The minimum inhibitory concentration (MIC) of cefsulodin against 45 patientstrains of Pseudomonas aeruginosa, most of which were isolated from the sputum, ranged from less than 1.56 to 800 μg/ml, and 70 percent of the strains tested were inhibited at concentrations lessthan 6.25 μg/ml. Against the patient strains of Pseudomonas aeruginosa, cefsulodin was 16-fold more active than SBPC, 8-fold more active than TIPC and 2-fold more active than PIPC, and was 2-fold less active than GM.
The minimum bactericidal concentration of cefsulodin, which was needed to kill 70per cent of 45 patient strains tested (70% MBC), was 12.5 μg/ml and this value was 8 times lower than that of PIPC or TIPC and 16 times lower than that of SBPC, and was 8 times higher than that of GM.
Then therapeutic effects of cefsulodin on 6 episodes of Pseudomonas infection in 5 patients with chronic obstructive pulmonary diseases were evaluated. The patients were treated by intravenous drip infusion of 1 to 2 grams of cefsulodin twice a day for 8 to 14 days. Clinical response was excellent in one, good in three, and fair or poor in two patients. Pseudomonas aeruginosa was eradicated from the sputum of 4 patients who showed excellent or good clinical responses, but the bacilli persisted in the sputum from the other 2 patients. No adverse symptom developed and no abnormalities were detected by renal, hepatic and haematological examinations during and in one patient even at the end of administration of a total amount of 56g of cefsulodin.

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In order to ascertain clinical usefulness of apalcillin (APPC) objectively, a well-controlled comparative study was performed at 99 institutions using sulbenicillin (SBPC) as the control drug in the patients of postoperative wound infections (Trial A) and postoperative localized peritonitis and/or dead space infections (Trial B).(Total number of patients were 113 in Trial A and 108 in Trial B). Either 1g of APPC or 5g of SBPC was administered to patients by i. v. drip infusion twice a day for 7 days in Trial A and 10 days in Trial B. The results obtained are as follows:
1) Overall clinical improvement rates were 91.5% in APPC group and 66.7% in SBPC group in Trial A, and 88. 7% in APPC group and 47.3% in SBPC group in Trial B. In both trials, APPC was significantly superior to SBPC.
2) When overall clinical improvement rates of both drugs were compared in subgroups divided by the depth of infections at the lesions, APPC was significantly superior to SBPC in all subgroups in both Trial A and B.
3) As to bacteriological effects, eradication rates of clinical isolates were 90% in APPC group, 50% in SBPC group in Trial A and 99% in APPC group, 51.4% in SBPC group in Trial B. Thus, APPC was significantly superior to SBPC in both Trial A and B.
4) Rates of clinical effectiveness judged by the surgeons for each patient were 86.4% in APPC group, 61.1% in SBPC group in Trial A and 75.5% in APPC group, 45.5% in SBPC group in Trial B. Thus, APPC was significantly superior to SBPC in both Trial A and B.
5) As to usefulness judged by the surgeons for each patient, APPC was significantly superior to SBPC in both Trial A and B.
6) As to elimination on improvement of clinical symptoms and findings, days needed for such elimination on improvement, and their elimination rate scored by points method, APPC was significantly superior to SBPC in all items.
7) Side effects were more frequent in SBPC group than in APPC group. This was because there were more cases of elevated GPT values in SBPC group.
When we evaluate the usefulness of APPC against post operative infections based on the above results, we can conclude APPC is obviously more useful than SBPC even at the one fifth dose of that of SBPC.

