enterotoxin C. No isolates produced TSST-1. A study of the MW2 CA-MRSA strain isolated from North Dakota in 1998 identified 18 toxins that were not found in any of five comparative hospital-derived strains.[44] The genes seh and seo, which encode for superantigen enterotoxins H and O, were found in close proximity to the SCCmec complex. Enterotoxins H and O have particularly high binding affinities for the major histocompatibility complex type II molecules and were reported only in this CA-MRSA isolate. Of interest, enterotoxin H is produced in disproportionate amounts compared with other super-antigens and is involved in acute toxic shock- like syndromes.[45]

Another virulence factor specific to CA-MRSA strains is the Panton-Valentine leucocidin (PVL) toxin. This is a bicomponent cytotoxin previously reported to be produced by less than 5% of S. aureus isolates. The toxin is encoded by two genes, lukS-PV and lukF-PV, which arecarried on a bacteriophage that has incorporated itself into the S. aureus chromosome. It is capable of destroying human leukocytes and inflicting severe tissue damage. It has been associated with necrotic skin lesions and severe necrotizing pneumonia in both children and adults.[46,47] One investigator characterized 14 CA-MRSA strains recovered from patients in France who had been healthy during the 18 months before becoming infected.[33] Most patients had skin or soft tissue infections, and two patients had necrotizing pneumonia. The PVL gene and lukE-lukD (leucocidin genes) were detected in all 14 isolates. Earlier studies have shown that PVL genes are rarely detected in MRSA isolates associated with hospital infections.[48] The authors concluded that the combination of mecA and the PVL gene have created a superadaptable S. aureus strain capable of spreading rapidly through the community.[35]

A recent study investigated the genetic relatedness of five community-acquired S. aureus isolates obtained from four consecutive pediatric patients who presented with sepsis syndrome and severe pneumonia over a 3-week period in 2000.[37] Two of the patients were infected with three MSSA isolates, whereas the other two were infected with MRSA. The two MRSA strains contained the SCCmec IV element that characterizes CA-MRSA isolates. Of interest, all five isolates contained the staphylococcal toxin genes sea, seh, and seo and the PVL genes lukS-PV and lukF-PV. Analysis with PFGE revealed only one difference among the strains: the two MRSA strains, unlike the MSSA strains, contained two bands reflecting the presence of the SCCmec IV element that distinguishes CA-MRSA from HA-MSSA. According to the researchers, the genetic relatedness of these isolates suggests that CA-MRSA infections arose from MSSA isolates that successfully incorporated the SCCmec IV element.

A small town in western Switzerland was the site of a large outbreak of skin infections from September 1999-2000.[43] Twenty-two students from a single third-grade classroom had 13 episodes of skin infections that included furuncles, abscesses, and cellulitis. Two patients were hospitalized, and the rest were treated with systemic antibiotics, with or without surgical drainage. All cultures grew MSSA. One of three clones isolated was positive for PVL. This clone was associated with nine persons, consisting of classmates, teachers, and family members who were either nasal carriers or infected. Nasal carriage was detected only after six students and three relatives were noted to have relapsing episodes of skin infections over a 13-month period. The authors suggested that PVL-positive S. aureus may easily spread between persons in close contact, infecting otherwise healthy children and adults. Because of their high virulence capability, skin infections can rapidly progress to severe necrotizing pneumonia with a high mortality rate.

Another investigation described the clonal distribution of PVL-carrying MRSA strains and their association with skin and soft tissue infections in the San Francisco Bay area.[49] A total of 671 isolates collected from inpatients and outpatients during 1997-2002 were evaluated for strain relatedness and virulence factors. Approximately 70% of PVL-carrying MRSA strains were isolated from jail inmates and patients receiving surgical treatment in outpatient settings specializing in skin and soft tissue infections. Although as many as nine clonal types were identified, the vast majority (88.5%) of PVL-carrying MRSA belonged to only two clonal groups. Of interest, these two clonal groups also carried the SCCmec IV resistance element and were more likely to be associated (p<0.0001) with skin and soft tissue infections than any other infection site. Overall, the data suggest that most CA-MRSA strains probably arose from successful MSSA strains that incorporated a variety of specific virulence factors, thus improving their ability to colonize and cause infection.[1]

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