CHEMOTHERAPY
Online ISSN : 1884-5894
Print ISSN : 0009-3165
ISSN-L : 0009-3165
Volume 34, Issue Supplement1
Displaying 1-50 of 77 articles from this issue
  • RYOICHI OKAMOTO, SHIZUKO IYOBE, SUSUMU MITSUHASHI
    1986 Volume 34 Issue Supplement1 Pages 1-10
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK is a new semi-synthetic derivative of dibekacin (DKB); with a broad spectrum of antibacterial activities. The antibacterial activity of HBK was compared with imikaiin (AMK) and gentamicin (GM). The results are iiimznurized as follows.
    1) HBK showed a broad spectrum of antibacterial activity igaipst gram-positive and gram-negative bacteria. HBK had greater activity against staphyldcocci than AMK. HBK was more effective than AM (against gram-negative bacteria, although HBK was slightly less active than GM.
    2) HBK had greater activity against GM-resistant S.aureus, S. marcescens and P. aeruginosa than AMK.
    3) Bactericidal activity of HBK against S. aureus, E. coli and P.aeruginosa was confirmad by determining the minimum bactericidal concentration (MBC).
    4) HBK was stable against aminoglycoside inactivating enzymes except for AAC (2') and A AC (6')-IV.
    5) The in vivo efficacy of HBK was higher than that of AMK and GM against mouse systemic infection with gram-positive and gram-negative bacteria including AMK-or GM-resistant ones.
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  • SACHIKO GOTO, MASATOSHI OGAWA, AKIYOSHI TSUJI, SHUICHI MIYAZAKI, YASUK ...
    1986 Volume 34 Issue Supplement1 Pages 11-32
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The in vitro and in vivo antibacterial action of HBK, a new aminoglycoside antibiotic, was compared with that of gentamicin, dibekacin, amikacin and netilmicin and the following result, were obtained.
    1. Similar to other aminoglycoside antibiotics, HBK had a broad antibacterial spectrum and its antibacterial activity and bactoicidal action compared favorably with the other drugs.
    2. HBK's antibacterial activity against GM-resistant P. irzconitans, S. marcescens and P. aeruginosa was superior to that of GM, DKB, and NTL and it was Just as effective as AMK. Moreover, against P. inconstans, S. marcescens and P. aeruginosa, which were resistant to various drugs including GM, DKB, NTL, AMK, and ASTM, HBK displayed no cross-resistance.
    3. During an in vivo infection treatment experiment against strains resistant to GM, DKB, AMK, and NTL, HBK displayed an excellent therapeutic effect.
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  • NAOKO YAMASHITA, KIMIKO UBUKATA, RITSUKO NONOGUCHI, AKIRA GOTOH, MARI ...
    1986 Volume 34 Issue Supplement1 Pages 33-40
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    We investigated the antibacterial activity of HBK using 237 strains of gentamicin (GM)-resistant staphylococci (S. aureus: 102 strains, coagulase negative staphylococci (CNS): 135 strains) and 17 strains of tobramycin (TOB)-resistant staphylococci (S. aureus: 6 strains, CNS: 11 strains) isolated from clinical materials submitted to the Central Clinical Laboratory, Teikyo University Hospital from January to April 1983. The results obtained are as follows.
    1. Compared with other aminoglycosides (AGs), HBK has the most excellent antibacterial activity against the above-described clinical isolates, and its MIC for S. aureus peaked at 1.56μg/ml whereas the MICs of HBK for CNS ranged from 0.2 to 0.78μg/ml.
    2. A few of the strains tested had MICs of 6. 25μg/ml or higher, but of these only very small number had MICs higher than 100 μ/ml.
    3. The substrate specificity of AGs-modifying enzymes extracted from strains resistant to GM, AMK, or TOB was also examined, HBK was the least modified by 2''-phosphotransferase, 6'-acetyltransferase, and 4', 4''-adenylyltransferase.
    4. It is considered from these results that the lowest modification of HBK by enzymes produced by staphylococci is the most important factor leading to the high antibacterial activity of HBK against these organisms.
    5. When the bactericidal activity of HBK against GM-resistant staphylococci was determined with time, the viable cells were reduced by the addition of HBK at concentrations higher than the MIC.
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  • TOYOKO OGURI, YASUYUKI HAYASHI
    1986 Volume 34 Issue Supplement1 Pages 41-57
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Antibacterial activity of HBK was examined and compared with that of Amikacin (AMK), Dibekacin (DKB), Gentamicin (GM), Tobramycin (TOB), Sisomicin (SISO) and Micronomycin (MCR) as the control drugs against the 1490 strains of bacteria, including 2 species of Staphylococcus, 3 species of group D Streptococcus, H. influenzae, 2 species of Citrobacaer, E. cloacae, S. marcescens, P. vulgaris, M. morganii, 5 species of Pseudomonas, A. putrefaciens, 2 species of Acinetobacter, A. xylosoxidans and F. nseningosepticum. Those strains were isolated from clinical specimens from 1981 to 1984.
    The results were as follows.
    1. HBK showed potent antibacterial activity against S. aureus and S. epidermidis, including strains highly resistant to GM and AMK.
    2. In group D Streptococcus, HBK and control drugs were less active against E. faecalis and E.faecium. But HBK was more active against E. avium than those of control drugs tested.
    3. HBK was potently active against to H. influenzae, and the activity of HBK was equivalent to that of AMK and inferior to that of GM.
    4. In Enterobacteriaceae and other Gram-negative bacilli, HBK like control drugs showed strongly active against C. diversus, P. vulgaris, A. putrefaciens, Acinetobacter and P. fluorescens. In these bacterial species, HBK and other aminoglycoside-resistant strains were few.
    5. HBK had similar activity to AMK but was more effective than other control drugs against S. marcescens, and P. aeruginosa. The antibacterial activity of HBK against the strains of P. putida and P. cepacia was almost equivalent to that of control drugs.
    6. HBK and control drugs showed poor antibacterial activities against P. maltophilia, A. xylosoxidans and F. meningoseptieum. In these bacterial species, almost all strains were resistant to HBK and other Aminoglycosides.
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  • TSUNEKAZU HARUTA, KANETSU OKURA, SHIGEKAZU KUROKI, YUTAKA KOBAYASHI
    1986 Volume 34 Issue Supplement1 Pages 58-60
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Study was made on the transfer of HBK into spinal fluid in four rabbits with S. aureus meningitis.
    The blood concentrations after intramuscular injection of HBK 5mg/kg were 26.4, 18.0, 13.8, 10.2, 7.38, 5.45, 2.81, and 2.00μg/ml on the average of 4 rabbits in order of 30, 60, 90, 120, 150, 180, 240, and 300 minutes. And it was trace in 360 minutes. On the other hand, according to paper disc method we used, the lowest limit of measurement was as high as 1.56μ/ml. The concentrations in spinal fluid were trace during 30-180 minutes in 2 rabbits, during 60-150 minutes in 1 rabbit, and at 150 minutes alone in the remaining 1 rabbit. At other hours detection was impossible. Assuming tentatively that trace is 1μg/ml or so, the percentage of maximum concentration spinal fluid to serum is a little less than 4%. Therefore, the transfer of HBK into spinal fluid was considered to be not better of various aminoglycosides.
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  • YUZO KAZUNO, SANAE TSUNETA, ATSUSHI TAMURA, SHINO SHIRAISHI, HIROMI TA ...
    1986 Volume 34 Issue Supplement1 Pages 61-71
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic, was synthesized from dibekacin (DKB). The antibacterial activity of HBK was compared with gentamicin (GM); amikacin (AMK) and DKB, in vitro and in vivo. The results are summarized as follows.
    1) HBK showed broad spectrum of antibacterial activity against gram-posiaive and gram-negative bacteria. HBK had superior activity against GM-resistant E. coil, P. inconstans and P. aeruginosa.
    2) HBK was more effective than AMK and DKB against clinical isolates, although HBK was slightly less active than GM. HBK had Superior activity against GM-resistaat staphylococci.
    3) HBK had potent bactericidal activity against S. aureus, E. coli, K. pneurnoniae and P. aeruginosa.
    4) In vivo, the protective effect was shown by injection of HBK on mouse systemic infections with gram-positive and grain-negative bacteria including GM-and DKB-resistant ones.
