CHEMOTHERAPY
Online ISSN : 1884-5894
Print ISSN : 0009-3165
ISSN-L : 0009-3165
Volume 32, Issue Supplement9
Displaying 1-50 of 103 articles from this issue
  • TEIZO MURATA, YUKIO SASAKI, MATSUHISA INOUE, SUSUMU MITSUHASHI
    1984 Volume 32 Issue Supplement9 Pages 1-13
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria, especially Pseudomonas aeruginosa. It was active than cefazolin against gram-negative bacteria, such as Proteus species, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii, Haemophilus influenzae and Neisseria gonorrhoeae, however, not so active as cefoperazone. Against P. aeruginosa, it was slightly less active than cefsulodin and cefoperazone, but more active than latamoxef. As with other beta-lactam antibiotics, there was only a small difference between the minimal inhibitory concentrations and the minimal bactericidal concentrations of AC-1370. It was relatively stable to the hydrolysis of beta-lactamases, especially against cephalosporinases. AC-1370 showed the unique antibacterial property that its activity was more potent in vivo than expected from in vitro and this was particularly true in P. aeruginosa infection tests; the therapeutic activity of AC-1370 was approximately two to six times more potent than that of cefoperazone, whereas its in vitro activity was lower than that of cefoperazone.
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  • TAKESHI YOKOTA, REIKO SEKIGUCHI, EIKO SUZUKI
    1984 Volume 32 Issue Supplement9 Pages 14-20
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Investigations were carried out on the stability of AC-1370 to various β-lactamases produced by gramnegative bacteria, on its binding affinity to penicillin-binding proteins (PBPs) of Escherichia coil and Pseudomonas aeruginosa, on the synergy of the drug with the serum complement and/or macrophages, and on its stimulating activity to the defense mechanism of host animals.
    It was found that AC-1370 possesses high binding affinity to the Ia and Ib fractions of PBPs of E. coli and P. aeruginosa. Since the Ia and Ib fractions are essential cross-linking enzymes for the murein-biosynthesis, the drug is assumed to show strong bactericidal effect by itself as well as a good synergy of bactericidal effect with the complement and macrophages. The obtained results agreed the above assumption. AC-1370, however, is hydrolyzed by cephalosporinase-type β-lactamases (Richmond's Ia and Ic), especially by Ic, in some extent, so that its antibacterial effect against weakly virulent gram-negative bacilli may be limited.
    Stimulation of immune-defense mechanisms in host animals by AC-1370 was weak if any. It is interest to see how the characteristics of AC-1370 reflect the clinical results.
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  • NOZOMU KOSAKAI, TOYOKO OGURI
    1984 Volume 32 Issue Supplement9 Pages 21-29
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    We studied the antibacterial activity of AC-1370 against 586 strains of S. pneumoniae, H. influenzae, C. freundii, P. vulgaris, P. mirabilis, P. morganii, P. rettgeri, P. inconstans, B. fragilis, Bacteroides sp. isolated from clinical materials in 1982, and compared the findings to those with other cephems.
    In our study with the above-mentioned clinical isolates, AC-1370 was not found to be greatly advantageous in any respect over other cephem antibiotics-especially, the cephem antibiotics of the third generation.
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  • KUNITOMO WATANABE, MIDORI BUNAI, MAKOTO AOKI, KAZUNOBU KAGAWA, KAKUYO ...
    1984 Volume 32 Issue Supplement9 Pages 30-41
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Bacteriological evaluation to anaerobes was made on AC-1370, a new cephem antibiotic as compared with other cephems, and the following results were obtained.
    1) AC-1370 showed a broad antianaerobic activity, its activity against gram-positive cocci was inferior to that of CPZ, CFX or CEZ, and against gram-negative rods was the activity of AC-1370 equal to or somewhat inferior to that of CEZ, CPZ or CFX. Among the various species of anaerobes examined, AC-1370 showed a good activity against P. micros and C. ramosum, and a less activity against B. fragilis group, E. lentum and C. difficile in general.
    2) AC-1370 was hydrolyzed by (3-lactamase derived from B. fragilis and B. bivius, however its hydrolysis rate was less than that of CMX.
    3) AC-1370 showed superior therapeutic effect than CMX against experimental polymicrobial infection in mice caused by E. coli and B. fragilis.
    4) Appearance of C. difficile in caecal contents was not observed when AC-1370 was administered to mice at a dose of 2mg/mouse for 7 days, contrary to the cases of CTX and CFX.
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  • TAKESHI NISHINO, YOSHIKI OBANA, HIROYUKI HASHIZUME, YUMIKO FUJINOBU, T ...
    1984 Volume 32 Issue Supplement9 Pages 42-59
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Bacteriological evaluation was attempted on AC-1370, a new cephalosporin, with cefazolin (CEZ), cefoperazone (CPZ), ceftazidime (CAZ) and carbenicillin (CBPC) as the control drugs.
    AC-1370 showed a broad antibacterial spectrum against gram-positive and gram-negative bacteria. Its antibacterial activity was equivalent to that of CEZ and inferior to that of CPZ and CAZ. Against P. aeruginosa, however, the antibacterial activity of AC-1370 was equivalent to that of CPZ.
    Studies were also conducted on the influence of various experimental conditions on antibacterial activity of AC-1370, and it was recognized that the drug is hardly affected by pH of culture or addition of horse serum, and slightly affected by inoculum size.
    Studies on the mode of the antibacterial activity of AC-1370 revealed its marked bactericidal action against any one of the bacterial strains used.
    As to the therapeutic effect in experimental intraperitoneal infections in mice, that of AC-1370 against E. coli were superior to that of CEZ and inferior to that of CPZ and CAZ. Against K. pneumoniae, AC-1370 was inferior to CPZ and CAZ. Against P. aeruginosa, AC-1370, although inferior to CAZ, was superior to that of CPZ and CBPC.
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  • YOSHIKI OBANA, HIROYUKI HASHIZUME, YUMIKO FUJINOBU, TAKESHI NISHINO, T ...
    1984 Volume 32 Issue Supplement9 Pages 60-67
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The therapeutic efficacies of AC-1370, a new cephem, were compared with those of cefoperazone (CPZ) and ceftazidime (CAZ) in experimental infections in mice, in an attempt to find out the activation on host defense mechanisms. Against experimental intraperitoneal infections caused by P. aeruginosa, the efficacy of AC-1370 was equivalent or superior to that of CPZ. The MICs of AC-1370 against the test strains, however, were inferior to those of CPZ. Against experimental urinary tract infections, the efficacy of AC-1370 was superior to that of CPZ and inferior to that of CAZ.
    Serum and organ levels of AC-1370 in infected mice were more durable than those of CPZ and CAZ.
    The relationship between AC-1370 and neutrophils was investigated. As a result of the therapeutic efficacy of AC-1370 on experimental infection in compromised mice, the efficacy of AC-1370 was more dependent on the neutrophils than that of CPZ. As to the migration and phagocytosis by neutrophils in drugtreated mice, AC-1370 activated the function of neutrophils.
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  • TSUNEKAZU HARUTA, KAN-ETSU OHKURA, SHIGEKAZU KUROKI, YUTAKA KOBAYASHI
    1984 Volume 32 Issue Supplement9 Pages 68-73
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The antibacterial activities of AC-1370 against 16 strains of P. aeruginosa, 44 strains of E. coli, 23 strains of K. pneumoniae, 7 strains of Serratia and 17 strains of S. aureus were compared with those of cefazolin, cefmetazole, latamoxef and cefotaxime.
