The antibiotic susceptibility of 375 strains of Pseudomonas aeruginosa isolated in the Clinical Laboratory of the Hokkaido University Hospital during 1966-1968 was determined. The yearly isolation rate of Pseudomonas aeruginosa from all clinical specimens sent for bacteriological examination ranged from 3.65% to 5.79%. The isolation rate was generally high in summer and autumn months.The isolated strains showed a good sensitivity to colistin, polymyxin B and gentamicin, the average of the minimum inhibitory concentration (MIC) being 6.3, 12.5 and 3.2 mcg/ml, respectively. The strains were highly resistant to streptomycin, chloramphenicol, tetracycline and kanamycin. The majority of them showed an MIC of 200 mcg/ml or more to these antibiotics. Carbenicillin was unique in the inhibitory pattern, showing an average MIC of 100 mcg/ml. Strains isolated from feces of the healthy persons were found to be more sensitive than those from clinical sources. The drug resistance appeared to be induced by the use of antibiotics in the hospital.

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1. The antibiotic susceptibility of 247 strains of Staphylococcus aureus isolated in Hokkaido during the year 1968 was studied. Generally, strains from inpatients and strains from large hospitals were more resistant than those from outpatients and those from small hospitals.
2. No resistant strain against methicillin, oxacillin and cephaloridine was found.
3. The sensitivity of strains from the Hokkaido University Hospital in 1968 was compared with that in 1966. Except for chloramphenicol, the percentage of resistant strains against common antibiotics was found to have decreased in 1968. The amounts of antibiotics used in the hospital has also been declining during these years, a fact indicating that the drug resistance of bacteria is closely related to the consumption of antibiotics.
4. The typability of strains from the Hokkaido University Hospital by the basic phage set was as low as 22.7%. The majority of the untypable strains was multi-resistant and lysable with phage 1371 and 1447, which were derived from untypable strains by means of cross culture method by FISK, and are seemingly related to the phage 80. These findings might suggest possible transduction of the drug resistance through some specific phages with simultaneous lysogenization.

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1) For the purpose of investigating the recent transference of pathogenic bacteria of the urinary tract infections, the study was carried out on the species isolated from the outpatients of urinary tract infections in 1968. It was clarified that Gram-negative bacteria were encountered mostly, i. e. Escherichia coli, Bacillus pneumoniae, Bacillus proteus and Bacillus pyocyaneus.
2) The sensitivity was examined by disk method and agar plate dilution method on the bacteria isolated from both out-and in-patients in 1968.
As the result, CER, MPI-PC, PC-G and EM demonstrated a good susceptibility to Gram-positive bacteria, while CER, Na, Ft and KM to Gram-negative bacteria.
3) The Ft sensitivity was examined with special reference on Gram-negative bacteria. The result revealed that this drug showed a quite excellent sensitivity to those bacteria almost equally to CET and Na, besides there encountered scarcely no resistant bacteria.

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ATP values in sarcoma cell of several kinds were studied, and the values using thin layer chromatography of DEAE-cellulose ionexchanger were determined, and the following results were obtained.
1) Almost parallel relationship was observed between the distribution of ATP values in liver homogenate and that of ATP values in YOSHIDA sarcoma cell homogenate.
2) The values in YOSHIDA sarcoma cell were observed higher than those of normal liver of the same time.
3) ATP amounts in AH 130 sarcoma cell were higher than the average values of normal rat liver homogenate.
4) ADP and AMP were observed in AH 130 sarcoma cell homogenate and EHRLICH sarcoma cell.The values were given about 1, 500 mcg/g and 2, 000 mcg/g respectively.

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On a new sulfa drug, sulfiodizole, of which structure has iodine molecule combined with that of sulfisomezole, several experimental studies were carried out and the results obtained were as follows.
1. The sensitivity tests of various sulfa drugs against Staphylococcus aureus and various Gramnegative bacilli were performed, resulting in on superiority of sulfiodizole to others.
2. The effect of sulfiodizole for prevention of abscess formation after inoculation to Staphylococcus aureus to the back of mice was almost equal to that of sulfisomezole.
3. In the determination of serum level of rabbits, the value varied in great ranges depending upon chemical or biological method used.
4. Urinary concentration of the drug in dog reached very high comparing with that of serum, bile and pancreatic juice, which were all low in general.
5. The peak value of tissue level ranked in order of liver, kidney, lung, serum and brain.
6. Eleven out-patients with various infections were medicated by sulfiodizole, being judged as effective in almost all cases.

