The Japanese Journal of Antibiotics
Online ISSN : 2186-5477
Print ISSN : 0368-2781
ISSN-L : 0368-2781
Volume 44, Issue 9
Displaying 1-12 of 12 articles from this issue
  • KIYOHIRO NISHIKAWA, CHIEKO SHIBASAKI, KATSUTOSHI TAKAHASHI, TOMIO TAKE ...
    1991 Volume 44 Issue 9 Pages 917-925
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    The effect of treatment schedule on antitumor activity of 15-deoxyspergualin (NKT-01) against P388 1eukemia was studied by changing each 2 out of 3 factors of administration schedule (number of injections, inlection interval, andinjection period) with the rest being constant.The antitumor activityof NKT-01 was shown to be strongly time-dependent;highere Mcacy was obtained with prolongation of treatment periodand with increasing the number of injections.The dosing interval seemed not to be a dominant factor regarding the activity of NKT-Ol.The strong dependency on treatment period was also observed in continuous infusion schedules by using Alzet 2001 osmotic minipump.The degree of dependency on infusion period was estimated to be3-to4-fold stronger than that on the infused dose by logarithmical plotting of the infusion periods and infused daily doses required to produce 130% of T/C (%).The effective dose range by the continuous infusion was slightly narrower than that by the repeated bolus inlections, although slightly higher maximal activity was obtained at the optimal dose.Hyperacute pharmacological toxicity caused bybolus injection of high dose (51.2 mg/kg) of NKT-01 did not occur by continuous infusion method even at much higher dose (409,6mg/kg/day).Cumulative gastrointestinal toxicity was observed by prolonged continuous infusion as well as repetitivetreatment schedule.From these results on antitumor activity and toxicity by various treatment schedules, recommendable clinical modality for NKT-01 seems to be the short-time infusion on every or every other day continuing for a few weeks.The results also suggest that NKT-01 may not have specific action to particular cell population of a certain cell cycle phase like cell cycle phasespecific agents, and seems to exhibit its antitumor activity through different modes of action from other antitumor drugs, of which details remained to be solved.
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  • HIROSHI YAMA, YOKO MURATA, KIYOHARU YAMANAKA, YUJI OGAWA, HIROYOSHI MI ...
    1991 Volume 44 Issue 9 Pages 926-940
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    We examined MICs of 6 oral new quinolones and 4 oral cephems against bacteria isolated from patients at 6 hospitals in Osaka during the period from January to June in 1990, and the following results were obtained.
    1. All speceis excluding Streptococcus pyogenes were more sensitive with less frequencies of resistance to new quinolones than to cephems. In new quinolones, tosufloxacin (TFLX) was the most active against Gram-positive cocci and ciprofloxacin (CPFX) and TFLX had the highest activities against Gram-negative rods.
    2. Resistant (MIC of CPFX≥3.13μg/ml) strains to new quinolones were observed at higher frequencies than 10% among Staphylococcus spp., Enterococcus faecalis, Citrobacter freumlii, Morganella morganii, Providencia rettgeri, Serratia spp., Pseudonomas aeruginosa, Psuedomonas ceeacia and Xanthomonas maltophilia.
    3. The frequency of Staphylococcus aureus resistant to new quinolones isolated from in-patients or urine was significantly higher than that from out-patients or other sources. On the other hand, there was no significant difference in resistance frequencies of P. aeruginosa due to types of patients or sources. But, there were significant differences in frequencies of resistant organisms of either species to new quinolones among hospitals.
    4.Twenty-seven strains (19.7%) of 137 S.aureus strains examined were methicillin-resistant, and they were similarly resistanto new quinolones also. Methicillin susceptible S. aureus were also similarly sensitive to new quinolones.
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  • KOICHI DEGUCHI, NOZOMI YOKOTA, MASAMI KOGUCHI, YUTAKA NAKANE, YUMIKO S ...
    1991 Volume 44 Issue 9 Pages 941-957
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In order to survey antibacterial activities of ofloxacin (OFLX) against 1,440 bacterial strains isolated from patients with community-acquired infections in 1987 and 1990, minimum inhibitory concentrations (MICs) of the drug as well as those of other new quinolones and oral cephems were determined. The following conclusions were reached.