    5) HBK was active against resistant the strains expressing aminoglycoside inactivating enzymes such as APH (3')-I, APH (3')-II, AAC (2'), AAC (3'), AAD (2'') and AAD (4).
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  • I. MICROBIOLOGIGAL ASSAY METHOD
    SACHIHIKO SHINKAI, NOBUYOSHI ISHIWATARI, MASATAKA FUJITA
    1986 Volume 34 Issue Supplement1 Pages 72-81
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Microbiological assay methods of HBK in biological fluids were studied.
    The assay methods using Bacillus subtilis ATCC 6633 as a test organism, Mycin assay agar arei (Peptone 5g, Beef-extract 3g and Agar 15g in 1, 000ml distilled water, q. s.) as an assay Medium and 0.1 M phosphate buffer (pH 8.0) as a diluent were most suitable for determining HBK levels in biological fluids;
    Accordingly, the lowest detectable concentrations of HBK by cup-plate, paper disc-plate and agar well method were 0.016μ/ml, 0.125μ/ml and 0.004μ/ml, respectively.
    As diluents, 0.1 M phosphate buffer (pH 8.0) could be used for urine samples, and pooled serum or chemistry control serum (for example, Moni-trol I) for serum samples.
    HBK was stable for the stability test periods at-20°C, 5°C and 25°C in buffer (pH 8.0), physiological saline, human serum and human urine.
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  • II. HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY METHOD
    IZUMI KOMIYA, NAYU MITOMI, MOTOHIRO NISHIO
    1986 Volume 34 Issue Supplement1 Pages 82-86
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    A procedure for the high-performance liquid chromatographic (HPLC) determination of HBK in serum (or plasma) urine, and bile is described using post-column derivatization with ο-phthalaldehyde. The technique involves extraction of HBK from biological samples by using a CM-Sephadex column and analysis by reverse-phase, ion-pair chromatography. Dibekacin is used as an internal standard. The accuracy of this HPLC assay is 2.7-3.8% in human serum and 1.0-1.7% in human urine. The HPLC assay of HBK in human serum and human urine correlates well with the microbiological assay.
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  • ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION AFTER SINGLE INTRAMUSCULAR ADMINISTRATION IN MALE RATS
    IZUMI KOMIYA, NAYU MITOMI, TAKASHI MATSUMOTO, MOTOHIRO NISHIO, TOSHIO ...
    1986 Volume 34 Issue Supplement1 Pages 87-94
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The absorption, distribution, metabolism and excretion of 3H-HBK were studied in male rats after intramuscular administration of 8H-HBK.
    1. 3H-HBK was rapidly absorbed from the muscle injected, and the maximal blood concentration was 1.97μg equivalent of HBK/ml 0.5 hr after intramuscular administration of 3H-HBK at the dose of 2mg potency/kg.
    2. The biological half-lives obtained from the blood concentration-time curve were 0.57 hr for the data in the first 3 hr, 4.07 hr for the data from 4 to 12 hr, and 104 hr for the data from 24 to 48 hr after the intramuscular administration of 3H-HBK.
    3. The cumulative urinary and fecal excretions of the radioactivity were 78.5% and 0.4% of the dose, respectively, within 120 hr after the intramuscular administration of 3H-HBK. The cumulative urinary excretion determined by the microbiological assay was 72.1% of the dose within 48 hr after the intramuscular administration of 3H-HBK, which was coincided with the cumulative urinary excretion of radioactivity.
    4. 3H-HBK was highly distributed in the kidneys.
    5. The great majority of the radioactivity excreted into urine until 24 hr after intramuscular administration of 3H-HBK was HBK itself and no metabolite was found in the urine.
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  • ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION AFTER SINGLE INTRAMUSCULAR ADMINISTRATION IN FEMALE RATS AND AFTER MULTIPLE INTRAMUSCULAR ADMINISTRATION IN MALE RATS
    IZUMI KOMIYA, NAYU MITOMI, TAKASHI MATSUMOTO, MOTOHIRO NISHIO, YOSHIO ...
    1986 Volume 34 Issue Supplement1 Pages 95-103
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The distribution and placental transfer were studied in pregnant rats after the single intramuscular administration of 3H-HBK at the dose of 2mg potency/kg. The absorption, distribution and excretion of 3H-HBK were also studied in male rats after multiple intramuscular dose (2 mg potency/kg).
    1. The radioactive concentration in the fetus was low when 3H-HBK was administered intramuscularly to 13 th-day and 18 th-day pregnant rats.
    2. The maximal milk concentration of radioactivity was 0.16μg equivalent of HBK/ml 4 hr after the intramuscular administration of 3H-HBK. The milk levels decreased more slowly thafn the blood levels.
    3. The blood level 8 hr after daily dose reached to the steady state around 9 th dose. The blood concentration-time curve until 8 hr after 14 th dose were almost the same as that after first administration.
    4. The tissue or organ levels of radioactivity after 14 th dose decreased more slowly than they did after first administration in the most tissues and organs, especially in trachea, adrenal, testis, tpididymis and sudmaxillary gland.
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  • TAKASHI YAMAMOTO, MASARU KOYAMA, KEIICHI NAKAGAWA
    1986 Volume 34 Issue Supplement1 Pages 104-116
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Tolerability, absorption and excretion of HBK were investigated by administering it intramuscularly (im) or by intravenous (iv) drip infusion to 35 healty male adult volunteers. The dosages were 1, 1.5, 2mg/kg, 100mg/man for im injection and 75mg/man, 100mg/man for iv drip infusion taking an infusion period of over 60 or 30 min., respectivily.
    1. Any Serious finding thought to be due to HBK was not seen for such investigations on tolerability as objective and subjective symptoms, physical examinations, general hematological tests, serum biochemistry and urinalysis. In clinical laboratory tests one day after the completion of the administration, one case was positive for granular casts but the correlation of this with HBK was unkown. It was thought that care should be taken for this in subsequent clinical trials.
    2. There was dose-responce relationship between the dosage and serum levels and the maximum serum level was 3.75 to 5.49μg/ml for im injection and 6.76 to 7.56μg/ml for iv drip infusion. The serum half lives were 1.5 to 3 hr for im injection and 2 to 3 hr for iv drip infusion. Changes in serum levels at the time of daily consecutive administration did not show tendency to accumulate.
    3. f: The 24-hr urinary excretion rates of HBK were 60 to 70% for im injection and 70 to 85% for iv drip infusion, showing similar results with other aminoglycosides.
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  • FUSANOSUKE YAMASAKU, YASUTOSHI SUZUKI, SACHIHIKO SHINKAI, TOMOKO SHOMU ...
    1986 Volume 34 Issue Supplement1 Pages 117-128
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Two groups of healthy adult subjects consisting of 4 subjects each were treated with HBK by i. m. route or by i. v. infusion route using rate constant infusion pump, and serum and urinary concentrations of HBK were determined by bioassay, EIA and HPLC methods. Among the three methods used for determination of HBK concentrations in biological fluids, EIA gave the most stable and reliable results. The results obtained by HPLC were sometimes similar to those obtained by EIA, but it was often that HPLC gave higher values for serum concentration and lower values for urinary concentration. On the other hand, results obtained by bioassay method showed scatterings, with low reliability.
    Following i. m. injection of 75 and 100mg, the serum concentrations as determined by EIA reached its peak of 3.7 and 4.9μg/ml, respectively, at 30 min after the administration, showing dose dependency. The peak concentration following i. v. infusion of 100mg for 1 hr was 6.4μg/ml, but from 2hr later the serum concentration became almost similar to that noted after i. m. injection. Changes in the serum concentration following 1. m. injection of 100mg HBK were similar to those observed with i. m. injection of DKB or AMK at the same dose. The serum concentration observed after i. v. infusion of HBK 100mg and FOM 1g simultaneously taking 1 hr was similar to that obtained after administration of each drug alone.
    The urinary recovery of HBK within 8 hr after administration as determined by EIA was 74 to 94% of the dose, being in this range when HBK was administered with FOM 1g combinedly.
    Analysis of results of EIA revealed T 1/2 values of mean serum concentration were 1.55 hr for i. v. route and 1.51 hr for 1. m. route, with mean distribution volume at mean serum concentration being 14. 6 and 15. 71, body clearance 108.9 and 120.1ml/min and renal clearance 99.5 and 90.3 ml/min, respectively.
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  • AKIRA SAITO, YASUMICHI KATO, KIYOFUMI ISHIKAWA, EINOSUKE ODAGAKI, MASA ...
