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[in Japanese]

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Ciprofloxacin (CPFX), a new pyridone carboxylic acid, was administered orally to the patients with chronic respiratory tract infection and its clinical efficacy and safety were studied in a multicenter open trial. The results and summarized as follows.
1. The efficacy rate for the patients with acute exacerbation as 52.5% (21/40) in 2 weektreatment, and 75.0% (24/32) in 4 week-treatment.
2. The efficacy rate for the patients with chronic phase was 23.1% (6/26) in 2 weektreatment, and 26.9% (7/26) in 4 week-treatment, but acute exacerbation was not observed in any of the patients.
3. CPFX was administered to 6 patients over 60 days for the prophylaxis of acute exacerbation. Only 2 patients had acute exacerbation in 2 and 3 months after the start of the therapy, respectively.
4. Bacteriological eradication rate was high except P. aeruginosa, for which the eradication rate was about 20%.
5. Side effects were observed in 3 patients, and abnormal findings of laboratory tests were observed in 5 patients, though they were not severe.
These results show that CPFX is a useful antimicrobial agent for the treatment of chronic respiratory tract infections.

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Imipenem/cilastatin sodium (IPM/CS) and amikacin sulfate (AMK) were administered to 111 patients with severe infections complicating hematological disorders. Of the 111 patients, 93 were included in the present analysis of efficacy and 108 in that of safety.
Twenty patients were evaluated as excellent, 37 as good, 8 as fair, and 28 as poor, with an overall rate of effectiveness of 61.3% (57/93).
The synergistic interaction of IPM and AMK against clinical isolates (6 strains) was assessed in vitro using the checker board technique. Synergistic and additive effects were observed in 66.7% and 33.3% of the samples, respectively.
Side effects were observed in 9 patients and abnormal laboratory test results in 2. These disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS and AMK.
From the above findings, IPM/CS with AMK is considered to be a useful antibiotic combination for the treatment of severe infections complicating hematological disorders.

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It has been reported in some studies that the combination of aztreonam (AZT) and clindamycin (CLDM) have high clinical effectiveness in the treatment of intractable infections. We, therefore, studied combined in vitro antibacterial activity of these 2 compounds using many freshly isolated strains.
1. AZT and CLDM in combination had synergistic effects on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae, which are sensitive or quasi-sensitive to CLDM, in the presence of CLDM at MIC or sub-MIC.
2. For Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa, which are not sensitive to CLDM, the 2 drugs in combination showed synergistic effects on some species and additive or slightly additive effects on most species in the presence of CLDM at those concentrations which are usually maintained in blood.
3. The 2 drugs showed no antagonism.

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In order to understand the clinical efficacy of cefteram pivoxil (CFTM) in the treatment of asympotomatic bacteriospermia, the following studies were performed.
1. Concentrations of CFTM in the semen after oral administration of 200mg to normal healthy adults (n=5) reached a maximum level of 0.66±0.04μg/ml in 5 hours after the administration, then decreased rapidly, and averaged 0.15±0.03μg/ml at 7 hours after administration.
2. Activities of CFTM, cefaclor (CCL) and lomefloxacin (LFLX) against bacteria which were detected in semen (n=65)(11 aerobic bacterial strains and 48 anaerobicbacterial strains) were retrospectively studied. The study of activities of these 3 agents against anaerobic bacteria showed that CFTM tended to be more active than CCL, LFLX, and similar tendency was noted in LFLX more than CCL against Peptostreptococcus sp. When penetration of antibiotic agents into semen is considered, however, some anaerobic bacteria as well as some aerobic bacteria may not be eradicated or inhibited, hence farther studies are needed to facilitate the selection of proper methods of administrationas well as that of effective antibiotics.

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Laboratory and clinical studies on cefpirome (CPR, HR 810), a newly developed cephem antibiotic, were perfomed. The results obtained are summarized as follows:
1. Absorption and elimination of the drug were examined in a total of 7 children including 3 cases of administered with 20mg/kg intravenous bolus injection (i.v.), 2 cases with 20 mg/kg drip infusion (d.i.v.) for 60 minutes and 2 cases with 40 mg/kg (d.i.v.) for 60 minutes. Maximum serum levels were attained immediately after i. v. or d. i. v. C_max´s were 233±7.6, 88.5±14.5, and 116±15μg/ml, respectively for the above 3 modes of administration. These values were determined using a bioassay method with Bacillus subtilis ATCC 6633. T 1/2 (β) ´s were 1.18±0.17, 1.61±0.28 and 2.68±0.83 hours, respectively.
Cumulative urinary recovery rates were 40.2-69.8% in a period of 0-6 hours after admissions.
2. Clinical efficacies were evaluated in a total of 20 patients with ages ranging from 9 months to 11 years. The treated cases were 6 cases of acute pneumonia, 4 cases of acute bronchitis, 4 cases of acute purulent tonsillitis, 2 cases of acute urinary tract infections, 2 cases of cellulitis, 1 case of purulent lympadenitis and 1 case of acute otitis media. The clinical efficacy rate was 94.7%.
Adverse reactions occurred in no patients. Abnomal changes in laboratory test values involved only 1 case with elevated GOT and GPT.
CPR was considerd to be a safe and useful drug in treating various infectious diseases in children.

