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Study group of latamoxef of obstetric and gynecological infections
ZENJIRO TAKASE, HIROKO SHIRAFUJI, SEIJI MATSUDA, MIKIHIKO TANNO, TAKAS ...
1983 Volume 36 Issue 1 Pages
1-15
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
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Latamoxef (LMOX) is a new antibiotic synthesized by Shionogi Research Laboratory. Chemically LMOX is especially unique with a sulfur atom replacing the oxygen atom in the 1 position of the conventional cephalosporin nucleus, and in addition, this antibiotic has a cephamycin-like structure.
The antibacterial activity of LMOX shows high potency against Gram-negative bacteria, but tends to be weak against Gram-positive bacteria.
The tissue levels of LMOX in humans after intravenous injection of 1 g were examined. The levels in uterine and adnexa uteri tissue at 1 hour after administration were 25.4 and 27.4 itigig respectively. LMOX was administered to 147 cases in infections of obstetric and gynecological field. The clinical effect according to disease was 94.6% for intrauterine infections, 95.0% for adnexitis, 87.0% intrapelvic infections, and 100% for external genital organ infections, making a total of 92.5%. The rate of occurrence of side effects or abnormal laboratory findings was similar to or slightly less than that seen with other beta-lactam antibiotics.
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GOHTA MASUDA, MASAYOSHI NEGISHI, CHENDEN YOUNG, TAKETO MUKAIYAMA, NAOK ...
1983 Volume 36 Issue 1 Pages
16-21
Published: January 25, 1983
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The antibacterial activity of latamoxef (LMOX) was assessed against clinical isolates comprising 54 strains of
Escherichia coli, 54 of
Klebsiella sp., 81 of
Serratia marcescens and 52 of
Bacteroides fragilis. Bacteriostatic and bactericidal activities were evaluated with special reference to the time of exposure of the organisms to the drug. The agar dilution MICs for a major number of test strains were; 0.1-0.2 μg for
E. coli and
Klebsiella sp., 0.39-3.13 μg for
S. marcescens, and 0.39-0.78 μg for
B. fragilis of this compound per ml. The MICs by the broth method were 2-8 times higher than those by the agar method for most strains of
E. coli, Klebsiella sp. and
S. marcescens. The broth MICs for
B. fragilis were generally slightly lower than those determined on agar. No significant difference was observed between the values of 24-h MLC (99.9% kill concentration with an incubation period of 24 hours) and the broth MIC, which suggests that this compound is a bactericidal drug. To evaluate the timed bactericidal activities of LMOX, the lowest concentrations of the drug producing 99.9% reduction of CFU after incubation of 3, 6 and 24 hours in broth medium were determined and designated as 3-h, 6-h and 24-h MLCs, respectively. The lowest drug concentrations producing no increase of CFU after 3, 6 and 24 hours of incubationan approximation to the theoretical bacteriostatic concentration were also determined and designated as 3-h, 6-h and 24-h MRCs, respectively. If the apparent mode of action was categorized to be bactericidal when the ratio of bactericidal concentration/bacteriostatic concentration was low (≤4) and bacteriostatic when high (≤8), then this drug was bacteriostatic to most of the Gram-negative organisms at short incubation periods (3-6 hours). The drug appeared to be bactericidal when the incubation time was prolonged to 24 hours. These results correspond favourably with those obtatined by the conventional timekill curve studies. The strains of
S. marcescens surviving after 24, 48 and 72 hours' incubation with LMOX in broth medium were examined for agar dilution MICs and designated as 24 h, 48 h and 72 h R-MICs, respectively. These R-MICs were compared with the MICs of the original strains. The median value of the 24 h R-MIC/MIC ratio was 1. However, the ratio increased to 8-16 and even to 64-256, although only for a small number of strains, if 48 h and 72 h R-MICs were used as the numerators.
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HIROYUKI ISOBE, TOMOYA TOYOURA, HARUO SAKAMOTO, YOSHIO YAMADA, JUN GOT ...
