A clinical study was performed on about Streptococcus faecalis infection in urinary tract which had been detected in the Department of Urology, Tokyo University Hospital from July 1980 to June 1983.
The annual incidence of S. faecalis isolated from urinary tract has increased from 8.5% to 15.2% in these periods in urology. In the other clinical departments, 1, 261 strains of S. faecalis were isolated in the same periods. Of these 1, 261 strains, 752 (59.6%) had been detected from urinary tract, and annual incidence of them has also increased as in urology.
In urology, 89.8% of the patients showed complicated urinary tract infections, and 36.2% of the patients had catheter indwelt. The percentage of the patients with single infection of S. faecalis was 64.3% in urology, but 36.9% in the other clinical departments. In case of multiple bacterial infection, 78.8% of the patients infected with gram-negative rods; Escherichia coli, Pseudomonas aeruginosa, Klebsiella spp., Proteus mirabilis and etc. Ampicillin resistant strains of S. faecalis were more frequently isolated as high as 52.5% in urology but were less did as 10.9% in the other clinical departments.
In clinical observations, most patients had no any significant clinical symptoms except 9 patients who developed, high fever, miction pain. In symptomatic cases, adequate combinative chemotherapy agents should be given when S. faecalis was isolated as an causative pathogen of the multiple bacterial infection.

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The concentration of an antibiotic transfered to the fluid of bronchoalveolar lavage were determined to investigate the kinetics of transfer of antibiotics to the bronchoalveolar system. After the intravenous injection of 2 g of piperacillin (PIPC), bronchoalveolar lavage (BAL) was performed, and then, bronchial lavage fluid (BLF) and bronchoalveolar lavage fluid (BALF) were collected separately. Blood samples were also collected on the same occasion. These procedures were undertaken 30, 40, 50, 60, 120 and 180 minutes after the intravenous injection of PIPC. The result obtained were as follows.
1) The blood level of PIPC reached the mean maximum of 82μg/ml in 30 minutes, gradually decreasing to a level of 11.4μg/ml 180 minutes later.
2) The BLF level of PIPC was almost constant at 0.36±0.23μg/ml (mean±standard deviation), showing no relation to the blood level.
3) The BALF level of PIPC, which averaged 0.61±0.29μg/ml, showed a pattern similar to that of the blood level. The BALF level reached the maximum after 50 minutes, a little later than the peak of the blood level, decreasing gradually thereafter.
4) The level of PIPC was higher in BALF than in BLF until 60 minutes after the injection, while it was conversely higher in BLF after 120 minutes or more.

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In 5 cases with normal renal function, pharmacokinetics of single and/or combined administration of cefsulodin (CFS) and cefmenoxime (CMX) were studied. The dosages of each drug were 1.0g and they were intravenously administered in this order; CFS, CMX and CFS+CMX, with one day interval. The serum and urinary levels were determined with high-performance liquid chromatography for CFS and bioassay using P. mirabilis ATCC 21100 as the test organisms for CMX. The parameters of pharmacokinetics were obtained by the two open compartment open model.
The conclusions were as follows ;
1. single administration of CFS or CMX: The serum levels of CFS or CMX were reached peak 15 min. after administration and gradually decreased with the passage of time. The serum half-lives of the β-phase of CFS or CMX were 2.05±0.73 hrs. and 0.97±0.18 hrs. respectively. The 8-hr. urinary recovery was 85.4±11.7% for CFS and 76.6±10.0% for CMX.
2. Combined administration of CFS and CMX: The serum levels of CFS or CMX were reached peak 15 min. after administration and gradually decreased with the passage of time. The serum half-lives of the β-phase of CFS or CMX were 2.05±0.73 hrs. and 0.97±0.18 hrs. respectively. The 8-hr. urinary recovery was 85.4±11.7% for CFS and 76.6±10.0% for CMX.
3. There were no significant difference between single administration of CFS or CMX and combined administration of CFS and CMX in parameters of pharmacokinetics.
4. No side effects were observed in this investigation.

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Penetration rate of cefotiam into human cornea was studied upon corneal transplantation. Twentytwo patients were given single administration of 1.0 g of cefotiam intravenously 10 to 120 minutes prior to corneal trephination. Blood sample was taken during the procedure. The concentrations of cefotiam in the cornea button and the sera were determined by agar well method.
Pharmacokinetic analysis revealed that the concentration of cefotiam in the cornea reached the maxi mum level (6.77μg/g) at 15 minutes after the intravenous administration, and decreased gradually thereafter. The concentration maintained 1.89μg/g level even at 90 minutes after the administration. The concentration of cefotiam in the cornea was higher than minimal inhibitory concentration (MIC) of various spectrum of bacteria except Pseudomonas aeruginosa that cause bacterial keratis These results demonstrate that intravenous administration of cefotiam can reach up to the suficicot level to treat bacterial keratitis in the cornea.