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Change in colonic florae was observed in patients who received colon surgery. Experience with kanamycin, given by mouth, indicated that this antibiotic was highly effective prophylactically on enteropathogenic Escherichia coli and Klebsiella especially when it was given together with phthalylsulfathiazole. However, it was ineffective on Alkaligenes, Proteus, α-and β-Streptococcus. Staphylococcus epidermidis and Yeast-like body, on the other hand, proliferated after the administration.
Mechanical cleansing of bowel with polymyxin had no influence on colonic florae.
Infectious complications were encountered in 2 of 15 patients ; one was peritonitis and the other was abscess of abdominal wall.
Considering the fate of Escherichia coli in the present study, the safe and porper use of kanamycin for preoperative preparation is within 3 days' administration and in combination with phthalylsulfathiazole.

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On cephalexin, fundamental and clinical experiments were performed.
1) The minimum inhibiting concentrations of cephalexin against Staphylococcus aureus from sputum of respiratory infectious diseases were divided to the two types. The first type was one group of peak titer 6.25mcg/ml and the second type was the other group of ≥100 mcg/ml.
2) Friedländer bacilli were more inhibited by cephalexin than cephaloridine.
3) The tissue concentrations of rats with cephalexin were measured by cup assay. The results of this experiment were that at one hour after indicated that they distribution were kidney>liver>lung>blood.
4) The infected mice by Staphylococcus aureus (Smith strain) were treated by cephalexin only and the combination therapy pf cephalexin and lysozyme i. p. The results of this therapeutic forms were that cephalexin+ lysozyme was best, and secondary good result was gained by cephalexin+lysozyme i. m.
5) Twelve cases of various infections including respiratory infectious diseases 6, urinary infections 5, cholecystitis 1 were treated by cephalexin (1. 5-3.0g/day). The significant effects were demonstrated in 9 of 12 cases.
There were no side, effects in all cases.

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Laboratory and clinical studies of cephalexin were made with the following results :
1. The MIC distribution of cephalexin against 85 out of 90 strains of Staph. aureus were 1.56 to 12.5 mcg/ml which result was considerably less sensitive than those of cephalothin and cephaloridine. Sixteen out of 21 strains of E. coli and 17 out of 24 strains of Klebsiella pneumoniae were both at the MIC distribution of 6.25 to 25 mcg/ml which result appeared to have not a great difference as shown in Staph. aureus. Staphylococcus and E. coli were more rapidly acquired the resistance to cephalexin than to cephalothin and cephaloridine in vitro.
2. The peak blood levels of cephalexin after a single oral administration of 500 mg were observed during 30 minutes to 1 hour with the average level of 12.3 mcg/ml. The average urinary recovery during 6 hours was 86%.
3. Cephalexin was evaluated clinically in 25 cases of various types of infections and a good clinical response was observed in the infections of respiratory tract and urinary tract without noticeable side effect. However, the drug seemed to be less effective against such sever infections as septicemia and endocarditis.

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After a single oral administration of 250 mg and 500 mg of cephalexin (CEX-T), the blood levels showed the peaks of 7.7 and 8.8 mcg/ml at the 1 st or 2 nd hour respectively, and were not detected at 6 th hour in 5 cases out of 6.
Forty-nine strains of Staphylococcus aureus isolated from surgical infections were inhibited to grow from 1.56 to 25 mcg/ml of CEX-T with plate dilution method.
CEX-T was found to be effective in 17 cases out of 20 with acute surgical infections. No significant side effects were observed.

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Cephalexin, an orally absorbed cephalosporin C, was studied through laboratory and clinical investigations and the following results were obtained :
1. Cephalexin was highly sensitive in vitro against Staph. aureus, but not sensitive against most strains of gram negative bacilli, excepting for some of E. coli and Klebsiella.
2. A high correlationship of sensitivities between cephalexin, cephalothin and cephaloridine was observed against Staph. aureus and gram negative bacilli.
3. The peak blood level was obtained at 1 hour after oral administration of cephalexin and the average blood levels with 500 mg at 30 minutes, 1, 4, and 6 hours were 2. 8, 6.4, 2.5 and 1.0 mcg/ml respectively.
4. Biliary concentrations after oral administration of 500 mg to one case were the peak of 10 mcg/ml at 2 hours and 1. 8 mcg/ml at 8 hours.
5. Urinary recoveries obtained durig 2 and 6 hours after 250 mg oral administration were 26.8% and 50.3% respectively at the average of 3 cases.
6. Clinical experiences of cephalexin were made with 7 cases of skin and soft tissue infections and all cases responsed clinically to the drug. No noticeable side effect was observed.

