It is known that many cases of infection with Pseudomonas aeruginosa or Serratia marcescens occur after administration of β-lactam antibiotics. Such phenomenon may result from alteration of microbial fiora by overgrowth of P. aeruginosa or S. marcescens that are resistant to many β-lactam antibiotics.
Attempts were made to analyze such phenomenon by experimental alteration of microbial population based on the ecological studies on Escherichia coli and P. aeruginosa. The results may be summarized as follows:
In mixed cultures of E. coli and P. aeruginosa, the former showed a growth pattern similar to that in a single culture regardless of the inoculum size of P. aeruginosa. The growth of P. aeruginosa, on the other hand, was inhibited when the inoculum size of E. coli was larger than or even the same as that of P. aeruginosa, showing growth curves lower than that of a single culture.
In mixed cultures of E. coli and S. marcescens, the growth of the latter was inhibited as compared with that in a single culture when the inoculum size of E. coli was larger than or the same as that of S. marcescens.
When the inoculum size of S. marcescens was larger, the growth of E. coli was inhibited as compared with that in a single culture.
In mixed cultures of two species, namely E. coli and P.aeruginosa, E. coli and S.marcescens and in those of three species, E. coli, P. aeruginosa, and S. marcescens, the addition of a β-lactam antibiotic inhibited the growth of E. coli. The smaller the inoculum size of E. coli, the more the inhibition of the growth by P. aeruginosa or S. marcescens or both.
Experimental alteration of the dominant species from E. coli to P. aeruginosa or from E. coli to S. marcescens induced with a β-lactam antibiotic proved that the larger the difference in M. I. C. between the two species, the easier the alteration of the microbial flora to occur.

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In order to establish a rational dosage and interval of administration of sulfamethoxazole-trimethoprim (ST) for the prophylaxis of urinary infections, the antibacterial activities against Escherichia coli were determined in the urine after administration of the drug. Four healthy male adults were administered dosages of 2, 1, 1/2 or 1/4 tablets of the drug and 100 mg of nitrofurantoin (NF), respectively. Small and large amounts of the organisms were inoculated into the sterilized urine obtained from persons who had taken the above drugs. The inoculated urine samples were cultured overnight, then the number of the organisms was counted to estimate the antibacterial activities.
NF does not seem to be suitable for prophylaxis, because of its short duration of activity in the urine. On the contrary, the activity of ST continued for a long time in the urine, even when administered in smaller dosages. Significant activity was recognized in the urine obtained after administration of 1/2 tablet at 48 hr or 1/4 tablet at 24 hr later. However, there was remarkable individual difference in the duration of activity of urine after that time.
Urine diluted 1:16 and 1:32 showed almost the same activities against the organisms after the administration of 1/4 tablet of ST per day for a month or just 1/4 tablet per day for 2 days. These facts seem to suggest that the administration of 1/2 tablet of ST at 2 day intervals or 1/4 tablet daily is rational.

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The optimum ratio of sulfamethoxazole (SMX) to trimethoprim (TMP) in the mixture for in vitro antibacterial activity to pathogenic aerobes was 24:1 and in contrast that to anaerobes was 1:24.
The optimum ratio of SMX to TMP in the mixture for oral adminstration was considered to be 2-5:1 for aerobes and 1:64-128 for anaerobes. These values were estimated from the results in the present experiment and the data reported by many investigators on the level of drug concentration in blood or organs following the oral administration of the drugs.

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Benzylpenicillin in several infusions produced PCG polymer for 4 hours and these were measured by UV absorption and gel chromatography.
The results were obtained as follows.
I. Degradation of PCG in phosphate buffered saline (pH 5) was higher than other pH solutions, especially at 322 nm.
2. In each infusion solutions, the degradation of PCG in 5% saccharose and 10% maltose solution was higher than others. It was measured by gel filtration that 0.1% of PCG volume was detected as PCG polymer at these solutions.
3. One ml of these solution was elicited to PCA reaction sensitized by and BPO-BSA serum. From the results of PCA, it was clarified that 4 hours stored PCG infusion solution had elicitogenicity.