    The activity of AC-1370 against P. aeruginosa was superior to the effects: of 4 kinds of antibiotics mentioned above. The activities against E. coli and K. pneumoniae were the same as cefazolin and its effect against Serratia was equivalent to that of cefmetazole. However its activity against S. aureus was inferior to that of those antibiotics.
    CSF concentrations of AC-13 70 were determined after single intravenous injection of 100mg/kg in 5 rabbits with experimental staphylococcal meningitis. The average maximum concentrations of 19.5±1.95μg/ml and 19.5±2.18μg/ml were obtained at 75 and 90 min., respectively after administration of AC-1370 with its CSF/serum ratio of 6.0%.
    Under the above experimental conditions, a CSF/serum ratio of area under the curve (AUC) showed 6.21% up to 60 min., 10.4% up to 120 min. and 13.8% up to 180 min. and CSF/serum ratio of half-life (T1/2) was 4.18.
    Based on these results it was considered that passage of AC-1370 into CSF was fairly good among cephems, so called as a third generation, and also elimination of AC-1370 from CSF was very slow.
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  • YUKIO SASAKI, TERUAKI NAKAMIYA, YOSHITERU HIROSE, MASATOSHI OGAWA, YAS ...
    1984 Volume 32 Issue Supplement9 Pages 74-93
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Bacteriological evaluation was attempted on AC-1370, a new cephalosporin, with cefazolin (CEZ), cefoperazone (CPZ), cefotaxime (CTX) and carbenicillin (CBPC) as the control drugs.
    AC-1370 showed a broad antibacterial spectrum against gram-positive and gram-negative bacteria. Its antibacterial activity was equivalent to that of CEZ and inferior to that of CPZ and CTX. Against P. aeruginosa, however, the antibacterial activity of AC-1370 was superior to CEZ, CTX and equivalent to CPZ.
    Studies were also conducted on the influence of various experimental conditions on antibacterial activity of this agent, and it was recognized that the drug is hardly affected by pH of culture or addition of horse serum, and slightly affected by inoculum size.
    The drug was highly stable to all types of β-lactamase as classified by Richimond except for that of P. vulgaris.
    As to the therapeutic effects in experimental infections in mice, that of AC-1370 against E. coil were superior to that of CEZ and inferior to that of CTX and CPZ. Against to K. pneumoniae, AC-1370 was also inferior to CPZ and CTX. Against P. aeruginosa, AC-1370 was superior to CBPC, CTX and CPZ.
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  • YOSHIHIRO KUMASAKA, HISASHI NAKAHATA, YUICHI HIRAI, KENICHI IMAMURA, K ...
    1984 Volume 32 Issue Supplement9 Pages 94-97
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Effect of AC-1370, a new semisynthetic cephalosporin antibiotic, on superoxide anion (O2-) production by human polymorphonuclear leukocytes (PMNs) was examined, and compared with that of cefazolin (CEZ), ceftizoxime (CZX), cefbuperazone (CBPZ).
    There has been observed a direct effect on O2-production by PMNs with both AC-1370 and CEZ, but not with CZX or CBPZ either, under the condition where 4×105 PMNs were stimulated with 200μg of each antibiotic. And this effect of AC-1370 was stronger than that of CEZ.
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  • TAKENORI OCHIAI, HIROSHI SATO, TAKEHIDE ASANO, [in Japanese], MATSUO N ...
    1984 Volume 32 Issue Supplement9 Pages 98-102
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Activities of AC-1370 to augument immunological features of the lymphocyte and the bacteriocidal effect of the neutrophile were evaluated in 5 patients who received surgery at the Second Department of Surgery, School of Medicine, Chiba University. AC-1370 was given intraveneously 4 gram daily for one week. The activities of the lymphocyte and the neutrophile were tested at the time of before and after AC-1370 treatment. Immunological activities of the lymphocyte in terms of PHA-P and Con A responses, and ADCC activity did not show any change by the treatment. Proportion of the subpopulation of the lymphocyte in terms of T cells, B cells, and IgG Fat+ T cells did not show any change, either. The bacteriocidal activity of the neutrophile decreased significantly one week after operation in the patients who did not receive AC-1370, however, decrease in the activity was not observed in the patients receiving AC-1370. These results suggested that AC-1370 have an ability to augument the bacteriocidal effect of the neutrophile.
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  • YOKO KAMEOKA, SEIJI MUTSUURA, SACHIKO YOSHIMOTO, MASAKAZU TAMURA, EIRO ...
    1984 Volume 32 Issue Supplement9 Pages 103-107
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    A new antibiotics, AC-1370 (AC) shows in vivo antimicrobial activities other than in vitro antibiotic activities. Therefore we investigated host defence enhancing activities of derivatives of AC and hydrolized AC (H-AC).
    Although there was no increasing of host defence activities with the pretreatment of 0.1mg/kg of H-AC in the immunosuppressed mice infected with E. coli, bactericidal activities of peritoneal exudate cells were significantly increased with the treatment of H-AC.
    It was also noted that enhancement of in vitro NBT reduction activities of human peripheral leukocytes with addition of 100μg/ml of H-AC.
    These results were indicated that AC-1370 had enhancing activities of neutrophilic function under certain experimental conditions.
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  • MASAMICHI AMANO, SHOICHI YAMAMOTO, NORIAKI SAITO, MANABU SUZUKI, HIROY ...
    1984 Volume 32 Issue Supplement9 Pages 108-113
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
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    A series of experiments on neutrophilic phagocytosis and bactericidal activity of bacteria was performed on normal subjects and patients with secondary pyelonephritis for the purpose of studing effects of AC-1370, a new cephalosporin, on human leucocyte functions. Organisms used in this study were Staphylococcus aureus labeled with 3H-lysine. Concentrations of AC-1370 were ranged from 100 mcg/ml to 0.01 mcg/ml.
    The results obtained could be summarized as below.
    1. Phagocytosis of normal subjects and pyelonephritis patients was markedly enhanced in proportion to the concentration of AC-1370, of which maximum effect was observed in normal subjects about three times in comparison with that of controls ungiven AC-1370 and also observed in the patients with pyelonephritis about two times.
    2. Bactericidal activity was moderately accelerated by the same proportion, of which maximum activity by Mine's criterion was obtained 0.457 in normal subjects and 0.560 in the patients with pyelonephritis.
    3. Attributing to our data reported in the series of 12 kinds of antibiotics on phagocytosis and bactericidal activity of human leucocytes, most of antibiotics suppressed them, a few of them enhanced. In the antibiotics studied, AC-1370 made the phagocytosis enhanced markedly in the normal subjects and moderately in the phagocytosis in pyelonephritis patients, it made the bactericidal activity accelerated modelately in both the normal and pyelonephritic subjects.
    4. Studies of AC-1370 on the antimicrobial activity and natural defense mechanism of the host against infections may contribute to our choice of antibiotic therapy.
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  • AKIMITSU TOMONAGA
    1984 Volume 32 Issue Supplement9 Pages 114-119
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
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    We evaluated the effect of AC-1370, a new injectable cephalosporin, on the neutrophil functions by the methods of polarization and superoxide production measurement.
    In vitro experiments, AC-1370 enhanced polarization slightly at the concentration of 20-100μg/ml and depressed 30% of control at the high concentration of 500μg/ml. AC-1370 enhanced superoxide production activity 20-30% at the concentration of 1-500μg/ml. No appreciable effect on polarization and superoxide production activity could be detected for cefazolin (CEZ) and cefoperazone (CPZ). In the evaluation of the change of neutrophil polarization and superoxide production activity of 4 or 5 healthy volunteers 1 hr or 4 hrs after intravenous drip infusion of 2 g AC-1370, CEZ or CPZ, AC-1370 showed a tendency to increase both functions, and CEZ and CPZ did not showed any appreciable change. In patients who received AC-1370 (2 g/day), CEZ (4 g/day) or CPZ (4 g/day) for one or two weeks, slight increase of polarization and marked enhancement of superoxide production activity were seen in patients treated with AC-1370.
