One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained.
1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were no significant differences between the two groups with respect to the background.
2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.0% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant.
3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained.
4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9%, respectively.
5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment.
The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

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The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders.
The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant.
Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

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In order to evaluate antimicrobial activity of cefetamet (CEMT), minimum inhibitory concentrations (MICs) of CEMT and control drugs were determined against Gram-negative rods mainly from complicated urinary tract infections examined in our laboratory from April to September of 1994.
The results are summarized as follows;
1. The obtained strains were Citrobacter diversus 20, Citrobacter freundii 30, Enterobacter aerogenes 20, Enterobacter cloacae 30, Serratia marcescens 30, Proteus mirabilis 30, Proteus vulgaris 20 and Morganella morganii 30 strains, a total of 210 strains.
2. Excluding some resistant strains, the MIC-distribution showed that CEMT had strong antimicrobial activities against those strains from the MIC-distribution of this investigation. Compared to reports on CEMT in 1989, the MIC₈₀, of CEMT in this investigation against clinical isolates were similar. The MIC_50's of CEMT against E. aerogenes, S. marcescens, P. mirabilis, P. vulgaris and M. morganii in the previous examination were equal to or similar to the current results, but the MIC_50's against C. freundii and E. cloacae were lower than the value of this report. The detection frequency of highly resistant strains of C. freundii and E. cloacae to cefteram and cefixime were similar to that of CEMT-resistant strains. Multiple drug resistant strains, among these bacterial species seemed to be increasing.
3. Compared to oral antibacterial agents of oxime cephems that were used in the past, CEMT showed higher peak values of urinary excretion concentration and higher blood levels were sustained for a longer period of time. CEMT-PI will be effective against urinary tract infections.

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An investigation was carried out to determine whether or not there had been any changes in the susceptibility of clinically isolated strains of Trichophyton mentagrophytes and Trichophyton rubrum (both leading causes of tinea) to bifonazole, an imidazole derivative and antifungal for topical use. Susceptibility was measured in 107 strains of these fungi isolated from clinical samples during a study on the treatment of tinea pedis with Mycospor® cream in 1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored prior to development of the drug. The results are as follows:
(1) There was no distinct difference in the susceptibility to bifonazole of T. mentagrophytes strains isolated before 1986 and those isolated in 1990 or 1995.
(2) T. rubrum strains isolated before 1986 were slightly more susceptible to bifonazole than those isolated in 1995, while the 1990 strains were slightly less susceptible than the 1995 strains, but the difference was not significant.
(3) The highest MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated from before 1986 and those in 1995 were relatively low, being 2.5μg/ml and 1.25μg/ml, respectively.
These results suggest that no resistance or reduced susceptibility to bifonazole has emerged among clinical isolates of dermatophytes since the development of the drug.

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The usefulness of bifonazole (Mycospor®), a topical imidazole antifungal agent approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor® cream was applied by 141 patients with tinea pedis once daily for 4 weeks, and the clinical efficacy and adverse reactions (as well as any correlations with the susceptibility of isolates and the mycological activity of the agent against these isolates) were studied. The results were then compared to those of a previous study. The following results were obtained.
1. Mycological activity
Mycological examination results became negative in 63.2% (36/57) of the patients with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea pedis, and in 74.7% (68/91) of all tinea pedis patients.
2. Mycological activity and MIC No correlation was found between the MICs of bifonazole against the pathogenic fungi and the rate of eradication on mycological examination.
3. Improvement of symptoms
The improvement rates for local symptoms were 82.5% for plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea pedis.
4. Clinical efficacy
Good clinical efficacies were found in 61.4% of the patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 71.7% of all patients.
5. Safety
Regarding adverse reactions, what seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The reaction decreased or disappeared in all cases.
6. Usefulness
Mycospor® was found to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 73.9% of all tinea pedis patients.
7. Comparison with former results The results obtained in the present clinical study were comparable to those obtained in patients with tinea pedis treate in a double-blind comparative study conducted during the development of as a new topical antifungal agent.
From the above results, Mycospor® cream was confirmed to be still useful, although it has been used widely for the topical treatment of cutaneous mycoses in the past 10 years since its approval.

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Ubenimex (Bestatin, Ubx) has been shown to have anti-tumor activity and immuno-modulating activities. Ubx has been used in immuno-therapy in combination with remission maintenance chemotherapy after induction of complete remission for adult acute non-lymphocytic leukemia (ANLL, AML). Daunomycin (DNR), arabinosylcytosine (Ara-C) and 6-mercaptopurine (6-MP) are used for the standard chemotherapy for ANLL. It is, however, believed that emergence of resistant cells to chemotherapy cause minimal residual leukemia resulting in poor prognosis. Ubx has been administered in combination with these chemotherapeutic agents. We examined the combinatorial effect of Ubx with DNR, Ara-C, 6-MP and etoposide on K562 leukemic cell line and the chemotherapeutic agent resistant cells derived from K562 cell line. Ubx showed growth inhibitory effects on these cell lines. A synergistic effect was observed on growth inhibition and with colony formation of parent K562 cell line when DNR and Ubx were used in combination. A combination of Ubx with Ara-C or etoposide showed additional effects on parent cells and other resistant cell lines. The combined growth inhibitory effect of 6-MP and Ubx was stronger than the effect of 6-MP alone. These results show that Ubx has a direct growth inhibitory effect on leukemic cells and additional or synergistic effects are obtained on K562 leukemic cell line and on chemotherapeutic agent resistant cells derived from the K562 cell line when Ubx is used combination with the above chemotherapeutic agents.

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