Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to methicillin and other commonly used antibiotics such as oxacillin, penicillin and amoxicillin. MRSA infection, occur most frequently among persons in hospitals and healthcare facilities who have weakened immune systems. MRSA infections that occur in healthy people who have not been recently hospitalized are known as community-associated MRSA infections.
Approximately only 10% of S. aureus isolates are susceptible to penicillin. However, many S. aureus strains, while resistant to penicillin, remain susceptible to penicillinase-stable penicillins, such as oxacillin and methicillin. Strains that are oxacillin and methicillin resistant, historically termed methicillin-resistant S. aureus (MRSA), are resistant to all ß-lactam agents, including cephalosporins and carbapenems. Hospital-associated MRSA isolates often are multiply resistant to other commonly used antimicrobial agents, including erythromycin, clindamycin, and tetracycline, while community-associated MRSA isolates are often resistant only to ß-lactam agents and erythromycin.
There are three resistance mechanisms contribute to methicillin resistance in S. aureus. These are (1) the classic type, which involves production of a supplemental penicillin-binding protein (PBP) that is encoded by a chromosomal mecA gene, (2) hyper ß-lactamase production, and (3) production of modified PBPs, which lowers the organism's affinity for ß-lactam antibiotics.
Strains that possess the mecA gene (classic type) are either homogeneous or heterogeneous in their expression of resistance. All cells in a culture may carry the genetic information for resistance, but only a small number may express the resistance in vitro. This phenomenon is termed heteroresistance/heterogeneous.
Accurate detection of methicillin resistance may be difficult due to the presence of two subpopulations (one susceptible and the other resistant) that may coexist within a culture of staphylococci. Cells expressing heteroresistance grow more slowly than the oxacillin-susceptible population because, only 1 in 104 to 1 in 108 cells in the test population express resistance and may be missed at temperatures above 35°C. Hence it is recommended that incubating isolates being tested against oxacillin, methicillin, or nafcillin at 33-35° C for a full 24 hours before reading.
Oxacillin and cefoxitin disks were used instead of methicillin to screen MRSA because oxacillin maintains its potency for longer duration than methicillin and is more likely to detect heteroresistant strains. However, cefoxitin is an even better inducer of the mecA gene and it gives clearer endpoints without intermediate result.
The Clinical and Laboratory Standards Institute (CLSI), recommends the cefoxitin disk screen test, the latex agglutination test for PBP2a, or a plate containing 6 μg/ml of oxacillin in Mueller-Hinton agar supplemented with NaCl (4% w/v) as alternative methods of testing for MRSA.
Click here for a review article on "Methicillin-Resistant Staphylococci" published in 1988.
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