Prevalence of drug resistant strains of Escherichia coli associated with or without hospital was investigated. The strains derived from the clinical specimens and the feces of hospitalized patients represented to be associated with hospital. The strains not associated with hospital were isolated from the bacteriuria obtained by general practitioners and the feces of normal people. Minimum inhibiting concentrations of these strains of four groups were measured for comparison.
The strains of E. coli derived from the clinical specimens of hospitalized patients were mostly resistant to streptomycin, chloramphenicol and tetracycline, and many strains obtained from the bacteriuria of general practitioners and the feces of inpatients were also resistant to three agents, whereas few resistant strains were detected in the feces of normal people. Aminobenzyl penicillin and kanamycin resistant strains were isolated from only the clinical specimens of the inpatients, whereas the strains in the other materials were mostly susceptible to both antibiotics. The strains derived from either the materials associated with or without hospital were mostly susceptible to nalidixic acid, nitrofurantoin and cephalexin.
The multiple drug resistant strains were exceedingly common in the clinical specimens of inpatients, while rare in the feces of normal people.

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The time inactivation curves of various antibiotics (Oxytetracycline OTC, Gentamicin GM, Colistin CL, Kanamycin KM, Aminobenzylpenicillin AB-PC, Cephaloridine CER) were obtained in E. coli. The curves were distinguished into three types; (1) exponential decline (GM, CL), (2) biphasic decline (AB-PC, KM), and (3) temporal depression of survivor (OTC, CER). To compare these bactericidal effects on E. coli, a new equation (CⁿT=K) was developed. Using the equation, the curves were analysed in terms of the time-concentration effects. The results revealed that these are two different patterns of bactericidal effects, namely treatment time dependent type (GM, CL and KM), and concentration dependent type (AB-PC and CER). OTC, however, was inapplicable to the present equation, because of its complicated response.

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Antitumor activities against implanted EHRLICH ascites carcinoma in mice were investigated by using substances obtained from 58 species of lichen, and the substances were adsorbed on anionic and cationic ion-exchanger resins. Adsorbed substances from Cetraria asahinae Sato, Cetrelia japonica (Zahlbr.) Culb. & Culb., Cladonia polydactyla (Flk.) Nyl. var. theiophila (Asah.) Asahina and Parmelia laevior Nyl. were recognized to have remarkable antitumor activities.
Gel-filtration of pastes obtained from 4 kinds of lichen was carried out with a Sephadex G-25 column. and UV sbsorption spectrum of each fraction was checked at 280 mu, Two fractions were separated from the pastes of Cetrelia japonica (Zahlbr.) Culb. & Culb., Cladonia polydactyla (Flk.) Nyl. var. theiophila (Asah.) Asahina and Parmelia laevior Nyl., and three fractions were separated from the paste of Cetraria asahinae Sato, respectively.
From the results of antitumor activities test for these 9 fractions, it was found that fraction I of Cetraria asahinae Sato indicated life prolongation effect on mice at rate of 80% in 40 days after administration of the fraction on a dose level of 0. 19 mg/mouse, and fraction I of other lichen indicated considerable life prolongation effect.
But all fraction did not indicate any effect against Sarcoma-180 (solid type).

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Combined effect of Josamycin (JM) and Chloramphenicol (CP) was examined by two dimentional tube dilution method, determination of growth curve in liquid medium, and crossed paper strip method toward Staphylococcus aureus. Effectiveness of the combination of the drugs was statistically judged.
On JM resistant (JM^r) strains, synergistic effect by the combination of both drugs was observed, whereas additive effect was obtained on JM sensitive (JM^s) strains.
Induced resistance to CP of CP^r strains was inhibited by the addition of JM. Mutation frequency of JM^s to JM^r was also decreased by using both drugs.

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1. The therapeutic efficacies of sulfamethoxazole (SMX) -trimethoprim (TMP) combination product and SMX alone were compared in acute uncomplicated cystitis by a double-blind technic.
2. The clinical material of this study consisted of a total of 257 patients, of which 215 patients were evaluated (97 patients for SMX-TMP combination product and 118 patients for SMX alone).
3. No significant difference was found between the clinical backgrounds of 2 treatment groups before the commencement of drug therapy.
4. The most frequently isolated bacterial strain was E. coli. The MIC distribution of the 87 strains of E. coli isolated from the urine cultures found its peak at O. 19 mcg/ml of TMP, whereas the majority of isolates had MICs of SMX greater than 100 mcg/ml. The potentiation of antimicrobial activities by combination of 2 drugs as assessed by the checkerboard method was demonstrated in 76 of 87 strains tested (87%).
5. The improvement of subjective symptoms assessed on the 4 th day of treatment indicated an improvement rate of 90.4% for SMX-TMP combination product and 78. 6 % for SMX alone (p<0. 05).
6. The changes of urinary findings in patients treated with SMX-TMP combination preparation as examined on the 4 th day of treatment gave improvement of pyuria in 87%, that of bacteriuria in 88. 2%, The normalization of pyuria was recorded in 69. 4% and that of bacteriuria in 80%, respectively. In contrast, the results of SMX therapy in 105 patients gave improvement of pyuria in 82% and that of bacteriuria in 76%. The normalization of pyuria was recorded in 66% and that of bacteriuria in 65%, respectively. There was a statistically significant difference between SMX-TMP combination product and SMX alone in normalizing bacteriuria (p<0. 05).
7. The evaluation of the clinical efficacy of drug therapy in acute uncomplicated cystitis was based on changes of the urinalysis findings. The SMX-TMP therapy gave an effective rate of 77%, whereas SMX-treated group gave an effective rate of 69%.
8. Subjective symptoms and urinalysis findings were re-assessed on the 8 th, that is, 4 days after the cessation of the drug therapy. The therapy of SMX-TMP combination product gave more favorable results than that of SMX alone with regard to subjective symptoms and the rate of aggravation by objective criteria.
9. The clinical results of patients treated by SMX alone were correlated with MISs of SMX of the urinary isolates.
10. Of 209 patients subjected to the analysis, there were 5 cases of untoward reactions, all belonging to the SMX-treated group. The major complaints were gastrointestinal troubles which were generally slight without necessitating withdrawal of the drug.

