For the purpose to compare the curative effect and side effect of cephradine (CED) with those of cephalexin (CEX), the comparative experiments have been carried out by means of a double blind method upon the patients of bacterial pneumonia in 14 institutions throughout the country. CED and CEX were administered orally for 2 weeks respectively at a daily dose of 2 g, and both subjective and objective symptoms were observed extremely in detail as well as various examinations were performed equally. The judgement of clinical effect was made by a physician in charge, and by a small committee composed of several physicians simultaneously. This committee read the chest X-ray films of all cases following a certain standard, and the judgement of severity and effect was made on every case equally. Then the envelope of drug allotment table was opened, and the comparison was made on the homogeneity of back ground factors of patients as well as the severity for both groups of drug administration, and the curative effect and side effect were determined statistically.
Among 117 cases of drug administration (58 cases of CED and 59 cases of CEX), 1 case of CED-ABPC combination was excluded from the object. No significant difference was observed between two groups of drug administration on the composition of age and sex, no significant difference was noticed between two groups on each symptom before the treatment. The effect judged by physician in charge revealed : excellent 9 : 11 (CED : CEX applied to following), good 35 : 35, fair 1 : 3, poor 5 : 5, worsened 2 : 1 and undecided 5 : 4, showing thus no significant difference between two groups. Side effect demonstrated rise of GOT and GPT 2 : 2, eruption 2 : 1 and gastrointestinal disorders 3 : 2, recognizing thus no significant difference between two groups.
The small committee omitted 27 cases of CED and 22 cases of CEX to compare strictly the drug effect against pneumonia. As for the adopted 31 cases of CED and 37 cases of CEX, no significant difference was observed between two groups on a classification of sex, while on a composition of age, a significant difference was noticed as CEX group included more aged over 60 years. No significant difference was observed between two groups on each symptom before the treatment, and yet on the judgement of severity, severe cases were rather more in CED group while mild cases were rather more in CEX group, though this means no significant difference. The clinical effects obtained were excellent 4 : 2, good 21 : 27, fair 4 : 0, poor 2 : 7 and worsened 0 : 1. No significant difference was observed thus there, although rather many excellent cases were obtained in CED group while rather many poor cases in CEX group.
The degrees of improvement of each symptom and finding 3 days, 7 days and 14 days after the start of treatment, were compared between two drugs and no significant difference was observed there.

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Thirty-two patients with acute genitourinary tract infections were treated with oral administration of 0. 5 g cephradine t. i. d. for 7 days and the following results were obtained.
1. Drug sensitivity of E. coli clinically obtained to cephradine was comparable with that to CEX.
2. On termination of the treatment, the symptoms were disappeared in 27 cases and pathogens were eliminated in 29 cases, respectively.
3. Among 32 patients, clinical cure was obtained in 23 on the 4 th day after start of the treatment and 29 on the 8 th day, respectively.
4. Reccurrence was noted in 4 cases out of 31 on whom follow up studies were complete.
5. With an exception of a case with allergic rash, no adverse effect on renal function, liver function and peripheral blood findings and also no gastrointestinal disturbances were observed.

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Enramycin (ERM) even in low concentrations lyses Escherichia coli spheroplasts and Bacillus megaterium protoplasts easily. ERM does not transform sensitve bacteria to protoplasts, not as by penicillin or cephalosporin derivatives. ERM has the action of the release of cellular constituents, US 260 mg absorbing materials. No distinct changes of DNA, RNA and protein amounts of Staphylococcus aureus are observed by exposition to ERM. So there are little possibility of ERM to cause inhibition of nucleic acids and protein synthesis. This report agrees with the result of previous paper about morphological study by electron microscopy. Both reports show the antibacterial mechanism of action of ERM is the impairment of cytoplasmic membrane.

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The β-lactamase from clinically isolated cephalosporin resistant Staphylococcus aureus strain No. 41 has been highly purified and characterized. The enzyme was purified by the following procedures : chromatography on DEAE-Sephadex A-50, chromatography on CM-Sephadex C-25, gel filtration on Sephadex G-100 and disc electrophoresis. From ultracentrifugation and gel filtration on Sephadex G-100, sedimentation coefficient was estimated to be 2. 3 and molecular weight to be 22, 000-24, 000.
The isoelectric point was estimated to be 9.5 by electrofocusing on carrier ampholine. The optional pH range of penicillinase activity showed at around 6, while cephalosporinase activity showed at around 5.
The enzyme inducibility was proportionated to the MIC of the substrate, cephalosporin derivative had very high inducibility of the penicillinase and cephalosporinase activity, especially cephalexin had the highest inducibility,
Iodine inhibited the enzyme activity, acted as a competitive inhibitor to the hydrolysis of penicillin-G, not as a competitive one to the hydrolysis of cephaloridine, also this inhibition was not allosteric one.
The ratio of enzyme activity as penicillinase and cephalosporinase expanded through the purification step. But substrate specificity was not proportionated to the MIC to the substrate, and an existance of other mechanism of resistance to the cephalosporins was suggested.