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We examined in vivo efficacy and in vitro activity of fluconazole, a novel triazole antifungal agent, and obtained results which are summarized as follows:
1. Fluconazole showed a higher serum concentration than ketoconazole after oral administration to mice. The 50% effective dose of fluconazole administered orally to mice was simillar to that of fluconazole injected to mice intraperitoneally in a systemic candidiasis model.
2. Prophylactic effects of fluconazole were excellent against systemic candidiasis, cryptococcosis and aspergillosis in mice in comparison with those of ketoconazole and miconazole.
3. The multiple administration of fluconazole effectively decreased the number of viable cells of Candida albicans colonized in kidneys of mice when the serum level of fluconazole was kept to exceed its IC₉₉ values against the inoculated pathogen. Thus, a good correlation between the in vitro activity of fluconazole and its in vivo efficacy was confirmed. In vivo efficacies of ketoconazole and miconazole, however, failed to reflect their marked in vitro activities.
4. C. albicans No.32 developed no drug-resistance to fluconazole during transfers in medium containing flconazole at a concentration of 1μg/ml.

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The in vitro antifungal abtivity of itraconazole (ITZ), a new oral triazole antifungal agent, against c1inical isolates from patients with systemic mycoses were compared with those of existing systemic antifungals, viz. ketoconazole (KCZ), miconazole or amphotericin B.The studies were performed with 65 isolates of pathogenic yeasts and 13 isolates of ASpergillus spp. using the agar dilution method on casitone agar. ITZ showed the most potent antifungal activities against isolates of pathogenic yeasts including severa1 Candida spp.(Candida parapsilosis, Candida krusei, Candida guilliermondii), Cryptococcus neofomans, Trichosporon cutaneum (MIC≤0.08μg/ml) and ASpergillus spp. including Aspergillus fumigatus (MIC≤5μg/ml).
On the other hand, activities of ITZ against isolates of other Candida spp. such as Candida albicans and Candida glabrata were lower than those of KCZ and other reference drugs. Some isolates of C. albicans and C. trqpicalis were not completely inhibited by ITZ even at concentratlons above 10μg/ml on casitone agar. However, in the mlcro-broth di1ution method uslng synthetlc amino acid medium, fungal as thet estmedium, ITZ completely inhibited the growth of all these isolates at drug concentrations of≤0.20μg/ml.

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In vitro antifungal activities of itraconazole (ITZ), a triazole antifungal agent, against clinical isolates obtained from patients with superficial and subcutaneous mycoses were examined using the agar dilution method on casitone agar. The clinical isolates tested were 7 species and 263 isolates including Trichophyton mentagrophytes (104 isolates), Trichoehyton rubrum (103 isolates), Microsporum canis (3 isolates), Epidermophyton floccosum (2 isolates), Candida albicans (32 isolates), Malassezia furfur (7 isolates) and Sporothrix schenckii (12 isolates). The results are summarized as follows:
1. MIC values of ITZ for the isolates of demlatophytes and M. furfur distributed in arange of<0.0012-5μg/ml indicating that ITZ had greater in vitro activities. These in vitro activities of ITZ were greater than those of clotrimazole or bifonazole.
2. C. albicans isolates were divided into 2 groups in terms of ITZ-susceptibilities, a high susceptibility group and low-susceptibility group with MIC values of 0.02-0.08μg/ml and>10μg/ml, respectively.
3. The in vitro activities of ITZ against S. schenckii isolates with a geometric mean MIC of 0.119μg/ml were greater than those of ketoconazole, miconazole or amphotericin B used as reference drugs.

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In vitro antifungal activities of itraconazole (ITZ), a new oral triazole antifungal agent, were studied against a wide range of medically important fungi including 16 genera, 37 species and 51 strains stocked in this center.
The test was carried out using the agar dilution method on Sabouraud dextrose agar.
ITZ showed equal or superior antifungal activities to ketoconazole against most strains of pathogenic yeasts, dimorphic fungi, non-pigmented hypomycetes, dermatophytes and dematiacious fungi. Although some strains of Candida albicans and Candida tropicalis were not completely inhibited by ITZ at concentrations up to 80 tig/ml, partial growth inhibitions were observed even at drug concentrations as low as 0.04μg/ml. The antifungal activity of ITZ against C. albicans was markedly influenced by medium composition, medium pH, inoculum size and incubation time.

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The therapeutic efficacy of itraconazole (ITZ), and oral triazole antifungal agent, was studied using several experimental fungal infections in animals. The following results were obtained:
1.ED₅₀ values of ITZ and of ketoconazole (KCZ) in a murine model of systemic candidiasis produced by intravenous challenge of Candida albicans alls were 32.9mg/kg and 224 mg/kg, respectively. ITZ suppressed the proliferation of Candida experimentally colonized in the GI-tract of mice and/or a secondary dissemination induced by prednisolone.
2.An oral dose of 40 mg/kg/day ITZ administered for experimental pulmonary cryptococcosis in mice inhibited the fungal proliferation in the lung and the dissemination to the brain.
3. ED₅₀ values of ITZ and KCZ for experimental systemic Aspergillus infection in mice were 103.6mg/kg and 882 mg/kg, respectively.
4.ITZ suppressed the development of local symptoms in guinea pigs with experimental dermatophytosis. Culture studies performed on cutaneous tissues from infected sites on day-19 postinfection revealed that ITZ treatment lowered the culture-positive rate to a greater extent than KCZ-treatment.
5.Plasma concentrations of ITZ after a single dose of 100mg/kg in mice were determined using the bioassay method: C_max was 11μg/ml and T 1/2 was 24 hours.
6.These results show that oral ITZ is highly effective in the treatment of deep-seated and superficial fungal infections produced in experimental animals.c

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