    No change was seen in patients treated with CEZ or CPZ. AC-1370 have been confirmed to have a higher in vivo effect than that expected from in vitro antibacterial activity. It was considered as one of this mechanism that AC-1370 could directly potentiate neutrophil functions resulting in enhancement of host defense activity.
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  • HARUO OHNISHI, HIROSHI KOSUZUME, HITOSHI INABA, HIDENORI MOCHIZUKI, YU ...
    1984 Volume 32 Issue Supplement9 Pages 120-126
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Effects of AC-1370, a novel semisynthetic cephalosporin, on host defense against infections and its target cells were investigated. AC-1370 exerted no effect on plaque forming cells and delayed type hypersensitivity but augmented phagocytosis by macrophages and neutrophils by in vitro application and also in vivo. In contrast, other β-lactam antibiotics either did not affect or rather suppressed these functions. Flow cytometry revealed that most of the cells binding AC-1370 were macrophages and that few neutrophils bound AC-1370. Culture supernatants of macrophages potentiated phagocytosis by neutrophils, and the culture supernatants of AC-1370-stimulated macrophages potentiated phagocytosis by neutrophils more potently than the culture supernatant of unstimulated macrophages did. The activities of these culture supernatants were resistant to heat treatment at 56° for 30 minutes but labile to the treatment with trypsin. These results suggest that AC-1370 potentiates phagocyte functions without affecting humoral and cellular immune responses and that the potentiating action of AC-1370 may be mediated by direct binding of the compound to macrophages and by indirect action on neutrophils through facilitating production of protein factor (s) by macrophages.
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  • HITOSHI INABA, HIDENORI MOCHIZUKI, SATOSHI KUSAKABE, HIROSHI KOSUZUME, ...
    1984 Volume 32 Issue Supplement9 Pages 127-130
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Significance of potentiation of host defense by AC-1370 was investigated in relation to the treatment of infectious diseases. AC-1370 defended mice from Candida albicans infections, though the compound did not show direct antifungal effects on C. albicans. Treatment of mice with cyclophosphamide made the animals susceptible to C. albicans infection, and AC-1370 defended cyclophosphamide-treated mice from C. albicans infection, Furthermore, AC-1370 restored the functions of neutrophils, which had been suppressed by cyclophosphamide treatment in vitro, to the level same as those of intact neutrophils. These results suggest that the potentiating action of AC-1370 on host defense may contribute to the treatment of infections.
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  • RIEKO OKANO, TOSHIHIDE ISHII, TEIZO MURATA, NOBUO KATO, HITOSHI INABA, ...
    1984 Volume 32 Issue Supplement9 Pages 131-136
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The microbiological assay methods for antibiotic concentration in body fluids after treatment of AC-1370 were described.
    Thin layer cup-plate method on Heart infusion agar inoculated with P. mirabilis 4 or K. pneumoniae IFO 3317 was the best in terms of assay sensitivity and clearness of growth inhibition zone. The determination limits by this method were 1.56μg/ml and 0.78μ/ml, when P. mirabilis 4 and K. pneumoniae IFO 3317 were used as test organisms, respectively.
    Although the sensitivity of thin layer disc-plate method was lower than that of thin layer cup-plate method, the former was suitable for the assay of small amount of samples, and the detectable ranges of using P. mirabilis 4 and K. pneumoniae IFO 3317 as test organisms, respectively.
    For the estimation of AC-1370 concentration in human serum, pooled human serum and Control Serum I were both suitable for the diluent of the standard solution of AC-1370, and for the determination of AC-1370 concentration in urine samples, phosphate buffered saline was available as the diluent.
    AC-1370 was stable in human plasma and urine at least for 2 weeks when stored at-20°C.
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  • TEIZO MURATA, YOSHIMASA MATSUZAWA, RIEKO OKANO, JUNKO TAIRA, NOBUO KAT ...
    1984 Volume 32 Issue Supplement9 Pages 137-144
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new parenteral cephalosporin derivative, was administered to experimental animals, such as mice, rats, rabbits, dogs and monkeys at a single dose of 50mg/kg.
    The plasma concentrations of AC-1370 after single intravenous administration were highest in monkeys, followed by rabbits, dogs, rats and mice, in this order, and the plasma half-lives of AC-1370 were 95.0, 67.2, 47.0, 23.3 and 17.0 minutes, respectively. Those of AC-1370 in mice, rats and dogs were almost comparable to those of cefazolin and longer than cefoperazone, cefotaxime and cefmetazole.
    AC-1370 was rapidly distributed into various tissues of mice after intravenous administration and the concentrations were high in the order of those in kidney, plasma, lung, myocardium, spleen and liver. The AC-1370 concentration in kidney was three times higher than that of cefazolin, however, its concentration in liver was about one tenth of that of cefazolin.
    Urinary recoveries of AC-1370 in dogs, rabbits and monkeys over a 8 hour period were ranged from 68.3% to 75.9% of the administration dose and biliary recoveries over a 6 hour period were 0.15% in dogs and 0.17% in rabbits. Probenecid had no influence on plasma concentration or urinary recovery of AC-1370, indicating AC-1370 was mainly excreted by glomerular filtration.
    The extent of serum protein binding of AC-1370 measured by centrifugal ultrafiltration method were 14.3% in humans, 5.7% in dogs, 8.6% in rabbits and 7.1% in rats. These values weresmaller than those of cefazolin or cefoperazone.
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  • YOSHIMASA MATSUZAWA, SEIKICHI SEKINE, TEIZO MURATA, NOBUO KATO
    1984 Volume 32 Issue Supplement9 Pages 145-156
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Absorption, distribution, metabolism and excretion of AC-1370 were studied in rats after single or repeated intravenous administration of 14C-AC-1370 to Fischer rats.
    1) After intravenous administration of 14C-AC-1370, biphasic decrease of the radioactivity in the plasma was observed. Plasma half life at the dose of 30mg/kg was 22 min. C0 and AUC were increased in proportion to the increase of dosage (30-200mg/kg), while T1/2 and kel did not change.
    2) After single intravenous injection, the tissue level of radioactivity was highest in the kidney followed by plasma, lung, skin, liver, heart, spleen and thymus. The radioactivity in the brain and the spinal cord was very low. Only a small amount of radioactivity passed through the placenta, and the transfer to the milk was also small.
    3) Within 72 hr after single intravenous injection, 84% and 9% of the given radioactivity were excreted in the urine and feces, respectively. About 4% of the doses was excreted in the bile within 24 hr.
    4) No metabolites were detected in the plasma at 15 and 30 min after injection and in the 2 and 6 hr pooled urine.
    5) Upon repeated intravenous administration twice a day, the radioactivity in the tissue increased gradually and plateaued at the 5th to the 9th administration. The radioactivity in theplasma after multiple injections was similar to that of the 1st administration. Distribution patterns of radioactivity after repeated administration were almost the same as that of a single administration. Excretion rates of radioactivity in the urine and feces were nearly constant during repeated administration.
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  • KATSUICHI NANBA, NOBUYUKI AKAZAWA, MASAAKI OKIMUNE, KAZUTOYO MIYATA, H ...