1983 Volume 36 Issue 1 Pages
22-30
Published: January 25, 1983
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Tissue concentrations of cefmetazole (CMZ) in rabbits were 17-49% of the blood levels at the corresponding time. Transfer pattern of CMZ was very similar to the pattern of the blood level, suggesting to be supposable the tissue concentration of CMZ.
The clinical trial was studied concentrating on the observation of side effects and laboratory findings, especially the change of transaminase after anesthesia with GOF (gas-oxygen-fluothane).
Four cases, who had anethesia with GOF, revealed the elevation of transaminase.
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TAKESHI MIYANO, TAKEO ARAI, KEIJIRO SURUGA
1983 Volume 36 Issue 1 Pages
31-36
Published: January 25, 1983
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Antibiotics excretion into the bile was studied using CMZ which was administered by drip infusion in 12 postoperative cases of congenital bile duct atresia patients who had hepatic portojejunostomy with SURUGA II type enterostomy with the following results.
Group I (correctable type children, with good bile flow, no jaundice): Excellent excretion was almost thesame as that seen in adult patients.
Group IIa (uncorrectable type children, with good bile flow, no jaundice): Excretion was poor but good depending on the amount of bile flow and liver function.
Group IIb (uncorrectable type children, with poor bile flow, jaundice): Excretion was very poor.
Group III (uncorrectable type infants, with good flow, no jaundice): Excretion was good depending on the amount of bile flow and liver function.
Our study indicates that antibiotics excretion into the bile in children is closely related to the condition of the hepatic function and biliary passage.
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MASATO SAITO, KAZUO SHIBATA, TAKESHI NISHINO, TERUO TANINO
1983 Volume 36 Issue 1 Pages
37-46
Published: January 25, 1983
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The combined actions of sisomicin (SISO), gentamicin (GM) and piperacillin (PIPC), cefmetazole (CMZ) against
Pseudomonas aeruginosa E-2 and
Serratia marcescens T-55 were studied. The following results were obtained.
1. The combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ using the checker board dilution method on
P. aeruginosa E-2 and
S. marcescens T-55 were found to have a synergistic effect and the minimum FIC index values were 0.38 in all combinations.
2. With the killing kinetic method, all combinations tested showed a synergistic effect.
3. A synergistic effect of the combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ was observed in the protective effect on experimental
P. aeruginosa E-2 and
S. marcescens T-55 infections in mice.
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KEISUKE SUNAKAWA, HIRONOBU AKITA, KEIJI JOZAKI, SATOSHI IWATA, YUKIO I ...
1983 Volume 36 Issue 1 Pages
47-54
Published: January 25, 1983
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Pharmacokinetics of gentamicin in children after intravenous infusion over 60 minutes were compared with that after intramuscular injection.
1. Mean measured peak serum levels after intravenous infusion of 2.5mg/kg and intramuscular injection of 2.0mg/kg were 6.1mu;g/ml at termination of infusion and 6.5mu;g/ml at 30 or 60 minutes after injection, respectively. Older children showed higher serum levels.
2. There was no difference in serum half-life between both modes of administration.
3. The AUC after intravenous infusion was slightly larger than that after intramuscular injection.
4. It was suggested that the efficacy and safety of the treatment by intravenous infusion in children are comparable to that by the intramuscular injection, and optimum single dose is 1.5-2.5mg/kg.
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TAKASHI NAKAMURA, IKUO HASHIMOTO, YASUO SAWADA, JIROH MIKAMI, MICHIKO ...
