MRSA: What it means for both large and small-animal practitioners (Proceedings)

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MRSA: What it means for both large and small-animal practitioners (Proceedings)


What is MRSA?

Staphylococcus aureus is an important human pathogen and is a significant cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices. Staphylococcus aureus can colonize the skin and nares of humans which facilitate its transmission, particularly in the healthcare setting.

Staphylococcus species are ubiquitous non-motile, non-spore-forming Gram positive cocci bacteria that produce catalase which grow primarily as facultative anaerobes. Taxonomically, the Staphylococcus genus falls under the phylum Firmicutes, class Bacilli, Bacillales order, and Staphylococcaceae family. Members of this genus are characterized by being round, typically 1μm in diameter and can be found as single cells, pairs, or tetrads though they are prone to clumping into bunches, giving rise to the cocci designation, a name derived from the Greek kókkus which means grain, seed, or berry. Phenotypically, the staphylococci are usually further classified according to the presence of the active coagulase enzymes which induces rabbit plasma to clot.

Staphylococci are found on the skin and on the mucous membranes of humans and animals; many strains are host specific and may or may not cause disease in the host. Commensal bacteria colonize the skin, filling an environmental niche and helping to protect the host from colonization by pathogenic bacteria by competing for nutrients and preventing the adherence of pathogenic bacteria. They can also directly deter pathogenic bacteria by excreting toxic metabolites which make the local environment untenable to other bacteria. In humans, commensal staphylococci are generally coagulase-negative species with S. epidermidis and S. hominis being the most commonly identified.

Methicillin-Resistant Staphylococcus aureus (MRSA) emerged in 1961 after the introduction of methicillin in 1959 for treatment of penicillin-resistant staphylococci. Since its emergence, MRSA has become an important problem in human medicine and presents a challenge to treatment due to its tendency to be multiply drug resistant.

Medical advances in therapeutics have continuously sought to overcome the bacteria's incursions. Prior to the development of antibiotics, little could be done against this and other bacteria. But the addition of penicillin to the clinical formulary in 1948 revolutionized medical management of infectious bacterial diseases. Penicillin and members of the beta-lactam antibiotic class are bacteriocidal as they target the bacterial enzymes involved in cell wall biosynthesis, known as the penicillin binding proteins (PBP), thereby preventing cross-linking of the peptidoglycans in the bacterial cell wall and inhibiting cell growth ). S. aureus soon adapted to the new environmental pressure with some strains developing resistance to the beta-lactam antibiotic within a year. These resistant strains produced penicillinases (also known as beta-lactamases) that attacked the penicillin's four-membered beta-lactam ring structure by disrupting the amide bond of the ring and inactivating the antibiotic. These plasmid-encoded penicillin-resistant strains soon became widespread and comprise the first wave of antibiotic resistance in the hospital setting, necessitating a new therapeutic option.

A new line of antibiotics, fortified against the beta-lactamases produced by the bacterium were developed to target these newly resistant strains. Methicillin, a beta-lactamase-resistant antibiotic was first used in 1959 and demonstrated efficacy in inhibiting cell wall synthesis by bacteria despite the presence of beta-lactamases. However reports of resistance to methicillin and members of its class surfaced by 1961, denoting the start of the second wave of antibiotic resistance. Though methicillin is no longer clinically utilized, S. aureus strains that exhibit resistance to the beta-lactamase antibiotic class are known as methicillin-resistant S. aureus (MRSA). In order to meet this classification, a MRSA strain must demonstrate a minimum inhibitory concentration (MIC) of oxacillin (a laboratory standard for the beta-lactamase class) ≥4μg/mL. Alternatively, a zone of inhibition ≤10mm around an oxacillin-impregnated disk would be considered resistant when performing a disk diffusion test. Staphylococcus aureus are further typed by the genes they actually carry. Several genetic epidemiological methods such as pulsed-field gel electrophoresis (PFGE) are utilized to study the differences between strains.

It stands to reason, therefore, that the presence of antibiotic resistance limits the clinician's ability to prescribe pharmacological agents that will curb the spread of the bacteria. Combine this with the presence of other virulence factors identified in S. aureus and it is evident that the bacterium poses a threat to the wellbeing of people and animals.