In order to compare the therapeutic effects and side effects of fosfomycin Na (FOM) with those of sulbenicillin Na (SBPC), a comparative clincal trial has been carried out in 115 patients with chronic respiratory tract infections at 25 institutions in Japan. Each of the patients was assigned to either of the drugs at random. Both drugs were administered as intravenous infusions at a dosage of 2g twice daily for 14 days.
In each patient, on the basis of detailedly recorded subjective and objective symptoms, laboratory test results and chest X-ray film findings, committee members consisting of several physicians who had not been informed of the drug actually given to each patient made an assessment on the severity, therapeutic results, and presence or absence of side effects. Subsequently, the key code for the drug abministered to each patient was opened and statistical analysis was carried out by making a comparison between the two groups (one received FOM and the other SBPC) with respect to background factors, clinical effectiveness, bacteriological effectiveness, degree of improvement and observed side effects.
Out of the 115 cases originally admitted to the trial, 13 cases were excluded because of failure to observe the treating regimen initially established, leaving 102 cases (56 from FOM group and 46 from SBPC group) for analysis. It was indicated that regarding background factors there was no significance between the two groups except that more cases of SBPC group had highly accelerated ESR value and that there were more cases in FOM group which had infections due to Pseudomonas and mixed infections, both with significance.
The clinical effectiveness were classified as excellent in 5 and 7 cases in FOM and SBPC group, respectively, as good in 22 and 17 cases ; as fair in 8 and 11 cases, as poor in 21 and 14 cases ; and as undecided in 0 and 1 case, respectively, with no significance. In the bacteriological effectiveness and the degree of improvement, there was no significance which is of importance in a comparison of both drugs. In regard to the incidence of side effects no significance was observed.

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In order to determine whether infusion of antibiotics into the urinary bladder, which is frequently used in clinical practices, is really effective, DKB was given by this route in 14 cases undergone transurethral operations. The patients were divided into two groups : one group received the drug at a dosage of 200 mg, and the other 400 mg. Observations were made on changes with time in blood drug levels, retaining time in the urinary bladder, recovery rate and absorbability from the urinary bladder. Moreover, a comparison was made with transitional changes in the blood levels following systemic administration of DKB, and significance of infusion therapy against MIC of Pseudomonas aeruginosa was investigated. The results are given below.
1. In the pilot study, 3 healthy male adults were given an infusion of 200 mg of DKB in the urinary bladder. The miximum blood level of 0.273μg/ml was reached within 1/2 hour, which fell gradually in function with time. At 120 minutes after administration, 0.193μg/ml of DKB was found, with recovery rate of 79.0%.
2. Patients with lower urinary tract infections secondary to transurethral operations were treated with 200 mg of DKB, which was given as an infusion into the urinary bladder, and determined for blood levels of DKB. At 0.5, 1, 1.5 and 2 hours after administration, mean blood levels of 1.31±0.44, 1.09±0.23, 1.07±0.37 and 0.95±0.38μg/ml, were found respectively, with a recovery rate of 49.0±13.5%.
3. Following an administration of 400 mg of DKB, the mean blood levels at 0.5, 1, 1.5 and 2 hours after administration were 2.08±0.60, 1.81±0.52, 2.07±0.14 and 1.79±0.15μg/ml respectively, recovery rate being 62.8±16.9%.
4. The absorption of DKB from the urinary bladder was increased in patients with lower urinary tract infections, since it was shown that the highest blood levels attained in treated groups (200 and 400μg/ml) were 4.8 and 7.7 times, respectively, as high as those recorded for the control group and that in 400 mg group blood levels were 1.6 times higher than those of 200 mg group.
5. From the fact that, when given as an infusion into the urinary bladder, blood levels once reached showed only a slight decrease with time and that remarkable increase in penetration into the tissue of urinary bladder was indicated from the recovery rate obtained in this study, we believe that this administration route is quite promising in the treatment of lower urinary tract infections.

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In this paper, the biliary excretion of SBPC and CEZ was clinically studied in 15 patients with obstructive jaundice after Percutaneous Transhepatic Cholangio-Drainage (PTC-D).
The sertm and bile levels were determined at daily intervals after one-hour intravenous infusion of the antibiotics.
The excretion rate was expressed as percent of the rate of peak levels of serum and those of bile.
The biliary excretion of the antibiotics showed a certain change at time intervals which was not correlated to kinds and dose of the antibiotics administered. Starting at day 4 after PTC-D, there was a period of about 3 weeks during which biliary excretion rate was decreased remarkably. These results would be valuable for the chemotherapy of patients with the biliary tract obstruction.