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Kinetics on degradation of streptomycin sulfate (SM) were investigated employing agar-plate disc assay method with Bacillus subtilis.
The minimum inhibitory concentration of SM was 10 pg/ml in this assay system without reference to pH of SM solution.
While, decrease in its activity was resulted in the loss of inhibiting zone around the discs, when SM solution adjusted to pH values ranging from 1. 5 to 9. 2 was heated at varying temperatures (60°C, 80°C and 90°C).
From both factors of time of heat-treatment and concentration of SM in disc for exhibiting the disappearance of inhibiting zone, stability constant (K) of SM was calculated according to the equation presented by us.
A series of experiments with SM solution pretreated under the stated conditions brought about the data to show that K values were found to be identical, having no relation with the concentration of SM in disc.
In addition, the results obtained by this biological assay method were almost similar to that obtained by a chemical analysis, azotometry.

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The antimycoplasmal activity of 40 antimicrobial and 14 antitumor agents to 13 Mycoplasma species were tested by method of the agar dilution and the microtiter assays. The following results were obtained.
1. All of the macrolide so far tested such as leucomycin, spiramycin, josamycin and tylosin, except for erythromycin and oleandomycin, showed high antimycoplasmal effect without no difference among Mycoplasma species. Lincomycin also inhibited the growth of Mycoplasma at lower concentration.
2. Tetracycline, oxytetracycline and demethylchlortetracycline were found to have high antimycoplasmal activity.
3. In the antitumor antibiotycs, bleomycin did not show antimycoplasma activity, but the others such as actinomycin D, mitomycin C, daunomycin and chromomycin A₃ showed strong activity against all strains of Mycoplasma tested.
4. On the other hand, 9 antitumor agents were generally insensitive.
5. Aminoglucoside antibiotics such as streptomycin, kanamycin, neomycin and paromomycin showed the middle sensitivity but the activity in this group differed according to Mycoplasma strains.
6. Chloramphenicol was sensitive at range from 6. 25 to 1. 25 μg/ml.
7. In naphthyridine derivatives, nalidixic acid was insensitive, but in piromidic acid there were differences in minimal inhibitory concentration against the tested strains.
8. The excellent susceptibility was observed in 5 nitrofurans derivatives without exception.
9. Penicillin-cephalosporin groups, polypeptides such as bacitracin, colistin and polymyxin-B, and all of 6 sulfa drugs were insensitive.
10. As compared with agar dilution method, the microtiter technique was superior in minimal concentration.

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The cytocidal action of anticancer antibiotics has been quantitatively studied on the single cells of suspension-grown L-1210 mouse leukemia cells (L-1210/C), using soft agar cloning assay method.
The typical characteristics in the cytocidal action of anticancer antibiotics is the concentration-dependent action. The rate of cell killing can be described by the equation Cⁿ·T=K, where C is the concentration of antibiotics, T is the exposure time required to kill 90% of a cell population exposed at the concentration C, n is any positive number, and K is a constant. When L-1210/C cell population is treated with an antibiotic under a constant exposure time, the rate of cell killing can be described by a first-order kinetics log S=-k (D-a) , where S is surviving fraction, D is the concentration of antibiotics, and k and a are constant. The value of a means the concentration over which the cellkilling action appears, and the value of k means the population reduction rate. The sensitivity of L-1210/C cells can be indicated either by the 90% mean lethal dose (MLD₉₀), expressed by a reciprocal of slope coefficient k, showing the concentration of antibiotics needed to kill 90% of cells, or by the minimum inhibitory concentration for 10⁶ cells (MIC/10⁶) indicated by (6/k) +a.
The anticancer agents which have these characteristics are proposed to call type I agents, which are divided into two subtypes : type Ia agents that show the time-independent action with large n value (n>>1) in the equation Cⁿ·T=K and type Ib agents that show the time-dependent action with the unity of n value around 1. 40. The type Ia agents are neocarzinostatin and carzinophyllin. Many others such as mitomycin C, daunorubicin, adriamycin, chromomycin A-3, dactionomycin, bleomycin A-2 complex, and bleomycin A-5 belong to type Ib agents.

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This study was undertaken to compare the changes in the enteric microflora of rhesus monkeys following oral dosing of bicyclomycin, ampicillin and kanamycin at 20 mg/kg twice daily for 25 days.
The numbers of aerobic and anaerobic bacteria in the various parts of the intestinal tract were not markedly changed by the repeated doses of bicyclomycin as well as ampicillin, and normal feces were excreted over the administration period of these antibiotics.
However, on the first day following the same dosing of kanamycin, the numbers of Bacteroides and Fusobacterium were markedly reduced in the intestines of all monkeys tested and severe diarrhea was observed.

