We evaluated the usefulness of the disk method using three disks (nitrocefin disk, penicillin G [PCG] disk and cefazolin [CEZ] disk) in detecting the β-lactamase production of clinical isolates from patients with urinary tract infections (UTI).
1) The sensitivity of nitrocefin disk was the highest among three disks and the sensitivities of PCG disk and CEZ disk were almost equal.
2) The degree of β-lactamase production was classified into three or five groups according to results of the above three disks. In a few combinations of species and drugs, a closer correlation with MIC distribution was present using the five-group classification due to the substrate specificity of pH disks. In general, however, the three-group classification was preferable for correlation with drug sensitivity.
3) In the three-group classification, we judged as negative when three disks were all negative, low when only nitrocefin disk was positive and high when nitrocefin disk was positive and either PCG or CEZ disk was positive. Out of 766 clinical isolates from UTI 599 (78.2%) were β-lactamase producing strains (high 31.5%, low 46.7%).
4) As for the correlation of β-lactamase production with drug-susceptibility using routine disks, the best correlation was observed in E. coli and clear correlation was in P. aeruginosa and Serratia.
Finally, the disk methods are not only simple and rapid but also useful to detect the β-lactamase production of clinical isolates from UTI.

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We evaluated fluorescence polarization immunoassay (FPIA) method for the determination of netilmicin (NTL) in human serum.
The following results were obtained:
1) Within-run coefficient of variation was less than 7%.
2) The calibration curve for NTL in FPIA method had been stabilized for 16 weeks.
3) Analytical recoveries of NTL from serum spiked with varying concentration of NTL averaged between 99.0-104.3%.
4) Dilution of NTL had been shown to be linear.
5) FPIA method was not interfered with hemoglobin (up to 400mg/dl) and bilirubin (up to 20mg/dl) in determination of NTL.
6) The relationship between FPIA (Y) and bioassay (X₁) or high performance liquidchromatography (X₂) was followed.
Y=0.783 X₁+0.581, r=0.904, Y=0.949 X₂-0.168, r=0.987.
Bioassay was measured about 20% higher than FPIA method.
We conclude that FPIA is a very reliable and reproducible method for clinical NTL level monitoring.

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Distribution of antimicrobial agents to the prostate has been investigated by using tissue removed at operation or by prostatic fluid. However, localization of the drugs in the prostatic tissue is not yet investigated in detail. In this study, we investigated the distribution of antimicrobial agents in the rat prostate by using microautoradiography.
After subcutaneous administration of ¹⁴C-cefmetazole (CMZ), prostatic gland was removed and frozen immediately in hexan-dry ice and was sectioned in a cryostat at 5μm thickness. Since CMZ is soluble in water, the section was lyophilized by the methods of STUMPF.
The results of the present study indicate that ¹⁴C-CMZ was distributed mainly to the connective tissue and interstitial tissue. The method employed in this study by us is an useful and reliable one for the investigation of distribution of chemotherapeutics in the prostatic tissue because each tissue can be directly and individually indicated.

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Clinical efficacy of combination therapy on 74 infections accompanied by hematological disease was studied mainly using cefmenoxime (CMX) at 11 centers in Kanagawa prefecture.
Most patients (57 cases) suffered from sepsis or suspected sepsis. Underlying diseases were leukemia in 58 cases and aplastic anemia in 6 cases. Granulocyte count was performed in 69 patients, and 53.6% of them were found to have below 500/μl. CMX was administered twice a day at 4g/day for 1-2 weeks in most cases; combination therapy was applied to 59.5%.
Overall efficacy rate was 54.4%. Efficacy rate was 66.7% for single CMX therapy and 47.4% for combination therapy. As for efficacy rate by infections, treatment was effective in 52.9% of patients with sepsis or suspected sepsis. As for efficacy rate by underlying diseases, treatment was effective in 56.6% of leukemic patients. As for efficacy rate by granulocyte counts, treatment was effective in 57.1% of patients having 50l/μl or over and in 54.5% of patients having 500/μl or below.
Causative organisms were defected in 29 cases; 62.5%(5/8) were eradicated.
Side effects were observed in 3 cases, but not severe.
These results suggested that chemotherapy mainly using CMX was useful to treat severe infections accompanied by hematological disease.

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NFLX concentrations, and the amount and weight of sputum were measured for hourly collected sputum samples (from 7: 00 am to 11:00 pm) in patients of chronic respiratory disease (9 DPB, 2 CB, and BE, IIP, PSS) with respiratory tract infection after NFLX administrationsat 8: 00 am, 12: 00 am, 6: 00 pm with 200mg each time.
The Clinical response was good in 4 cases (33.3%), fair in 7 cases (58.3%), poor in 1 case (8.4%) among 12 cases, and there were 2 cases whose clinical efficacy could not judge. The mean amount of sputum was 54 ml/day, and the mean specific gravity of sputum in a day was 0.93 in 14 patients. As the hourly changes of the amount of sputum, expectorated peak (47.6% of a day) was recognized between 10: 00 am to 2: 00 pm. NFLX concentration in hourly sputum was low in the morning and it increased according to administrated time. The peak level of NFLX concentration in sputum was recognized between 4: 00 pm to 5: 00 pm in DPB group (0.32μg/ml), and 8: 00 pm to 9: 00 pm in non-DPB group (0.33μg/ml).
In DPB group, the patients with secondary bronchobronchiolar dilation had lower NFLX concentrations than those without secondary dilation in the morning sputa. NFLX penetration into sputum was considered to delay in the patients with severe air way damage.