1983 Volume 36 Issue 1 Pages
55-70
Published: January 25, 1983
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An antibiotic drug of aminoglycoside group, gentamicin (GM) for parenteral use was used to 14 hospitalized patients; 5 with acute or subacute cholecystitis, 6 with acute peritonitis (4 cases were due to acute appendicitis, a case was torsion of right ovarian cyst and a case was cecal CROHN'S disease), 1 with fistula ani and abscess, and 2 with localized peritonitis after gastrectomy due to gastric ulcer. GM in a dose of 60 mg were administered by intravenous drip infusion for 1 to 2 hours, twice a day for 4 to 12 days. To the cases of biliary tract infection, GM was treated for preoperative chemotherapy and to the other cases GM was treated for postoperative chemotherapy. Clinical response was excellent in 7 cases, good in 6 cases, fair in 1 case and poor in none. No adverse effect was observed. The organisms were isolated in 7 cases, 7 were
Escherichia coli, 2 were
Klebsiella pneumoniae and 3 were
Bacteroides fragilis. The MICs for GM were 0.78-1.56 augiml in 108 and 106 cells/ml, except
B. fragilis.
Before the operation of above cases, GM in a dose of 60mg (a case was 40mg) were administered by intravenous drip infusion for 1 to 2 hours in 7 cases (3 biliary tract infection, 2 acute peritonitis and 2 gastric ulcer) and 7 cases by intramuscularly. The materials of common duct bile, gall bladder bile, gall bladder wall, the appendix and other tissues, ascites and serum samples were taken during the operation. GM concentration was measured by bioassay method with
Bacillus subtilis ATCC 6633 as test organism. GM concentrations in bile and gall bladder wall after intravenous drip infusion were higher than those after intramuscular administration. In the appendicitis with localized peritonitis, GM concentration in the appendix wall with catarrhal appendicitis was 0.90μ/g after intramuscular administration. In the cases with diffuse. peritonitis and catarrhal appendicitis, GM concentrations in appendixes were 1.18μ/g and 1.37μ/g after intravenous drip infusion.
Therefore, it was supposed that GM could be used safety and usefully by intravenous drip infusion than that by intramuscular administration.
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TAIJIRO ISHIYAMA, TATSUO MIYAYAMA, NAOKI SUGAYA, HARUO NOMOTO, MASAKUN ...
1983 Volume 36 Issue 1 Pages
71-75
Published: January 25, 1983
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Prophylaxis effect and clinical therapy of combination use of cefotiam (CTM), sulbenicillin (SBPC) and cefsulodin (CFS) have been investigated, and the results were as follows.
1. Prophylaxis effect of CTM-SBPC combination therapy was very useful. CTM-SBPC combination therapy was performed to patients who are at high risk for infectious complications. Prophylaxis effect of CTM-SBPC was judged by fever over 38°C, and was better than usual antibiotic treatment.
2. CTM-SPBC-CFS combination therapy was performed against severe infections during early remission, and the overall effectiveness rate was 83.3% (5/6).
3. No remarkable side effect was observed in this investigation.
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ISSEI TANAKA, SIZUAKI HOSOMA, HISASHI OSIRO, YASUZI YAMAMOTO, KEIZO SU ...
1983 Volume 36 Issue 1 Pages
76-83
Published: January 25, 1983
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CTM (1.0g/100ml) was administered through intravenous drip infusion 1 hour for abdominal operative patients, and subsequent CTM excretions into biliary tract and ascites were studied.
1. The serum concentration of CTM was about 44μg/ml in the peak level at the end of the administration and decreased gradually in the simulation curve. The effective serum concentration was maintained until 6 hours and its value was 2.5μg/ml after 6 hours.
2. The excretion of CTM into ascites was studied in 11 cases. The simulation curve, which was described by computer system, showed the peak level in ascites was 20.3 μg/ml at 1.74 hours after the administration and the concentration at 6 hours was 7.0μg/ml. In infected group, CTM was significantly excreted into ascites more rapidly and higher than in noninfected group; the maximum level was 29μg/ml and the effective level was kept up to 6 hours.
