On a new kanamycin (KM) derivative, amino deoxykanamycin (kanendomycin, AKM), several basic experiments were carried out comparing with KM, and the following results were obtained.
1. The sensitivity of Staphylococcus aureus against AKM was generally superi or to KM, being confirmed in four-fold higher dilution.
2. The sensitivity of variou s gram negative bacilli against AKM was equal or superior to that of KM.
3. The inhibitory effect of AKM against subcutaneous Staphylococcus infection of mice was equal to that of KM.
4. The cross-over test to rabbits showed that serum level was higher on the occasion of KM injection in one case, and the same in the other.
5. The urine level following intraven ous injection to dog was as high as 1, 000 to 5, 000 mcg/ml, but the bile concentration was relatively low showing one-third of serum concentration.
6. After intramuscular injection of AKM 2 mg/kg to mice, there was no detectable organ level. When dose was raised to 80 mg/kg, various organ levels were comparable to KM injection. The peak level ranked in order of kidney, serum, lung, spleen and liver.

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On a new antimicrobial agent, antibiophagine (abbreviated as AB-PH hereafter) which had been introduced from Belgium, some experimental studies were carried out and the results obtained were as follows.
1. The antibacterial activities of AB-PH to various microorganisms depended upon the strains tested, ranging from no inhibition at 10-fold dilution plate to obvious inhibition at the concentration as low as 320-fold dilution.
2. There seeme d to be a correlation between the antibacterial activity of each strain and the result of streptomycin sensitivity disc.
3. AB-PH was considered to have intensive bactericidal action.
4. The intramuscular injection of AB-PH to mice infected subcutaneously by Staphylococcus aureus. or Klebsiella isolated from clinical specimens resulted in some inhibitory effect for abscess format ion.
5. The peak values of tissue level following intramuscular injection to mice ranked in order of kidney, serum, spleen and lung at the time of 30 minutes or 1 hour.
6. Serum levels were unmeasurable after intramuscular injectio n of 4 ml of AB-PH to 3 volunteers, however, urinary levels attained detectable ones, showing mean excretory rate of 38% by 4 hours. On the case of oral administration, both of serum and urine levels were undetectable.

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Thirty-five cases of acute cystitis and 10 cases of acute urethritis were treated by oral administration of aminobenzyl penicillin: 1 g daily, every 6 hours, for average 7 days.
The greater parts of urinary isolate were E. coil or Staphylococci, both of which had the good sensitivity to aminobenzyl penicillin.
Excellent results w ere obtained in 11 cases of 35 cystitis cases and in 9 cases of 10 urethritis cases.
Five cases of gastrointestinal disturbance and 2 cases of rash were observed in total 45 cases.

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Multi-drug resistances were confirmed in many of 198 clinical isolates from surgical infectious diseases from Jan. 1967 to Jan. 1968.
One hundred cases of surgical infectious diseases of tetracycline resistant bacteria were treated successfully by small dosis parenteral administration of pyrrolidinomethyl tetracycline.
Some considerations against the selection of antibiotics for surgical infectious diseasns were based on sensitivity test by disc method.

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A disc agar plate method, using 2, 6-dichlorophenol indophenol as the indicator, for the routine testing of the susceptibility to chemotherapeutic agents of Mycoplasma species has been developed. Of the 10 drugs used, 17 Mycoplasma cultures were highly sensitive in erythromycin, tetracycline, chloramphenicol, lincomycin, streptomycin and kanamycin, low in cephaloridine and nalidixic acid and not at all in penicillin and sulfisoxazole.

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One hundred strains of shigelli were selected at random stock cultures in this laboratory and their resistance to 13 drugs was determined to establish a convenient method of assay of drug-resistance. Assay was performed by agar dilution method and level of resistance was expressed by maximal concentration (MAC) of drug which allowed bacterial growth. Serial two fold dilutions of drug were added to each plate.
It was found that decrease in inoculum size on assay plate resulted in a significant decrease in level of resistance to drugs, especially to SA, CL, FT and FZ, but constant value of drug-resistance was obtained when inoculum size below 10⁴ microorganisms was used. Mutants developed at a high frequen cy of about 10^-4 on assay plates containing aminocyclitol drugs such as KM, PRM, FRM and GNT, and level of their resistance was found to be 2 to 4 times higher than that of original sensitive strains. Therefore one loopful inoculum of overnight broth culture caused the development of many mutant colonies on assay plate and level of resistance of mutant colonies was taken as that of original sensitive strains. Decrease of inoculum size could eliminate such error caused by development of mutants. Distribution spectrum of resistance to TC, AB-PC, FT and FZ was slightly different between the strains of Sh. sonnei and Sh. flexneri. Considering from the results described above, one loop of 100 fold dilution of overnight broth culture was used for inoculum size on assay plate. In most cases, minimal concentration of drug (MIC) which inhibits bacterial growth was found to correspond to the concentration of two-fold MAC.
Most strains of shigelli were found to be resistant to TC, CP, SM and SA or to the combinations thereof, few strains being resistant to AB-PC or NA and mostly sensitive to other drugs. Distribution pattern of TC (or CP) sensitive and resistant strains was very sharp, but another group of low level of resistant strains exhibited in case of SM or SA.

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Laboratory and clinical studies on cephalexin were made, and the following results were obtained.
The MIC distributions of cephalexin were mostly 1. 56 to 3. 13 mcg/ml against Staph. aureus and 6. 25 to 12. 5 mcg/ml against E. coli. Cephalexin was considerably sensitive to Proteus, but not sensitive to Strept. faecalis and Pseudomonas.
The peak blood le vel of cephalexin after a single oral administration of 500 mg was 13. 9 mcg/ml at one hour and the peak with 1, 000 mg reached about two times of 500 mg. Cephalexin was no more observed in the blood after 8 hours, and it was excreted in the urine as cephalexin itself at the rate of 70 to 100% during 6 hours. The average concentration of cephalexin in umbilical cord blood of 33 cases was about 4 mcginal at 2 hours which value was about half of that of maternal blood. The level in umbilical cord blood after 5 hours was higher than that of maternal blood and it could be observed even at 7 hours after single administration. It was also observed in amniotic fluid and milk to such. extent as 1 to 4 mcg/ml and 2. 8 to 4. 5 mcg/ml respectively, and this level in amiotic fluid sustained until 9 hours.
Cephalexin was clinically evaluated at the daily dosage of 1, 1. 5 and 2 g in 93 cases of various types of infections as follows; 13 cases of internal genital organ infections, I case of gonorrhea, 4 cases of vulvar abscess, 4 cases of post-operative wound infections, 3 cases of puerperal mastitis, 62 cases of acute cystitis, 5 cases of chronic cystitis, 4 cases of urinary tract infections after operation of uterine cancer and 4 cases of pyelitis. A good clinical result was observed in those cases, and there observed no adverse reaction on renal and hepatic function and almost no noticeable side effect.

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A thin layer chromatographic assay method for separation and determination of AB-PC and MCI-PC in mixture was developed using a bioautographic technique. The measurement of the diameters of the inhibition zone was used as the mean of quantitation. With the conditions described, the values determined with this measurement is proportional to the amount of the penicillins present on the developed chromatogram. This method is useful for the separatory determination of AB-PC and MCI-P. 0 in serum or urine after simultaneous administration of both penicillins.

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