    1984 Volume 32 Issue Supplement9 Pages 157-162
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The pharrnacokinetics of AC-1370, a new cephalosporin derivative, were investigated in 4 patients and experimental animals with renal insufficiency. In patients, serum and urinary concentrations of AC-1370 were determined by bioassay. In experimental animals, serum, urinary and biliary concentrations of AC-1370 were determined by radioassay.
    The following results were obtained.
    1) In patients with various degree of renal' impairment, serum levels and half-lives (β) were higher in proportion to highering of serum creatinine, and urinary recovery rates were decreased. There were linear correlations between the creatinine clearance and the elimination rate constant.
    2) In experimental renal insufficiency rats, urinary recovery rate and Ccr were 20% and 0.2ml/mm, and these values were lower than those in normal rats (60% and 0.9ml/min), whereas biliary recovery rate was higher than normal rats (6% vs 2%).
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  • AKIRA SAITO, YASUMICHI KATO, KIYOFUMI ISHIKAWA, EINOSUKE ODAGAKI, MASA ...
    1984 Volume 32 Issue Supplement9 Pages 163-174
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The antibacterial activity of AC-1370, a new cephem antibiotic, was tested against each 27 clinical isolates of 7 species, using plate dilution method with inoculum size of 106 cells/ml. The peak concentrations of AC-1370 in MIC distributions were obtained at 12.5-50 Agiml for S. aureus, 6.3 for E. coli, 3.1 for K. pneumoniae, 1.6 for P. mirabilis, and >100 for Serratia sp. The above mentioned activity was inferior to that of every reference drug; CTM, CMZ, CTX and LMOX. The peak concentrations of AC-1370 for P. morganii and P. aeruginosa were 12.5 and 12.5μg/ml respectively, which were almost same as those of CTX and LMOX.
    Pharmacokinetics of AC-1370 were investigated in 6 healthy male volunteers. Intravenous administration of the drug at a dose of 0.5 g or 1.0 g yielded that mean plasma levels measured by bioassay method were 56.9μg/ml at a dose of 0.5 g and 120.3μg/ml at a dose of 1.0 g after 5 minutes, respectively, after 1 hour, 17.1 and 38.2 and after 4 hours, 3.8 and 8.9μg/ml. The β-phase biological half-lives of the drug were estimated to be 1.92 and 1.74 hours, respectively. The urinary excretion rates within 8 hours were 81.0% at a dose of 0.5 g, and 86.4% at a dose of 1.0g, respectively.
    Twenty four patients with bacterial infections were treated with AC-1370 at a daily dose of 2 g twice a day by intravenous drip infusion. The clinical response to the treatment was excellent in 16 cases, good in 3 cases, fair in 3 cases, poor in 1 case and unevaluable in 1 case. The effectiveness rate was calculated as 82.6% (19 cases out of evaluable 23 cases).
    As side effects, eruption occurred in one patient, and eosinophilia was observed in one patient.
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  • FUMIO NAGAHAMA
    1984 Volume 32 Issue Supplement9 Pages 175-184
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    30 patients in total, studied; male 19, female 11, under 59 years old 11, over 60 years old 19 (63.3%); the grades of their infections over moderately 22 (73.3%), the underlying diseases, such as D.M., atrial fibrillation, lung cancer, Wegener's granulomatosis, COLD, lung emphysema, lung tbc, cured, pneumoconiosis, cystlung, bronchiectasis, cerebrovascular disease and uterine cancer, were treated with new antibiotics AC-1370, exploited by Ajinomoto and Mochida pharmaceutical Co.
    AC-1370 was given 1.0 g one time, usually two times a day intravenously, duration 7 to 30 days, average 14.2 days, total doses, used, 7 to 60 g, average 28 g, clinical effects: excellent 5, good 22, (90.0%). Bacteriological findings before AC-1370 treatments were 17 strains, including Ps. aeruginosa and K. pneumoniae each 4 strains, S. marcescens 2 strains, Pr. morganii, Ps. putida, Str. pneumoniae, Str. salivarius, A. xylosoxidans, α-Streptococcus and Micrococcus, each one strain and their AC-1370 treatments after, eradicated 7 (41.2%), decreased 3 (17.6%), replaced 5 (29.4%), unchanged 2 (11.8%). Side effects: one patient showed temporary skin rash with the slight elevations of S-GOT and S-GPT, one patient showed slight temporally elevation of S-GPT, and three slight temporally eosinophilias.
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  • KAZUO TAKEBE
    1984 Volume 32 Issue Supplement9 Pages 185-196
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
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    To evaluate the clinical efficacy of AC-1370, the drug was given for treatment to 35 patients, including 2 with acute tonsilitis, 3 with acute bronchitis, 7 with chronic bronchitis, 7 with pneumonia, 1 with acute cystitis, 5 with chronic cystitis, 7 with acute pyelonephritis, 1 with biliary tract infection, 1 with acute bacterial colitis, and 1 with pelvic peritonitis.
    Response was excellent in 8 patients, good in 19 and poor in 8. The clinical efficacy rate of AC-1370 was 77.1%. The bacteriological efficacy rate classified by isolated bacteria in AC-1370 treatment was 92%.
    Side effects and abnormal laboratory findings following the treatment were not observed.
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  • KIKUO ONUMA, SEIICHI AONUMA, AKIRA WATANABE, MASAKO SASAKI, KOTARO OIZ ...
    1984 Volume 32 Issue Supplement9 Pages 197-201
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The MICs of AC-1370 against 120 bacterial strains from patients sputum were compared with those of cefmetazole, cefotiam, cefoperazone and ceftizoxime by Dynatech MIC-2000 system, and the efficacy of AC-1370 in the treatment of eight patients (four patients with pneumonia, one with lung abscess, two with acute exacerbation of chronic respiratory tract infection and one with abscess of the chest wall) was evaluated.
    The results of in vitro tests revealed that AC-1370 was active against Klebsiella pneumoniae (MIC50=3.13μg/ml, 20 strains) but was not so active against Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa as all or some of the above four other antibacterial agents.
    Two or three grams of AC-1370 per day were given to the patients by intravenous drip infusion, . Clinical response to the treatment with AC-1370 was good in all of seven community-acquired respiratory infections. Three strains of Haemophilus influenzae and one strain of Streptococcus pneumoniae were considered to be cousative organisms in four patients and were all eradicated. This drug was not effective against a patient with chest wall abscess combined with lung cancer. As for side effects during the treatment, eruption occurred in two cases, elevation of S-GPT values in one and eosinophilia in one. But all of theses abnormalities were slight and were normalized soon after cessation of the drug.
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  • IZUMI HAYASHI, TATSUYA ABE
    1984 Volume 32 Issue Supplement9 Pages 202-206
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Clinical investigations were performed on AC-1370, a new cephalosporin.
    AC-1370 was administered to a total of 13 patients with respiratory tract infections including 10 cases of pneumonia and each one case of pneumonia and pyothorax, acute bronchitis, acute exacerbation of chronic bronchitis.
    The drug was administered at a daily dose of 2g for five days in one case, 10 days in one case, 14 days in 10 cases and 17 days in one case.
    The drug was discontinued after five days' therapy in one case because of drug fever.
    The following four potential pathogens were recovered from the sputum at a start of the treatment with AC-1370, one strain each of β-Streptococcus, P. aeruginosa, S. pneumoniae, H. influenzae. All of them were eradicated during the treatment with AC-1370.
    The clinical response to the treatment with AC-1370 was excellent in six cases, good in six cases and fair in one case.
    A drug fever was observed in one case of pneumonia.
    A slight elevation of serum transaminase was observed in two cases and eosinophilia in one case.
    From the above results, it is concluded that AC-1370 is one of effective and useful the third generation cephems against RTIs.