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Blood level of cyclophosphamide (Endoxan, Ex) after peroral administration has not yet been fully elucidated, in spite of its wide clinical application as a masked form of antitumor agents. The present study was designed to determine the reasonable peroral dose of Ex by measuring blood and urinary level and comparing them with the values in the intravenous route.
The blood levels of total Ex (i. e. indirectly reactive substances for NBP reagent) and its metabolites were measured in consecutive 2 nd, 6 th and 24 th hours according to FRIEDMAN-MORITA'S method after 200 mg Ex administration in the form of tablet containing 50 mg (T-Group) or granule (G-Group) containing 50 mg a gram. Difference of the form of drug, i. e. between tablets and granules, and of the administration routes, i. e. between peroral and intravenous route were compared. Thirty-six patients cinluding malignant lymphoma, carcinoma of skin, breast and thyroid without any gastrointestinal disorders, were materials for the present study and their body weights ranged 50-56 kg.
As previously reported on 43 patients of malignant tumor, the mean blood levels after intravenous administration of 500 mg Ex were, as the total substances, 7. 4 μg/ml in 1st, 6. 5 μg/ml in 2 nd, 6.7 pg/ml in 3 rd and 3. 8μg/ml in 24 th hour, respectively, and as metabolites form, 3. 2 jug/ml in 1st, 2. 8 μg/ml in 2 nd, 2. 4μg/ml in 3 rd and 3. 0 dug/ml in 24 th hour, respectively.
Maximal activation rates (directly reactive substance over indirectly reactive substance) in 24 hours after intravenous administration showed 79%. Mean maximal blood level was obtained after 6 hours in single peroral administration of 200 mg Ex. The levels in G-Group showed 7. 8 μg/ml in total substances and 5. 4 μg/ml in metabolites, respectively, and those in T-Group were 5. 8 μg/ml in total substances and 4. 6μg/ml in metabolites, showing higher value in G-Group. The blood levels of 24 hours after peroral administration were somewhat higher than those after 6 hours in T-Group, but the former was slightly lower than the latter in G-Group. Since the difference between the values in 6 th and 24 th hour was minimal, it might be suggested that the blood level was not so much affected by the dose given perorally.
The blood levels after peroral administration of 500 mg Ex, were similar to those of 200 mg, showing 6.2μg/ml in total substances and 3. 2μg/ml in metabolites in T-Group and 11. 6 fig/ml in the former and 6. 1μg/ml in the latter in G-Group, respectively. It was noticed, therefore, that there might be no differences in metabolites between the administration route and dosis.
Urinary excretion of Ex after 200 mg peroral administration were minimal within initial 2 hours, but 6-20% and 25-50% of Ex were excreted for subsequent 4 and following 18 hours and its activation rates was approximately 50%.
The blood levels of consecutive 1st, 7 th, 14 th and 21 st days after peroral administration of 200 mg Ex per day, were almost unchanged both in T-and G-Group, revealing the same level as in single administration of 200 mg a day. Even in the peroral administration of consecutively decreasing dose, such as 500 mg on 1 st, 300 mg on 2 nd, 200 mg on 3 rd and 100 mg on 4 th day, the blood level of Ex was not altered and this was lowered and disappeared by 3 rd day after the administration was discontinued.
From the results obtained, peroral administration of 200 to 300 mg Ex per day was recommended as the necessary and sufficient maintenance dose.

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A patient with cryptococcal meningtis was treated with continuous ventricular drainage, amphotericin B and 5-fluorocytosine (5-FC). Cryptococcus neoformans disappeared and apparent cure was achieved. In the course of therapy, withdrawal of 5-FC aggravated the CSF findings in spite of continuous ' administration of amphotericin B, but re-administration of the drug yielded rapid improvement.
Determination of minimal inhibitory concentrations of 5°FC for Cryptococcus neoformans cultured from patient's cerebrospinal fluid indicated 12. 5 μg/ml repeatedly.
Serum and cerebrospinal concentrations of 5-FC were as follows : 62 to 100μg/ml, 32 to 40μg/ml, respectively with a dosage of 10 g/day;50 to 79μg/ml, 25μg/ml, 7g/day; 10 to 50μg/ml, 10 to 17.5 μg/ml, 5g/day.
Significant evidence of toxicity was not observed.

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1) Two hundreds and nineteen strains, with minimal inhibitory concentration of 12.5μg/ml or higher for gentamicin, were isolated from 6 hospitals in Tokyo and Chiba.They were Pseudomonas aeruginosa (73 strains), Providence (56 strains), Proteus sp. (36 strains), Klebsiella-Enterobacter-Serratia (33 strains), E. coli (9 strains), Alcaligenes (5 strains), Acinetobacter (4 strains), Citrobacter (3 strains) and Pseudomonas cepacia.
2) Incidence and species of bacteria resistant to gentamicin varied in each hospital. The major sources of these bacteria were urine and pus.
3) These bacteria are commonly resistant to kanamycin, dibekacin and tobramycin. Of these Pseudomonas aeruginosa, Proteus sp. and Providence, 3strains were inhibited by kanamycin and dibekacin and 12 strains by tobramycin at the concentration of 6.3μg/ml.
4) Forty-seven strains of 73 Pseudomonas aeruginosa, 33 strains of 56 Providence and 22 strains of 33 Proteus sp. were susceptible to 6.3μg/ml of amikacin.

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