Drug resistance of 84 strains of Serratia marcescens isolated from clinical specimens during 1974-1975 was investigated against 10 drugs, i. e., 2 β-lactam antibiotics, 4 aminoglycoside antibiotics, tetracycline, chloramphenicol, sulfanilamide, and nalidixic acid. Transfer of R factors was tested by conjugation. Escherichia coli χ 1037 (met^- rifampicin-resistant) was used as a recipient strain. The results were as follows.
1. Aminoglycoside antibiotics and chloramphenicol showed good antibacterial activity, but among these antibiotics, gentamicin showed the most excellent antibacterial activity.
2. Drug-resistance patterns of 84 strains were as follows : 14. 3% was quadruple-resistant, 25. 0% triple-resistant, 39. 3% double-resistant and 21. 4% single-resistant.
3. In the transfer experiment of resistance to E. coli χ 1037, 14 exconjugants were obtained. R (ABPC) factor was found to be most frequently demonstrated.
4. Among TC-resistant strains (64), one strain could transfer TC resistance to E. coli χ 1037.

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An orally administrable cephalosporin ; Cephalexin could also be administrable through rectum as rectal capsule. That is, absorption of cephalexin through rectum turned out to be as high as that through small intestine. But, there are large amounts of Cephalosporinase-producing Gram-negative bacteria in rectum in contrast of the few Gram-negative rods in small intestine. Therefore, rectal capsule should contain not only cephalexin but also the drugs which inhibit the functions of these bacteria, or neutralize the Caphalosprinase activity produced by these bacteria. The most excellent additive drugs which allow the best rectal absorption of cephalexin could be Cephalosporinase inhibitors which have no antibacterial activity and are not absorbed through intestine.

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For the purpose of comparison of the therapeutic effects and side effects between Apalcillin (APPC) and Carbenicillin (CBPC), a comparative clinical study was carried out in 142 patients with chronic respiratory tract infections at 31 institutions in Japan.
Either of APPC or CBPC was assigned to each patient at random. Administration was performed by intravenous drip infusions for a fixed period of 14 days and the daily dosage was fixed at 2g (APPC) or 4 g (CBPC).
A committee consisting of several physicians who had not been informed of the name of actually given drug, made a judgement on the severity, therapeutic results and presence or absence of side effects in each patient based on the detailed subjective and objective symptoms, laboratory findings and chest X-ray films. Subsequently, the key code for the drug administered to each patient was opened and a statistical analysis was carried out by a comparison between two groups (APPC group and CBPC group) with respect to background factors, clinical effectiveness, bacteriological effectiveness, degree of improvement and side effects.
Out of 142 cases originally admitted to the trial, 16 cases were excluded bacause of failure to meet the initially established protocol and 126 cases (67 from APPC group and 59 from CBPC group) were used for the analysis of effectiveness while the analysis of side effects was done in 141 cases (75 from APPC group and 66 from CBPC group).
It was indicated that there was no significant difference between the two groups regarding background factors except body weight, PaCO₂ and ESR. Clinical effects of APPC were good in 40 cases, fair in 7 cases, poor in 19 cases and unknown in 1 case and those of CBPC were excellent in 3 cases, good in 32 cases, fair in 15 cases, poor in 7 cases and unknown in 2 cases. There was no statistically significant difference between the both groups concerning clinical effectiveness, bacteriological effectiveness and the degree of improvement. As to the incidence of side effects, no statistically significant difference was observed between the both groups.

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In order to study the efficacy, safety and usefulness of apalcillin (APPC), a new synthetic penicillin, a comparative study was carried out by an envelope method on complicated urinary tract infections, using sulbenicillin (SBPC) as a control drug, and following results were obtained.
(1) Total number of 108 cases was treated with a daily dose of either 2g of APPC or 4g of SBPC y intravenous drip infusion for 5 days. The efficacy was evaluated according to the method by the U. T. I.-Committee in 101 cases out of 108 cases, consisting of 52 cases in the APPC-group and 49 cases in the SBPC-group. Seven cases were excluded and dropped out.
The clinical safety, was evaluated in 107 cases, consisting of 54 cases in the APPC-group and 53 cases in the SBPC-group.
The usefulness based on the results of the efficacy and safety of the drug was evaluated in 105 cases, consisting of 51 cases in the APPC-group and 54 cases in the SBPC-group.
(2) For the various background factors, there were no statistically significant differences between the APPC-group and the SBPC-group.
(3) There were no significant differences for the overall clinical efficacy, the efficacy on pyuria and bacteriuria, and appearance and replacement of strains isolated from urine after the treatment. As for the bacteriological response, the eradication rate against Escherichia coli was significantly higher in the APPC-group than the SBPC-group (P<O. 05). While the eradication rate against such as Klebsiella, Proteus, Pseudomonas tended to be higher in the APPC-group than the SBPC-group, any significant differences were not observed.
On the other hand, significant improvement of fever was noted in the SBPC-group in comparison with the APPC-group.
(4) There were no significant differences between 2 groups in the efficacy rate by the presence of catheterization, severity of pyuria, and the type and site of infections etc. before the treatment. (5) There were also no significant differences between 2 groups in the results of the evaluation for the usefulness.
(6) The incidence of side effects was 3. 7% and 7. 5% in the APPC-group and SBPC-group respectively, but no significant differences were found between them. In both 2 groups. slight and transient elevation of serum transaminase was observed in some cases during the treatment, but discontinuation of the drugs was not necessary at all.
(7) By above mentioned results, it was suggested that APPC is effective on chronic complicated urinary tract infections and less incident of side effect, and therefor it is clinically useful drug in this field.