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  • TUGUSHI ITOH
    1984 Volume 32 Issue Supplement9 Pages 207-212
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was given to 11 patients with respiratory infections (6 cases with pneumonia, 2 cases with pulmonary suppuration, 1 case with pyothorax, 2 cases with secondary infection of chronic lung diseases). The drug was administered intravenously by drip injection twice a day with the doses of 1 or 2 g for 8 to 15 days. The clinical effect to AC-1370 treatment was excellent in 2 cases, good in 6 cases, fair in 2 cases and unevaluable in 1 case.
    Side effects with AC-1370 were observed in 2 cases consisting of skin eruption with drug fever and skin eruption, and two cases showed slight elevation of GOT, and of GOT and GPT. The penetration rate of AC-1370 from blood into lung was measured in lung tissues extracted from patients with lung cancer. The average ratios of tissue level vs. serum level were 3 8.2% at 1 hour, 51% at 2 hours, and 55% at 3 hours after administration.
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  • MIEKO KAWAI
    1984 Volume 32 Issue Supplement9 Pages 213-216
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was given to 10 patients, 7 of respiratory tract infections, 2 of urinary tract infections and 1 of biliary tract infection. The drug was administered intravenously by drip infusion at daily dose of 1, 000mg or 2, 000mg.
    1) Efficacy rate was counted 86.7% in RTI, 100% in UTI and biliary tract infection. The overall efficacy rate was 90%.
    2) No clinical adverse effect and no abnormality of laboratory findings were observed.
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  • JINGORO SHIMADA
    1984 Volume 32 Issue Supplement9 Pages 217-230
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephem antibiotic, was studied clinically, and the following results were obtained:
    1. Antibacterial activity
    MICs of AC-1370 for clinical isolates were determined and compared with those of cefoperazone, ceftizoxime, latamoxef, cefotaxime, cefmenoxime and cefpiramide. Antibacterial activity of AC-1370 against such clinical isolates as P. rnirabilis and Indole (+) Proteus was almost on the same level as those of cefpiramide, and against E. coli was its activity slightly inferior to cefpiramide. Antibacterial activity of AC-1370 against P. aeruginosa was slightly inferior to those of cefoperazone and cefpiramide, but stronger than cefotaxime, latamoxef, ceftizoxime and cefmenoxime.
    2. Absorption and excretion
    The serum and urinary concentrations of AC-1370 were determined in 5 healthy volunteers after 1.0g intravenous administration and were compared, in a cross-over manner, with those of cefoperazone. Influence of probenecid on the concentrations was also investigated.
    The serum concentration of AC-1370 at 5 minutes after administration averaged 146.1 btgfml, and after that the concentration decreased with the half-life (β-phase) of 1.71 hours. The serum concentration of AC-1370 was slightly lower than that of cefoperazone until 15 minutes after administration, but was almostthe same as cefoperazone after such period. The urinary recovery rate up to 12 hours averaged 88.6%, which was 2.7 times as high as that of cefoperazone. The average total clearance of AC-1370 was 134.0ml/min slightly higher than that of cefoperazone, but renal clearance of 114.7ml/min was 3.0 times higher than cefoperazone.
    The combination use of probenecid with AC-1370 showed no significant difference on the serum concentration, half-life and urinary recovery rate when compared with single administration of AC-1370.
    3. Clinical results
    AC-1370 was administered to 6 patients including 4 cases of pneumonia, I case of cholecystitis and 1 case of chronic pyelonephritis at a daily close of 2 to 4 grams for 6 to 19 days. The clinical response was excellent in 2 cases, good in 3 cases and fair in 1 case. In the course of clinical study, slight anorexia was observed in one case as a side effect but no abnormal laboratory findings were noted.
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  • SATOSHI OHI, TEPPEI KUMADA, KYOICHI TOTSUKA
    1984 Volume 32 Issue Supplement9 Pages 231-236
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    We made preclinical and clinical studies of AC-1370, a lately developed cephalosporin antibiotic, in internal medicine.
    The MICs of AC-1370 against clinical isolates were such that the MICs against E. coli were in the range from 1.6 to 12.5μg/ml, with a peak at 3.2μg/ml; the peak MICs against Klebsiella, at 1.6 to 3.2μg/ml, and the MICs against Enterobacter were bimodal, with peaks at 1.6 to 3.2μg/ml and not less than 100μg/ml. The MICs against Serratia were distributed widely in the range of 3.2μg/ml or more; and those against P. aeruginosa, in the range from 1.6 to 25μg/ml, with a peak at 6.3 to 12.5μg/ml.
    Two healthy adult men were injected intravenously with 1 g of AC-1370, respectively; and the levels of the agent in the blood were 96 and 122μg/ml in 5 minutes, 42 and 52μg/ml in 30 minutes, 27 and 33μg/ml in 1 hour, and 3.5 and 5.3μgiml in 6 hours. In other words, the half-lives of the agent in the blood of these subjects were 1.88 and 2.25 hours. The rates of recovery from the urine were 91.5 and 88.6% during the first 6 hours.
    Five inpatients, comprising 4 with urinary tract infections (1 with acute pyelonephritis and 3 with chronic pyelonephritis) and the other with acute cholecystitis, were treated with AC-1370 to evaluate its efficacy. E. coli, P. morganii and P. aeruginosa were the pathogens of 3 of the patients; another had polymicrobial infection with S. faecalis and Serratia, and the other also had polymicrobial infection with E. coli and Klebsiella. The patients with urinary tract infections were given 1g of AC-1370 by intravenous drip, twice daily, and the patient with cholecystitis, 2 g by intravenous drip, twice daily. One of the patients with urinary tract infections showed an “excellent, ” and the other 3, a “good” response, and the patient with cholecystitis, a “good” response to the treatment.
    Neither any side effects of the agent were observed nor any abnormalities were found by laboratory studies.
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  • OTOHIKO KUNII, TAKASHI KOMATSU, HAJIME NISHIYA, YASUO ONO, JUN YOKOTA, ...
    1984 Volume 32 Issue Supplement9 Pages 237-245
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new broad spectrum cephalosporin antibiotic, was evaluated in vitro against a variety of human pathogens.
    The activity of AC-1370 was equivalent to that of cefazolin against E. coli, Klebsiella and Proteus. Against P. aeruginosa it was more effective than latamoxef and cefmetazole and less effective than cefoperazone.
    AC-1370 was administered to five patients 2 g per day for 7 to 11 days. They have been suffered from pneumonia, cholecystitis, pyelonephritis, or biliary tract infection. Their clinical course showed that AC-1370 was effective to all their diseases.
    Neither clinical side effect nor abnormal laboratory finding was found.
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  • KAZUYOSHI WATANABE, TSUNEO HAMAMOTO, JUNKO HIBINO, KAZUHIKO SHIINA, AK ...
    1984 Volume 32 Issue Supplement9 Pages 246-250
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 is a new cephalosporin antibiotics against a broad spectrum of gram-positive and gram-negative microorganisms especially Pseudomonas sp.
    AC-1370 was used in the treatment of 10 cases of respiratory infectious diseases, 5 cases of pneumonia, 3 cases of chronic bronchitis, one case of diffuse panbronchiolitis and one case of acute bronchitis, AC-1370 was administered intravenously at a dose of 1.0×2.0g twice daily for 4 to 21 days and results obtained were excellent in one case, good in 4 cases, fair in 2 cases, poor in 2 cases and not determined in one case.
    Adverse reaction such as drug eruption, fever, nausea, diarrhea and vascular pain were not observed. Abnormal laboratory findings were not observed.
    From the above clinical studies, AC-1370 would be a clinically useful antibiotics against the respiratory infectious disease.