    1. Comparison of the MIC distribution for strains isolated in 1987 with those in 1990 suggested a tendency toward an increase in the frequency of OFLX-resistant isolates with the passage of time of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus vulgaris, Morganella morganii, Providencia spp., and Acinetobacter calcoaceticus. Most common elevations of MIC values against these bacteria were observed in MIC80, and MIC90 values, while no significant alternation was observed in MIC50 values. However, MIC50'S of OFLX against Serratia marcescens and Pseudomonas aeruginosa were relatively high for strains isolated in both 1987 and 1990.
    Most of the OFLX-resistant strains of S. aureus seemed to be methicillin-resistant (MRSA). Furthermore, MIC80 of OFLX against coagulase-negative staphylococci was high in strains isolated in both 1987 and 1990.
    2. Susceptibility of Streptococcus spp. was evaluated only in strains isolated in 1990. The results were comparable to those reported by others in the early 1980s.
    3. Bacteria which showed no or infrequent emergence of OFLX-resistant strains evenin 1990 were Proteus mirabilis, Haemophilus influenzae, Neisseria gonorrhoeae, Campylobacter spp. and Peptostreptococcus spp.
    4. Recently isolated strains from patients with community-acquired infections showed a tendency toward an increase of the frequency of OFLX-resistant strains among many bacteria. However, the bacteria which contained high percentages of OFLX-resistant strains except for MRSA were so-called less-virulent bacteria, and in the other bacteria elevations of MIC values were only observed in MIC80 and MIC90. These results suggested that OFLX preserved a potent antibacterial activity against bacteria which were major causative pathogens in community-acquired infections.
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  • MASAO OOISHI, MASUYA MIYAO, OSAMU OKAZAKI
    1991 Volume 44 Issue 9 Pages 958-963
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    We studied the intraocular penetration of DR-3355, a new quinolone derivative in white mature rabbits.
    DR-3355 concentration in the aqueous humor reached the maximum, 1.06μg/ml, at 2 hours after oral administration of 20mg/kg in single dose. Six hours after it was 0.37μg/ml.
    At 2 hours, the concentration ratio in the aqueous humor and serum was 23.3%.
    The pharmacokinetic parameters of DR-3355 levels in both of the aqueous humor and serum were: Cmax, 1.02μg/ml and 4.56μg/ml; Tmax, 1.42 hours and 1.47 hours; T 1/2, 0.96 hours and 1.57 hours; and AUC, 3.91μg·hr/ml and 19.70μg·hr/ml, respectively.
    At 2 hours after oral administration, the ocular tissue concentrations were 3.84-16.10μg/g in the outer parts of the eye, and 0.70-13.52μg/g or ml in the inner parts of the eye. Those concentrations decreased to about 1/2 to 1/32 in the outer parts, and 1/2 to 1/7 in the inner parts of the eye at 6 hours.
    Those ocular tissue concentrations of DR-3355 exceeded the MIC90 of the compound against various bacteria of ocular pathogens, such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae and Serratia marcescens.
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  • A PHARMACOKINETIC STUDY ON CEFIXIME IN PEDIATRICS
    HARUHI NAKAMURA, NAOICHI IWAI
    1991 Volume 44 Issue 9 Pages 964-978
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    A pharmacokinetic study on cefixime (CFIX) 5% granules for pediatric use was performed, and pharmacokinetic parameter were calculated.
    1. Six school chidren were administered orally with CFIX granules at a dose level of 3 mg/kg either at 30 minutes before meal or at 30 minutes after meal on a crossoverdesign, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax, Cmax, T 1/2 and urinary excretion rate (0-12 hours) following the administration before meal were 3.33±0.42 hours, 1.03 ±0.17μg/ml, 2.31 ± 0.26 hours and 15.3 ±2.2%, respectively, Tmax, Cmax, T 1/2 and urinary excretion rate following the the administration after meal were 4.00±0.52 hours, 0.90±0.09 μg/ml, 3.11-1-0.21 hours and 11.3 ± 1.6%, respectively. Earlier Tmax, higher Cr., and higher urinaryexcretion rate were observed when the drug was administered before meal than when administered after meal. These differences between the 2 groups were not statistically significant.