3. CTM excretion into biliary tract was studied in 12 operated gall stone cases. The samples of the bile in common bile duct, the bile in gall bladder and the wall of gall bladder were obtained during the operation at 2.5 hours after the administration; each level was remarkably high, 529.25±328.10μg/ml, 366.98±401.86μg/ml, 70.75±93.88μ/g, respectively. In these cases, 6 had nonvisualized cholecystogram, 3 had white bile and 4 had mild liver disorder with increased transaminase. In the cases of nonvisualized cholecystogram the levels in gall bladder bile and gall bladder wall were significantly lower than in visualized cases; 43.5±67.5vs. 691±315g/ml, 3.3±2.4vs. 151.7±83.7μg/g, respectively. In the cases with white bile, the level in gall bladder bile was significantly lower than nonwhite bile cases; 0.23±0.21vs. 489±393 μg/ml, respectively. In the cases with liver disorder, the level in bile of common bile duct was lower than that of normal liver cases; 196±22.3vs. 729±234μg/ml, respectively.
4. In 4 cases had external bile drainage because of choledocholithiasis (1 case) and malignant biliary tumor (3 cases) with obstructive jaundice, serial CTM levels in the bile were measured. In a choledocholithiasis case whose hepatic damage was mild, CTM level in the bile was 152μg/ml after 2 hours of the administration as the maximum, and effectively maintained up to 6 hours. However, the cases who had severe liver damage with obstructive jaundice showed remarkably low levels of bile CTM concentration. In these cases, CTM excretion into the bile was remarkably low.
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AKIRA ITO, KUNIHIKO SHINDO, HIROSHI SAKAMOTO, FUMIHIKO SANO, YOSHIAKI ...
1983 Volume 36 Issue 1 Pages
84-92
Published: January 25, 1983
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Ten patients with sepsis and pneumonia complicated by leukemia or lung cancer were treated with cefoxitin (CFX) at daily dose of 6 g.
The following results were obtained.
1. Clinical effects of CFX were good in 5 patients, fair in 2 and poor in 3 with effective rate of 50%.
2. Out of 8 patients with sepsis, 5 showed good response to CFX and effective rate was 62.5%.
3. Bacteriological outcomes were eradicated in 1, unchanged in 1, replaced in 2 and unknown in 6 cases.
4. Diarrhea was observed in 1 patient but this was not considered related to CFX therapy.
5. No abnormal laboratory finding due to CFX was observed.
6. It should be considered that 6 g or more of CFX is given in case of severe infections, such as sepsisor pneumonia complicated by serious underlying diseases.
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TAKASHI MOTOHIRO, KOICHI TANAKA, TATSUHIKO KOGA, YASUSHI SHIMADA, NAOF ...
1983 Volume 36 Issue 1 Pages
93-102
Published: January 25, 1983
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The newly developed cefadroxil (CDX) dry syrup in a mean daily dose of 32.9 mg/kg t. i. d. or q. i. d. was administered to children for a period of 8 days on the average; viz. a total of 64 cases consisting of 39 cases of tonsillitis, 2 of tonsillitis complicated with otitis media, 1 of bronchitis, 1 of pneumonia, 14 of scarlet fever, and 7 of urinary tract infections; and its clinical and bacteriological effects, and adverse reactions wer examined, leading to the following results.
1. The clinical effects were “good” or “excellent” in any of 39 cases of tonsillitis, 2 of tonsillitis complicated with otitis media, 1 of pneumonia, 14 of scarlet fever, and 7 of urinary tract infections, and “fair” only in a case of bronchitis, showing the high efficacy of 98.4%.
2. The clinical effects by daily dose were compared only in the great cases of tonsillitis between the 2 daily dose groups of 30mg/kg or below and 31 to 40 mg/kg, and both groups showed “good” or “excellent” results, but the latter group revealed that the excellent rate was greater by 20.8% than that of the former group.
3. The frequency of daily administration was 3 times or 4 times and the cases of 4 times administration were few in any disease. In comparison of clinical effects between the 3 times group and the 4 times group in the whole cases, no significant difference was observed between both groups but it is desirable to make the 4 times administration in view of the pharmacokinetics.
4. The bacteriological effects could be judged in 15 cases, namely bacteria were eradicated in 14 cases and unchanged in 1 case, showing a good result of the eradication rate as 93.3%.
