Thirty one episodes of infection in 28 patients with acute leukemia were treated with a large dose of aminoglycoside (Tobramycin; TOB, Amikacin; AMK) in combination with penicillin (PC) and cephalosporin (CEPs)(regimen A: TOB+PC+CEPs, regimen B: AMK+PC+CEPs). TOB (120-180mg × 3/day) and AMK (300-400mg/day) were administered for about one hour by i. v. drip infusion at every 8 hours.
Mean dose of TOB and AMK was 7.0mg/kg/day and 19.8mg/kg/day, respectively and duration ranged from 4 to 19 days for TOB and from 3 to 27 days for AMK, respectively. Twenty five causative organisms, which were obtained from 16 episodes of infection, were mainly composed with Pseudomonas aeruginosa, Klebsiella, Serratia sp. and Enterobacter. The clinical effectiveness was recognized at 68.8% in regimen A and 73.3% in regimen B, respectively. The total response rate of regimen A+B was 71.1%. Only one patient, who was treated with AMK+CEPs for 14 days, showed a transient renal impairment, however, it was improved 10 days after the cessation of chemotherapy.
Studies on serum concentration of TOB and AMK, which were done in normal volunteer, showed that the highest concentration of both agents were never beyond the toxic level, when they were administered in one hour by i. v drip infusion.
In conclusion, the administration of a large dose of aminoglycoside by i. v drip infusion should be recommended for the treatment of serious infection in acute leukemia.

View full abstract

The experimental murine pneumoniae models due to Pseudomonas aeruginosa have been studied, and the results were as follows:
1) The aerosol exposure system was superior in the infected method with challenge organisms to others. And the numbers of bacteria in lungs of mice were correlated with those in glass nebulizer.
2) The intraperitoneal injection of cyclophosphamide to mice increased in the fixation of bacteria in lungs of mice. The dose of cyclophosphamide was best at 250mg/kg, and the infection was started at 5 days after the administration of cyclophosphamide.
3) In this aerosol exposure system, the preliminary clearance of bacteria in lungs of mice was observed, and all mice were dead in 30-48 hours.
4) The histological changes in lungs of mice were observed in this aerosol exposure infection, and that proved the murine pneumoniae due to P. aeruginosa.

View full abstract

In order to evaluate the effectiveness and safety of mezlocillin (MZPC), a multi clinical double blind comparative study against carbenicillin (CBPC) was conducted in patients with chronic complicated urinary tract infections. The patients were treated for 5 days with a dose of 2g b. i. d. of either MZPC or CBPC i. v. Total 203 patients were entered into the trial. Out of 203 cases, the comparison of the efficacy judged according to the criteria prepared by UTI Committee was made for 156 cases (MZPC; 81, CBPC; 75), whereas the comparison of the safety and utility judged by attending doctors was made for 200 cases (MZPC; 98, CBPC; 102), and of improvement judged also by attending doctors for 164 cases (MZPC; 84, CBPC; 80).
Having no significant differences in the various background factors of the patients between the MZPC and CBPC groups, the two groups were judged to be comparable.
Comparison between the two treatment groups was made in view of the over-all clinical efficacy, the efficacy on pyuria and bacteriuria, bacteriological responses, improvement of subjective symptoms, the final global improvement rate, usefulness, and occurrence of the adverse reactions to the drugs, and the following results were obtained.
1) In the comparison of the overall clinical efficacy, the MZPC treatment showed its efficacy rate of 37.0% and the CBPC treatment of 24.0%, indicating a trend of superiority of MZPC over CBPC.
In the comparison of the effect on bacteriuria, the elimination rate with MZPC was 25.9% while 13.3% with CBPC showing a tendency of superiority of MZPC. However, the trial showed a statistically significant superiority of the MZPC treatment to the CBPC treatment when elimination rate and decreasing rate are combined as well as when elimination rate, decreasing rate and also replacement rate are jointly judged.
2) Bacteriological responses, i. e. elimination rate of isolated strains, were 58.0% with MZPC treatment and 41.69% with CBPC treatment. The difference between the two groups was statistically significant. When stratified with species of isolated strains, MZPC showed superior activity against E. coil to that of CBPC.
3) In the final global improvement rating (FGIR), overall safety rating and usefulness judged by attending doctors, MZPC treatment showed a superior tendency to CBPC in the item of FGIR stratified by catheterization. There were no significant differences between the two treatment groups in the other categories.
4) Adverse reactions to the drugs were noted in 4.1% of the patients of the MZPC and in 4.9% the CBPC treatment.
Incidence rate of adverse reactions showed no significant difference between the two groups.
The aforementioned results justify to conclude that MZPC is a highly useful and safe drug for the treatment of chronic complicated urinary tract infections.

View full abstract

For the purpose to base on the clinical application of cefoperasone (CPZ) in the field of obstetrics and gynecology, pharmacokinetic analysis of CPZ during and following 1g or 2g drip infusion for 1 hour was studied on 27 cases of patients.
The serum, myometrium, endometrium, portio vaginala, oviduct, ovarium and abdominal ascites. concentrations of CPZ were measured and these data were analyzed by using two or three compartment model.
CPZ was rapidly distributed to these tissues, so, transitional velocity constants between the serum. and these tissues were large, and then, these tissues concentrations were correlated with the serum concentration.
The serum and these tissues concentrations were calculated for the pharmacokinetic parameters, . and these simulation curves were shown.

View full abstract

Broncasma Berna (B. B) prepared from multivalent killed bacterial preparation demonstrated previously a growth-inhibiting effect against EHRLICH ascites carcinoma in mice. Its antitumor potency was enhanced, under certain circumstances, in combination with mitomycin C, cytosine arabinoside, cyclophosphamide and 5-fluorouracil.
In this work the effects of B. B, zymosan, MFC (combined administration of mitomycin C, 5-fluorouracil and cytosine arabinoside) and B. B with MFC on the phagocytic function of the reticuloendothelial system (RES) of ICR mice were investigated. The function of the RES was estimated by measuring the rate of clearance of colloidal carbon particles from systemic blood according to the method of BIOZZI G. et al.
Either a single or multiple administration of B. B, made intraperitoneally, subcutaneously or intranasally, markedly increased the mean value of phagocytic indexes. The phagocytic index level of the intranasal administration group was nearly equal to that of the zymosan-treated group. Zymosan is a well-known RES stimulant. The corrected phagocytic index was also enhanced markedly in the B. B-treated groups.
The phagocytic index of MFC-treated group varied with the dose; it decreased apparently with the number of injection. The combined administration of B. B and MFC increased the phagocytic index to a higher level than that of the mice receiving only MFC.
Furthermore, the weight of thymus and spleen was by the administration of B. B changed significantly as compared with the control (P<0.05 and P<0.01, respectively).
In conclusion, it was clearly shown that the phagocytic function of the RES was stimulated in ICR mice by the administration of B. B alone or in combination with MFC under certain conditions.

View full abstract