    2. Five school children were administered orally with CFIX granules at 30 minutes after meal at a dose level of either 3 mg/kg or 6 mg/kg on a crossover design, and serum concentrations and urinary excretion rates of CFIX were determined. C. and AUC at a dose level of 3 mg/kg were 1.01 ± 0.26 mg/ml and 5.86± 1.13 ug hr/ml, respectively, and Cmax and AUC at a dose level of 6 mg/kg were 1.76 ±0.29, μg/ml, 12.54± 1.77 μgμhr/ml, respectively. A dose response relationship was thus observed.
    Seven infants (3mg/kg) and 3 infants (6mg/kg) were administered orally with CFIX granules at 30 minutes after meal. Cmax and AUC at a dose level of 3 mg/kg were 2.45-10.26, μg/ml, 33.50± 17.62, μg·hr/ml, respectively, and Cmax and AUC at a dose levelof 6 mg/kg were 4.42 ± 0.98μg/ml, 66.85 ± 25.19 μg·hr/ml, respectively. A dose response was observed.
    3. Eleven school children, 5 younger children and 7 infants were administered orally with CFIX granules at a dose level of 3 mg/kg at 30 minutes after meal, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax in school children, younger children and infants were 3.82 ±0.33 hours, 5.20±0.49 hours and 5.43±0.37 hours, respectively. Earlier Tmax's were observed in school children than in other children. Cmax in school children, younger children and infants were 0.95±0.12 μg/ml, 0.56 ± 0.06 μg/ml and 2.45 ±0.26, ag/ml, respectively. It seemed to be the highest in the infants, then followed by the school children and the younger children.
    T 1/2 in school children, younger children and infants were 2.85 0.18 hours, 3.94±0.96 hours, and 6.72 ±1.31 hours. Longer T 1/2's were observed in the infants. As for AUC andurinary excretion rate, higher AUC and urinary excretion were observed in infants than in the other children.
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  • KIYOSHI KITAMURA, FUMIMARO TAKAKU, TAMOTSU MIYAZAKI, AKIRA MIURA, HIDE ...
    1991 Volume 44 Issue 9 Pages 979-986
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    The effectiveness of sulbactam/cefoperazone (SBT/CPZ) on severe infections associated with hematological diseases was evaluated in a nation-wide multicenter clinical study. SBT/CPZ (4-6 g/day), a 1: 1 combination of SBT and CPZ, was given intravenously to 437 patients with hematological disorders.
    The underlying diseases included acute nonlymphocytic leukemia, acute lymphocytic leukemia, malignant lymphoma, multiple myeloma, myelodysplastic syndrome and others. Thus, 94.3% of the patients had hematological malignancies. The complicating infections included sepsis in 41 cases; sepsis suspected in 205; pneumonia in 47; urinary tract infection in 15; fever of unknown origin in 59; and others in 70. Clinical efficacies of SBT/CPZ were as follows; markedly effective, 83 cases; effective, 170; fairly effective, 59; and ineffective, 110. The efficacy rate (markedly effective plus effective) was 60.0% as a whole. The efficacy rate of SBT/CPZ in sepsis and suspected cases, which accounted for 56.3% of the infections, was 59%. Mild side effects such as skin rash were observed in 15 patients (3.1%). As for abnormal laboratory test results, transient increases in GOT, GPT, Al-P, LDH, etc. were observed in 42 patients (8.6%). Therefore, SBT/CPZ is considered to be a useful drug in empiric therapy for severe infections associated with hematological diseases.
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  • TISSUE CONCENTRATION AND CLINICAL EFFICACY
    TAKASHI HIRAYAMA, MIKIO SAITOH
    1991 Volume 44 Issue 9 Pages 987-992
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    A clinical study on cefuzonam (CZON), a new parenteral cephalosporin antibiotic, was performed in 22 patients with acute appendicitis. CZON in a dose of 1 g was administrated by intravenous bolus injection or intravenous drip infusion for 60 minutes.
