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In S aureus, resistance to penicillin is conferred through inheritance, or new acquisition of, the beta-lactamase encoding gene balZ. Beta-lactamase efficiently opens the penicillin beta-lactam ring, rendering the antibiotic ineffective. Resistance to penicillin emerged in the early 1950s , initially in hospital settings and later spreading into the community at large. By the late 1950s, more than 50% of S aureus strains were resistant to penicillin and today, fewer than 10% respond to this antibiotic.
The semisynthetic penicillin derivative methicillin was introduced 1n 1959, in part to address penicillin resistance. However, the first cases of methicillin-resistant S aureus (MRSA) were reported in the early 1960s in the United Kingdom, Japan, Australia, and the United States. With continued use of semisynthetic penicillin antibiotics, 3 worldwide health care associated pandemic strains emerged in the 1960s and 1970s. Two additional strains have emerged in community settings. While methicillin has been replaced with oxacillin in the United States, the term MRSA continues to be used to describe the broad family of beta-lactam resistant S aureus.
Methicillin resistance is most commonly attributed to acquisition of the mecA gene that encodes a penicillin binding protein (PBP 2a) with low binding affinity for beta-lactam antibiotics. S aureus acquires the mecA gene through transfer and incorporation of a mobile genetic element (the staphylococcus cassette chromosome [SCC]) which contains the mecA gene (horizontal transmission). In addition to the mecA gene, the SCC may contain additional antibiotic resistance genes, or genes that encode toxins or virulence factors (such as Panton-Valentine leukocidin (PVL) and xxx). Investigators now recognize 5 major SCC elements based on gene composition and the setting they were originally identified in (either health care or community- associated). While the emergence of resistant MRSA in the community setting was anticipated by infection control experts, gene analysis suggests that the community-associated strains did not originate from hospital pathogens, but instead appear to represent a distinct pathway for emergence of resistant S aureus.
| Toxins |
CAMRSA |
HAMRSA |
| PVL |
77% of isolates |
4% of isolates |
| -Enterotoxin a |
58% |
4% |
| -Enterotoxin c |
50% |
0% |
| -Enterotoxin k |
62% |
0% |
| PFGE type |
US 300 |
US 100 |
| Antibiotic Resistance |
Beta-lactam resistant only |
Multiple Resistant |
| PFGE=pulsed-field gel electrophoresis. |
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Overall, health-care strains are resistant to multiple antibiotics (multi-drug resistance), an adaptive advantage in settings where large amounts of antibiotics are used. In contrast, community strains are associated with more frequent expression of toxins and virulence factors.
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