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  • KATSUNORI UENO, YOSHIJI YAMANE, KEIMEI MASHIMO
    1984 Volume 32 Issue Supplement9 Pages 251-253
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephalosporin antibiotics, was administered parentally to 9 patients with various infectious disease (pneumonia 5, acute bronchitis 1, acute pyelonephritis 1, acute cholecystitis 1 and sepsis 1). The clinical efficacy was excellent in 1 case, good in 4 cases, poor in 3 cases, unknown in 1 case.
    Vomiting was observed in 1 case but disappeared after withdrawal.
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  • KEIICHI NAKAGAWA, MASARU KOYAMA, TAKASHI YAMAMOTO, FUKUO IIJIMA, ICHIR ...
    1984 Volume 32 Issue Supplement9 Pages 254-263
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a cephem antibiotic developed in Japan, has a broad antibacterial spectrum, and potent antibacterial activities especially against gram-negative rods, including Pseudomonas aeruginosa. When one patient with cystitis was given 1 g of AC-1370 by intravenous one-shot injection, the level of the agent in the blood was 83.0 μg/ml in hour, 16.8μg/ml in 6 hours, and 11.1μg/ml in 8 hours, with such a long halflife as 3.06 hours.
    A total of 15 patients, made up of 6 with pneumonia, another with diffuse panbronchiolitis, another with infection as a complication of pulmonary emphysema, 4 with acute pyelonephritis, another with urinary tract infection, and the other 2 with biliary infections, were given 1g of AC-1370 2 or 3 times daily, for 7 to 31 consecutive days.
    Seven of the 8 patients with respiratory tract infections and 4 of the 5 with urinary tract infections showed a “good” to “excellent” response, and both of the 2 patients with biliary tract infections, a “good” response to the treatment.
    Rashes were clinically observed as a side effect of the agent in one; and laboratory studies revealed an elevation of GOT and GPT in one and eosinophilia in another of the patients.
    From these findings, AC-1370 may be said to be one of the clinically useful cephem antibiotics.
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  • NAOHIKO CHONABAYASHI, YOSHITAKA NAKAMORI, KUNIHIKO YOSHIMURA, TATSUO N ...
    1984 Volume 32 Issue Supplement9 Pages 264-272
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Clinical study of AC-1370, a new cephem derivative, was made in the treatment of respiratory infection including 16 cases of airway and small airway infection, 1 case of empyema and 1 case of pneumonia. As the pneumonia was diagnosed to be due to mycoplasma later, this case was excluded from clinical effect judgement.
    The results were obtained as follows:
    1) AC-1370 was found to be effective in 71% of 7 cases of airway infection and 67% of 9 cases of small airway infection.
    2) AC-1370 showed fine efficacy for the case of empyema due to anaerobic bacteria.
    3) AC-1370 showed excellent effect for the infection due to Haemophilus influenzae, Streptococcus pneumoniae and anaerobic bacteria, however, poorly effective for the infection due to Pseudomonas aeruginosa.
    4) Although no clinical side effect was caused by AC-1370, eosinophilia in 1 patient and elevation of GOT and GPT in 2 patients were found as abnormal laboratory data after this therapy. Mild elevation of GOT and GPT in one case continued till the 8th day from the cessation of the therapy, but other abnormal findings were alleviated rapidly following cessation of AC-1370.
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  • TAKASHI INAMATSU, KAORU SHIMADA, KYOKO URAYAMA
    1984 Volume 32 Issue Supplement9 Pages 273-276
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    New cephalosporin, AC-1370 was given for 10 cases of infection, seen in 8 aged patients with various underlying diseases. Satisfactory results were obtained, in one of 2 pneumonia, one of 2 pyelonephritis, 3 of 6 chr. cystitis.
    No adverse effect was noted in these cases.
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  • HIROYOSHI ISHIBASHI, MASARU SUZUKI, KAZUKO OKABE, JUNZABURO KABE
    1984 Volume 32 Issue Supplement9 Pages 277-280
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was used in 10 patients, evaluable cases being 9 cases of broncho-pulmonary infections. Daily doses of AC-1370 ranged from 1g to 2g.
    Clinical effects in 4 cases of acute pneumonia were assessed as good in all 4 cases. In 1 case of diffuse panbronchiolitis, 1 case of chronic bronchitis and 1 case of chronic pneumonia response were good respectively. In 1 case of lung abscess and 1 case of secondary infection (pneumonia) of lung cancer response were poor. Causative organisms were K. pneumoniae (1 case), H. influenzae (2 cases) and Enterobacter (1 case). After AC-1370 K. pneumoniae and H. influenzae were eradicated. Enterobacter was replaced to M. morganii and Acinetobacter. No evidence of side effect was noted. Labolatorical abnormalities were detected in 2 cases transient γ-GTP and Al-P elevation was noted. 1 case of granulocytopenia (26% of 4, 200 WBC) was noted after 2 weeks drug administration.
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  • HIROSHI OSHITANI, HIROAKI TAKEDA, TOMOKO NIHEI, SHIN KAWAI, HIROYUKI K ...
    1984 Volume 32 Issue Supplement9 Pages 281-284
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The effect of AC-1370 were clinically evaluated in 9 cases with respiratory tract infections (6 cases of chronic bronchitis, 2 cases of pneumonia and one of lower respiratory tract infection with lung cancer). AC-1370 was administered 1g twice a day with drip infusion. Three cases among 6 with chronic bronchitis were those which were not effective on previously administered anti-bacterial agent. The case with lower respiratory tract infection was combined with lung cancer in terminal stage.
    The results of clinical response were good in 4 cases and poor in 2 cases among 6 patients with chronic bronchitis, good in all 2 cases with pneumonia and poor in one case with lower respiratory tract infection. The effective rate in total was 67%.
    As to the side effect, the slight and transient elevation of serum BUN and creatinine was observed in one case, but there is no other abnormality in patient's symptom and laboratory findings.
    From the results, it was considered that AC-1370 would be expected to be useful for the treatment of patients with common lower respiratory tract infections.
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  • SEIJI MITA, YOSHIO KOBAYASHI, IPPEI FUJIMORI
    1984 Volume 32 Issue Supplement9 Pages 285-290
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new parenteral cephalosporin, was evaluated clinically for 12 patients (15 cases) aged 36-77 years with respiratory tract infection (4 cases) and with urinary tract infection (11 cases). A daily dose of AC-1370 was 1-2 g by intravenous injection twice a day and duration of AC-1370 therapy was for 5 to 9 days.
    The results were as follows.
    1. The clinical response to AC-1370 therapy of respiratory tract infection was good in 2 cases, fair in one case, and poor in one case, and that of urinary tract infection was excellent in 2 cases, good in 4 cases, and fair in 2 cases.
    The efficacy rate was 67%.
    2. In the laboratory data, abnormal elevation of serum Al-P, as a side effect, was observed in one case after the administration of AC-1370.
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  • AKIRA ITO, HIROSHI TAKAHASHI, KUNIHIKO SHINDO, KOHKICHI FUKUSHIMA, HID ...
    1984 Volume 32 Issue Supplement9 Pages 291-299
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was clinically evaluated. The results obtained were summarized as follows:
    1) Antibacterial activity of AC-1370 against clinical isolates of P. aeruginosa was superior to that of CFX, CTM and CZX, although its activity against E. coli was inferior to that of CFX, CTM and CZX.
    2) The activity against K. pneumoniae, S. marcescens, P. cepacia and A. calcoaceticus was almost same as that of CFX and CTM.