    In the appendices, concentrations of CZON were 0.066-21.7μg/g in normal or slight catarrhal cases, 0.173-11.7μg/g in moderate phlegmous cases and 0.116-12.1μg/g in serious gangrenous perforated cases. The concentration of CZON in appendixes was not directly proportional to the degree of pathological change of inflammation.
    6 patients with acute peritonitis due to perforated appendicitis were treated with CZON of 2 g/day for 5-10days. The clinical effect was good in5cases, fair in 1 case of the above 6. The clinical efficacy rate was 83%.
    Side effects were not notable in the patients.
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  • Tamio HIRATANI, Yukiyo ASAGI, Atsuko MATSUSAKA, Katsuhisa UCHIDA, Hide ...
    1991 Volume 44 Issue 9 Pages 993-1006
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In vitro antifungal activities of amorolfine (MT-861), a newly developed morpholine antimycotic agent, against a wide range of pathogenic fungal strains were investigated using an agar-dilution method with an imidazole antifungal agent, clotrimazole (CTZ), as the reference drug. The results showed that MT-861 had a broad antifungal spectrum, and was active against all of the pathogenic fungi tested except nonpigmented filamentous fungi such as aspergilli and penicillia. Dermatophytes and Malassezia furfur was the most highly susceptible to MT-861. Antifungal activities of MT-861 against most strains of these fungi as well as those against most strains of dimorphic fungi were higher than those of CTZ. By contrast, MT-861 showed lower activities against pathogenic yeasts such as Candida albicans than CTZ. Several assay conditions, such as inoculum size of fungi, incubation time, media pH and compositions including serum supplementation, affected MT-861 activities against C. albicans and, to lesser extents, those against Trichophyton mentagrophytes. MIC values of MT-861 against C. albicans and other Candida spp., were the lowest on casitone agar. MT-861 exerted fungicidal actions toward susceptible fungi such as T. mentagrophytes and Sporothrix schenckii at relatively low concentrations, and these activities were increased when the time of incubation was extended beyond 24 hours after inoculation of testing organisms. Susceptibilities of any strains of C. albicans and C. glabrata to MT-861 were not reduced by as many as 15 successive transfers in MT-861 containing media.
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  • KATSUHISA UCHIDA, KOJI AOKI, HIDEYO YAMAGUCHI
    1991 Volume 44 Issue 9 Pages 1007-1012
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In vitro antifungal activities of amorolfine (MT-861), a new morpholine antifungal agent, were examined using an agar-dilution method, in comparison with those of 2 other antifungal agents, clotrimazole (CTZ) and bifonazole (BFZ), against 182 clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, and Epidermophyton floccosum, which had been freshly isolated from a total of 182 cutaneous mycotic patients with various typesof dermatophytes or cutaneous candidiasis. Antifungal activities of the 3 drugs against T. rubrum were in the order of MT-861>CTZ>BFZ, with the lowest average MIC values (0.0070μg/ml) obtained with MT-861. The average MIC value of MT-861 for clinical isolates from patients with pedis was roughly 2.3-fold higher than that for those from patients with tinea corpotis.
    Out of 3 drugs tested MT-861 exhibited the most potent activities against clinical isolates of T mentagrophytes, M. canis, and E. floccosum with average MIC values of 0.0267, 0.0079, and 0.0018μg/ml, respectively.
    MIC values of MT-861 against isolates of Candida albicans ranged from 0.01 to 10, ug/ml, and the average value (0.1762μg/ml) was the lowest of the 3 drugs.
