The pharmacokinetics of 3 parenteral cephems and sulbactam were studied in healthy volunteer and patients with impaired renal function.
CEPR (a cephalosporin) was administered by drip infusion at a dose of 2, 000mg and serum levels was determined by high pressure liquid chromatography.
CTT (a new cephamycin), CPZ (a cephalosporin) and SBT (a new β-lactamase inhibitor) were injected intravenously at a dose of 500mg respectively and each level in serum and urine was determined by bioassay.
Pharmacokinetic analysis of these antibiotics were performed by the one compartment open model and the following results were obtained.
1) The serum concentration and T_1/2 of CEPR in patients with impaired renal function were higher than in healthy volunteer regardless of the degree of renal impairment.
2) T_1/2 of CTT increased in parallel with the degree of renal impairment and there was the significant correlation between Ccr and T_1/2 (P<0.01).
As renal function declined, the urinary excretion decreased.
3) The serum concentration and T_1/2 of CPZ in patients with impaired renal function were higher than in healthy volunteer regardless of the degree of renal impairment. In only one case associated with liver damage, T_1/2 was very high and the urinary recovery was equal to that of the healthy volunteer.
4) T_1/2 of SBT increased in parallel with the degree of renal impairment and there was thesignificant correlation between Ccr and T_1/2 (P<0.05).
In case of chemotherapy by antibiotics with long T_1/2 and excreted mainly from the kidney, it is suggested that lower dose or longer intervals of administration should be employed according to Ccr in patients with impaired renal function especially in aged people.

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The effects of cefotaxime (CTX), cefasolin (CEZ) and carbenicillin (CBPC) on the morphology and on the binding affinity to penicillin-binding proteins of Escherichia coil K-12 and Pseudomonas aeruginosa E-2 were studied.
The following results were obtained.
1) The filamentous forms of E. coli K-12 were observed by phase-contrast microscopy and scanning electron microscopy at lower concentrations of CTX than those of CEZ.
However, the range of concentrations inducing filament formation was broader than that of CEZ.
Spheroplast-like structures and cell lysis were observed when the concentration of CTX was high.
It seemed that these morphological alteration of P. aeruginosa E-2 treated with CTX were similar to those seen with CBPC, and that spheroplast-like structures were observed when the concentration of CTX was 1, 600μg/ml.
Possible influences on the ability to form spheroplasts were studied using stabilisers. As a result, it was found that spheroplasts of P. aeruginosa E-2 treated with CTX were similar to that seen with CBPC.
2) CTX was found to demonstrate the strongest affinity to the penicillin- binding protein 3 of E. coli K-12 and P. aeruginosa E-2, followed by 1 a and 1 b in declining order.

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The frequency of multiply resistant strains in Staphylococcus aureus increased from 18.6% in the latter half of 1980 to 35.9% in the first half of 1982. These multiply resistant S. aureus were recovered primarily from pus, sputum, urine and blood. The antimicrobial susceptibilities of 100 multiply resistant S. aureus were determined by the agar dilution technique. Rifampicin was active against all but one strains tested at ≤0.05μg/ml. At ≤0.4μg/ml, doxycycline, minocycline and fusidic acid inhibited 82, 92 and 97 strains, respectively. Vancomycin and DL-8280 were also active against 99 strains at ≤3.1μg/ml. The multiply resistant S. aureus showed bimodal susceptibility pattern to gentamicin, tobramycin, micronomycin, josamycin, lincomycin and clindamycin, Among cephems examined, cephaloridine was most active with MIC₅₀ of 6.3μg/ml. The MIC₅₀ of cefmetazole and cefotiam was 12.5μg/ml. The MIC₅₀ of other cephems were ≤25μg/ml. The MIC₅₀ of cloxacillin and flucloxacillin was 1.6 and 0.8μg/ml. Methicillin and oxacillin were less active. Other penicillins have MIC₅₀, of ≥25μg/ml