    1986 Volume 34 Issue Supplement1 Pages 129-137
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The antibacterial activity of HBK, a new aminoglycoside antibiotic, was tested against each 27 clinical isolates of 6 species and 54 clinical isolates of one species, using plate dilution method with inoculum size of 106 cells/ml. The peak concentrations of HBK in MIC distributions were obtined at 0.2-6.3μg/ml for S. aureus, 0.8-12.5 for E. coli 0.2-25 for Klebsiella spp., 0.44-6.3 for P. mirabilis, 0.8-12.5 for M. morganii, 3.1-50 for S. marcescens, and 0.4-25 for P. aeruginosa.
    Pharmacokinetics of HBK were investigated in 6 male healthy volunteers after single intramuscular 1.5mg/kg administration. The mean peak concentration in serum was 9.0μg/ml, the mean serum halflife was 1.5 hours, and the urinary excretion rate was 69.7% within 8 hours.
    Thirteen patients with respiratory and urinary infections were treated intramascularly or intravenously with HBK at a daily dose of 100 to 200mg.
    Clinical response was excellent in 5 cases, good in 6 cases, fair in 1 case, and poor in 1 case. The effectiveness rate was calculated as 84.6%.
    No side effect was observed. As to laboratory findings, elevations of GOT, GPT was observed.
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  • IN VITRO ANTIBACTERIAL ACTIVITY OF HBK AND ITS THERAPEUTIC EFFICACY ON RESPIRATORY TRACT AND URINARY TRACT INFECTIONS BY INTRAMUSCULAR INJECTION
    SEIICHI AONUMA, REIKO SASAKI, NORIKO OTANI, KIKUO ONUMA, AKIRA WATANAB ...
    1986 Volume 34 Issue Supplement1 Pages 138-146
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK. new aminoglycoside antibiotic, was shown that is possessed a broad antimicrobial spectrum coverina. Gram-positive cocci and Gram-negative bacilli.
    Minimal inhibitory concentrations of the agent against each 20 clinical isolates of S. aureus, E. coli, K. pneutnoniae, S. tnarcescens, E. cloacae and P. aeruginosa were determined by use of MIC 2000 system. At a concentration of 0.39μg/ml, HBK inhibited all the strains of S. aureus, and at a concentration of 3.13μg/ml, this drug inhibited 85, 100, 80, 80 and 70 per cent of the strains of E. coli, K. pneumoniae, S. tnarcescens, E. cloacae and P. aeruginosa, respectively.
    Ten patients suffering from respiratory tract infections and three patients of urinary tract infections received intramuscularly 50 or 100mg of HBK twice a day. One patient showed an excellent an4 nine good xlinical response, while one other patient responded only fairly and other two poorly. No undeserable symptoms and signs including deafness due to administration of the drug were observed. In one case slight elevations of serum GOT and slight decrease in white bloodcell count were observed, and in another case slight elevation of serum creatinine and slight elevation of serum potassium.
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  • SERUM AND SPUTUM LEVELS OF HBK AND ITS THERAPEUTIC EFFICACY ON RESPIRATORY TRACT AND URINARY TRACT INFECTIONS BY DRIP INTRAVENOUS INFUSION
    SEIICHI AONUMA, REIKO ONO, NORIKO OTANI, KIKUO ONUMA, AKIRA WATANABE, ...
    1986 Volume 34 Issue Supplement1 Pages 147-150
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was drip-infused intravenously with a dose of 75mg to a patient of diffuse panbronchiolitis, and then the serum at the end of drip intravenous infusion and the sputum for two hours from the end of drip infusion were stored at -80°C. These serum and sputum levels of HBK were measured by bioassay method. The serum level was 6.76μg/ml and the sputum level, was 0.67μg/ml.
    Six patients suffering from respiratory tract infections and five patients with urinary tract infections were treated with HBK by drip intravenous infusion at a dose of 150mg or 200mg a day. Five patients showed an excellent and four good response, while one other patient responded only fairly and the other poorly. No undesirable symptoms and signs including deafness and no abnormalities in clinical laboratory findings were observed during and after administration of the drug.
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  • IZUMI HAYASHI
    1986 Volume 34 Issue Supplement1 Pages 151-155
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
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    Clinical evaluation of HBK was performed in five patients with RTI. They were consisted of three males and two females.
    HBK was given intravenously by drip infusion in daily dose of 200mg in two divided portions.
    The duration of administration were 14 days in three cases, 11 days and 17 days in one case each.
    A total of two strains comprising H. aphrophaus and H. inguenzae were identified from the sputum before administration of HBK. All of them were eradicated by HBK after administration.
    The clinical efficacy rate was 100%(5/5); Excellent in two cases and Good in three cases.
    There was no side effects and abnormal findings in laboratory test values after admitgatration of HBK in any of the patients.
    From the above results, it is concluded that HBK is effective, safety and useful new aminoglycoside.
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  • KENICHI OKAYAMA, MINORU SATOH, YUMIKO MURAYAMA, REIKO SAITOH, MASANORI ...
    1986 Volume 34 Issue Supplement1 Pages 156-171
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was examined on its in vitro bacteriological activity against clinically isolated strains. HBK was found to be more active against, strains, of S. aureus, S. epidermidis, E. coli, E. cloacae, K. pneumoniae and P. aeruginosa than AMK.
    HBK was given to 40 patients: 28 with urinary tract infections, 1 with cholecystitis and 11 with respiratory tract infections. The drug was administered intramusculary at total: dose of 300-4000mg. The Efficacy rate was counted 75% in urinary tract infections and 90.9% in respiratory tract issieetions.
    HBK was given to 8 patients: 3 with urinary tract infections, 5 with respiratory tract infections. The drug was administered intravenously by drip infusion at total dose of 100-2100mg. The gfficacy rate was counted 100% in urinary tract infections and 80% in respiratory tract infections.
    In 4 cases elevation of S-GOT and S-GPT was observed. In 1 case elevation of BUN was observed.
    HBK was considered to be a useful antibiotic for the treatment of infections.
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  • ATSUSHI SAITO, JINGORO SHIMADA, MASAHISA OHMORI, KOHYA SHIBA, TAKEHISA ...
    1986 Volume 34 Issue Supplement1 Pages 172-183
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycosidic antibiotic, was studied fundamentally and clinically with following results.
    1. Antibacterial activity
    As to the distribution of MICs of HBK for fresh clinical isolates of gram negative rods, E. coli and K. pneumoniae were inhibited of growth at concentrations of 0.2-≥100μg/ml, E. cloacae at 0.78-25μg/ml, C. freundii at 0.39-42. 5μg/ml, S. marcescens at 1.56-≥100μg/ml and P. aeruginosa at 0.2-12.5 μg/ml. Thus, HBK showed high activities even against DKB resistant strains.
    2. Absorption and excretion
    No significant difference was seen in blood level and urinary excretion between ampule preparation and vial preparation of HBK.
    Following one single intramuscular dose of 100mg of HBK (in vial) and DKB, blood level reached its peak at 30 min after the injection for both drugs with the peak level being 7.39μg/ml for the former and 5.98μg/m/for the latter. Susequently, the blood levels decreased gradually with halflives of 2.11 hr and 1.88 hr, respectively. The cumulative urinary recovery rate within the first 8 hr was 67.7% for HBK and 58.9 for DKB.
    3. Clinical results
    Clinically, HBK was used in the treatment of 10 cases. The clinical results for 9 assessable cases were excellent in 2 cases, goocl in 4 cases, fair in 1 case and poor in 2 cases.
    As the side effects, mild renal damage was seen in 1 case which received HBK as 1. v. drip infusion.
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  • SHIN KAWAI, MASAHIKO YOSHIDA, HIROSHI OSHITANI, HIROYUKI KOBAYASHI
    1986 Volume 34 Issue Supplement1 Pages 184-188
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic, was administered to 18 cases of respiratory tract infection (RTI) at a dose of 50mg or 75mg twice a day by intramuscular injection and 100mg twice a day by intravenous drip infusion.
    The 14 patients treated by intramuscular injection consisted of 8 cases of chronic bronchitis, 5cases of bronchopneumonia and one case of acute bronchitis.
    In the 8 chronic bronchitis cases, HBK proved effective in 5 cases and poor in the other 3 cases. In the 5 pneumonia cases, 2 cases were effective and the other 3 cases were poor. One acute bronchitis case was effective.
