Inactivation of Methicillin, Oxacillin, Cloxacillin, and Cephalothin by Staphylococcal Penicillinase

Bacterial resistance to penicillins and cephalosporins

“…they contain a small proportion of individuals with a high intrinsic (genotypic) resistance (Knox & Smith, 1961 ;Chabbert, Baudens, & others, 1965 ;Seligman & Hewitt, 1965). Methicillin-resistant staphylococci are also resistant to isoxazolyl penicillins (Eriksen & Erichsen, 1964) and to quinacillin . It has been claimed (Stewart & Holt, 1963 ;Eriksen & Erichsen, 1964) that the resistance of these strains is due to an increased ability on their part to destroy methicillin and isoxazolyl penicillins ; however, Knox & Smith (1963) and Ayliffe & Barber (1963), using the same strains, showed that methicillin resistance was not caused by increased 'methicillinase' activity, but was due to the intrinsic mechanism.…”

“…Methicillin-resistant staphylococci are also resistant to isoxazolyl penicillins (Eriksen & Erichsen, 1964) and to quinacillin . It has been claimed (Stewart & Holt, 1963 ;Eriksen & Erichsen, 1964) that the resistance of these strains is due to an increased ability on their part to destroy methicillin and isoxazolyl penicillins ; however, Knox & Smith (1963) and Ayliffe & Barber (1963), using the same strains, showed that methicillin resistance was not caused by increased 'methicillinase' activity, but was due to the intrinsic mechanism. Seligman (1966) showed that penicillinase-negative mutants of 5 methicillin-resistant, penicillinase-producing Staph.…”

“…aureus strains have been isolated in Great Britain (Colley & others, 1965), and further strains have been found in France (Chabbert & others, 1965), Germany (Stille & Brandis, 1965), Denmark (Eriksen & Erichsen, 1964), Sweden, Spain, Argentina and U.S.A. (Isenberg, 1965 ;Benner, Bennett, & others, 1965). It is interesting that relatively few strains have been isolated in U.S.A., where large scale use of methicillin and the isoxazolyl penicillins is comparable to that in Europe.…”

Inactivation of Cephalothin and Cephaloridine by Staphylococcus aureus

“…We have observed that cephaloridine is more active than cephalothin against penicillinase-nonproducing coagulase-positive staphylococci, but about 15% of the penicillinase producers, when a large inoculum is tested, require much larger amounts of cephaloridine than of cephalothin for inhibition of growth. Slow inactivation of cephalothin by penicillinase-producing staphylococci has been reported (Ayliffe and Barber, 1963; Knox and Smith, 1963; Eriksen and Ericksen, 1964;Gravenkemper, Brodie, and Kirby, 1965), and one group has presented evidence suggesting elaboration of a "cephalosporinase" by 63% of the strains tested (Chang and Weinstein, 1964).…”