We evaluated the in vitro antimicrobial activity of SS 717, a new imidazole antimycotic, and compared it with those of clotrimazole (CTZ), cloconazole (CCZ) and bifonazole (BFZ).
SS 717 exhibited potent activity against a wide variety of fungi, especially Candida glabrata, Trichophyton, Microsporum, Aspergillus and Fonsecaea spp.
It was much more potent against filamentous than against yeast-like fungi. Among the yeast-like fungi tested, C. glabrata was more sensitive to SS 717 than to CTZ, CCZ or BFZ. Against clinical isolates of dermatophytes, SS 717 also showed lower geometric mean MIC values than did CTZ, CCZ or BFZ. It exhibited moderate activity against Gram-positive bacteria, but Gram-negative were insensitive to it.
The in vitro antifungal activity of SS 717 was not much affected by changes in assay medium, pH of the medium, inoculum size, incubation period or addition of serum.

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We studied the therapeutic effect of various concentrations of SS 717 cream and solution formulations on experimental cutaneous Trichophyton mentagrophytes infection in guinea pigs in comparison with those of bifonazole cream and solution formulations.
The evaluation of the therapeutic effect was made in terms of the average lesion score and the rate of appearance of positive cultures from infected skin sections.
SS 717 cream and solution (0.25, 0.5, 1 and 2 %) were effective in treating a dermatophyte model for 14 consecutive days when treatment was initiated 5 days after infection.
Excellent therapeutic efficacy of SS 717 cream was observed in the order of 1 %, 0.5 % and 0.25 %, but no significant differences were detected between the 1 % and 2 % cream treated groups.
The therapeutic activity of SS 717 1 % cream and solution was superior or equivalent to those of bifonazole 1 % cream and solution.
The protective effect of pretreatment with 1 % SS 717 cream on an experimental dermatophytosis was also confirmed and the data showed a prophylactic effect against infection for 24-72 h.

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We analyzed the antitumor effect of a new platinum analogue, NK 121, against fresh human tumor cells and established tumor cell lines, and compared it with CDDP using the succinate dehydrogenase inhibition (SDI) chemosensitivity test. As the target cells, highly purified fresh tumor cells were obtained from three patients with malignant ascites due to gastric adenocarcinoma, two patients with pancreatic cancer, and two patients with ovarian cancer. The established KATO-III and C-1 cell lines were used for comparison. Tumor cells were cultured with 0.01-80 μg/ml of NK 121 or CDDP for 4 days, and following incubation the antitumor effect of NK 121 and CDDP was evaluated by the SDI test.
For fresh human tumor cells from patients treated with CDDP, the antitumor effect of NK 121 was superior to that of CDDP at concentrations below 5-10 μg/ml. In addision, for tumor cells from patients not treated with CDDP, the inhibition rate of NK 121 was similar to that of CDDP at concentrations less than 1-5 μg/ml. For KATO-III cells, the inhibition rate of CDDP was higher than that of NK 121 at concentrations above 20 μg/ml, but there was no difference in antitumor activity between the two agents under 10 μg/ml. For C-1 cells, there was also no difference between the two agents at concentrations less than 1 μg/ml.
Thus, NK 121 had a similar antitumor potency to CDDP at concentrations corresponding to the clinically achievable plasma levels which had been found in phase I trials.

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We conducted a footpad swelling test to clarify whether a delayed type hypersensitivity (DTH) reaction against tumor antigen is potentiated by oral administration of D fraction extracted and purified from fruit body of Grifola frondosa (maitake), with a ratio of β-glucan to protein of 7: 3. When the antigen was injected in D fraction administered tumorbearing mice (D-mice), footpad swelling was observed, suggesting that a DTH reaction against the tumor antigen was potentiated by oral administration of D-fraction. Winn assay was carried out with whole spleen cells from D-mice and Lyt-2^-spleen cells in which Lyt-2⁺ cells corresponding to cytotoxic T cells (CTL) were eliminated by treating with anti-Lyt-2 monoclonal antibody and complement. Even after CTL were eliminated, tumor neutralizing activity was at no time impaired, indicating that spleen cells other than CTL play a leading role in tumor cytotoxicity.
We hypothesize from the above results, that a DTH reaction, manifested by the combined action of delayed hypersensitivity T cells (Tdh) and macrophages (MΦ), was potentiated by oral administration of D-fraction. Even when CTL are absent, there is a high degree of tumor involution. But D-fraction did not activate gut-associated lymphoid tissue (GALT) and Peyer's patch (PP), by oral administration.

