Rational choice of penicillins and cephalosporins based on parallel in-vitro and in-vivo tests.
Because of the unavailability of strictly comparable data, seven representative penicillins and the five cephalosporins currently used in Britain were evaluated in parallel, both in vitro and in vivo. Penicillin sensitive and resistant strains of Staphylococcus aureus and Proteus mirabilis were the main test organisms. Minimum bacteriocidal concentrations of cloxacillin, flucloxacillin, cephalothin, and cephazolin in serum were much higher than conventional minimum inhibitory concentrations in the absence of serum. Cephalexin and cephradine showed the smallest divergence in these values. Staph, aureus beta-lactamase caused least damage to methicillin and cephradine, whereas enzymes from Escherichia, Klebsiella, and Bacillus cereus had least effect against cephradine followed by cephalexin. In mouse protection experiments, highly protein-bound antibiotics had relatively low efficacy. Cephradine had the highest mean activity followed closely by cephaloridine and cephalexin. From the data, cephradine was the cephalosporin of choice, and firm decisions were also made about the choice of penicillins.
D000818:Animals; D002510:Cephalosporinase / Q000494:pharmacology; D002511:Cephalosporins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004341:Drug Evaluation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010403:Penicillin Resistance; D010405:Penicillinase / Q000494:pharmacology; D010406:Penicillins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011512:Proteus Infections / Q000188:drug therapy; D011513:Proteus mirabilis / Q000187:drug effects* / Q000201:enzymology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology
D002511:Cephalosporins; D010406:Penicillins; D002510:Cephalosporinase; D010405:Penicillinase