    Four patients were treated by intravenous drip infusion: 3 cases of pneumonia and one case of acute bronchitis. In the 3 pneumonia cases, one case was effective and the other 2 responded poor. The treatment of the acute bronchitis case was not effective.
    No side effects were observed, but a slight elevation of the serum transaminase and serum alkaline phosphatase was noticed in one case each.
    In this study, the effectiveness of HBK against RTI was not very good, but many of these cases had severe underlying diseases.
    It is suggested that HBK is one of a useful and safe drug for the treatment of RTI cases without severe underlying diseases.
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  • TEPPEI KUMADA, SATOSHI OOI, KYOICHI TOTSUKA, KIHACHIRO SHIMIZU
    1986 Volume 34 Issue Supplement1 Pages 189-192
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was administered to 8 patients With chronic urinary tract infections and one patient wit acute pyelonephritis. The drug was effective in 3 and poor in 6, and replacement of the causatil bacterium occured in 2.
    Two strains of E. coli, one of Serratia and 2 of P. aeruginosa were eliminated, but one strain wick of S. aureus, E. coli and 3 of P. aeruginosa were not. As the replacement bacteria, one strain eat of S. faecalis and P. aeruginosa appeared.
    There were no side effects or abnormal laboratory test values due to the administration of the drug.
    The dosage should be reviewed because there were many cases with a poor result in this study.
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  • KEISUKE TOYAMA, SHINICHIRO OKAMOTO, HIROSHI UCHIDA, YASUHIKO ANDO
    1986 Volume 34 Issue Supplement1 Pages 193-198
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside, was evaluated clinically for 19 infections of patients with hematological diseases. HBK was administrated mainly by one-hour drip intravenous infusion at a daily dose 100-400mg for 3 to 23 days. Daily dose and duration of HBK therapy were modified according to the patient's condition.
    After one-hour drip intravenous infusion of 100mg HBK, maximum blood concentrations were distributed from 4.42μg/ml to 10. 98μg/ml.
    Two cases with septicemia, 6 possible septicemia and 4 other inifections were treated with HBK alone, and 3 septcemia and 4 possible septicemia were treated with HBK combined with other chemotherapy. All 5 cases with septicemia responded to HBK alone or combination chemotherapy In 10 cases with possible septicemia, the clinical response to HBK alone and combination therapy were observed in 4 and 1, respectively. The cases with other infections all responded to HBK alone. The overall response rate was 72%, no significant side effect was observed after the administration of HBK.
    From the above results, HBK was expected to be useful in the treatment of infection, especially septicemia, of hematological patients.
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  • MASARU KOYAMA, TAKASHI YAMAMOTO, RYUJI AKIYOSHI, KATSUHITO ITO, YOSHIA ...
    1986 Volume 34 Issue Supplement1 Pages 199-204
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a newly developed aminoglycoside antibiotic, was used in 8 cases of urinary tract infections (UTIs), 3 cases of respiratory tract infections (RTIs) and 1 case of cholecystitis.
    HBK was administrated twice a day at daily dose of 100-150 mg by intramuscular injection or 150-200 mg by drip infusion. The HBK therapy was continued for 6-12 days and the total dose ranged from 550-1725 mg.
    The clinical effects were rated as follows: in 8 cases of UTIs, 2 cases, “excellent”, 4 cases, “good”, 1 case, “fair” and 1 case, “poor” in 3 cases of RTIs, 2 cases, “good” and 1 case, “poor”; in 1 case of cholecystitis, “good”. The overall efficacy rate was 75%. The bacteriological efficacy showed that: E. coli eradicated in all 3 cases, P. aeruginosa remained unchanged in 2 cases, P. mirabilis, P. vulgaris and A. anitratus eradicated in 1 case each, in the 1 case in which M. margastii and S. liquefaciens were observed. S. liquefacaciens remained unchanged, M. morganii eradicated and was replacad by Enterococcus.
    In regard to side effects, eosinophilia and the appearance of urticaria were observed in 1 case but they disappeared wben administration of HBK was discontinued. Otherwise, no adnormal laboratory findings were observed.
    From these results, HBK is considered to be a safe and useful aminoglycoside.
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  • TETSURO UKAI, SUMIO YAMAOKA, YOSHIJI YAMANE, KEIMEI MASHIMO
    1986 Volume 34 Issue Supplement1 Pages 205-208
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic, was studied for its clinical efficacy with 5 cases 4 with UTI and 1 with pneumonia, at a daily dose from 150 mg to 200 mg by intramuscular injection or dr intravenous ii jection.
    Clinical response was good in all cases. Causative organisms including E. coli, Klebsiella, P aersiginosa and E. faecalis were all eradicated or eupressed bacteriologically.
    No adverse reactions were seen in any cases and abnormal clinical laboratory data were shown in I case with slightly elevated GOT.
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  • FUYHIKO HIGASHI, MASAHIKO NAKAMURA, KAZUMI ARIKAWA, KEIICHI YAMAGAMI, ...
    1986 Volume 34 Issue Supplement1 Pages 209-213
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK is a new aminoglycoside derivative with broad spectrum (Gram positive bacteria, Gram negative bacteria).
    Intramuscular administration of HBK at a daily dose of 150mg or 200mg was performed in 8-patients (6 cases with pneumonia, 2 with acute pyelonephritis), and intravenous administration at a daily dose of 200 mg was performed in 10 patients with pneumonia.
    HBK was effective in 76.9% in cases with pneumonia and in all cases with acute pyelonephritis.
    No side effects were noted.
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  • MASAYOSHI NEGISHI, CHENDEN YUNG, GOHTA MASUDA
    1986 Volume 34 Issue Supplement1 Pages 214-217
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic derived from dibekacin, was administrated to three cases with urinary tract infection and two cases with respiratory tract infection. Efficacy and safety of HBK were studied. HBK saved clinical symptoms rapidly in two cases with urinary tract infection caused by E. coli. These organisms were disappeared from urine within five days. In a case of pyelonephritis with renal stone, rapid improvement of clinical symptoms was observed by dosage of HBK, but no organism was detected.
    On the other hand, in a case with bronchitis caused by Streptococcus penurnoniae, the improvement of clinical symptoms was not satisfactory though the etiological organism was temporally eradicated with HBK atone. A combination therapy with other antibiotics is recommended.
    No side effects or abnormal laboratory finding related to HBK were observed except for I case with a transient elevation of GPT.
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  • YOSHIO KOBAYASHI, KEIICHI HARADA, IPPEI FUJIMORI
    1986 Volume 34 Issue Supplement1 Pages 218-222
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a newly developed aminoglycoside antibiotic, was given to 11 patients with suspected bacterial infection.
    Out of these 11 patients, however, 4 patients were excluded because of lack of sufficient symptoms or laboratory findings of bacterial infection.
    Out of 7 patients, 1 with pneumonia, 1 with acute bronchitis and 1 with acute pyelonephritis due to Escherichia coil were successfully treated with administration of twice a day of 50 to 75mg of HBK intramusculary, respectively.
    The clinical effects of administration of twice a day of 50 to 75mg HBK on two patients with acute exacerbation of chronic bronchitis and acute pyelonephritis due to Klebsiella pneumoniae were poor.
    Two patients with unexplained fever complicated with leukemia were successfully treated with twice a day of 75 or 100mg of HBK, one hour by drip infusion.
    The injectional pain was observed in one, patient with acute pyelonephritis. Transients elevations of serum enzymes were observed in 3 patients.
    The serum concentration of HBK of 5 of 8 patients given HBK intramusculary were evaluated. Out of these patients were given 50 to 75mg intramusculary.
    The peak of serum concentration of HBK of these 4 patients from 3.28 to 4.55μg/ml was observed 30 or 60 minutes after the administration.
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  • TADASHI TAKIGAMI
    1986 Volume 34 Issue Supplement1 Pages 223-228
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK is a novel amino acid-containing arninoglycoside antibiitic, with a broad antibacterial spectrum, including Pseudomonas aeruginosa, some kanamycin-, gentamicin-, and tobramycin-resistant organisms.
    Clinical investigations on HBK by intramuscular injection was already discussed and its clinical effectiveness was estimated 68%. Its side effects were very rare.
    I tried HBK therapy by intravenous drip infusion in 9 episodes of 5 patients who were suffering from UTI or RTI and the results obtained were as follows.
