The possibility that the nephrotoxicity of netilmicin may be potentiated by the concomitant administration of 10% low molecular weight dextran (dextran) or cephalothin was examined in rabbits. Netilmicin, dextran and cephalothin were given once daily in dosage of 100 mg, 25ml and 2g/kg/day respectively. Netilmicin was injected intramuscularly and the other two drugs intravenously for 10 days. The abnormality in serum creatinine and proximal tubules was more remarkable in netilmicin-dextran combination than in netilmicin or dextran alone.
On the other hand, concerning the three rabbits injected with netilmicin and cephalothin, the renal damage was less in two and more severe in one than that of the rabbits injected with either netilmicin or cephalothin alone.

View full abstract

Efficacy and safety of cefmenoxime (CMX, SCE-1365) and cefotiam (CTM) were compared by a randomized, double blind method. CMX as well as CTM were administered daily 2 gms, i. e. 2 times of 1 gm intravenous drip infusion, for consecutive 7 to 14 days. In total 162 cases, which consist of each 81 CMX and CTM allocated cases, were subjected to the analysis, and the following results were obtained.
1) In the distribution of patient-characteristics (background factor) between CMX and CTM allocated group, the statistical analysis showed there was no bias, which will virtually influence on the results.
2) Overall clinical efficacy rates of CMX and CTM were 77.0% and 60.3% respectively. CMX showed significantly higher clinical efficacy rate than CMX.(P<0.05).
3) As for the clinical efficacy rate by standard criteria, proposed by the representative investigators committee of this study, clinical efficacy rate of CMX and CTM were 71.6% and 58.8% respectively, and the higher clinical efficacy rate of CMX than CTM was shown.
4) Assessment of clinical usefulness judged by the physicians in charge revealed the higher clinical usefulness of CMX than CTM.
5) Reg.irding the bacteriulogical effect, CMX showed the higher elimination rate of H. infiuenzae than CTM.(P<0.1).
6) Improvement (if the puruleucy of sputum and rale were significantly faster in CMX than CTM.(P<0.05). In the stratified group, consisting of the cases whose prior chemotherapies were ineffective, CMX showed significantly higher clinical efficacy rate than CTM.
7) The incidence of side effects and the abnormal change of laboratory findings were significantly less in CMX than CTM, and there was no severe adverse reaction in either medication.
From the results of clinical response and side effects, it is considered that CMX clearly has a greater clinical usefulness than CTM in the treatment of chronic respiratory tract infections.

View full abstract

A study on the disc sensitivity test for sulfamethoxazole-trimethoprim combination (20:1) was performed under the experimental condition already standardized by KANAZAWA.
Discs containing 400 μg of SMX, 20 μg of TMP and 400 μg of SMX-TMP combination (20:1) were used and the following results were obtained.
1) Synergy between SMX and TMP could be simply detected by the comparison of inhibition zone around discs containing 400 μg of SMX and of SMX-TMP combination.
2) The two components diffused from discs into agar plate, maintaining an approximate 20:1 ratio of concentration.
3) The primary regression equations representing relationship between MICs and diameters (D) of inhibition zones were as follows:
D (mm)=42.0-12.6 log MIC (μg/ml) in SMX and D=29.0-13.2 log MIC in TMP, indicating that the diffusion-rates of the two components in agar plate were approximately near.
4) Susceptibilities to SMX-TMP combination (20:1) of 124 strains of 19 species were determined by the 2-fold agar dilution method in parallel with the single-disc method using SMX-TMP discs containing 400 μg.
The experiments demonstrated significant correlation between MICs by the dilution method and diameters of inhibition zones by the disc method in each of conventional assay of the over-night (about 16 hours) incubation and delayed assay of 24 hour incubation.
Analysis of the data obtained revealed the primary regression equation to be D=42.0-12.5 log MIC in conventional assay and D=51.3-16.7 log MIC in delayed assay, respectively.
The range of variations in MICs estimated from the diameters of inhibition zone by the disc test was then calculated in comparison with that in MICs determined by the two-fold agar dilution method, as a reference for the experimetal errors which may be involved in the estimation of MIC by the disc method.

