A study was undertaken in 4 cases of urinary tract infection due to Ps. aeruginosa and 1 case of empyema due to mixed infection of S. epidermidis and Serratia marcescens to observe therapeutic effects and side effects of fosfomycin (FOM-Na) given by one shot i. v. injection. In addition, organisms isolated from patients were determined for their susceptibility to FOM-Na.
1) In cases of urinary tract infection, since subjective symptoms were not observed before thetrial began, response to FOM-Na was assessed only bacteriologically on the basis of the number of organisms and classified as excellent in 2 and ineffective in 2 cases. In one case of empyema the response to treatment was evaluated as excellent both clinically and bacteriologically.
2) In regard to side effects, no one complained of any symptoms related to the treatment, and laboratory findings including serum Na, ALP, GOT, GPT and BUN remained unaffected during the study.
3) Determinations of susceptibility of isolated Ps. aeruginosa to FOM-Na revealed that 57% of MIC sdistributed in the range of 12.5μg/ml. On the other hand, MICs for S.epidermidis and Serratia marcescens were found to be 3.12 μg/ml.
The number of cases included in the study was small, but our findings suggest that FOM-Na is an antibiotic expected to be valuable in the treatment of urinary tract infections due to Ps. aeruginosa and respiratory tract infections due to Serratia.

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A total of 8 children comprising 6 with osteomyelitis and 2 with suspected osteomyelitis were treated with fosfomycin (FOM-Na) at doses of 200 to 390 mg/kg per day (divided in 4) for a period of 32 days on an average. Seven of them were given the drug by one shot i. v. injection, while the remaining one was by drip infusion. Clinical and bacteriological studies were performed together with observation on side effects, with following results :
1) Response to FOM-Na was evaluated clinically to be good in all cases treated with this drug. On the other hand, bacteriological response was assessable in 2 cases due to S. aureus and one case due to Ps. aeruginosa, and found to be good in all of them.
2) Only one strain of Ps. aeruginosa was determined for susceptibility against FOM-Na, and its MIC value was shown to be 12.5, μg/ml.
3) As side effects, vascular pain and rash associated with itching developed in two cases and one case, respectively. In the latter case, however, since rash disappeared without discontinuance of medication of FOM-Na, it was difficult to ascribe the side effect observed in this case to treatment with FOM-Na.
Apart from patients with underlying disease which might affect values of GOT, GPT or LDH, all patients were free from abnormal elevation in GPT, AL-P, LDH, or BUN values excluding one patient in whom a slight increase in GOT was noted. No influences on serum electrolytes, e. g. Na, K or Cl were observed.
Although the number of cases studied here was small, effect of FOM-Na on children with real or suspected osteomyelitis was evaluated as good.

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The uptake and distribution of bleomycin, a kind of watersoluble antibiotic, were previously studied in mice with methylcholanthrene induced glioma by means of biological and radioactive assaywith ¹⁴C-bleomycin A₂. The result obtained showed that a relative large amount of bleomycin may be taken up selectively in glioma after intravenous administration, and about two-thirds of bleomycin distributed in glioma may remain in active form with antimicrobial activity. Furthermore, a tendency was clinically noted that the more malignant was the tumor, the higher was the uptake of bleomycin.
In has been thought that administration of drug in depot preparation, permitting slow release of the drug contained from an administration site, may change the distribution and uptake of drug in tumortissue and may change its effectiveness. The present study was designed to study the influence of the vehicles of bleomycin for depot preparations with special reference to the chemotherapy of brain tumor.
As the first step of the experiments, the binding affinity of the drug to serum protein, which is said to be closely related to the distribution and antitumor activity of the drug, was investigated byequilibrium dialysis. Evidence obtained indicated that bleomycin A₂, main component of commercial bleomycin, has low affinity of binding to horse serum proteins and bleomycin A₅ has moderate, though mitomycin C, another kind of antitumor antibiotic, has high affinity.
As the next step, the following three kinds of preparations containing bleomycin (supplied by Nippon Kayaku Co., Ltd.) were employed for depot administration ; so called oil bleomycin (suspending vehicle : sesame oil : 99%, aluminum monostearate : 1%), solid bleomycin (sesame oil : 17. 8%, Witepsol E 85 : 80. 8%, Tween 80 : 2. 2%), and paste bleomycin (sesame oil : 54%, bleached beeswax : 24%, polyvinyl pyrrolidone : 22%).
The dissolution curves of active bleomycin from three depot types of vehicles to saline were studied in vitro. Fifty per cent of bleomycin contained was dissolved from depot preparations to placed salinewithin 24 to 96 hours. Then, the distribution and uptake of active bleomycin in the organs and tumor investigated in mice with subcutaneously transplanted glioma. As a result, it was clear that a few hours after administration, the distribution and uptake of active bleomycin in the organs and tumor tissue after oil bleomycin administration usually exceeded those after saline bleomycin administration and maintained considerably high level for longer time.
As the final step, the effects of depot bleomycin on the tumor growth and body weight change were studied in above mentioned experimental animals. Evidence indicated that intramuscular administration of oil bleomycin (15 mg/kg x 5) apparently supressed the transplanted glioma growth, but no significant difference between the effect of oil bleomycin and saline bleomycin on the tumor growth was observed in this trial. Based on these results, it may be concluded that the application of depot preparations for administration of bleomycin changes the distribution and uptake of the drug in the organs and tumor tissue and possibly results in increase of the effectiveness of the drug against tumor and reduction of the systemic toxicity, if the compositions of depot preparations would be improved.