    1. HBK was used in 2 cases from UTI. Its clinical effects were good and excellent.
    2. HBK failed in 2 cases from severe pneumonia in the combination with MZPC and CMX, respectively.
    3. HBK was used in the exacerbation of infection from bronchiectasis in the combination with CMX. It showed excellent effect in 4 of 5 episodes.
    4. No serious side effects and abnormalities in laboratory findings were seen.
    5. Drip infusion use of HBK is hopeful in the treatment of severe infections, hapecially in the combination with simultaneous CMX.
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  • KOUICHI WADA, TAKAO MORIMOTO, HAJIMU TAKEDA, MASAAKI ARAKAWA
    1986 Volume 34 Issue Supplement1 Pages 229-233
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic, was either intramuscularly or intravenously administrated to 8 patients with respiratory tract infection and one with fever of unknown origin. The patients received the drug for 5 to 21 days in a dose of 50-400mg/day.
    Clinical effects were excellent in one case, good in 2, fair in one, poor in 2 and undetermined in 3, showing 50% of efficacy rate.
    Neither side effects nor abnormal laboratory findings possible related to the drug were observed in any of these cases.
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  • FUSANOSUKE YAMASAKU, YASUTOSHI SUZUKI
    1986 Volume 34 Issue Supplement1 Pages 234-237
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was administered to a patient with staphylococcal septicaemia and eight patients with urinary tract infection. 75mg twice a day for 47 days of HBK were effective to septicaemia, MIC of HBK against causative S. aureus was 0.39μg/ml, occurred from subcutaneous abscess in a patient with pancreatic cancer. Four strains of E. coli, two of P. aeruginosa and each one of E. cloacae and P. rettgeri were isolated from eight episodes of urinary tract infections complicated in eight patients with neurogenic disorders based on cerebrovascular disease. MIC of HBK against these causative organisms were from 0.39 to 3.13μg/ml. All eight causative organisms were eradicated except one case changed to P. tnirabilis by the administration of 50mg twice a day for 5 to 15 days of HBK, but clinical effects on fever were not gained in two cases. No abnormality of laboratory findings was observed.
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  • TAKESHI NAKAMURA, SHIGEKI OHTAKE, KUNIO KONDO, SHINOBU NAKAMURA, SABUR ...
    1986 Volume 34 Issue Supplement1 Pages 238-246
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Clinical and pharmacological studies on HBK, a newly developed aminoglycoside antibiotic, were carried out on 20 patients.
    HBK was administered intramuscularly to 5 patients and intravenously to 15 patients.
    Out of 11 cases of urinary tract infection, efficacies were observed in 10.
    Especially in 7 cases, clinical and bacteriological effects of HBK were excellent. In 9 cases with respiratory tract infection treated with HBK, five proved to be effective.
    Pharmacokinetic analysis showed that half-life of HBK was 3.22±2.77 hrs.(mean±S. D.) and Vd was 12.80±4.30l/man.
    MIC6 of HBK, dibekacin (DKB), gentamicin (GM) and amikacin (AMK) against clinically isolated organisms were determined. MIC6 of HBK were almostly the same as those of AMK, and agaist E. faecalis, MIC6 of HBK were superior to those of AMK.
    Side effects were observed in 3 cases, 1 case on elevation of transaminase, 1 case on elevation of BUN and creatinine, and the other in thrombocytopenia and elevation of LDH.
    In all 3 cases, abnormalities disappeared when HBK administration was stopped. Abnormality of the 8 th cerebral nerve was not observed.
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  • YURUKO OKAMOTO, KEIGO MAEHARA, KANSHI MASE, YUBE IIDA, MUNETO YOSHIOKA ...
    1986 Volume 34 Issue Supplement1 Pages 247-260
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a newly developed derivative of dibekacin, was examined on its antibacterial activity in vitro, as well as on its clinical usefulness. The results obtained were as follows:
    1) Antibacterial activity in vitro: MIC of HBK against bacterial strains isolated from clinical infection foci were estimated and compared with those of amikacin (AMK) and gentamicin (GM).
    Among the three antibiotics examined, HBK was most active against P. morganii strains, while HBK was found to be least active against Serratia strains. Some of the GM-resistant strains of S. aureus, E. coli, and K. pneumoniae showed considerable sensitivity to HBK, but, in general, strains of these species and those of P. mirabilis and P. rettgeri showed sensitivity to the three aminoglycosides in the following order: GM>HBK>AMK.
    The three antibiotics showed similar sensitivity distribution as to the strains of P. aeruginosa, E. cloacae or those of C. freundii.
    2) Clinical trials: Twelve patients, in total, with infections, all having some underlying diseases, were treated with HBK.
    Nine (RTI 3, UTI 5, phlegmon 1) of them were treated with HBK 50-100 mg ×1-2/day intramuscularly: Six of them well responded to the therapy, while the remaining three failed, i. e. each one having pneumonia complicating amyotrophic lateral sclerosis, RTI complicating lung cancer, and UTI with indwelling catheter, respectively.
    Further, three cases (RTI 2, BTI 1) were administered with HBK 100 mg×2/day by intravenous drip infusion: One of them, a patient with acute exacerbation of chronic bronchitis complicating cerebral infarction, well responded to the treatment.
    None of the cases showed clinical side effects. As to the abnormal laboratory findings attributable to the drug, one patient with renal impairment showed elevation of BUN and S-Cr. after the i. m. HBK therapy in spite of sparing dosages. In another patient treated intravenously, eosinophilia up to 13. 5% was observed.
    These results obtained should suggest the clinical availability of HBK.
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  • FUMIO MIKI, YOSHIYASU IKUNO, EIJI INOUE, MASAKAZU TERAGAKI, KANAME AKI ...
    1986 Volume 34 Issue Supplement1 Pages 261-266
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside, was investigated and the following results were obtained.
    The peak of susceptibility distribution of clinically isolated S. aureus, E. coil, K. pnsutnoniae, P. mirabilis, P.vulgaris, P. aeruginosa against HBK was 0.39 to 0.78μg/ml, 1. 56 to 6.25μg/ml, 0.39 to 1.56μg/ml, 3.13μg/ml, 0.78 to 1. 56μg/ml and 0.78 to 1.56μg/ml, respectively.
    Antibacterial activity of HBK against P. mirabilis was inferior to that of GM. The antibacterial activity of HBK against E. coil and K. pneumoniae was slightly inferior to that of GM, but no significant difference was recognized in antibacterial activity between HBK and GM against S. aureus, P. vulgaris and P. aeruginosa.
    HBK at a dose of 50 or 75 mg, twice a day was intramuscularly given to 1 case of pneumonia, 1 case of infected pulmonaly congestion+chronic cystitis, 3 cases of chronic cystitis and 1 case of pyelonephritis. The therapeutic results obtained were good in 2 cases, fair in 1 case, and poor in 3 cases.
    HBK at a dose of 100 mg twice a day was intravenously drip-infused to 1 case of infected bronchiectasis and 1 case of acute cystitis. The excellent clinical responses were obtained in both cases.
    No side effect was observed in both intramuscularly and intravenously administered cases.
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  • YOSHIHITO NIKI, MASARU SUMI, YOSHIHISA NAKAGAWA, JIRO HINO, MASATOSHI ...
    1986 Volume 34 Issue Supplement1 Pages 267-271
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Experimental and clinical studies were conducted on a newly developed aminoglycoside antibiotic HBK and the following results were obtained.
    1) The antibacterial activity of HBK against: clinical isolates was compared to that of gentamicin (GM), tobramycin (TOB), and amikacin (AMK). As, a result, the antibacterial activity of HBK against S. aurcus, E coli and K. pneumoniae was superior to AMK but slightly inferior to TOB and GM. The antibacterial activity of HBK against Proteus spp., was similar to AMK. Against P. aeruginosa and P. cepacia, HBK showed a similar MIC to GM, and the peak MIC value of HBK was 12.5 μg/ml against P. aeruginosa.
    2) The maximum blood concentration after a drip infusion., of 75 mg over 1 hour was 2.51 to 3.80 μg/ml, and the urinary excretion rate until 6 th hour was 78.7%.
    3) The clinical effect of HBK was examined in 9 cases of respiratory infections. HBK was given at a dose of 75 to 100 mg twice a day by intramuscular injection or intravenous drip infusion for 5 to 12 days. Of 8 evaluable cases, there were 4 effective cases, 1 slightly effective case and 3 noneffective cases. The efficacy rate was 50%. Neither side-effects nor abnormal, laboratory test results were obaecved except for a slight rise in BUN and eosinophilia which were observed in each 1 case.