    3) AC-1370 was given to 13 patients: 8 respiratory infection cases, 2 cholecytistis cases, 2 sepsis cases and 1 urinary tract infection case. Clinical response to AC-1370 treatment was excellent in 4 cases, good in 4 cases, fair in 1 case and poor in 4 cases with effective rate of 61.5% (8 case of 13 cases).
    4) Bacteriological response in the above 13 cases was eradicated in 1 case, persisted in 1 case and colonization in 3 cases, and the remaining 8 cases were unevaluable.
    5) Neither side effect nor abnormality in laboratory findings was observed.
    6) The drug is expected to be a useful antibiotic, if an adequate selection of patients is considered.
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  • FUMIO MATSUMOTO, MASARU YAMAMOTO, MASATO MIZUGUCHI, TAKAYUKI TAKAHASHI ...
    1984 Volume 32 Issue Supplement9 Pages 300-308
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    The studies on antimicrobial activity, absorption, excretion and clinical evaluation of AC-1370, a new cephem, were performed, and the following results were obtained:
    1) The antibacterial activity of AC-1370 was examined against each 50 clinical isolates of 7 species. AC-1370 showed the most strong activity against S. pyogenes among them, the MIC80 value being 0.39μg/ml. According to each curve of cumulative percent on MICs, the activity against the remaining 6 species was judged as in order of P. mirabilis, K. pneumoniae, E. voli, S. marcescens, E. cloacae, P. aeruginosa and S. aureus.
    The MIC80 values for these species corresponded to 0.39, 1.56, 6.25, 25, 25, 25, 12.5 and 25μg/ml, respectively.
    2) The peak serum concentration of 68.6μg/ml in a sepsis patient was attained at the end of intravenous drip infusion with a dose of 1.0 g over a period of 1 hour. The serum concentration was gradually decreased with the half life of 1.74 hours, and the concentration at 8 hours from administration was 1.1μg/ml.
    The serum concentrations in a renal insufficient patient with Ccr of 15 ml/min. and two chronic renal insufficient patients with hemodialysis were respectively 122.0μg/ml and 121.3 126.4μg/ml at 5 minutes from a single bolus intravenous administration of 1.0 g, and 54 and 17.6 18.5μg/ml at 4 hours. The results suggested that AC-1370 was excreted by dialysis.
    3) AC-1370 was administered to 6 patients with infectious diseases consisting of each one case of chronic bronchitis, localized peritonitis and urinary tract infection and of 3 cases of sepsis at a daily dose of 1 to 2 g. All the cases were evaluated clinically as good response. Neither side effects nor abnormal laboratory findings were observed.
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  • SHIGEKI ODAGIRI, HIROTADA IKEDA, KANEO SUZUKI, KOOU MUROHASHI, TAMOTSU ...
    1984 Volume 32 Issue Supplement9 Pages 309-316
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephalosporin antibiotic, was used in the treatment of respiratory tract infections: 12 cases of pneumonia, 1 case of pulmonary suppuration, 6 cases of chronic bronchitis and 4 cases of bronchiectasis. The drug was administered by intravenous drip infusion at a daily dose of 2 g twice a day for the periods of 4 to 14 days.
    In eight out of 23 cases, causative bacteria were isolated from sputum.
    The clinical efficacy was excellent in 7 cases, good in 9 cases, poor in 3 cases and unevaluable in 3 cases. The rate of efficacy was 85.0%.
    Neither side effect nor abnormal laboratory findings attributable to this drug were observed.
    The above results suggested that AC-1370 is a useful drug for severe respiratory tract infections.
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  • HAJIMU TAKEDA, MORITO IWANAGA, KOUICHI WADA, TAKAO MORIMOTO, MASAAKI A ...
    1984 Volume 32 Issue Supplement9 Pages 317-322
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 is a new parenteral cephalosporin antibiotic. The antibiotic was intravenously administrated to two patients with acute cystitis, each one patient with acute pyelonephritis, acute tonsillitis, chronic bronchitis, chronic bronchiolitis and fever of unknown origin, and eight patients with pneumonia. These patients received the drug for 3 to 38 days in doses of 1 to 4g/day. Twelve of these patients responded well in the therapy. Rash with and without fever were recognized as adversed effect in two patients.
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  • YOSHIMARU USUDA, OSAMU SEKINE, NOBUKI AOKI
    1984 Volume 32 Issue Supplement9 Pages 323-331
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was administered to 16 cases (respiratory tract infections 10 cases; urinary tract infections 3 cases; biliary tract infections 2 cases). They received 0.5-2.0g of AC-1370 by intravenous injection over a period of 3-5 minutes or 30-60 minutes once or twice daily. One case was excluded from the evaluation of clinical effect (Case 16 was prophylactic chemotherapy). Clinical effects of 15 cases were excellent in 3 cases (2 cases of respiratory tract infections, one case of urinary tract infection), good in 9 cases (5 cases of respiratory tract infections, 2 cases of urinary tract infections, 2 cases of biliary tract infections), fair in one case of respiratory tract infection, and poor in 2 cases of respiratory tract infections. Among 16 cases treated with AC-1370, serious adverse reactions were not observed.
    Serum and urine levels of AC-1370 were studied in 4 cases during the therapy with AC-1370. Elevation of serum levels and prolongation of serum half-life of AC-1370 correlated with the degree of renal dysfunction. Urinary excretion of AC-1370 decreased in parallel with the degree of renal dysfunction. Dosage modification of AC-1370 is necessary in patients with renal dysfunction.
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  • YASUTOSHI SUZUKI, FUSANOSUKE YAMASAKU
    1984 Volume 32 Issue Supplement9 Pages 332-336
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was used in 10 cases (bronchiectasis 1 case, pneumonia 3 cases, cholecystitis 4 cases, chronic pyelonephritis 1 case and acute pyelonephritis with sepsis in 1 case). Efficacy was evaluated to be excellent in 2 cases, good in 6 cases and poor in 2 cases. AC-1370 was effective in 8 out of 10 cases in total for a rate of effectiveness of 80%. Adverse reaction to AC-1370 consisted of 1 case of skin rash and 1 case of slightly elevated GOT and GPT.
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  • KENZO TAKAGI, KENICHI YAMAKI, RYUJIRO SUZUKI, IKUO YAMAKAWA, MICHIHIRO ...
    1984 Volume 32 Issue Supplement9 Pages 337-342
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was administered to 20 patients with respiratory tract infection. The drug was administered by D. I. injection twice a day with the dosis of 1 to 2g and total dosis ranged from 12 to 40g.
    The following results were obtained.
    1) Clinical response to the therapy was excellent in 3 cases, good in 11 cases, fair in 4 cases and poor in 2 cases. Effective rate was 70.0%.
    2) As for side effects, the elevation of GOT and GPT was found in 2 cases, but it was transient.
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  • MASAHITO KATO, JOICHI KATO, KAZUO YOSHITOMO, KUNIO NANJO, TOSHIHIKO TA ...
    1984 Volume 32 Issue Supplement9 Pages 343-348
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Laboratory and clinical studies on AC-1370 were performed and the following results were obtained.
    1) Minimum inhibitory concentration (MIC) of AC-1370 were determined in 172 clinical isolates of S. aureus (25 strains) and Gram-negative bacilli (E. coli, K. pneumoniae, S. marcescens, Proteus and P. aeruginosa) compared with those of CPZ. Although the activity of AC-1370 was equal to that of CPZ against P.mirabilis, it was several grades inferior to CPZ against S. aureus and other Gram-negative bacilli.