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  • KATSUHISA UCHIDA, KOJI AOKI, HIDEYO YAMAGUCHI
    1991 Volume 44 Issue 9 Pages 1013-1019
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In vitro antifungal activities of a new morpholine agent, amorolfine (MT-861) were investigated, against 39 strains of Malassezia furfur (11 stock cultures and 28 clinical isolates) and 8 strains (stock cultures) of Malassezia pachydermatis, in comparison with those of 2 reference drugs, clotrimazole (CTZ) and bifbnazole (BFZ). Of the 3 antifungal agents, MT-861 exhibited strongest antifungal activities against the stockc ultures of M. furfur and M. pachydermatis with average MIC values of 0.428 and 0.174μg/ml, respectively; and the average BFZ activity was less than 1/10, and the average CTZ activity was 1/100, of the average MT-861 activity.
    All of the clinical isolates of M.furfur also showed high susceptibilities, though they were more susceptible to BFZ and CTZ.
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  • KATSUHISA UCHIDA, ATSUKO MATSUZAKA, HIDEYO YAMAGUCHI
    1991 Volume 44 Issue 9 Pages 1020-1031
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Therapeutic effects of cream and solution of amorolfine (MT-861), a new morpholine antifungal agent, were investigated using 1% cream and solution of bifonazole (BFZ) as the reference drug inTrichophyton mentagrophytes-infected guinea pig to evaluate the usefulness of MT-861. The results obtaind are summarized as follows.
    1. Once-a-day topical applications of 0.125, 0.5, and 1% MT-861 cream preparations starting day-5 postinfection were therapeutically effective. The effectiveness increased with increasing concentrations of active preparations, reaching nearly the maximum level at 0.5%. The treatment with 0.5% or 1% MT-861 cream preparation produced significantly greater improvement of clinical symptoms and culture results than did the treatment with the 1% BFZ cream preparation.
    2. Treatment of 7 days or longer with 0.5 or 1% cream of MT-861 was required to produce therapeutic effect. Close relationships were observed between chitin contents of skin lesions and the presence of the pathogen in the lesions after 1, 2 and 3 weeks of treatment.
    3. When MT-861 solutions were applied once daily for 2 weeks, the effectiveness increased as drug concentrations increased similarly to the cream treatment. A significant difference was observed (P < 0.05-0.001) in degrees of lesions and culture results between the treatment with MT-861 and with BFZ control solutions.
    Thus, excellent therapeutic effectiveness in theTrichophytoninfection model of guinea pigs was obtained by treatment with both the cream and the solution of MT-861. Once a day dosage of 0.5% drug concentration produced adequate effectiveness. A high clinical usefulness is expected in the treatment of fungal infections of the skin using MT-861.
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  • KATSUHISA UCHIDA, HIDEYO YAMAGUCHI
    1991 Volume 44 Issue 9 Pages 1032-1041
    Published: September 25, 1991
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In order to assess the extent of dermal retention of amorolfine (MT-861), a new morpholine antifungal agent, cream preparations of MT-861 were applied to the skin on the back of guinea pigs and the protective effect was determined regarding the topical treatment on the development of infection induced by subsequent inoculation with conidia of Trichophyton mentagrophytes. One per cent bifonazole (BFZ) cream was used as the reference drug. The results are summarized as follows.
    1. Pretreatment with 0.125, 0.25 or 0.5% MT-861 preparation 1 to 3 days before infection significantly reduced the extent of lesion developed compared to the untreated control at postinfection day-12 and day-19 measurements.
    2. Cultures of specimens taken from the skin lesion performed on postinfection day-19 showed that pretreatment with 0.125, 0.25 or 0.5% MT-861 cream 1 day before infection significantly lowered the number of culture-positive skin lesions compared to that of untreated control.
    3. No significant difference was observed among the 3 experimental groups of animals pretreated with MT-861 preparations 1 to 3 days before infection in extent of lesions developed, though the mycological protective effect of the drug appeared to decrease with increasing time intervals between drug-pretreatment and fungal challenge.
    4. A 0.5% MT-861 preparation had an equal or superior infection-preventive effect to 1% BFZ preparation as far as severity of lesion and recovery of fungi were concerned.
    5. The potent and prolonged protective action by MT-861 preparations against the development of fungal infection strongly suggests that MT-861 retains in the skin tissue in an active fromfor substantially long periods of time.
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