Comparative beta-lactamase resistance and antistaphylococcal activities of parenterally and orally administered cephalosporins

Abstract

Two parenterally administered cephalosporins (cephalothin and cephapirin) and four orally administered cephalosporins (cephalexin, cephradine, cefatrizine, and cefaclor) were investigated by use of 29 beta-lactamase-producing strains of Staphylococcus aureus for determination of their relative rates of hydrolysis (RH) by beta-lactamase (RH of penicillin G =100) and their antistaphylococcal activities. Cephalothin (RH less than 0.01) and cephapirin (RH = 0.1) were relatively stable in the presence of staphylococcal beta-lactamase. Cephalexin and cephradine (RH of each = 0.3) were less stable than cephalothin and cephapirin but more stable than cefatrizine (RH = 1.4) and cefaclor (RH = 3.4). Agents that were more resistant to hydrolysis were affected less by the size of the inoculum when tested against large ;(10(7)) and small (10(3)) inocula of beta-lactamase-producing staphylococci than those that were hydrolyzed rapidly. Cephalothin and cephapirin were four to eight times more active than the orally administered cephalosporins against 10(3) staphylococci. Cephalosporins that are relatively stable in the presence of staphylococcal bata-lactamase may be preferable to less stable ones for treatment of serious infections due to beta-lactamase-producing staphylococci.