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The serum and urinary concentrations of cefotaxime, ceftizoxime and cefmenoxime in healthy male volunteers who were given 1-g 1-hr constant infusion were determined in a cross-over study using bioassay and high-performance liquid chromatography (HPLC). The values from the two different methods agreed well with the regression coefficients of 0.988 or higher except the values of cefotaxime obtained from bioassay, which were slightly higher than those from HPLC, owing to the formation of the desacetyl metabolite. The mean peak serum concentrations determined by bioassay at the end of infusion were 58.1μg/ml for ceftizoxime, 53.4μg/ml for cefmenoxime, and 48.8μg/ml for cefotaxime. The serum half-lives of the β-phase by pharmacokinetic analysis using a two-compartment open model were 1.61 hrs for ceftizoxime, 1.19 hrs for cefotaxime, and 1.03 hrs for cefmenoxime. Ceftizoxime proved to be the longest-acting, as evidenced by its serum concentration as high as 1.16μg/ml even at 8 hrs, whereas the concentrations of the other two antibiotics did not reach 1.0μg/ml at 6 hrs.
The 8- hr urinary recovery by bioassay was 79.9% for ceftizoxime, 62.0% for cefmenoxime, and 55.1% cefotaxime and, by HPLC, 49.3% for cefotaxime and 15.3% for its desacetyl metabolite.
The 80% MICs of these antibiotics for most susceptible strains were less than 0.2μg/ ml for E. coli, Klebsiella spp., Proteus spp. and H. influenzae, and less than 3.13μg/ ml for Serratia spp. Duration of serum concentrations equivalent to these two 80% MICs was 12 and 5.8 hrs for ceftizoxime, 8.1 and 3.6 hrs for cefotaxime, and 7.0 and 3.4 hrs for cefmenoxime. Ceftizoxime persisted in the serum longer than any other antibiotic tested, and provided therapeutically effective concentrations even when the dose was halved.

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1) We administered cefotetan to patients with complicated urinary tract infections either at a single dose of 2g/day or in two divided doses of 1g each per day and studied whether the different methods of administration would affect the clinical efficacy, or its effect on bacteriuria or pyuria.
2) Of those patients in whom we could study the therapeutic results 69 patients received 1g twice a day and 77 patients received 2g once a day. If we lood at their background factors, almost all of the patients were elderly patients and 60% of them were catheter-bearing patients; 47% of the patients suffered from multiple bacteria infections so that this patient group can be described as suffering from rather complicated urinary tract infections. However, there was no significant difference in regard to background factors between the two groups. The efficacy rates based on UTI judgmental criteria for the two groups was as follows: overall clinical efficacy was 67% in the 1g×2 group and 57% in the 2g×1 group, the bacteriological effect was 59%, in the 1g×2 group and 48% in the 2g×1 group and the efficacy on pyuria was 57% in the 1g×2 group and 52% in the 2g×1 group. Thus statistically no significant difference was observed between the two groups. However, in regard to overall clinical efficacy the 1g×2 group exhibited slightly superior results in comparison with the 2g×1 group.
The clinical effect based on the judgment of the attending physician was 59% in the 1g×2 group and 48% in the 2g-1 group so that this rate was about 10% lower than the above-mentioned efficacy rate based on UTI judgmental criteria.
3) No notable abnormalities were reported in regard to side-effects or clinical test results.

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Hydronephrosis was induced by the constriction of unilateral ureter in mice. Those treated mice were divided into four groups, Group A consisted of mice which had one hydronephritic kidney, Group B had a pair of hydronephritic kidney and normal kidney, Group C had one normal kidney, Control had a pair of normal kidney.
Absorption and excretion after 50mg/kg subcutaneous administration of next antibiotics, piperacillin (PIPC), carbenicillin (CBPC), cefoperazone (CPZ), cefazolin (CEZ), and tobramycin (TOB) were examined using four groups.
Serum, kidney and liver levels in Group B and Group C showed a similar pattern to those of Control. The above level of Group A was widely different from Control. That is, serum level was highly maintained on TOB, and followed in the order of CEZ, CBPC, CPZ and PIPC. Liver level was highly maintained on CEZ and CBPC, and was lowly maintained on TOB, while CPZ and PIPC were similar to those of Control. Kidney level was highly maintained on TOB, and followed in order of CEZ, CBPC, CPZ and PIPC.

