No abstract

No abstract

No abstract

isolates from patients later treated with cefazolin. Upon receipt, the isolates were classified and tested for response to 12 commercial antibiotics. A single passage of the organism was made, and samples were frozen at -70 C for additional trials.Antibiotic disks. Cephalothin 30-,ug disks were purchased from BBL. The 30-iAg cefazolin disks were prepared in the BBL laboratories under controlled conditions conforming to their commercial production of susceptibility disks. The disks were assayed for stability over a 1-year period in both BBL and our laboratories and found to have no significant loss in potency when stored at 4 C. The assays were performed by the FDA performance plate test method described in the Federal Register for cephalosporin disks (2).Disk susceptibility tests. The procedure employed was essentially that of Bauer and Kirby (1) and later was detailed in the Federal Register (3). Clinical isolates first were grown in Trypticase soy broth, adjusted to a standard optical density, and swabbed on the surface of a petri dish containing Mueller-Hinton agar (BBL). Duplicate disks were placed on the agar surface with sterile forceps. All plates were incubated at 37 C for 18 h.

Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs.