Differential Inactivation of Cephapirin vs. Cephalothin by Penicillin-Resistant Strains of Staphylococcus aureus: A Preliminary Study

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Abstract
The bactericidal effectiveness of cephapirin and cephalothin against small (∼105) and large (∼108) inocula of penicillin-resistant Staphylococcus aureus was evaluated. With the smaller inoculum, no differences in bactericidal activity between the two drugs (tested at 2 and 40 µg/ml) were seen after incubation for 2, 4, 6, or 24 hr. Neither cephalosporin effectively killed a larger inoculum in a concentration 250 times the minimal bactericidal concentration for selected strains. Total inactivation of cephapirin (40 µg/ml) by eight of 13 strains was demonstrated with the larger inoculum. These preliminary studies indicate that inactivation of cephapirin is pH-dependent. No strain inactivated cephapirin in ≤4 hr. Inactivation was independent of temperature at 37 C and 42 C. Although cephalothin was resistant to inactivation under the same conditions, the inoculum required to inactivate cephapirin was not killed by 100 µg of cephalothin/ml. Although strains of S. aureus that slowly inactivate cephapirin appear to be prevalent, no strain that rapidly inactivates this cephalosporin was identified.

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