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Acute pyelonephritis was induced by the treatment with a renal toxic agent, β-bromoethylamine hydrobromide (BEA) in mice. Those treated mice were divided into four groups, Group A consisted of mice which had one pyelonephritic kidney, Group B had a pair of pyelonephritic kidneys, Group C had one normal kidney, Control had a pair of normal kidneys.
Absorption and excretion after 50mg/ kg subcutaneous administration of next antibiotics, piperacillin (PIPC), carbenicillin (CBPC), cefoperazone (CPZ), cefazolin (CEZ) and tobramycin (TOB) were examined using four groups.
Serum, kidney and liver levels in Group C showed a similar pattern to those of Control. The above level of Group A and Group B were widely different from Control. That is, serum level was highly maintained on TOB, and followed in the order of CEZ, CBPC, CPZ and PIPC. Liver level was highly maintained on TOB, CBPC and CEZ, while CPZ and PIPC were similar to those of Control. Kidney level was highly maintained on all antibiotics. Urinary excretion of PIPC, CBPC and TOB were reduced one half to one third of Control, while CEZ was similar to those of Control.

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Partially reduced kidney was induced by the reduction with a radio knife in mice. Those treated mice were divided into four groups. Group A consisted of mice which had one partially reduced kidney, Group B had a pair of partially reduced kidney and normal kidney, Group C had one normal kidney, Control had a pair of normal kidneys.
Absorption and excretion after 50mg/kg subcutaneous administration of next antibiotics, piperacillin (PIPC), carbenicillin (CBPC), cefoperazone (CPZ), cefazolin (CEZ) and tobramycin (TOB) were examined using four groups.
Serum, kidney and liver levels in Group B and Group C showed a similar pattern to those of Control. The above level of Group A was widely different from Control. That is, serum level was highly maintained on TOB, and followed in order of CEZ, CBPC, CPZ and PIPC. Liver level was highly maintained on TOB and CEZ, while PIPC, CBPC and CPZ were similar to those of Control. Kidney level was highly maintained on all antibiotics. Urinary excretion of PIPC and CPZ were reduced one half to one third to those of Control, and CEZ was reduced three quarters to those of Control, while CBPC and TOB were similar to those of Control.

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This study reports on a clinical evaluation of cefoxitin (Merxin) which is responsible for the property of resistance to degradation by bacterial β-lactamase in the treatment of severe pleuropulmonary diseases.
Subjects included two patients with pulmonary abscess and one with thoracic empyema (from which 2-8 strains of anaerobes with single aerobe were isolated), and one patient with thoracic empyema (from which 4 strains of anaerobes were isolated). Seventeen of 20 organisms isolated from these four patients were non-sporeforming anaerobic bacteria other than Bacteroides fragilis. All anaerobes were found to be sensitive to cefoxitin.
Cefoxitin was administered in a dosage of 2g/ day IV infusion over a period of 60 minutes in divided dosages every 12 hours (total dosage: 34-210g) concomitantly with lincomycin or clindamycin for all four patients.
Cefoxitin therapy proved effective for the patient with pulmonary abscess and for the two patients with thoracic empyema in the acute phase. However, one patient with pulmonary abscess complicated by a thickened cavity wall did not respond well to cefoxitin even though it was administered over an extended period of time.
Moderate granulocytopenia accompanied by thrombocytopenia appeared in one patient on the third week of chemotherapy. This side effect disappeared gradually with the cessation of cefoxitin. Other side effects, such as rash, phlebitis, or liver damage, were not observed.

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