EDUCATION & DEBATE Fortnightly Review

Methicillin resistance in Staphylococcus aureus Staphylococcus aureus is renowned for countering almost any antibiotic challenge. Its history since the advent of penicillin is one of increasing resistance to antibiotics. Methicillin was the first semisynthetic penicillin resistant to penicillinase to be derived from the penicillin nucleus and was a major advance in the treatment of staphylococcal infections. Because of its toxicity and ineffectiveness if given orally it was gradually superseded by newer penicillinase resistant penicillins such as flucloxacillin. However, methicillin is still used for susceptibility testing of staphylococci in the laboratory and so methicillin resistance is an indicator of flucloxacillin resistance. Staphylococcal resistance to methicillin is not due to the destruction of the antibiotic by a bacterial enzyme such as P-lactamase but is related to decreased affinity of the organism's penicillin binding proteins for methicillin and also the synthesis of an extra penicillin binding protein with very low affinity for P-lactam antibiotics. Methicillin resistance in staphylococci was reported in 1961, soon after the introduction of methicillin, and naturally occurring strains may have been around before the advent of methicillin.'-3 There was a gradual increase in methicillin resistance in England throughout the 1960s, but during the 1970s attention was focused on the Gram negative bacteria, with some complacency about Gram positive bacteria. Various epidemic strains of methicillin resistant S aureus (EMRSA) appeared in the 1980s.4 The first of these, EMRSA-1, bore many resemblances to a strain that caused large outbreaks in hospitals in eastern Australia in the late 1970s.' It probably first appeared in England in 1980-1 and went on to cause majo-r endemic and epidemic problems. These were centred in hospitals in the North East Thames region of London, but also spread widely to hospitals in other parts of London and outside London." Since then