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We tried to evaluate the efficacy of Flucytosine and Amphotericin B (AMPH) on pulmonary and cerebral mycosis.
We established a new technique of measuring antifungal activity of Flucytosine and AMPH, which is more rapid and stable than that previously reported. In this method, homogenized spore of 10⁵/ml cultured on MÜELLER-HINTON Broth (M. H. Broth) supplemented with 4% glucose were inoculated on M. H. Agar supplemented with 4% glucose for AMPH and on Yeast Morphology Agar (Y. M. Agar) for Flucytosine. It was noticed that many strains of three crucial pathogenic fungi isolated frequently from clinical specimens were susceptibile almost equally to Flucytosine and AMPH. A few strains resistant to Flucytosine were observed.
Bioassays for Flucytosine in serum, urine and cerebrospinal fluid (CSF) were performed readily by our new technique using Staphylococcus aureus 209 P (S. aureus 209 P) as the test organism.
The serum peak levels were 16.5-177μg/ml at 1-3 hours after administration of Flucytosine g orally. The accumulation of this drug could be demonstrated on a few case. In two cases sputum concentrations of Flucytosine were measured. Ratios of maximum sputum level to peak serum concentration were 17% and 57.3%. In other cases ratios of maximum CSF level to peak serum level were 50% and 69%.
Serum concentrations of AMPH were found to be low when instillated into trachea.
On six cases of pulmonary and cerebral mycosis, the clinical results supported by our new bioassays were observed. Noteworthy side effects were observed in two cases administered AMPH, therefore it is important to determine appropriate doses and route of administration. On the other hand side effects of Flucytosine were few. At the chemotherapy of mycosis the effort to improve the host conditions may be required.

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1. Fourteen patients with biliary tract infection were treated clinically with Minocycline, and resulted in an excellent response in 2, good in 8, poor in 4, Reversible elevation of serum-GOT and GPT, was seen following MINO administration in one patient.
2. MINO was more active than TC or DOXY against E. coli, Klebsiella, Streptococcus faecals, Serratia and Proteus.
3. Two patients received 100mg or 200mg of MINO by constant intravenous infusion for 120 min utes. Bile was sampled by the PTC needle just after the correct puncture of intrahepatic bile duct before injection of radiopaque material, and MINO concentration in bile was measured. MINO concentration in bile of the patients with bile duct obstruction was 0.32μg/ml (MINO 100 mg administration), 1.2μg/ml (MINO 200 mg administration). One patient received 200mg of MINO by constant intravenous infusion after releasing the obstruction of Bile duct. The concentration of MINO rose up significantly. Maximum concentration of MINO in bile was 7.8μg/ml.

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Minimal inhibitory concentrations (MIC) of Minocycline (MINO) and Gentamicin (GM) were determined by plate dilution method on P. aeruginosa 67 strains and Serratia sp. 47 strains isolated from urinary tract infections. The MICs of MINO were more than 25μg/ml against P. aeruginosa, and the most level of MIC was 12.5μg/ml against Serratia sp. In cross sensitivity, MINO was less effective than GM against the both species. In correlation between MIC and disc sensitivity, MINO showed good agreement against Serratia sp. but poor against P. aeruginosa, especially disc sensitive strains. On the other hand, GM showed good coincidence against the both species.
The mean peak serum level in two normal adults to whom 100 mg of MINO were given by intravenous drip infusion for two hours, was 1.37μg/ml at two hours, and the mean urinary recovery rate was 2.85% within 6 hours.
Sixteen cases with complicated urinary tract infections by P. aeruginosa and Serratia sp. were treated with 200 mg of MINO per day for 5 to 7 days. Excellent or good effect was obtained in 4 of 14 cases. Two cases dropped out. Side effects were not observed in this series, but laboratory findings showed slight elevation of BUN in two cases and transient elevation of GPT in one case.

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Amikacin was administered intramuscularly to a total of 25 cases with chronic complicated urinary tract infections in dosages of 400mg/day for a period of 5 days.
The following results were obtained.
1. The overall effectiveness rate was 68%(excellent; 3, moderate; 14, poor; 8 cases).
2. On bacteriological response, eradicated rate was 53%.
3. In sensitivity of AMK and GM to S. marcescens of 17 strains, 11 strains were GM resistant. On the other hand, 3 strains only were AMK resistant.
4. No side effects and laboratory findings were noticed before and after administration of amikacin.