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One hundred strains of S. marcescens isolated from patients with urinary tract infections in 1980 and 1981 were studied for serotyping and susceptibility of, 28 kinds of antimicrobials. As for serotypes, 0-4 was detected in 26 strains (26%), followed by 0-5 in 15 and 0-3 in 10, however, non-typable was recognized in 18 strains. Among 19 kinds of β-lactams ceftazidime showed strongest antibacterial activities against S. marcescens. MIC₈₀ of ceftazidime was 1.56μg/ml and azthreonam 6.25μg/ml, cefmenoxime and ceftizoxime 12.5μg/ml, latamoxef, cefbuperazone, cefotaxime and ceftriaxone each 25μg/ml followed with inoculum sized of 10⁶ cells/ml.
Antibacterial activities of aminoglycosides against S. marcescens were weak. Habekacin demonstrated MIC₅₀ 25μg/ml and MIC₈₀ 50μg/ml in 10⁶ cells/ml inoculation. MIC₅₀ and MIC₈₀ of fosfomycin, with same inoculum size, were 25 and 200μg/ml.

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F-G agar, buffered charcoal-yeast extract agar (B-CYE agar), or YPH agar has been used as susceptibility testing media for Legionella. The result of our examination showed that YPH agar was not able to support the growth of Legionella species and Legionella-like organisms, and therefore this agar could not be used for susceptibility testing. Also, it has been well known that activated charcoal in the B-CYE agar could inactivate some antimicrobial agents.
Buffered starch-yeast extract agar (B-SYE agar) is newly devised medium for the susceptibility test for Legionella and Legionella-like organisms. This agar was modified from B-CYE agar. A base medium of B-SYE agar was prepared as follows; ten grams of N-[2-acetamide]-2-aminoethansulfonic acid (ACES) buffer, 2.6g of potassium hydroxide, 10 g of yeast extract, 5 g of monosodium glutamate, 15g of soluble starch and 15 g of agar were dissolved altogether in 980ml of distilled water, and sterilized by autocleaving at 121°C for 15 minutes. And then, 10ml of each filter-sterilized solution of L-cysteine hydrochloride (40mg/ml) and ferric pyrophosphate (25mg/ml) was added. The medium was adjusted to pH 6.9±0.05 with each of filter-sterilized solution of 1 N KOH or 1 N HCl.
B-SYE agar supported the growth of all of the 20 strains of Legionella and Legionella-like organisms which were isolated from clinical and environmental sources. According to the comparison of BSYE agar and B-CYE agar, B-SYE agar did not inactivate the antimicrobial agents except minocycline than that of B-CYE agar. Minocycline inhibited by B-SYE agar probably because of binding of the antibiotics to Fe⁺⁺ in the medium.

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Susceptibility to fosfomycin (FOM) of 159 clinical isolates of Campylobacter jejuni was tested by a new method using Nutrient agar (Difco) supplemented with 5% horse-defibrinated blood and 0.2% MgCl₂ as test plates. The minimal inhibitory concentrations (MIC) of FOM against 50 and 90% of the strains were 3.13 and 25μg/ml, respectively. These values were almost equivalent as those of ampicillin, kanamycin, and nalidixic acid and slightly higher than those of erythromycin and midecamycin. MICs of erythromycin against the C. jejuni strains were also tested by the new method as well as by the standard method and it was revealed that there was no difference between the values obtained by the two methods.

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In order to comfirm the utility of AT-2266, a new synthetic antimicrobial agent, we carried out a double-blind comparative study with cephalexin compound granules (L-CEX) in the treatment of superficial suppurative skin and soft tissue infections.
A total of 226 cases are participated in the study and 204 cases were evaluated in the efficacy (101 for AT-2266 group and 103 for L-CEX group) and 223 cases in safety (113 for AT-2266 group and 110 for L-CEX group).
Results obtained are as follows;
1) In the evaluation of clinical efficacy, the efficacy rate covering “cured”and “remarkably improved” was 71.3% for AT-2266 group and 73.8% for L-CEX group, and, in addition, the rate including “moderate improved” was 87.1% and 85.4%, respectively. No significant difference was observed between the two groups.
2) As for bacteriological response, no significant difference in the elimination rate was observed; 73.7% for AT-2266 group and 85.7% for L-CEX group. The peaks of MICs of AT-2266 and CEX were 0.78μg/ml and 3.13μg/ml against isolated S. aureus, 0.39μg/ml and 1.56μg/ml against isolated S. epidermidis, respectively.
3) As for safety evaluation, adverse reactions were observed in 11 cases treated with AT-2266 and in 4 cases treated with L-CEX, and abnormal laboratory findings were observed in 2 cases each group (one case in L-CEX group was discontinued). No significant difference was found between AT-2266 group and L-CEX group.
4) In gloval utility rating, according to the clinical efficacy and safety evaluation, the acceptability rate covering “remarkable useful” and “useful” was 74.3% for AT-2266 group and 85.4% for L-CEX group. There was no significant difference between the two groups.

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