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  • OSAMU KURIMURA, HIDEO SASAKI, EIJI KANETO, FUMIHIRO FUKUHARA, TOMOYA M ...
    1986 Volume 34 Issue Supplement1 Pages 272-280
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The antimicrobial activities of HBK were compared with those of GM, AMK and TOB against clinically isolated 526 strains of 28 species described below.
    Gram positive cocci: S. aureus, S. epidermidis, α-Streptococcus, β-Streptococcus and S. faecalis
    Gram negative bacilli: E. coli, Shigella, spp., S. typhi, Salmonella spp., K. pneumoniae, K. osytoca, C. freundii, S. marcescens, Enterobatter app., P.vulgaris, P. mirabilis, P. rettgeri, P. morganii, P. inconstans, P. aeruginosa, P. maltophilia, P. cepacia, V. parahaemolyticus, V alginolyticus, Aeromonas app., A. calcoaceticus, Flavobacterium app. and H. influenzae.
    In general, antimicrobial activities of HBK were almost the same as those of AMK, and somewhat inferior to GM and TOB. But GM and TOB showed high MIC values against some strains of S. aureus, S. epidermidis, P.vulgaris and P. aeruginosa, which were sensitive to HBK.
    HBK was administered to 10 cases with respiratory trtt infection and 2 cases with urinary tract infection. The clinical responses were good n 4 cases of respiratory tract infection and 2 cases of urinary tract infection and poor in 3 cases of respiratory tract infection. Remaining 3 cases of respiratory tract infection the clinical efficacies could not evaluated. As to the side effect, tinnitus and slight elevation of transaminase value was observed in each one case.
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  • MASAKAZU TAMURA, SOICHIRO UEDA, TOSHIHIRO GOTO, EIRO TSUBURA
    1986 Volume 34 Issue Supplement1 Pages 281-283
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The clinical effects of HBK, a new aminoglycoside antibiotics, was studied in 4 patients, 2 with chronic, bronchitis, one with bronchiectasis and one with obstructive pneumonia, All these patients had various underlying diseases.
    This antibiotics was administered intramuscularly 150 mg a day for 5-8 days in 3 patients and in one patient, was given intravenously by drip 200 mg a day in combination with PIPC for 14 days.
    Clinical response was good in two and poor in two patients.
    In bacteriological examinations, one strain in 5 strains isolated from 3 patients was eradicated after this treatment, but other 4 strains were persisted.
    No side effects and no abnormal laboratory findings was observed.
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  • YOSHIRO SAWAE, KAORU OKADA, YUKIO KUMAGAI, YOSHIYUKI NIHO, IWAO YAMADA
    1986 Volume 34 Issue Supplement1 Pages 284-299
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Laboratory and clinical studies were performed on HBK, a new semisynthetic aminoglycoside, and results were as follows.
    1) Antimicrobial activity
    MICs of HBK gainsi various clinical isolates were determined with the inoculum size of 106 cells/ml. MIC80 values were 0.78 μg/ml for S. aureus, E. coli, K. pneumoniae, 1.56 for Eaterobgcter sp., 3.13 for P. aeruginosa, 6.25 for Proteus sp., 12.5 for S. marcescens, and>100 for E. faecalis. HBK was more active against resistant strains of DKB, AMK and GM, but it was less active against Proteus sp. than DKB and GM.
    2. Serum concentration and urinary excretion
    Serum concentrations of HBK were measured in four healthy adults, given intramuscularly or intravenously 100 mg of HBK. The peaks of mean serum concentrations were 5. 94 >g/ml at the intramuscular injection and 7.85 >g/ml at the 30 min.-intravenous drip infusion and their trough values after 6 hours were 0.97 and 0.63 >g/ml respectively. T 1/2 or T 1/2 (β) were 2.0 and 2.1 hours and AUCs were 19.7 and 17.3 >g hr/ml, respectively. Six hour-urinary excretion rates were 60. 9% at the intramuscular injection and 55.5% at the 30 min.-drip infusion.
    There were good correlations between HBK concentrations measured by EIA method or SLFIA method and ones by bioassay, method. EIA method was better than SLFA method for clinical use.
    3) Clinical efficacy
    Six patients with RTI, 4 with UTI and 3 with bacteremia and others were treated with HBK daily dose of 75-300 mg for 4-22 days. Clinical responses were excellent in 2 patients, good in 3, fair in 2, poor in 5, and unknown in a patient. Dizziness was observed in a patient and there was no chenge of laboratory data.
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  • KINJI YOKOTA, TAKEO YOKOTA, HITOSHI NAGANO
    1986 Volume 34 Issue Supplement1 Pages 300-305
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    We conducted a clinical study on HBK, a newly developed aminoglycoside antibiotic.
    1) Subjects adapted in this study were 14 in-patients with acute pneumonia, bronchitis, pulmonary empyema, etc. All the patients had suffered from chronic respiratory diseases as underlying diseases. HBK 150-200 mg in twice a day was given by either intramuscular injections or intravenous dripinfusion over 1 hour for 4 to 18 days (mean 7.7 days). Pathogenic bacteria suspected from sputum were K. pneumoniae in 2 cases, H. influenzue in 2 cases, P. aeruginosa in 3 cases, E. coli in 1 case, S. aureus in 1 case and unknown in 6 cases.
    2) Clinical results revealed “excellent” in 0 case, “good” in 9 cases, “fair” in 3 cases and “poor” in -2 cases. Thus, an efficacy rate was 64%.
    3) Side-effects were noted in 1 case of mild eruption, 2 cases of eosinophilia, 2 cases of renal disturbance and 1 case of hearing impairment including suspected cases. All the symptoms were mild and did not necessitate withdrawal of the therapy.
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  • MASAHIRO TAKAMOTO, YASUKO HARADA, YOSHINARI KITAHARA, TSUNEO ISHIBASHI ...
    1986 Volume 34 Issue Supplement1 Pages 306-316
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was applied to the treatment of 19 cases with respiratory tradt infections and 1 case with urinary tract infection. The drug was administrated by, intramuscular injection or intravenous drip infusion (0.5-1 hr) at a daily dose of 100-200 mg twice a day.
    The results obtained were as follows.
    1) Clinical results
    HBK was intramuscularly injected to 12 cases. Subjects were 6 cases of bronchitis, 3 cases of pneumonia, 2 cases of infected bulls and 1 case of lung abscess. Clinical response to therapy was good in 5 cases, fair in 2 cases and poor in 4 cases (excluding 1 case for combination with CMX). Effective rate was 45.5%.
    HBK was administrated to 8 cases including 7 cases of bronchitis and 1 case of acute pyejonephritis by intravenous drip infusion. Clinical response to therapy was excellent in 1 case, good in 4 cases, fair in 2 cases and poor in 1 case. Effective rate was 62.5%.
    2) Serum levels
    In intramuscular injection, the peak serum levels of HBK observed in one hour after administration were 3. 21-5. 43μg/ml at a dose of 50 mg, 8.16-5.17μg/ml at a dose of 75mg and 4.57μg/nd at a dose of 100 mg respectively. In intravenous drip infusion, those of HBK observed just after administration were 5.34μg/ml at a dose of 50 mg, 5.12-8.68μg/ml at a dose of 75 mg and 5. 59-11.39μg/ml at a dose of 100 mg respectively.
    There was no tendency of accumulation of the drug in both methods.
    3) Side effect
    In 1 case with intravenous drip infusion (200 mg/day), transient hearing loss was observed after the end of administration. However, this hearing loss was different from ototoxic pattern peculiar to aminoglycoside antibiotics and it seemed unlikely to be causally related to HBK. Laboratory examinations showed no abnormality.
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  • YOSHITERU SHIGENO
    1986 Volume 34 Issue Supplement1 Pages 317-331
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Fundamental and clinical studies on HBK, a novel aminoglycoside antibiotic, were carried out with following results.
    1) Antibacterial activity: The in vitro antibacterial activity of HBK was tested by the serial microbroth dilution method using MIC 2000 system (Dynatek Co.). The minimum inhibitory concentrations (MICs) of HBK against total 336 strains consisting of 26 standard strains and 310 clinical isolates were compared with those of gentamicin (GM), tobramycin (TOB), dibekacin, (DKB) and amikacin (AMK). The activity of HBK was higher than that of AMK, although it was 50 to 100% of SISO and GM. However, HBK showed the highest activity among these antibiotics against the resistant strains.
