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The time rates of binding of three antibiotics of similar chemical structure, each with differing degrees of protein binding, were determined. Cephaloridine, which is 10% bound by serum proteins, was bound at a more rapid rate than cephalothin, which is 40% bound by serum protein. Cefazolin, bound 80%, required for longest time period for maximum binding to occur. The rate of protein binding appears directly related to the total percentage bound. The data from this study indicate that prolonged rates of binding of highly protein-bound drugs may influence pharmacological studies.

Seven serotypes of Klebsiella pneumoniae isolated from different patients demonstrated resistance to the same eight antibiotics. A plasmid carrying resistance determinants to these antibiotics and mercury salts could be transferred in toto to a plasmidless strain of Escherichia coli. All E. coli transconjugants showed the same antibiotic resistance pattern. Digestion with restriction endonucleases yielded patterns that were identical for each of the R-factor transferred from the multiply resistant serotypes. Moreover, deoxyribonucleic acid-deoxyribonucleic acid hybridization demonstrated identity between the probe, pMAC20 (an R-factor from one serotype), and all R-factors isolated from the multiply resistant strains of K. pneumoniae and the E. coli transconjugants tested.

The concentrations of metronidazole, clindamycin, chloramphenicol, cefoxitin, ticarcillin, and moxalactam in the serum, femurs, and scapulae of normal rats were measured microbiologically 0.5, 1, 1, and 4 h after intravenous injection of 15-, 15-, 20-, 40-, 75-, and 30-mg/kg doses of the respective drugs. By 0.5 h metronidazole reached levels of 3.0 micrograms/g in compact femoral bone and 2.7 micrograms/g in cancellous scapular bone. Clindamycin and chloramphenicol reached levels of 8.1 and 6.1 micrograms/g, respectively, at 0.5 h. Cefoxitin penetrated bone to a level of 2.6 micrograms/g, whereas ticarcillin and moxalactam failed to reach significant levels in bone after single intravenous doses.

Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.