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In a double blind study the clinical efficacy and safety of KW-1062 60 mg b. i. d. or t. i. d. was compared with that of DKB 50 mg b. i. d. or t. i. d. in 136 hospitalized patients, suffering from respiratory infection.
1. One hundred and five patients (56 in KW-1062 group and 49 in DKB group) comprizing 62 patients with pneumonia (29 in KW-1062 group and 33 in DKB group), 36 patients with secondary RTI (23 in KW-1062 group and 13 in DKB group) and 7 patients with lung abscess (4 in KW-1062 and 3 in DKB group) were evaluated on clinical efficacy by the Committee members, separately from physicians in charge.
Overall clinical success was obtained in 27 patients (48.2%) treated with KW-1062 and in 22 patients (44.9%) treated with DKB. There was no significant difference between the 2 treatment grcups.
In treatment of pneumonia, KW-1062 with the clinical success rate of 69%, tended to be significantly more effective than DKB with that of 42.4%.
2. Out of 136 patients, 121 patients (65 in KW-1062 group and 56 in DKB group) comprizing 85 patients with pneumonia (43 in KW-1062 group and 42 in DKB), 29 patients with secondary RTI (18 in KW-1062 and 11 in DKB group) and 7 patients (4 in KW-1062 and 3 in DKB) were evaluated on the clinical efficacy by physicians in charge.
Overall clinical success rate was 64.5% in KW-1062 group and 64.3% in DKB group, not being significantly different between the 2 treatment groups. In treatment of secondary RTI, KW-1062 was significantly more effective than DKB.
There was no significant differences between the 2 treatment groups with regard to the rate of usefulness judged by physicians in charge.
3. The adverse reactions of KW-1062 and DKB were similar in type and frequency, except that the elevation of s-GOT was observed significantly more frequently in patients treated with DKB than in those with KW-1062.

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Sisomicin (SISO) and Dibekacin (DKB) were compared in a randomized, double-blind study of 137 patients with respiratory teact infection and the results were as follows:
1. In a total of 137 patients, 35 patients were excluded from the evaluation of clinical efficacy and usefulness by the Committee members (who are representatives of the investigators of the study), and 18 patients were excluded by the controllers.
The safety of the drugs was evaluated in 136 patients, excepting 1 patient whose treatment was remarkably deviated from the protocol.
2. One hundred and two patients (53 SISO-treated patients and 49 DKB-treated patients) were evaluated for clinical efficacy by the Committee members consisted of 67 patients with pneumonia (34 SISO-treated patients and 33 DKB-treated patients), 31 patients, with secondary respiratory tract infections (18 SISO-treated patients and 13 DKB-treated patients) and 4 patients with lung abscess (1 SISO-treated patient and 3 DKB-treated patients).
As to the background characteristics of these patients, there were significant differences in agedistribution and in pre-treatment chemotherapy in the patients with lung abscess. In the patients with pneumonia of secondary respiratory tract infections, the two treatment groups were comparable as to the background characteristics.
One hundred and nineteen patients (63 SISO-treated patients and 56 DKB-treated patients) were evaluated for clinical efficacy and usefulness by the physicians in charge. There were no significant differences in the background characteristics between the both treatment groups.
3. The overall favorable response rate in all patients evaluated by the Committee members (102 patients) was 57% with SISO and 45% with DKB, without significant differences between the both treatment groups. SISO was significantly more effective than DKB in the patients with pneumonia and was as effective as DKB in the patients with secondary tract infections or lung abscess. There were no significant differences in clinical efficacy evaluated by the physicians in charge (119 patients) between the both treatment groups.
4. No significant differences were observed in the frequency of side effects or abnormal laboratory findings between the both treatment groups.
5. The rate of usefulness in all cases evaluated by the physicians in charge (119 patients) was 59% with SISO and 64% with DKB, without significant differences between the both treatment groups.

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