Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology
- Franklin D Lowy, MD
Franklin D Lowy, MD
- Professor of Medicine and Pathology & Cell Biology (in Epidemiology)
- Columbia University, College of Physicians and Surgeons
Methicillin is a semisynthetic beta-lactamase–resistant penicillin that was introduced in 1959; shortly thereafter, isolates of Staphylococcus aureus and coagulase-negative staphylococci with methicillin resistance were described. Outbreaks of methicillin-resistant S. aureus (MRSA) infection occurred in Europe in the early 1960s . Subsequently, these organisms have emerged as major nosocomial and community-acquired pathogens.
Three pandemic MRSA clones have been traced back to the original 1959 MRSA isolates in Denmark and England . In addition, molecular typing of MRSA strains collected from many geographic areas has revealed that five major MRSA clones emerged worldwide by 2002 . The epidemic community-associated MRSA strains in the early 2000s appear to have emerged from earlier epidemic clones [4-6].
Our understanding of the genetic mechanisms responsible for methicillin resistance will be reviewed here. Virulence determinants for community-acquired MRSA are discussed separately, as are mechanisms for S. aureus with reduced susceptibility to vancomycin. (See "Virulence determinants of community-acquired methicillin-resistant Staphylococcus aureus" and "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin".)
Methicillin resistance requires the presence of the mec gene; strains lacking a mec gene are not methicillin resistant. Methicillin resistance is defined in the clinical microbiology laboratory as an oxacillin minimum inhibitory concentration (MIC) ≥4 mcg/mL . Other methods of detection, such as the use of the cefoxitin disk diffusion test or one of several polymerase chain reactions to detect the mec gene, are also used. Isolates resistant to oxacillin or methicillin are also resistant to all beta-lactam agents, including cephalosporins (with the exception of ceftaroline and ceftobiprole, fifth-generation cephalosporins). MICs of ≤2 mcg/mL are considered susceptible.
MOLECULAR MECHANISM OF METHICILLIN RESISTANCE
mec gene — The presence of the mec gene is an absolute requirement for S. aureus to express methicillin resistance. The mec gene is absent from susceptible strains and present in all resistant strains [8-10]. The structural component of the mec gene, mecA, encodes the penicillin-binding protein 2a (PBP2a) that establishes resistance to methicillin and other semisynthetic penicillinase-resistant beta-lactams.
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- MOLECULAR MECHANISM OF METHICILLIN RESISTANCE
- mec gene
- - Penicillin-binding protein 2a
- - Staphylococcal chromosomal cassette mec (SCCmec)
- - Origin in coagulase-negative staphylococci
- EXPRESSION OF METHICILLIN RESISTANCE
- fem genes
- Borderline resistance
- LABORATORY DETECTION
- Rapid testing
- Antimicrobial susceptibility testing
- - Elevated vancomycin MIC