Beginning with Alexander Fleming's discovery of penicillin there has been an ever escalating arms race between microbes and
the doctors that treat life-threatening infection. Fleming's discovery saved countless lives; however, it did not take long
for bacteria to respond by developing mechanisms for resistance. Staphylococcus aureus was amongst the first to develop resistance to penicillin. Most penicillin resistance was, and continues to be, secondary
to the production of beta-lactamase. Scientists responded by developing beta-lactam antibiotics which are resistant to the
effects of beta-lactamase as well as other classes of antibiotics which are not effected by beta-lactamase.
Methicillin is a beta-lactamase resistant penicillin developed in the 1950's. Shortly after its introduction the first methicillin-resistant
Staphylococcus aureus (MRSA) isolates were identified in Great Britain. MRSA rapidly spread across the globe. MRSA developed resistance by acquiring
a plasmid the coded for a novel penicillin binding protein in the cell wall, penicillin-binding protein 2a (PBP2a). PBP2a
was unique in that this mutation makes the organism resistant to all beta-lactam antibiotics (penicillins, cephalosporins,
and carbapenems). Methicillin is no longer used clinically so methicillin resistance itself is of little concern. Instead
oxacillin, a more stable drug, is used in antimicrobial sensitivity testing. Methicillin/oxacillin resistance is important
since an organism that is resistant to methicillin/oxacillin will be resistant to all beta-lactam antibiotics. The term MRSA
is still used to describe such isolates, however, a more appropriate term would be beta-lactam resistant Staphylococcus aureus.
PBP2a is coded by the mecA gene that is found on a large mobile genetic element called the staphylococcal chromosomal cassette
mec (SCCmec). There are four SCCmec commonly identified. Each codes for a different combination of antimicrobial resistance
in addition to the PBP2a. As a result, MRSA is commonly resistant to multiple classes of antimicrobials.
MRSA isolates commonly encountered in veterinary patients
MRSA in people
Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been considered a healthcare-associated pathogen in patients with established risk factors. More
recently, however, MRSA infections have been described in community-dwelling patients without established risk factors for
the acquisition of MRSA. MRSA has become a worldwide problem, although its prevalence varies considerably among countries.
Consistently high prevalence rates are found in the USA, South America, Japan and southern Europe, whereas prevalence rates
are low in Scandinavia, The Netherlands and Switzerland. Several investigators have suggested that the epidemiology of MRSA
is changing, as infections are increasingly reported in healthy community-dwelling individuals without healthcare-associated
risk factors for the acquisition of MRSA]. Clusters and outbreaks of these so-called CA-MRSA infections have been described
in more-or-less 'closed populations', such as Native Americans, men who have sex with men, prison inmates, children attending
childcare centers, military recruits, and competitive sports participants]. Moreover, CA-MRSA has now been introduced from
its site of origin in the community into the hospital setting]. At some hospitals, CA-MRSA strains are even displacing classic
hospital-acquired strains of MRSA.
The spectrum of clinical infections caused by CA-MRSA is similar to that caused by methicillin-susceptible S. aureus, but clearly distinct from that caused by HA-MRSA. Whereas HA-MRSA commonly causes bloodstream infections and infections
of the urinary and respiratory tracts, CA-MRSA has predominantly been isolated from skin and soft tissue infections, such
as abscesses, cellulitis, folliculitis and impetigo. Although CA-MRSA infections are commonly mild, they may also be severe,
and can result in hospitalization and/or death. For example, necrotizing fasciitis caused by CA-MRSA has recently been reported
as an emerging clinical entity. In addition to skin and soft tissue infections, severe necrotizing pneumonia due to CA-MRSA
has occasionally been described in young patients without known healthcare-associated risk factors for the acquisition of
MRSA. The observed clinical spectrum of infections caused by CA-MRSA has been associated with the presence of Panton–Valentine
leukocidin genes, which code for the production of cytotoxins that cause tissue necrosis and leukocyte destruction. However,
other exotoxin genes or combinations of genes could also be important pathogenic factors.