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Cephalexin, a new oral cephalosporin C, was evaluated through laboratory and clinical investigations and the results were obtained as follows :
1. The MIC values of cephalexin against clinically isolated strains of Staph. aureus and E. coli were distributed mostly between 1. 56 to 12. 5 mcg/ml and 6. 25 to 25 mcg/ml respectively.
2. Cephalexin was well absorbed by oral administration. After single oral administration of the increasing doses, high blood levels were obtained in proportion to the dose and the peak was at one hour. Urinary recovery obtained during 12 hours was about 80% of the given dose. There could not be observed any cumulative tendency in blood levels or urinary recoveries after repeated administration to healthy volunteers.
3. Clinical response of cephalexin was studied on urinary tract infection on the daily dosages of 1 g and 2 g. No difference of the response was observed between 1 g and 2 g in the infections except the cases of camplicated pyelonephritis in which the response of 2 g was statistically better than that of 1 g. There was observed no side effect and no adverse reaction on clinical laboratory findings, although some mild digestive side effects were encountered. It is considered that cephalexin is an effective antibiotic to the infections of urinary tract with few side effect.

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The stability of aminocyclohexyl-penicillin against penicillinase was studied, comparing with that of the other penicillins. The following results were obtained.
1) Aminocyclohexyl-penicillin was more stable than aminobenzyl-penicillin against penicillinase.
2) Methyl-phenyl-isoxazolyl-penicillin was the most stable against penicillinase.
3) The stability of aminocyclohexyl-penicillin against penicillinase was near to that of penicillin G.

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We observed the therapeutic effect against syphilis and pyoderma and antigenecity of enduracidin (EDC). The results were summarized as follows.
1. The skin tests with EDC were positive in 2 of 97 cases.
2. The results of passive cutaneous anaphylaxis test and complement fixation test on the serum of 10 patients with EDC therapy was negative in all.
3. EDC injection was effective in 5 of 8 patients with syphilis.
4. EDC ointment was applied to 16 cases with pyoderma. It was effective in 14 cases.
5. In 3 of 24 cases treated with EDC, the side effects were observed clinically.

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In order to clarify the clinical significance of per rectum administration of antibiotic substance, examinations were carried out with a suppository containing 250 mg of erythromycin base.
a) Antibiotic concentrations in the blood
Antibiotic blood concentrations were determined in 5 healthy women following administration of a suppository containing 250 mg of erythromycin base. The TORII's superposition method was used employing Streptococcus haemolyticus as the test organism. The rectum administration was carried out 3 times at weekly intervals by the cross over technique. Separate from the per rectum administration, 25 mg erythromycin base tablets were given to the same subjects for oral administration as control.
The mean blood levels following the per rectum administration were as follows : at 1 hour, 0.30 ± 0.0077 mcg/ml ; and at 2 hours, 0. 24 ± 0. 077 mcs/ml. The peak level was reached at 4 hours, being 0. 45 ± 0. 077 mcg/ml. The blood levels, thereafter, declined rapidly.
On the other hand, the mean blood level following oral administration of the 250 mg tablets of erythromycin base was 1.08 ± 0.243 mcg/ml, at the peak. At 4 hours (when the blood level in the per rectum group was at its peak as mentioned above), the blood level in the oral administration group was 0.64 ± 0.243 mcg/ml. Variations in blood levels thereafter showed no difference between the two groups.
b) Clinical results
The erythromycin suppository was administered to clinical case of upper respiratory infection, puerperal mastitis, and urinary tract infection in doses of 1 g daily for 2 to 5 days and to clinical cases of pyodermia of newborn in doses of 3.75 mg daily for 5 days. The drug was found excellent in 1 of 22 eases diagnosed as above, good in 10, fair in 2, poor in 6, and indeterminable in 3.
The per rectum administration of antibiotic substance had no particular side effects excepting that a mild sensation of rectal irritation was complained of in some of the cases.

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A study was made on thiamphenicol glycinate hydrochloride (TP-G), a new chemotherapeutic, as to the effect on in vitro bacterial growth as well as the therapeutic effect on the mice infected with pathogenic bacteria. The results were summarized as follows.
1) It has been found that TP-G has same in vitro activities as thiamphenicol (TP). And it is assumed that antimicrobial activity of TP-G is elicited because it readily undergoes hydrolysis and is converted to TP.
2) The therapeutic effects of TP-G have been proven to be even superior to those of chloramphenicol succinate (CP-S) on the mice infected with various pathogenic bacteria and rickettsia, when administrated subcutaneously.

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A new bioassay system to estimate sulfonamide was investigated. A thin layer cup method by using a synthetic medium modified SAUTON's prescription, and spore suspension of Bacillus subtilis PCI 219 as a test microorganism was found.
Applying this bioassay, blood levels of three sulfonamides were determined, being compared with BRATTON-MARSHALL's chemical assay.

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