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The binding components to 8-lactam antibiotics in rat liver paste were investigated using ¹⁴C-cefazolin. Major and minor components firmly bound to 14C-cefazolin were found in the 10⁵× G supernatant of rat liver paste. The major component was identical with ligandin reported by KORNGUTH et al. The binding of 14C-cefazolin to ligandin was relatively stable, and 25% of the complex was dissociated by re-gel filtration. The binding of ¹⁴C-cefazolin to ligandin was 1. 56 μg/100 μg and was lower than that to rat serum albumin. The binding depended on the antibiotic concentrations and met FRETNDLICH's equilibrium absorption isotherms. The molecular weight of the minor components was larger than that of ligandin. The 10⁵× G supernatant of rat liver paste was fractionated by ion exchange gel filtration. Cefazolin and dicloxacillin were bound to other components, which participate in reversible binding to the antibiotics.

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Five mg of benzylpenicillin (PCG), ampicillin (ABPC), sulbenicillin (SBPC), carbenicillin (CBPC), . cefazolin (CEZ), cephaloridine (CER), cephalothin (CET), kanamycin (KM) or erythromycin (EM) were intravenously injected to mice, twice a day, five times in total, respectively. All mice were sacrificed at five hours after the last injection. The microflora and volatile fatty acid composition in cecal contents were examined by selective culture and gas chromatographic analysis.
(1) The number of Enterobacteriaceae and streptococci in PCG treated mice and the number of Enterobacteriaceae in ABPC treated mice were markedly increased with a concomitant decrease in the number of lactobacilli. On the other hand, in SBPC and CBPC treated mice, the number of cul turable bacteria was markedly decreased. Fusiform bacteria could not be detected in these four groups. Acetic, propionic and n-butyric acids were markedly decreased and furfural was detected in these four groups.
(2) In CEZ treated mice, there were considerable differences in microflora and fatty acid composition among individuals : some mice showed patterns very similar to those observed in SBPC treated. mice ; while others showed decreased in the number of culturable cecal bacteria and fusiform bacteria and in concentration of acetic, propionic and n-butyric acids. In CER, CET or KM treated mice, the number of culturable cecal bacteria and fusiform bacteria tended to decrease. There was no considerable alteration in the concentration of these volatile fatty acids in comparison with those of the untreated control.
On the other hand, in EM treated mice, Bacteroidaceae was detected and the number of fusiform. bacteria was slightly decreased. The concentration of propionic acid was decreased, but n-butyric acid was slightly increased. Furfural was detected only in some of CEZ treated mice.
(3) Changes in the microflora and volatile fatty acid composition in cecal contents of mice after intravenous injection of various antibiotics appear to be resulted from the differences in the drug concentrations of cecal contents and in antibacterial spectrum of these drugs.
(4) From these findings and the results of orally administered experiments (previous experiments), marked decrease in the number of anaerobic bacteria, especially of lactobacilli and a disapperarance of fusiform bacteria appear to result in production of furfural.

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The effects of cyclophosphamide (CY), FT-207 (FT), mitomycin-C (MMC), hydrocortisone (CS) and antimicrobial antibiotics (cephalothin-CET, ampicillin-ABPC, kanamycin-KM) on thymocytes, T-and B-lymphocytes in the spleen of mice were studied. The total dose of each agent given to mice was about half the LD₅₀. A single large dose of CY preferentially retarded the B-cell restoration, whereas the continuous treatment with relatively small dose of CY retarded the T-cell restoration. On the second day after the CY-treatment, its suppressive effect was noticed mainly on B-cells, resulting in an increased proportion of T-cells. This selective suppression of B-cells by the CY-treatment was most remarkable on stimulation with lipopolysaccharide. The increase in the proportion of T-cells in the lymphoid organs by the CY-treatment was not due to the accumulation of T-cells, judging from results obtained from adoptive transfer experiment with 51Cr-labeled lymphocytes. CS also caused selective suppression of B-cells without antigenic stimulation. MMC suppressed the number of spleen cells slightly and no selectivity among T- and B-cells was apparent. FT decreased the number of thymocytes but did not suppress the number of spleen cells. Commonly used antibiotics, such as CET, ABPC and KM did not suppress the number of the murine lymphoid cells.

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Comparative studies of the incorporation of amino acids into ribosomal and non-ribosomal proteins were carried out employing various antibiotics, inhibitors of protein synthesis, as well as mutants of E. coli thermosensitive for some stages of protein synthesis.
With mutants having thermosensitive amino acyl tRNA synthetase, a significantly decreased incorporation into soluble protein was observed than that into ribosomal proteins.
It was found that the incorporation of amino acids into ribosomal proteins were less inhibited than that into non-ribosomal proteins by various antibiotics.

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