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The pharmacokinetics of cefsulodin (CFS), a new semisynthetic cephalosporin antibiotic again. Pseudomonas aeruginosa, were examined in 6 normal subjects and 12 patients with impaired rem functions on the basis of a one-compartment open model. Each subject was injected a single 250 mg dose of cefsulodin intramuscularly, and serum and urinary concentrations were measured by a bioassay. The mean peak serum concentration of cefsulodin was 9.1 μg/ml at 1 hour after administration in normal subjects. The mean serum half-life of cefsulodin was calculated for 1.22 hours in normal subjects, and increased in patients along with increasing impairment of renal function. A significant linear correlation between the elimination rate constant and the endogeneous creatinine clearance was demonstrated (P<0.01). In normal subjects, 69.4% of the administered dose was excreted in the 6- hour urine. The urinary excretion rate declined gradually in patients as a degree of renal impairment advanced.

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A pharmacokinetic study of dibekacin, 3', 4'-dideoxykanamycin B (DKB) was conducted in 4 healthy subjects and 7 patients with impaired renal function whose creatinine clearances (Ccr) were more than 40 ml/min, in order to obtain basic data for intravenous drip infusion. Serum levels of DKB were determined with three methods, bioassay, radioimmunoassay (RIA), and enzymeimmunoassay EIA), and the correlations were examined among three methods.
The mean maximum serum concentration of DKB after 1-hour iv constant infusion of 100 mg in healthy subjects was 8.41 μg/ml, which was higher than the theoretical maximum serum concentration (6.78 μg/ml) after im injection of a single dose of 100 mg. However, there was no significant differences in the serum half-lives (T_1/2) and the serum levels in β-phase between the two routes of administration. While the mean T_1/2 in β-phase after 1-hour iv constant infusion was 2.02 hr in healthy subjects, it was 5.33 hr in two patients whose Ccr's were 48 ml/min. The maxima serum levels of healthy subjects after iv constant infusion of a dose which was normalized by body surface area were compared with those of patients. In this experiment, the maximum serum level did not increase as Ccr decreased. This was expressed in terms of the increase of the volume of distribution in low Ccr patients. A good linear relationship between Ccr and heniatocrit value (Ht) was obtained. Therefore, the increase of the volume of distribution in patients would be partially caused by the decrease of Ht.
The correlative coefficient between the two values determined by bioassay and RIA was 0.926 and that between bioassay and EIA was 0.972. The serum levels determined by EIA were 1.3-1.8μg/ml lower than those determined by bioassay when the serum levels determined by bioassay were 8-l0μg/ml. If this is taken into consideration, both RIA and EIA will be usefull methods for a monitor of the serum levels of DKB.

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1.0g of ceftizoxime was injected by one-shot intravenously preceeding 44 orthopedic surgeries. The bone marrow blood from vertebra, femoral neck, ilium and tibia was taken intraoperatively as a specimen.
The concentrations of ceftizoxime in 57 specimens were examined. The average concentration of ceftizoxime was 56.6 μg/ml at 30 min., 41.0 μg/ml at 60 min., 29.0 μg/ml at 90 min., 24.3 μg/ml at 120 min., 13.2 μg/ml at 150 min., and 5.9 μg/ml at 180 min. after injection.
S. aureus, S. epidermidis, E. coli and Klebsiella have been frequently isolated from bone and joints infections. It is reported that 3.13 μg/ml of ceftizoxime concentration inhibits 70% of these clinical isolates. From this fact and our results, it is concluded that ceftizoxime is anticipated to have a great value in prophylatic antibiotics and treatment of bone and joints infections.

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The 10 strains out of 50 gram negative rods, which were isolated at the clinical labolatory in the hospital of the Institute of Medical Science, University of Tokyo and determined as resistant against cephaloridine and sensitive to chloramphenicol by routine paper disk method, were highly resistant to cephaloridine (MIC≥1, 600 μg/ml) and relatively sensitive to chloramphenicol (MIC≤12. 5μg/ml).
The synergistic effect of CER and small doses of CP was revealed in nine strains of these ten strains.
In order to investigate the mechanism of this synergistic effects, β-lactamase activities were measured by microiodometric assay.
It was suggested that the mechanism of this synergistic effect might not be due to leak out of β-lactamase, might be due to the stronger suppression of β-lactamase production than that of protein synthesis.

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