    2) Absorption and Excretion: The pharmacokinetic study was made in four patients by the bioassay method. Serum levels of HBK were -measured in two patients given by intramuscular injection. of 50 mg and one patient intravenous drip infusion of 100 mg.
    The peak concentration in serum was 5.2μg/ml and 8.8μg/ml at 30 min. and one hour after administration by intramuscular injection, respectively, and 4.24μg/ml at one hour after the beginning of intravenous drip infusion. In the case of sputum, the peak concentration was 0.32μg/ml at 3 t4 hours and 1.76 μg/ml at 2 to S. hours after intramuscular injection, and 1.32 μg/ml at 3 to 4 hours after the beginning of intravenous drip infusion.
    The urinary recovery rate of HBK until 6 hours after intramuscular administration of 50 mg was 51.2%.
    3) Transition of bacteria in sputum: S. aurests in the sputum of a patient with chronic bronchitis began to decrease from the initial 107 cfu/ml to 105 cfu/ml for the first 6 hours after intramuscular injection, and was completely eliminated on the third day of treatment. However, H. influenzae in two patients and P. aeruginosa in one patient were not eliminated from the sputa in spite of 7 days treatment, and S. pneumonia. was isolated from the sputum on the third day of treatment in one case.
    4) Clinical evaluation and adverse reaction: Twenty four and 10 out of 34 patients with respiratory infections (pneumonia in 15, lung abscess in 1, chronic bronchitis in 8, bronchiectasis in 5, diffuse panbronchiolitis (D. P. B.) in 2, bronchial asthma with infection in 2 and pulmonary tuberculosis in 1) were treated by intramuscular injection and intravenous drip infusion, respectively. The efficacy rate was 60.6% in total (That of the former was 65.2% and the latter was 50.0%).
    Four out of total patients showed the following adverse reactions: eruption, slight elevation of BUN, slight elevation of S-GOT and S-GPT, and slight decreasernent of creatinine-clearance in each patient.
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  • TOSHIAKI YOSHIDA, MASASHI YAMAMOTO, KAZUNORI OHISHI, MIKIO TAGUCHI, MA ...
    1986 Volume 34 Issue Supplement1 Pages 332-343
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Laboratory and clinical studies on a new aminoglycoside antibiotic HBK were performed, comparing the results with other aminoglycoside antibiotics. HBK was tested in vitro with respiratory pathogenic organisms, using the agar dilution method to determine the minimum inhibitory concentrations. HBK was more active in vitro against Staphylococcus aureus, Ecchsrichsa coli, Klebsiella pneumoniae and Encerobacter species than the other broad-spectrum aminoglycoside antibiotics tested, i. e, dibekacin, gentamicin, amikacin and tobramycin; it was less active against Pseudomonas aeruginosa than dibekacin' and tobramycin. Synergy of HBK with cefsulodin could be demonstrated against respiratory isolated of Pseudomonas aerusinosa.
    HBK at a dose of 75 mg was injected intramuscularly into one patient with chronic bronchitis. The peak serum concentration of this patient was 8. 09μg/ml, the serum half-life being 109 min. HBK at a dose of 100 me was infused intravenously over 60 min into, one patient with bronchiectasis. The peak serum concentration of this patient was 11.84μg/ml, the serum half-life being 108 min. The intrabronchial secretion level of HBK was 1.38 perril, and the maximum sputum level was 1.15μg/ml. The ratio of maximum sputum level to peak serum concentration was 10.1%. After intratracheal injection of HBK 100 mg/saline 2ml, HBK 50 mg/saline 2ml and HBK 25 mg/saline 2 ml into rabbits, serum concentrations reached peak values within 30 min and were demonstrated the concentration dependence.
    Twelve patients with respiratory infections were treated with HBK intramuscularly. Clinical responses were excellent in one, good in nine, fair in one and poor in one. A good clinical response was observed in all of two respiratory infections treated with HBK inhalation. Nine patients with respiratory infections were treated with HBK intravenously. Clinical responses were good in six and fair in three. HBK was effective in 83%, 100% and 67% of those cases with intramuscular, inhalant and intravenous administration respectively. The feeling of fullness in the ear was observed in one patient
    The data indicate that HBK is one of the most effective and useful broad-spectrum aminoglycoside antibiotics for the treatment of respiratory bacterial infections.
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  • NORIAKI TANAKA, YOSHIO TAKAGI, SATORU OKAYAMA, KAZUNORI OHNO, SHIGERU ...
    1986 Volume 34 Issue Supplement1 Pages 344-357
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The new antibacterial agent, HBK was studied experimentally and clinically.
    The results were as follows:
    1) Antibacterial activity
    E. coli, P. mirabilis, K. pneumoniae, Indole (+) Proteus spp., Enterobacter spp., Citrobacter spp. P. aeruginosa and S. epidermidis were sensitive but, S. marcescens, E. faecalis and NF-GNR (except P. aeruginosa) were resistant to HBK.
    HBK displays marked antibacterial activity against DKB-resistant bacteria, which were K. pneumoniae, P. mirabilis, Indole (+) Proteus spp., Enterobacter app., Citrobacter spp., S. marcescens, P. aeruginosa.
    2) Clinical Effects
    Twenty patients with chronic complicated urinary tract infection, were trated with HBK. Clinical response was excellent in 2, good in 9, poor in 9, and therefore the overall effectiveness rite was 55%(5 days treatment, 100-200 mg/day)
    3) Side effects
    No subjective and objective adverse effect was seen in any cases and clinical laboratory rest showed transient elevation, of U-NAG/U-Creatinine in 2 cases and U-β2-Microglobulin/U-Creatinine in one case.
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  • SEIGI TSUCHIDA, TAKASHI MORITA, TADASHI NISHIMOTO, HITOSHI TAKADA, SHI ...
    1986 Volume 34 Issue Supplement1 Pages 358-367
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Clinical evaluation of HBK a new aminoglycoside antibiptip, was performed on urinary tract infection. HBK was administered to 36 patients with complicated urinary tract infection and one with acute simple pyelonephritis at a daily dose of 100 mg, 150 mg or 200 mg twice a day by intramuscular injection for 5-6 days. Thirty one of 37 cases were evaluated by the criteria of UTI committee, and the clinical response to HBK treatment was moderate in 15 cases and poor in 16 cases with 48% effectiveness rate. Abnormal laboratory findings were demonstrated in 5 cases. Elevation of GOT, GPT and Al-Pate in 1 case, elevation of GOT and GPT in 2 cases and slightly elevation of Al-Pase in 1 case and eosinophilia in 1 case were noted.
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  • HIROMICHI ISHIKAWA, KENKICHI KOISO, KOJI KIKUCHI, ATSUSHI TSURUTA, SHI ...
    1986 Volume 34 Issue Supplement1 Pages 368-375
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside antibiotic, was studied clinically. One hundred mg of HBK were given to 18 patients with urological infection twice a day by drip infusion.
    Seven of 18 patients were evaluated according to the UTI Committee criteria for clinical evaluation in complicated U. T. I.
    Four of 7 patients showed excellent or good response.
    No side effects were seen in all 18 patients.
    As for laboratory findings, there were 3 cases with slight liver dysfunction after the treatment of HBK.
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  • TAKASHI TOMINAGA
    1986 Volume 34 Issue Supplement1 Pages 376-390
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside, was used in the treatment of urological infections, and its theia. peuitic efficacy and safety were evaluated.
    Forty-eight patieits with complicated urinary tract infections (UTI) were treated with The overall clinical efficacy-by doctor's evaluation was excellint in 10, good in 26, fair in 2 and poor in 10, an eficacy rate of 75%.
    The clinical efficacy in three patients with acute simple pyelonephritis and three patients with genital infections (prostatitis in 2 and epididymitis in 1) was 66.7% and 100%, respectively.
    The clinical effect on 45 complicated UTIs, was investigated in accordance with the 2nd Edition of Critria for Clinical Evaluation of Antimicrobial Agent on Urinasy Tract Infections and was found to be excellent in 10 cases, moderate in 10 and poor in 25.
    During the treatment, no side effects were noted and no abnormal laboratory findings were observed.
