Abstract
The antibiotics studied were the cefems. The MIC for ceftezole (CTZ), cefazolin (CEZ), cephalothin (CET), cephaloridine (CER) and cephapirin (CEPR) were determined by incubation in assay cultures for limited periods of time using Staphylococcus aureus 209P JC-l as the test organism and heart infusion broth (HI broth, Difco) as the assay medium. Bacterial growth was measured using a biorecorder (Toyo Kagaku) that was designed to record automatically the optical density (O.D.) of turbid broth in twelve L-shaped test tubes (L-tubes) continuously or at designated points during incubation with constant shaking at a prescribed temperature. Eleven L-tubes containing 10 ml aliquots of HI broth to which were added serial ten-fold dilutions of antibiotic (100 to 0.10μg/ml) and one control L-tube containing antibiotic-free HI broth were inoculated with 106 test organisms per ml and incubated at 37°C with constant shaking. At the end of 1 and 3 h of incubation, 10μl of broth from each tube were transferred to tubes con-taining 10 ml of fresh broth and were incubated at 37°C with shaking in the biorecorder. The time required for the O.D. to reach T-0.10 (equivalent to 108 organisms per ml) was determined by continuous readings at 5 min intervals. The difference in time for reaching an O.D, of T-0.10 between the antibiotic culture and the control was expressed as growth retardation time.
In summary, exposure of the test microorganism to 1.56μg/ml of CER for 1 h resulted in a delay in bacterial growth of up to 6h, and exposure to an increased concentration of 6.25μg/ml led to a delay of more than 15h. However, an increase in antibiotic concentration from 1.56 to 6.25μg/ml for the other four cefems resulted in prolonged growth lags that did not exceed 5h.
The organism showed a delay in growth by more than 15h after exposure to CER for a period of 3h, even with an antibiotic concentration as low as 1.56μg/ml resulted in a delay in growth by more than 15h. In addition, exposure to a comparable concentration of CEPR resulted in a delay of 12h. For the other three cefems, a three-hour exposure at concentrations of 1.56μg/ml led to growth lags of 5.4 to 6.6h, and exposures to increased concentrations of 6.25μg/ml re-sulted in a delay by more than 13, 7.2 and 7.6h with CET, CTZ and CEZ respectively. Analysis demonstrated no significant differences in lag time with exposure to 1.56μg/ml.
Significantly, the results indicate that there are marked pharmacodynamic differences among these cefems that are currently used in daily clinical practice.
