The susceptibility to several commonly used antimicrobial agents was examined on approximately 900 isolates of various anaerobes from clinical specimens between October 1965 to May 1975, and the changes of susceptibility were investigated. Antimicrobial agents tested were penicillin G (PC-G), ampicillin (AB-PC), cephaloridine (CER), erythromycin (EM), josamycin (JM), lincomycin (LCM), clindamycin (CLDM), chloramphenicol (CP) and tetracycline (TC). And thiamphenicol (TP) and doxycycline (DOTC) were also used against recently isolated organisms. Minimal inhibitory concentrations (MIC) were determined with agar plate dilution method.
The activity of PC-G, AB-PC and CER against almost all strains of anaerobes was good at 12.5 μg/ml or less, but a marked increase of resistant strains of Bacteroides was recognized.
EM, JM and LCM had similar activity against anaerobes, and were effective to most strains of anaerobes except for Veillonella, Bacteroides and Fusobacterium. CLDM was highly active against almost all strains of anaerobes, and more active than the two macrolides and LCM. But recently, significant increase in resistant strains was observed among Bacteroides.
CP had good activity against all strains of anaerobes, and the increase of resistant strains was not recognized. TP had a similar good activity as CP.
While, activity of TC against all anaerobes was poor at the level of 25 μg/ml or more. DOTC was more active than TC against all strains tested.

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The results of laboratory studies on doxycycline intravenous are summarized as follows:
1. The standard curves of doxycycline in five dilution systems were compared. Zones of growth inhibition were largest in the phosphate buffer solution at pH 7.2 and smallest in human serum. Lung system was close to the buffer system, liver system close to the serum system, and kidney system intermediate.
2. The doxycycline concentrations in blood of healthy male adults were compared by crossover method. The concentration following intravenous injection of 200 mg, dissolved in 40 ml of 20% glucose and injected in 5 minutes, was higher than that after oral administration of 200 mg immediately after the injection, but was same after 3 hours and thenafter.
3. No tendency of accumulation was observed in six volunteers injected intravenously with 100-200 mg of doxycycline daily for three days.
4. In a patient with chronic broncho-bronchitis injected intravenously with 200 mg, the blood level reached a peak of 4.8 mcg/ml after 30 minutes, while the sputum- level reached a peak of 1.8 mcg/ml after 90 minutes. The sputum level was 30-40% that of serum.
5. The urinary excretion of doxycycline was 94 mg/day (47.0%) after a single intravenous injection of 200 mg, and 53 mg/day (26.5%) after a single oral administration of 200 mg.

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The MICs of sulfobenzylpenicillin (SB-PC) were determined by the two-fold serial agar-dilution method for 108 bacterial strains of 21 species. The diameters of inhibition zones of these bacterial strains by the 30μg and 200μg SB-PC discs were also measured.
The relation between the MIC and the diameter of the inhibition zone was found to be expressed as a primary regression line in all cases of the conventional method (cultured for about 16 hours), delayed assay method (cultured for about 24 hours) and rapid methods (5-6 hours and 3-4 hours culture methods). Thus, it was confirmed that the single-disc method can be employed for the susceptibility test of SB-PC.
Subsequently, variations of MICs obtained by the disc-diffusion method were compared with those obtained by the serial agar-dilution method.

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Distribution of the bleomycin A₂ suspended in sesame oil (Oil Bleo Suspension) in rat organs and tumors after the intramuscular administration was investigated by bioassay, the effect of intratumor administration of the suspension on the growth of rat mammary carcinoma induced by 7, 12-dimethylbenz (a) anthracene was also studied.
The oil suspension showed a protracted concentration in either tumor or organ tissues, but showed similar inhibitory effects on rat mammary carcinoma to those by regular bleomycin solution.
Further studies should be performed on the effect of bleomycin A₅ in sesami oil on mammary carcinoma.