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  • KEISHI OKADA, NOBORU NAKAJIMA, TOSHIFUMI KAWASHIMA, HIDESHI MIYAKITA, ...
    1986 Volume 34 Issue Supplement1 Pages 391-402
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK was developed as a useful antibiotic for bacteria resistant to other aminoglycoside antibiotics.
    Fundamental study: From results of absorption and excretion (100 mg intramuscular administration) in healthy volunteers, the average-of penk serum level of HBK was 9.00μg/ml (15 min. after injection), AMK was 6.71μg/ml (30 min. after injection) and T1/2s were 2.09 and 1.44 hr. respectively. Fifty per-cent and over of HBK and AMK were excreted in urine within the first 4 hours, and the urinary recovery rates within the first 24 hours were 74.6, 84.3% respectively.
    Clinical study: 18 patients with complicated urinary tract, infections and 3 patients with other infections were treated with intramuscular administration or 1 hour drip-infusion of HBK at the dose of 100-200 mg for 5-7 days. The clinical results of 12 cases were assessed by; UTI Drug Efficacy Evaluation Criteria. The results were rated as excellent in 1 case, good in 3 cases and poor in 8 cases with an efficacy rate of 33%. Bacteriologically, 11 out of 19 (58;sv) strains were eradicated. Six out of 12 mixed infections were rated as good in only 1 case and poor in other 5 cases, so the efficacy rate became lower. As to the case with acute prostatitis, acute uncomplicated pyelonephritis and acute epididymitis, the Doctor's evaluation was “excellent” in all 3 cases.
    No side effect was observed in these 21 cases and abnormal laboratory findings such as a slight elevations of S-GOT and S-GPT, S-GOT, S-GPT and Al-P in one case each were observed after treatment.
    From these results it is suggested that is a safe AGs and useful for moderate infections of the field of urology.
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  • ABSORPTION, EXECRETION AND ITS CLINICAL EVALUATION ON COMPLICATED URINARY TRACT INFECTION ADMINISTERED BY L M. INJECTION
    KEIZO SUZUKI, HIDEKI TAMAI, ICHIRO NAGAKUBO, MASANORI YANAOKA, HARUYOS ...
    1986 Volume 34 Issue Supplement1 Pages 403-417
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    We studied a new member of aminoglycoside antibiotics, HBK and obtained the following results.
    1. When it was administered by i. m. injection to healthy male adult volunteers at a dose of 75mg, the peak serum concentration after 1/2 hour ranged from 5.06±1.48-5.25±0.73 μg/ml (n=4). The serum concentration gradually decreased over the next 6 hours, disappearing mostly from serum. The urinary recovery rate up to 6 hours ranged from 45.2±15.6-8.5%. In a cross-over study with DKB as a control drug, no significant difference was observed.
    2. Clinically, HBK was administered to treat on 31 cases of chronic complicated UTI. The daily dose was from 100-150 mg with single or 2 divided doses, and the duration of administrition averaged for 5 days, In 27 cases evaluable by the criteria of UTI committee, it was judged to be effective in 13 cases, the overall efficacy rate being 48%, The bacteriological response was potent on both GPC and GNB except on strains of E. faecalis and NF-GNR.
    3. In regard to its safety, except for two cases in which slight elevations of GOT, GPT and BUN were observed, there were no significant abnormal values. No subjective side reactions occured, additionally there was no problem with tolerance to intramuscular injection.
    4. HBK proved to be superior to DKB in in vitro susceptibility on the clinical iscilates. However, its efficacy rate was lower rthan expected. This reason is thought to be the following reasons, i. e, in this clinical ria1s the patients treated involved many infections including compromised hosts with insensitive causative bacteria to HBK. The further studies should be necessary especially for such stubborn UTI.
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  • IN THE TREATMENT OF INFECTION IN UROLOGICAL FIELD
    ISAO HIRANO, KEIZO SUZUKI, HIDEKI TAMAI, YORIO NAIDE, TAMIO FUJITA, TA ...
    1986 Volume 34 Issue Supplement1 Pages 418-427
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    A new member of aminoglycosides, HBK was administered in the treatment of infections in urological field and its therapeutic efficacy and safety were evaluated.
    A total of 22 cases were treated with HBK at a daily dose of 100mg, 150mg or 200mg.
    The drug was given by i. v. drip infusion. Of 22 cases, there were 1 cases of chronic complicated urinary tract infections. Out of these cases, 16 were assesed by the criteria of UTI Committee with an global efficacy rate of 69%.
    In general, the efficacy of HBK cases with indwelt catheters was rather unsatisfactory, while favourable results were obtained cases without catheters. Good response was obtained in one case of acute simple pyelonephritis.
    In laboratory investigations, no abnormal value was observed except two cases of slight elevations of transaminase.
    From these results obtaigied, HBK was of no significant problem in safety when compared with otheraminoglycoside antibiotics.
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  • MASANOBU HORIE, SHIGERU FUJIHIRO, HIDEZI HAYASHI, AKIHISA TAKEDA, YOSH ...
    1986 Volume 34 Issue Supplement1 Pages 428-443
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Antimicrobial activities against urinary bacteria, serum levels, urinary recovery and clinical efficacies on complicated urinary tract infections of HBK, a new aminoglycoside antibiotic, were studied.
    The results were summarized as follows;
    1) MICs of HBK for 18-reference strains, 100 ampicillin resistant E. coli, 28 S. marcescens and 50 P. aeruginosa which were isolated from urinary tract infections were found to be generally equal to those of gentamicin, but superior to those of amikacin.
    2) An average of peak serum level of HBK was 5.77μg/ml at 0.5-1 hours after intramuscular administration (100 mg) in healthy two volunteers.
    Urinary recovery rate for 6 hours averaged about 60%.
    3) Twelve patients with complicated urinary tract infections were treated with intramuscular administration of HBK at the dose of 100 mg twice a day for 5 days.
    As to overall clinical efficacies of those patients, moderate response was seen only in 1 patient and poor response in 11 patients. The overall effectiveness rate became 8%.
    The unexpected results seemed to be due to unsuitable patients with complicated type of infection.
    4) Ten patients with complicated urinary tract infections were treated with drip-infusion of HBK (100 mg × 2/day). Overall clinical efficacies of studies were excellent in 4, moderate in 1 and poor in 5 patients, the overall effectiveness rate being 50%.
    5) Side effects were evaluated in all 23 patients. Mild diarrhea was seen in 1 patient, and moderate and transient elevation of GOT, GPT and Al-pase were obsered respectivery 2, 1 and 1 patient.
    HBK was considered to be useful and safe new aminoglycoside in the treatment of complicated urinary tract infections.
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  • SHUTARO MIZUTANI, SHOZO HOSOKAWA, NAOMITSU NISHIMOTO, SUSUMU MIYOSHI, ...
    1986 Volume 34 Issue Supplement1 Pages 444-452
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    A total of 15 cases of complicated urinary tract infections were treated with HBK at 0.1g/day. HBK was injected intramuscularly once a day for a period of 5 days. Simultaneously 500 ml of L V. fluid was administered as a concomitant therapy. Clinical results were rated as excellent in 3 cases, good in 5 cases and poor in 7 cases with an overall efficacy rate of 53%. Pyuria was normalized in 5 cases, improved in 2 cases and unchanged in 8 cases. As to the results for bacteriuria, organisms disappeared in 6 cases, were replaced by other organisms in 5 cases and persisted in 4 cases.
    Regarding adverse reactions, in none of the cases subjective symptoms including vertigo and hypacusia were seen, while as laboratory abnormalities eosinophilia was seen in 1 case and a slight elevation in transaminase in another 1 case.
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  • MASUYOSHI HARADA, AKIRA FUJII, SOICHI ARAKAWA, NOBUMASA KATAOKA, AKIO ...
    1986 Volume 34 Issue Supplement1 Pages 453-458
    Published: March 31, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    HBK, a new aminoglycoside, was determined of its utility for complicated urinary tract infections with _foliowing results.
    (1) A total of 18 cases of complicated urinary tract infections rvere treated with HBK and results obtained were assessed according to the Criteria for Assessment of Drug Efficacy for UTI with an efficacy rate of 72%.
    (2) In none of the cases adverse reactions were observed either subjectively or objectively. Laboratory findings revealed slight abnormalities in 2 cases (slight elevation in GOT, GPT and eosinophils), but all of these abnormalities were transient in nature.
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