    2) Clinical trial of AC-1370 was performed in 16 patients, 10 with pneumonia, 1 with lung abscess, 2 with acute bronchitis, 1 with acute bronchiolitis, 1 with D.P.B. and 1 with biliary tract infection. Response of respiratory tract infections was excellent in 2, good in 9, fair in 3 and poor in 1, and that of biliary tract infection was fair. Effectiveness rate was 68.8%. Bacteriologically, organisms were eradicated in 3 cases (1 with S. pneumoniae and 2 with E. agglomerans), and replaced in 1 case (P. aeruginosa, Acinetobacter) out of 4 from whom causative organism was detected before therapy.
    3) Side effect and adverse reactions were observed in 8 out of 16 cases including skin eruption with eosinophilia (3)(with elevation of GOT and Al-P (1) and with that of GPT (1)), elevation of transaminase (3), decrease of WBC and RBC (1) and positive coombs test (1), respectively.
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  • HIROYOSHI SAWADA, MASAROU TASHIMA, YOUICHIROU IZUMI, HIROTO ISHIKURA, ...
    1984 Volume 32 Issue Supplement9 Pages 349-352
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370 was applied to 10 patients with various infections.
    Nine patients had hematological malignancies, and a case had lupus erythematosus. Excellent or goodresults were obtained in a case of two cases with septicemia, all 3 cases with respiratory infections, a casewith tonsillitis, a case of 3 cases with fever of unknown origin, secondary to intensive chemotherapy, a caseof pyelitis. No side effect was obtained.
    It is expected that this antibiotic may constitute an advance in the antibiotic treatment.
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  • MICHIYASU NAKANISHI, NOBUO SAKURAI, TAKAKO MURAYAMA, NOBUO MAEKAWA, NO ...
    1984 Volume 32 Issue Supplement9 Pages 353-358
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephalosporin antibiotic, was applied for the treatment of 14 patients with respiratory tract infections.
    The drug was administered intravenously, 2-4 g/day, divided into two doses, for the period of 3 to 22 days.
    The results were as follows, excellent in three cases, good in four cases, slightly good in three cases, ineffective in one case.
    Remaining three cases were excluded due to unsuitability for the trial. Effectiveness rate was 63.6%. Side effect was found in one case (rash), and abnormal laboratory data were found in three cases.
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  • YURUKO OKAMOTO, KEIGO MAEHARA, KANSHI MASE, SEIBUN YONEZU, MUNETO YOSH ...
    1984 Volume 32 Issue Supplement9 Pages 359-380
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephem invented by AJINOMOTO Co. and developed by MOCHIDA Pharmaceutical Co., was examined on its antibacterial activity in vitro as well as on its clinical effectiveness. The results obtained were as follows:
    1) Antibacterial activity in vitro: Bacterial strains isolated from human infection foci were examined on their sensitivities against AC-1370 in comparison with those against cefoperazone (CPZ), cefotaxime (CTX), and cefazolin (CEZ).
    Strains of each species showed sensitivities against those antibiotics in the orders as follows:
    S. aureus: CEZ>CTX>CPZ>AC-1370 E. coll. CTX>CPZ>CEZ AC-1370 Klebsiella: CTX>CPZ>CEZ>AC-1370 Serratia: CTX>CPZ AC-1370 CEZ E. cloacae: CTX>CPZ>AC-1370 CEZ P. aeruginosa: CPZ t AC-1370>CTX P. mirabilis: CTX CPZ AC-1370>CEZ Indole (+) Proteus: CTX>CPZ>AC-1370 I, : CEZ
    2) Blood levels and urinary excretion: A 38y old male suffering from bronchial asthma with normal renal function was administered with i.v. drip infusion of 1 g AC-1370 for one hour. The blood level of the drug rose up to the peak of 92 μg/ml at the end of the infusion, gradually descending down to 1.1 gg/ml six hours thereafter. 88.3% of the dose was recovered from his urine in seven hours.
    Taking this opportunity, the lengths of the inhibitory zones produced by AC-1370 on agar plates (“Band Culture Method” OKUBO) were compared among the drug solutions diluted with fresh human serum, inactivated human serum, “monitrol” serum, and phosphate buffer: The inhibitory zone was longest when the solution was made of fresh human serum.
    3) Clinical trials: Eighteen patients (RTI 12, UTI 3, BTI 2, and subcutaneous phlegmon 1) were treated with AC-1370 0.5-2.0 g twice daily by d.i. Two of the RTI cases were dropped out during the administration as they were diagnosed as pulmonary tuberculosis. Eleven of the remaining 16 cases (68.8%) well responded to the therapy, and two fairly. Neither clinical untoward reactions nor abnormal laboratory findings attributable to the drug administration were observed except for GOT and GPT elevation in two of the patients.
    Considering the reported evidence that AC-1370 shows significant in vivo activity against experimental infections despite its relatively weak antibacterial activity in vitro, the drug should become one of the useful chemotherapeutics in the clinic.
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  • FUMIO MIKI, KENJI TAKAMATSU
    1984 Volume 32 Issue Supplement9 Pages 381-386
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    AC-1370, a new cephem antibiotic, was studied bacteriologically and clinically and the following results were obtained:
    MICs of AC-1370 was determined against clinical isolates of various species. The peak of MIC distribution curve was observed at 12.5 μg/ml for S. aureus, at 3.13 μg/ml for E. colt, at 100 μg/ml for K. pneumoniae, at 1.56 and not less than 100 μ/ml for P. mirabilis, at 100 μg/ml for P. vulgaris, and at 100 μg/ml for P. aeruginosa.
    AC-1370 was administered to 9 patients including 7 cases of bacterial pneumonia, 1 case of chronic bronchitis and 1 case of chronic cystitis at a daily dose of 1 to 4 grams twice a day for 2 to 15 days by intravenous drip infusion. The clinical response was excellent in 1 case, good in 2 cases and poor in 4 cases for7 cases of pneumonia, and good in each case of chronic bornchitis and cystitis.
    Neither side effect nor abnormal laboratory findings were observed.
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  • YOSHIHITO NIKI, JIRO HINO, MASATOSHI WATANABE, MASAYOSHI KAWANISHI, NI ...
    1984 Volume 32 Issue Supplement9 Pages 387-394
    Published: December 25, 1984
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Fundamental and clinical studies of AC-1370, a new injectable cephem, were carried out, and the following results were obtained.
    1) Sensitivities of clinically isolated strains to AC-1370 were tested by agar plate dilution method and compared with those of cefazolin (CEZ), cefmetazole (CMZ) and cefoperazone (CPZ).
    The MICs of AC-1370 against S. aureus were inferior to those of CEZ, CMZ and CPZ. Antimicrobial activities of AC-1370 against gram negative bacterias except Ps. aeruginosa were almost equal or inferior to those of CMZ. The MICs against Ps. aeruginosa were superior to those of CMZ but inferior to CPZ and the peak MIC value of AC-1370 was 100μg/ml.
    2) The quantitative NBT reduction test of murine alveolar macrophages in vitro was accelerated in the presence of 100 μg/ml of AC-1370, but not in the same concentration of cefmenoxime (CMX).
    3) The maximum serum levels after 1.0 g drip infusion of AC-1370 over a period of 1 hour was 47.0 μg/ml; 10.01.tgiml at 2 hours and 3.6 μg/ml at 4 hours from after start of infusion.
    The urinary excretion rate of AC-1370 up to 6 hours was 92.1%. 4) Eleven patients with respiratory tract infections were administered with doses of 1.0 g of AC-1370 twice a day by drip infusion ranging from 4-21 days.
    The clinical efficacy was good in 6, fair in 3, poor in 1, unevaluable in 1. The effective rate was 60.0%.
    Eruption was observed in one patient but no abnormal laboratory findings were observed.
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