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In order to assess the potential nephrotoxicity exerted by various antibiotics with therapeutic dosis, effects of antibiotics administered into Wistar rat in vitro and in vivo were investigated in terms of protein synthesis, nucleic acid metablism and stability of lysosome.
Kanamycin, streptomycin, gentamicin, colistin as well as chloramphenicol inhibited the incorporation of orotic acid-6-¹⁴C into rat renal nuclear RNA.
The incorporation of orotic acid-6-¹⁴C into RNA of the free polysome fraction of the rat kidney slices was inhibited by kanamycin, streptomycin, colistin and tetracycline.
The incorporation of L-leucine-¹⁴C into the free polysome fraction was demonstrated to be reduced by streptomycin, chloramphenicol and tetracycline administered in vivo.
The incorporation of orotic acid-6-¹⁴C into RNA of the bound polysome fraction of rat kidney slices was reduced by kanamycin, streptomycin, chloramphenicol and cephalothin. The incorporation of L-leucine-¹⁴C into the bound polysomes fromes fraction was inhibited by streptomycin and colistin.
Marked reduction of the incorporation of L-leucine-¹⁴C into the free polysome fraction was noticed by kanamycin, streptomycin, gentamicin and chloramphenicol added directly to cell-free protein synthesis system. Also, marked reduction of the incorporation of L-leucine-¹⁴C into the bound polysome fraction was manifested by kanamycin, streptomycin, gentamicin and colistin.
Stability of lysosome was disturbed by either kanamycin or streptomycin.
Clinical implication of these nephrotoxicity of antibiotics was discussed.

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In order to assess the potential nephrotoxicity by various antibiotics with therapeutic concentration, effects of antibiotics administered to in vitro system were investigated in terms of protein synthesis and nucleic acid metabolism.
Kanamycin, streptomycin, gentamicin and colistin added to the incubation medium at the concentration of 10 μg/ml with kidney slices were demonstrated to inhibit the incorporation of orotic acid-6-¹⁴C into nuclear RNA.
The incorporation of orotic acid-6-¹⁴C into RNA of free polysomes prepared from human kidney slices was inhibited by kanamycin, streptomycin, gentamicin, colistin and chloramphenicol.
Significant reduction of the incorporation of L-leucine-¹⁴C into free polysome fraction was noticed by kanamycin, streptomycin and gentamicin added directly to cell free protein-synthesis system.
The incorporation of orotic acid-6-¹⁴C into RNA of bound polysome fraction prepared from human kidney slices was inhibited by kanamycin, streptomycin, gentamicin and colistin.
Inhibition of the incorporation of L-leucine-¹⁴C into bound polysome fraction was noticed when kanamycin, gentamicin and colistin were added directly in cell-free system.

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Streptococcus pneumoniae is, even now, important pathogen of respiratory infections. It annually forms 20 to 30 per cent of the causative bacteria of respiratory infections determined by our quantitative sputum culture method. And recently resistant strains against some antibiotics were reported. Therefore 64 strains of respiratory pathogenic Streptococcus pneumoniae isolated more than 107ml from sputa were studied on the susceptibility to 17 antibacterial agents and serotype, with following results :
1. There was no noticeable resistant strain against penicillins. Antibacterial activities of penicillins were in order Amoxycillin≅PC-904≥Benzylpenicillin≅Ampicillin≅Piperacillin>Ticarcillin.
2. There was no resistant strains against cephalosporins. Antibacterial activities were Cephaloridine >Cefazolin>Cefoxitin<Cephalexin.
3. Resistant strains against Chloramphenicol, Thiamphenicol and Doxycycline were respectively 57.4%, 57.8% and 62.3%. 52.6% of 64 strains were resistant against all of them.
4. There was no resistant strain against Clindamycin, Erythromycin and Josamycin. Antibacterial activities were Clindamycin>Erythromycin≥Josamycin.
5. Serotypes of 54 strains were examined, and only 5 strains were type III and the others were non-typable.

