Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen in human hospitals and extended care facilities. Important contributors to the increasing importance of this pathogen include:

• Pattern of resistance to a wide range of antibiotics
  
• Opportunistic nature of the pathogen Staph. aureus is a commensal organism in people. The nasopharynx is the major source of the organism, although it can also be carried in other sites, including the intestinal tract. Studies have shown that up to 30% of people have Staph. aureus in their nose at any point in time.

MRSA strains are not considered more intrinsically pathogenic than other coagulase-positive Staph. spp.

The problem arises when MRSA colonizes a susceptible host (hospitalized patient, immunocompromised or debilitated individuals) and subsequently causes an opportunistic infection that fails to respond to conventional treatment.

The major mode of transmission is direct contact.

There are 2 mechanisms of resistance in methicillin-resistant Staphylococcus (MRS) organisms:

• Penicillin-binding proteins: All penicillins and cephalosporins (ß-lactams) require binding to a penicillin-binding protein (PBP) located in the bacterial cell wall to initiate their activity. MRSA produce a defective low-affinity PBP (PBP2a) due to the presence and activation of the mecA gene.
  
  Penicillin's and Cephalosporin's binding affinity to PBP2a is very low disabling its ability to disrupt cell wall synthesis and rendering the drug ineffective. Expression of PBP2a on a Staphylococcus organism confers resistance to ALL penicillins and cephalosporins.
  
• Cell-wall thickening: MRSA also possess a thick cell wall that makes penetration by antibiotics difficult, conferring resistance to multiple antibiotics (not just ß-lactams).

MRSA has been reported in animals (mostly in Europe) but is considered uncommon in domestic pets and rarely causes disease. When present, MRSAs are exactly the same organism that colonize people, based on extensive genetic marker testing. Studies to date indicate that although MRSAs can be transmitted from people to pets, they are not considered part of the normal colonizing flora and only transiently colonize domestic pets.

• Methicillin resistance can be tested using any of the beta-lactamase stable penicillin drugs (including methicillin) although oxacillin is most commonly used. The mecA gene is inducible so in clinical practice a patient may appear to have a sensitive Staph when in fact the antibiotic induces resistance. In the lab this means MRSAs may appear sensitive to oxacillin after 24 h incubation but not after 48 h.
  
• Cefoxitin is a much better inducer of the mecA gene, so potential resistance (if present) is seen in the first 24 h more reliably, and is currently the recommended test.
  
• Latex agglutination test for the PBP2a protein is becoming a more routine assay in human medicine as the quickest test for MRSA detection. However, preliminary work on veterinary pathogens has shown it to be less reliable as an indicator of methicillin resistance (see back page).