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Eight patients with head and neck cancer received the local treatment with bleomycin oil suspension in our clinic. Usually one ml of the preparation containing 15 mg units of bleomycin was injected into the marginal parts of the tumor 3 to 4 fractionated doses.
As a result, 6 cases of the disappearance or marked regression of the tumor (75%) and 2 cases of no response were recorded.
Side effects observed in 5 out of 8 patients include pain in the tumor after injection (4 cases), pyrexia (2 cases), lassitude (1 case) and anorexia (1 case).
The fact that the complete cure of some tumors in smaller size than 1 cm in diameter and a satisfactory palliative effect even in more advanced tumors were achieved with this therapy, led us to such a conclusion that local injection of bleomycin oil suspension may be of great advantage for the management of recurrent or advanced but localized tumors of the head and neck.

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Combination therapy with cephalothin and tobramycin was applied to chronic respiratory tract infections caused chiefly by gram-negative rods. And following results were obtained.
1) Clinical responses in the infections caused by Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus were satisfactory.
2) The satifactory clinical effects, such as body temperature, volume and nature of sputum, and erythrocytes sedimentation rate were observed in 40 % of patients with Pseudomonas aeruginosa infections, however, the organisms in the sputa were not decreased in the course of this therapy.
3) No significant side effects were observed in the laboratory tests as well as in the clinical observations except for one case (No. 11).

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The overall incidence of gram-negative bacilli (GNB) response for human infections in Japan is on the increase. This trend was confirmed by data obtained through questionnaires sent to 31 medical institutions and reports from a few urological departments of university hospitals.
However, the incidence (about 80%) of GNB responsible for urinary tract infections (UTI) has shown no increase since 1970.
Of these causative GNB, the most frequent is E. coli particularly in the urological field, followed by Klebsiella, Pseudomonas and Proteus group.
A study by disc method of the susceptibility of GNB isolated from patients in the urological service at Keio University to 11 different antimicrobial agents gave the following findings.
GNB isolated from out-patients were more sensitive than those from in-patients to various agents.
This trend was found to apply to E. coli, Proteus, Klebsiella and Pseudomonas strains, with the former two organisms the most prominent. Antimicrobial agents that proved more active against isolate sfrom out-patients than against those from in-patients were typically β-lactam an tibiotics, which were followed by kanamycin, nalidixic acid showed this trend only against E. coli strains.
A further analysis, which the susceptibility of organisms isolated in 1970 and 1971 was compared with that of organisms isolated in 1973 and 1974, revealed that the isolates were generally more susceptible.
This tendency was pronounced in the Proteus group, which showed increased susceptibility to 7 of the 11 agents tested.
The agents that showed increased activity against the isolates were streptomycin and tetracyclines. Chloramphenicol followed after two agents.
It would follow the susceptibility of an organism is enhanced with decreasing chance of its contact with particular antimicrobial agents.

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