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IgA system with special reference to secretory IgA was studied on the patients treated with immunosuppressive agents. And the relationship between the occurrence of infection and secretory IgA level was discussed in this paper. The results were as follows.
1) Infection occurred in 9 cases out of 19 patients treated with immunosuppressive agents.
2) Peripheral neutrophil and lymphocyte counts were decreased significantly by immunosuppressive treatments. The frequency of infection increased as peripheral neutrophil counts decreased.
3) In the pre-treated patients, serum IgA and IgG levels were significantly higher than those of normal adults. High levels of them may be due to the primary diseases. The effects of immuno-suppressive treatments on serum IgA, M and G were not clear.
Secretory (salivary) IgA levels from the patients treated with immunosuppressive agents were also significantly higher than those of normal adults. This high level of S-IgA was thought to be caused. by primary diseases. In spite of immunosuppressive treatments, salivary IgA levels were not decreased below normal levels. The correlation between the occurrence of infection and salivary IgA levels was not found. It was suspected that the salivary IgA levels were not so important as the peripheral neutrophil counts against infections in the secondary immunodeficient states.

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T-1220 was administered to 27 patients with chronic urinary tract infections.
Twenty cases were available for analysis of clinical evaluation of T-1220. Excellent results were observed in 7 cases, good in 8, and poor in 5. Effective rate was 75%.
Urinary organisms isolated from the patients were 9 Serratia, 5 Pseudomonas, 3 Citrobacter, 2 E. coil and 1 Enterobacter. Clinical effects were observed in all cases of Pseudomonas, E. colt and Enterobacter, 6 of Serratia and 1 of Citrobacter.
As side effect with T-1220, drug eruption was noticed in 1 of 27 cases.

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T-1220 is a newly developed semisynthetic compound of aminobenzylpenicillin and has a broad spectrum of antibacterial activity.
The present animal test was carried out to evaluate ototoxicity and safety of T-1220 to auditory system in 45 rats of Wistar strain. T-1220 was given to 20 rats at doses of 500 mg/kg and 1, 000 mg/kg i. v. daily for 4 weeks. As control test, kanamycin (KM) and physiological saline were administered for 4 weeks. KM was given to 20 rats at doses of 200 mg/kg and 400 mg/kg i. m. daily for 4 weeks and physiological saline was injected to 5 rats i. v. daily for 4 weeks. Differential frequency pinna reflex test in wide range from 20, 000 Hz to 200 Hz was performed before and during the administration weekly to measure frequency range of increased threshold and loss of pinna reflex in the rats.
The following results were obtained.
1) The differential frequency pinna reflex test revealed that pinna reflex in non-treated animals was more sensitive in 200, 2, 000, 3, 000, 4, 000, 6, 000, 8, 000, 10, 000, 12, 000, 15, 000 and 20, 000 Hz in the. rats than in Hartley guinea pigs.
2) In 10 rats receiving KM at 200 mg/kg/day i. m. for 4 weeks, there was no animal with pinna reflex loss at any frequencies tested. Increase in threshold of pinna reflex was almost within 10 dB.
3) In 8 rats given KM at dose of 400 mg/kg/day i. m. for 4 weeks (2 rats were died at 2 nd week), 2 showed extensive loss of pinna reflex extending from 20, 000 Hz to 200 Hz, and another one indicated loss of pinna reflex in range from 20, 000 Hz to 2, 000 Hz. Loss of pinna reflex limited to 20, 000 Hz to 15, 000 Hz occurred in another one rat. Another one showed increase in threshold (14 to 16 dB) in 15, 000, 12, 000, 10, 000 and 8, 000 Hz. 18 dB increase in threshold at 15, 000 Hz was seen in one animal.In the remaining 2, increase in threshold was less than 10 dB.
4) In 10 rats treated with T-1220 at dose of 500 mg/kg i. v. daily for 4 weeks, there was no animal with loss of pinna reflex. Increase in threshold amost always remained within 10 dB.
5) In 10 rats given T-1220 at dose of 1, 000 mg/kg i. v. daily for 4 weeks, there was no animal with loss of pinna reflex. Increase of threshold almost always remained within 10 dB.
6) The present study suggests that administration of T-1220 at doses of 2, 000 mg/day and 4, 000 mg/ day, respectively, may be enough safe in man to auditory system.

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