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SUMMARY The rates of destruction of benzylpenicillin, cephaloridine, cephalothin and (in some cases) cloxacillin by cocci from induced cultures of 17 strains of Staphylococcus aureus were measured. Rates of destruction of cephaloridine, relative in each case to those of benzylpenicillin, by the 10 methicillin- resistant strains were not significantly different from those by the 7 methicillin- sensitive strains. Vmax for cephaloridine and cephalothin were about 0.2 % and o.oog %, respectively, that for benzylpenicillin ; cloxacillin was destroyed still more slowly. The inactivation of the cephalosporins is almost certainly brought about by the action of penicillinase. Notwithstanding its greater stability to staphylococcal penicillinase, cephalothin is less effective than cephaloridine at suppressing the growth of the methicillin-resistant strains, although there is cross-resistance between methicillin, cloxacillin, cephalothin and cephaloridine. INTRODUCTtON Cephaloridine, a semisynthetic cephalosporin introduced for therapeutic use in I 964 (Muggleton, O'Callaghan & Stevens, 1964), has been shown in many laboratory trials to be highly effective in vitro against penicillinase-producing strains of Staphylo- coccus aureus. The most comprehensive of these studies to date seems to be that made by Vymola & Hejzlar (1966), who studied the sensitivities of 800 strains of clinically isolated S. aureus which were benzylpenicillin-resistant. The general conclusion reached by the workers who did laboratory trials is that cephaloridine is more active against staphylococci than is cloxacillin, especially in the presence of serum (Barber & Waterworth, 1964), and that it is at least as effective as cephalothin, in vivo and in vitro (Thornton & Andriole, 1966). Three recent papers (Ridley & Phillips, 1965; Benner, Bennett, Brodie & Kirby, 1965 ; Hye-Knudsen, 1966) have indicated that cephaloridine is inactivated relatively rapidly by staphylococcal penicillinase, and from the first two of these papers it might be concluded that methicillin-resistant strains possess some special abiIity to destroy cephaloridine ; however, all three reports give only qualitative results. The present work was done to determine whether methicillin-resistant S. aureus strains inactivate cephaloridine and cephalothin more rapidly, either relatively or absolutely, than do methicillin-sensitive strains. Quantitative measurements were made of the breakdown of benzylpenicillin, cephaloridine and cephalothin, by ten naturally occurring methicillin-resistant and seven methicillin-sensitive S. aureus strains. Cross- resistance between methicillin, cephaloridine and cephalothin was also examined.

Stability of Cephaloridine and Cephalothin to Staphylococcal Penicillinase