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This experiment was performed on adult rabbits in order to detect bone marrow toxicity of gentamicin.
Thirty minutes after a 40 mg single intramuscular injection of gentamicin into rabbits (13mg/kg), the maximum concentration of gentamicin in plasma reached to the level of 40mcg/ml. No abnormalities were detected in blood counts, bone marrow morphology and ferrokinetics after intramuscular injections of gentamicin at dose of 13mg/kg daily for 32 days. BUN and serum creatinine level did not vary from the normal range at the termination of the experiment.
These results led us to assume that direct myelotoxicity is negligible in the clinical use of gentamicin.

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The binding of penicillin G and other 29 antibiotics to the bovine plasma proteins, a part of the pharmacokinetics of antibiotics, was investigated by the ultrafiltrating technique at 4°C.
As the rates of the binding, inactivation, recovery and binding activity, following values were obtained in order : 64. 9 to 82. 7%, 11. 96 to 56. 85%, 7. 77 to 25. 75% and 8. 9 to 34. 11% in penicillin antibiotics; 0 to 61. 4%, 0 to 10. 66%, 0. 49 to 12. 8% and 14. 91 to 41. 72% in glycoside antibiotics; 91. 0 to 99. 9%, 16. 0 to 46. 19%, 44. 98 to 71. 01% and 4. 33 to 21. 06% in tetracycline antibiotics; 55. 22 to 94. 1%, 5. 37 to 57. 36%, 1. 32 to 31. 5% and 9. 66 to 40. 65% in macrolide antibiotics; and 72. 6 to 95. 68%, 14. 34 to 51. 85%, 8. 19 to 30. 12%, and 17. 28 to 41. 54% in chloramphenicol antibiotics, respectively.
Optimum pH of the binding of antibiotics to the plasma proteins was in the range 5. 0 to 8. 0, i. e. 8. 0 in penicillin antibiotics, 5. 0 in glycoside antibiotics, 7. 0 to 8. 0 in tetracycline antibiotics, 6. 0 to 7. 0 in macrolide antibiotics, and 7. 0 to 8. 0 in chloramphenicol antibiotics, respectively.

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The binding of penicillin G and other 29 antibiotics to rabbit or rat liver microsomes, a part of the pharmacokinetics of antibiotics, was investigated by the ultrafiltrating technique at 4°C. The rates of inactivation of antibiotics by liver microsomes were 3. 1 to 74. 5% and those by liver mitochondria were 2. 2 to 51. 9%. Most of antibiotics were inactivated by microsomes more greatly than by mitochondria.
As the rates of the binding, inactivation, recovery and binding activity, following values were obtained in order : 49. 68 to 75. 55%, O. 89 to 34. 55%, 2. 21 to 18. 59% and 23. 19 to 40. 62% in penicillin antibiotics; 93. 48 to 98. 92%, 2. 61 to 46. 4%, 45. 87 to 63. 75% and 5. 98 to 19. 6% in glycoside antibiotics; 81. 42 to 95. 84%, 18. 52 to 60. 52%, 7.81 to 42. 48% and 14. 16 to 39. 65% in tetracycline antibiotics; 44. 81 to 92. 18%, 2. 27 to 52. 26%, 0 to 22. 41% and 15. 35 to 54. 0% in macrolide antibiotics; and 63. 06 to 88. 66%, 5. 87 to 64. 13%, 8. 57 to 21. 23% and 13. 96 to 43. 01%, respectively.
Species or sex differences in the binding of antibiotics to liver microsomes were hardly observed.

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Lividomycin inhibited incorporation of acetate-1-¹⁴C, glutamic acid-1-¹⁴C, leucine-1-¹⁴C, and glycine1-¹⁴C into protein of Mycobacterium smegmatis (strain Jucho). Incorporation of acetate-1-¹⁴C and glycine1-¹⁴C into nucleic acids was also inhibited, but incorporation of these compounds into lipids was not inhibited in the presence of lividomycin. Incorporation of uridine-2-¹⁴C into nucleic acids was significantly inhibited, but incorporation of thymidine-2-¹⁴C into the nucleic acid fraction was not inhibited in the presence of the antibiotic. It is suggested that lividomycin inhibits the synthesis of protein, probably as a result of inhibition of RNA synthesis.

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Twelve chemotherapeutics were tested in vitro for their activities against M. pneumoniae Mac and 6 strains isolated from sick patients in 1967 to 1968.
Erythromycin, leucomycin, oleandomycin and spiramycin of macrolide group as well as panfuran-S inhibited the growth of M. pneumoniae at the concentration of less than 0. 1 mcg per ml with or e exception. Tetracyclines, lincomycin and viomycin were moderately effective and the latter two revealed variablc activity to different strains. Kanamycin showed the inhibitory activity at rather high concentrations. Phenoxymethylpenicillin-K, cephaloridine, polymxin B and colistin were ineffective.

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