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80 women with acute uncomplicated cystitis were randomly allocated to treatment with the following oral dose of cinoxacin: A; 800mg single dose, B; 1, 600mg single dose, C; 400mg every 12 hours for 3 days, D; 400mg every 12 hours for 7 days. Eight women were excluded from the study. Of these, one was excluded because of loss to clinical follow-up, one because of negative urine culture on entrance into the study, and six because of resistance of initial microorganism to cinoxacin. Persistence of bacteriuria was observed in 2 of 19 patients and decrease of bacteriuria in one, in the 800mg single dose group. In the 1, 600mg single dose group and conventional treatment groups (800mg daily for 3-7 days), all of initial pathogens were eradicated.
There were no significant differences in the clinical efficacy between the treatment regimens. No significant difference was observed in the recurrence 7 days after treatment between the four treatment regimens.
We concluded that single dose therapy with cinoxacin for uncomplicated cystitis in women is as effective as conventional therapy with a 3-day or 7-day course of the same agent.

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L-105, a new semisynthetic cephem antibiotic, was administered intravenously at a dose of 1g twice a day for two weeks to 10 patients with complicated urinary tract infection and urogenital malignant tumor as underlying disease. The therapeutic efficacy and safety of the drug were evaluated. The results obtained were as follows.
1) Overall effectiveness rate according to the Criteria by UTI Committee was 50% after five days and 50% after treatment.
2) Clinical efficacy evaluated according to the symptoms and pyuria was moderate in 7, and poor in 3 cases after five days. After treatment, the efficacy was excellent in 3, moderate in 6, and poor in one.
3) As side effects, subjective and objective abnormalities were not seen in any case, and no abnormal finding was observed in laboratory tests.
From the results, it is considered that L-105 is an effective and safe antibiotic for the complicated urinary tract infections.

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Comparative double-blind studies of cefixime (CFIX), a new oral cephalosporin antibiotic, and cefaclor (CCL) were conducted to elucidate the efficacy, safety and usefulness of both drugs in the treatment of bacterial bronchitis.
CFIX was given orally in a daily dosage of 200mg, and CCL in a daily dosage of 750mg for seven days.
The efficacy rate was 76.7% in a total of 90 cases of the CFIX group and 78.4% in a total of 102 cases of the CCL group, without significant differences.
Even when classified by type of disease, there was no significant difference in clinical effects between the two treatment groups in either acute or chronic type of bronchitis.
There was no significant difference in clinical effect between the two treatment groups judged by either the doctors in charge or by the committee members.
The rate of eradication of the causative organisms was 69.4% in the CFIX group and 66.7% in the CCL group, without significant difference. However, the eradication rate for H. infiuenzae in particular was higher in the CFIX group than that in the CCL group, although the difference was not statistically significant.
There were also no significant differences between the two treatment groups either in incidence of side effects or of abnormality of loboratory findings.
CFIX was evaluated to be very useful or useful in the treatment of bronchitis, both acute and chronic types, in 78.8% of those patients treated with it. The usefulness rate was 77.4% for those treated with CCL. The difference in the rate was not statistically significant.
From the results mentioned above, it is concluded that CFIX is highly effective and useful in the treatment of bacterial bronchitis at a dosage of 200 mg/day (bid) and is equivalent to CCL at a dosage of 750mg/day (tid).

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Efficacy, safety and usefulness of cefixime (CFIX), a new oral cephem, in the treatment of bacterial pneumonia, were evaluated by the double-blind comparative method using amoxicillin (AMPC) as a reference drug.
Patients with bacterial pneumonia, aged 16 or older, were treated by oral administration of either 200mg of CFIX twice a day or of 500mg of AMPC four times a day for 14 days.
Out of a total of 222 patients thus treated, 172 patients (82 with CFIX: 90 with AMPC) were used for comparative evaluation of clinical efficacy, 208 patients (100 with CFIX: 108 with AMPC) for that of safety, and 170 patients (82 with CFIX: 88 with AMPC) for that of usefulness.
There were no significant differences in characteristics of the patients between the two treatment groups, except that susceptibility to AMPC of the causative organisms which had been isolated from the patients belonging to the AMPC treatment group was significantly lower than that of the patients treated with CFIX.
Rate of cure was 73.5% in the patients treated with CFIX, and 78.6% in those treated with AMPC. When patients with viral or mycoplasmal pneumonia were included in the evaluation, a slight degree of decline in the cure rates was observed, i. e. 70.7% with CFIX and 73.3% in the AMPC-treatment groups.
Thus, there was no difference in efficacy rates between the two treatment groups.
Decrease in amount of purulent sputum on the fourth and 15 th days of the treatment was more marked in the CFIX treatment group than in the AMPC group and was statistically significant.
Bacteriological effects were examined in a total of 41 of the bacteriologically documented cases (20 patients treated with CFIX: 21 with AMPC). Rate of eradication of the causative organisms was 100% in the CFIX group and 81% in the AMPC group.
Side effects observed were mainly due to functional disturbances of gastrointestinal tracts including nausea, epigastric pain, diarrhea and so forth. Incidences were 2.0% in the CFIX group and 6.4, in the AMPC group.
Abnormalities in laboratory findings, mainly a slight degree of elevation in serum transaminases, were detected both during and after the treatment. These incidences were 17.2% in the CFIX grout and 24.7% in the AMPC group. This difference between the two treatment groups in the incidence of abnormal laboratory findings was not statistically significant.
Taking efficacy and safety into consideration, the usefulness of both drugs in the treatment of bacterial pneumonia or lung abscess is estimated as follows:
CFIX was evaluated to be very useful or useful in 72.1% of the patients treated with it, and AMPC in 77.9% of the patients so treated.
From the results mentioned above, it is concluded that CFIX is one of oral cephems with high utility in the treatment of bacterial pneumonia or lung abscess, when administered in a twice daily dosage of 200mg.

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