View full abstract

Ceftizoxime (FK 749, CZX), a new parenteral cephalosporin antibiotic resistant to β-lactamase, was studied with special reference to excretion into bile and tissue concentrations of gallbladder and liver. The following results were obtained;
1) Antibacterial activity
Antibacterial activities of CZX against 21 strains isolated from bile of patients with cholecystectomy were superior to that of CEZ or CTM. CZX was more active against Escherichia coli and Klebsiella pneumoniae which were frequently isolated from bile than that of CEZ or CTM, and was highly active against strains of Proteus morganii, Serratia marcescens and Enterobacter aerogenes which were almost resistant to CEZ and CTM.
2) Bile and tissue levels
Bile and tissue levels of CZX and CEZ were determined at about 2 hours following intravenous bolus injection of 2 grams in 11 cases and 8 cases with cholecystectomy. Mean bile levels in gallbladder and common duct were 159.4 and 154.0μg/ml in CZX group, on the other hand were 138.7 and 128.8μg/ml in CEZ group. Mean tissue levels in wall of gallbladder was 31.9μg/g in CZX group, on the other hand was 29.9μg/g in CEZ group.
Biliary level of CZX was higher than that of CEZ.
3) Biliary levels in patients with external biliary fistula
Peak level in bile was obtained with 131.9μg/ml in average from 1 to 2 hour following intravenous bolus injection of 2g CZX, and thereafter was decreased but high level in bile was also obtained with 18.9μg/ml in average from 5 to 6 hour.
In 4 cases, biliary levels of CZX were compared with that of CEZ by cross-over method. As a result, biliary level of CZX was higher than that of CEZ during 1 to 5 hour following injection.
4) Clinical results
Out of 13 cases treated with CZX for surgical infections including postoperative meningitis and diffuse peritonitis, the results were excellent in 4 cases, good in 5 cases, and the overall efficacy was 69.2%. Especially, in 2 cases of postoperative meningitis, 3 cases of peritonitis due to perforation of appendix or pyometra, each one case of lymphangitis, mastitis, osteomyelitis and phlegmon, satisfactory effects were obtained in all cases.
No adverse reaction was observed in any of the cases, nor was there any marker changes due to administration of CZX in laboratory findings including peripheral blood examinations, hepatic and renal functions.
From above mentioned results with antibacterial activity, excretion into bile, tissue concentrations of common duct and clinical applications, ceftizoxime seemed to be a useful cephalosporin antibiotic in surgical infections such as a biliary tract infection in particular.

View full abstract

Cefmetazole (CMZ) in amount of two grams was administered to patients by onc shot intravenous injection previously to surgery of hip joint in number of 35 cases. Bone marrow blood and venous blood, taken at the time through the operation were centrifuged. CML was assayed by thinlayer disc plate method on the obtained supernatant and serum, employing Micrococcus luteus, ATCC 9341 as a test organism. In 60% of cases, bone marrow concentration was found to be higher than that in serum. Pharmacokinetic analysis also revealed that bone marrow concentrations were slightly higher than serum. The ratio of concentration in bone marrow to serum appeared to be constant and independent to sampling times. Bone marrow concentration (Y) was in good positive correlation with serum concentrations (X), the equation of linear regression being Y=1.21X-2.75. CMZ is thought to be of an enough strength as an antibiotics to prevent an infection in cases of major surgery of skeletal tissue in the field of orthopedic surgery.

View full abstract

A double-blind comparative clinical trial was carried out to study the clinical usefulness of cefmenoxime in bacterial pneumonia and pulmonary suppuration using cefotiam as reference drug. Both the drugs were given in dose of 1g, twice a day, by intravenous drip infusion for 14 days.
The results obtained are as follows.
1) A total 211 patients entered into the trial, 106 on cefmenoxime and 105 on cefotiam.
2) The overall clinical efficacy rate (excellent and good responses/total cases) was 85.5%(59/69) for cefmenoxime and 83.3%(55/66) for cefotiam. No significant difference was observed between the cefmenoxime treatment group and the cefotiam treatment group.
3) The clinical efficacy rate judged by the parametric scoring was 68.8%(44/64) for cefmenoxime and 80.0%(48/60) for cefotiam. Statistical tests revealed no significant difference between the two groups.
4) The clinical efficacy rate assessed by the standard criteria was 73.1%(49/67) for cefmenoxime and 75.4%(49/65) for cefotiam, with no significant difference.
5) The bacteriological responses of patients to cefmenoxime and cefotiam were favorable in 89.2%(33/37) and 88.2%(30/34), respectively. No significant difference was observed.
6) The incidence of side effects and abnormal laboratory findings caused by the treatment was 15.2%(16/105) for cefmenoxime and 19.0%(20/105) for cefotiam, with no significant difference.
7) As for the usefulness of the both treatments, physicians judged to be “completely satisfied” or “satisfied” with cefmenoxime in 76.8% of cases (53/69) and with cefotiam in 76.1%(51/67). Statistical tests showed no significant difference.
Cefmenoxime thus showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of bacterial pneumonia and pulmonary suppuration, and it has been concluded that cefmenoxlme will be a useful addition to the antibiotics for the therapy of these pulmonary infections.

View full abstract