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The results of clinical studies on OE-7 (erythromycin stearate, enteric coated granule) were as follows.
(1) Thirty-two cases with respiratory infections were treated with OE-7 by the oral route of 300mg every 6 hours in 5 cases and 400 mg every 8 hours in 27 cases. In 28 of 32 cases (87.5%) OE-7 was effective.
Gram-positive cocci, namely pneumococcus, α-and β-streptococcus, staphylococcus etc. are the most important pathogens in acute respiratory infections statistically and the most of them are susceptible to many chemotherapeutic agents, especially to erythromycin and penicillin. This is the case also with our studies.
Acute exacerbation of asthmatic patients are frequently complicated with secondary respiratory infections caused by those pathogens and sometimes this condition in turn exacerbate asthmatic states.
In our studies OE-7 displayed a good effect to such cases.
(2) As the side effect gastrointestinal disturbances were slightly observed in 8 of 32 cases and allergic reactions in none.
Hepatic and renal function tests examined in 17 cases revealed no change after treatment.
(3) The mean serum concentration of OE-7 by the oral route of 300 mg every 6 hours revealed about two times higher levels than by the same route of 400 mg every 8 hours, the peak was both reached after 3 hours after ingestion, 1.96 mcg/ml and 0.97 mcg/ml respectively.
This experiment was done for 5 healthy persons in the condition of free food ingestion and cross over in one week interval.

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[in Japanese]

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[in Japanese]

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Sulfobenzyl-penicillin (SB-PC) is currently being investigated for use in man. The purpose of this study was to evaluate effect of SB-PC on Salmonella typhosa and biliary excretion of SB-PC in disease of the biliary tract.
1) Clinically, typhoid carriers without cholelithiasis were initiated with 4.0 g/day of SB-PC. Stool and bile became negative for Salmonella typhosa 14 days after initial treatment.
2) In typhoid carriers with cholelithiasis, Salmonella typhosa were not isolated from bile, wall of the gallbladder and surface of gallstone, but were isolated from nuclei of gallstones. The treatment of typhoid carriers with cholelithiasis may belong to a most difficult problem.
3) Biliary excretion of SB-PC in the patient given a single dose of 2.0 g/day im. was markedly dependent on characteristics of the patient, situation of external drainage and volume of bile excretion. High concentration in bile in some patient was 298 μg/ml at 3 hours after administration.
4) In intravenous administration of a single dose of 6.0 g, maximum concentration in bile was about 2,000 μg/ml at 2 hours after administration and bactericidal concentration was obtained for resistant bacteria (Pseudomonas, Proteus, etc.) in biliary infection.
5) As side effects, pain and redness were infrequent after im. administration. Toxicity was not experienced in the patients injected intravenously.

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In vitro studies were undertaken on clinically isolated strains of various bacteria to examine the antibacterial activity of ampicillin (AB-PC), carbenicillin (CB-PC), sulbenicillin (SB-PC), cephalothin (CET), cefazolin (CEZ) and gentamicin (GM).
Fifty three % of Escherichia coil strains, 53.3% of Citrobacter sp., 80% of Proteus mirabills, 42.9% of Morganella and 80% of Bacteroides sp. were susceptible (MIC being not higher than 12.5 μg/ml) to AB-PC. The eight other species were not so susceptible to this penicillin.
CB-PC and SB-PC were almost as effective as AB-PC against Escherichia coil and Citrobactersp. They were less active against Kiebsiella sp., but more active against Enterobacter sp., Serratia sp., indole-positive Proteus group and Pseudomonas sp. than AB-PC. SB-PC was more effective than CB-PC against Pseudomonas sp. The strains of Pseudomonas sp. which were resistant to higher concentrations of CB-PC and SB-PC were pyocyanine-negative strains.
All strains (100%) of Escherichia coil, Klebsiella sp. and Citrobacter sp. were susceptible to CET and CEZ, while none of Enterobacter sp., Serratia sp., Proteus vulgaris, Morganella, Rettgerella, Providencia and Pseudomonas sp. were susceptible to these cephalosporins. The MICs of CET and CEZ against Bacteroides sp. were moderately low.
Some strains of Providencia and Alkaligenes sp. were resistant to GM but the other 10 species were not resistant to this antibiotic, though it showed comparatively high MICs against Bacteroidessp.
When seen from the MIC distribution of each antibiotic, there was a tendency that the strains isolated from the pus were more resistant than those isolated from the other sources (urine, sputum and bile).

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MIC of amoxicillin (AMPC), ampicillin (ABPC) and cephalexin (CEX) against bacteria detected from the patients suffering from urinary infections was determined and the clinical efficacy of AMPC was examined.
As the result of determining MIC of AMPC against the detected Escherichia coli, 85.4% showed the value of <6.25mcg/ml. AMPC and ABPC seem to be well correlated with each other regarding MIC, and AMPC showed 1-2-stage lower concentration than CEX.
In connection to clinical efficacy of AMPC, the oral administration at a daily dose of 750mg gave the effectiveness rate of 92.5%. Few side effects were caused by administering AMPC and this is an excellent drug for healing acute simple urinary infections.

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