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Synergism between cefazolin (CEZ) and imipenem (IPM) against methicillin-resistantStaphyococcus aureus (MRSA) was confirmed by (1) an in vitro checkerboard method, (2) in an in vitro kinetic model for the bactericidal test and (3) several experimental infection models for the protection test.
(1) A combination of CEZ and IPM synergistically inhibited 45 (83%) of the 54 MRSA strains on agar by a checkerboard method: FIC indices for 25 of the 45 strains were 0.25 or lower and those for the remaining 20 strains ranged from 0.25 to 0.5. This synergism was also recognized in several culture conditions such as high inoculum (about 10⁸ cfu/ml), low temperature (30°C) and supplement of 4 % NaCl.
(2) In an in vitro kinetic model simulating human plasma concentrations at their usual clinical doses of 2.0g (CEZ) and 0.5g (IPM), the bactericidal activity of CEZ and IPM in combination was by far stronger than that of each drug alone.
(3) Against systemic infection in normal mice the synergism was also recognized at a ratio of 4:1 or higher (CEZ to IPM). The FED indices for 6 of the 8 MRSA strains were not more than 0.5 (synergism) and those for the other strains were 0.57 and 0.63 (additive). This combination was also synergistically active against systemic and subcutaneous infections in neutropenic mice and endocarditis in rats.
The results suggest that the combination of CEZ and IPM is useful in treating refractory MRSA infections.

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We evaluated the usefulness of inhalation therapy with cephem antibiotics in 48 patients with bacterial respiratory infections: u cases of bronchiectasis, 5 of diffuse panhronchiolitis (DPB), 8 of chronic pulmonary emphysema complicated with infection, and 15 of chronic bronchitis. The causa-tive organisms isolated from these patients were 2 strains of Staphylococcus aureus, 8 of Streptococcus pneumoniae, 6 of Branhamella catarrhalis, 13 of Haemophilus influenzae, 4 of Klebsiella pneumoniae, 1 of Serratia marcescens, and 46 strains of Pseudomonas aeruginosa, respectively, A total of eighty episodes of infections were mainly treated with cephem antibiotics. The MICs of causative organisms, except for Pseudomonas aeruginosa strains, were below 6.25μg/ml. Inhalation therapy against pathogenic organisms, sensitive to cephem antibiotics, provided good bacteriological effect in all episodes. However, the efficacy rate in the 46 episodes of Pseudomonas aeruginosa infection was as low as 34.7%. This decreased the overall efficacy rate to 59%. The serum concentration of each cephem antibiotic after inhalation therapy was below the detection limit at a dose of 100 mg per inhalation, but urinary excretion was observed. The serum concentration of each drug was measurable by increasing the inhalation dose. From the date of in vitro experiments employing a mixed culture system of a mucoid Pseudomonas aeruginosa strain, viable and destroyed polymorphonuclear leukocytes, human sera and different concentrations of ceftazidime, it was presumed that destroyed polymorphonuclear leukocytes inactivated not only ceftazidime but also complement component. This observation supports the low efficacy rate of the inhalation therapy with cephem antibiotics in the patients with chronic Pseudomonas aeruginosa infections, whose sputum contained a large amount of destroyed neutrophils.

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We studied the clinical effect of PSK, a protein-bound polysaccharide, in 32 cases of recurrent genital herpes. PSK was orally administered at 3.0g per day. The therapeutic efficacy was evaluated by comparing the duration of the illness and the frequency of recurrence before and during administration. The average duration of illness before the treatment was 8.4 days, which decreased to 4.6 days during administration of the drug. The frequency of recurrence before treatment was 3.2 times per 3 months, which decreased to 1.5 times per 3 months during the treatment. There were no side effects. Our data indicate that PSK is useful in treating recurrent genital herpes.

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A pepsin-treated human immunoglobulin preparation was administered to 18 surgical patients with severe bacterial infections in a dose of 7.5g. This immunoglobulin treatment was concomitant with administration of antibiotics, unlike in conventional studies where immunoglobulin administration is preceded by antibiotic treatment. The relation between the clinical response and the susceptibility of isolated organisms to the antibiotic was studied to evaluate the clinical efficacy of the inununoglobulin preparation separately from that of the antibiotics. The results were as follows 1) The clinical efficacy was excellent or good in 12 of the 18 patients (overall efficacy rate 66.7%). 2) An efficacy rate of 50% was obtained even in patients with MICs of not less than 12.5μg/ml, who were unlikely to respond to the antibiotics. These results indicate that the clinical efficacy of immunoglobulin preparations used concomitantly with antibiotics in severe infections can be evaluated in the same manner as in actual clinical situations.

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