5. No adverse reaction was observed and the laboratory test values showed eosinophilia in 7 cases (15.9%) and abnormal elevations of GPT in 1 case (4.5%), of GOT and GPT in 2 case (9.1%), of LDH in 1 case (4.8%) and of BUN in 1 case (4.8%), but 4 of the 7 cases with eosinophilia seemed attributable to underlying diseases or objective diseases.
From the above it can be said that this preparation is a useful drug in mild bacterial diseases.
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YUTAKA KANAZAWA, TOSHIO KURAMATA, KIYOYUKI MATSUMOTO
1983 Volume 36 Issue 1 Pages
103-110
Published: January 25, 1983
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Susceptibilities of 101 strains of 34 bacterial species to cefsulodin (CFS) were determined by the 2-foldagar dilution method in parallel with the diameter of inhibition zone by the single-disc method, under the experimental condition established by KANAZAWA.
The experiments demonstrated significant correlation between MIC by the dilution method and diameter of inhibition zone in each of conventional assay of the over-night (about 16 hours) incubation, delayed assay (about 24 hours incubation), and rapid assay (about 3-4 or 5-6 hours incubation), thus confirming applicability of the single-disc assay for CFS.
Analysis of the data obtained by using CFS disc containing 30μg revealed the primary regression equation to be: D (diameter, mm)=30.0-12.1 log MIC (μg/ml) in nventional assay, D=36.3-15.6 log MIC (μg/ml) in delayed assay, D=25.2-9.0 log MIC (μg/ml) in 5-6 hours rapid assay, and D=20.4-6.4 log MIC (μg/ml) in 3-4 hours rapid assay, spectively.
The range of variations in MICs estimated from the diameters of inhibition zone by the disc test was then calculated in comparison with that in MICs determined by the 2-fold agar dilution assays, as eference for the experimental errors which may be involved in the estimation of MICs of CFS by the single-disc assay.
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JUN IGARI, NOZOMU KOSAKAI, TOYOKO OGURI
1983 Volume 36 Issue 1 Pages
111-116
Published: January 25, 1983
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The present study concern
in vitro observation on the susceptibility to 20 antibacterial agents of the strains of
Flavobacterium meningosepticum from clinical specimens at Juntendo University Hospital during the 1 year period of 1981. The tests for susceptibility of the 144 strains to the drugs were all performed by the serial 2-fold agar plate dilution method on MUELLER HINTON agar (Difco), standardized by the Japan Society of Chemotherapy using the Microplanter apparatus with one loop of approximately 10
8cells/ml. The antibacterial agents tested were as follows; ampicillin, sulbenicillin, piperacillin, mezlocillin, cefazolin, cefmetazole, cefoperazone, cefotaxime, ceftizoxime, kanamycin, gentamicin, tobramycin, amikacin, tetracycline, doxycycline, minocycline, nali-dixic acid, pipemidic acid, erythromycin and clindamycin.
1. Thirty-seven per cent of the strains were isolated from sputum, 23% from urine (≥10
5ml), and 18% from pus and exudate. Only 3 and 2 strains were isolated from cerebrospinal fluid and blood, respectively.
2. A large number of the strains tested were highly resistant to ABPC, SBPC, CEZ, KM, TOB, AMK, PPA and EM, and moderately resistant to PIPC, MZPC, CMZ, CPZ, CTX, CZX, GM, TC and NA. The most of the strains were highly sensitive to MINO, CLDM and DOXY in this order. There was no strain resistant to MINO in this study.
3. The yearly change of the antibacterial activities of DOXY, MINO, CLDM was not significant and 9% of the strains in 1981 were highly resistant to CLDM. The strains resistant to EM were more frequently seen in 1981 than in 1974-1976.
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MATSUHISA INOUE, SHINJI MASUYOSHI, SUSUMU MITSUHASHI
1983 Volume 36 Issue 1 Pages
117-123
Published: January 25, 1983
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Cefotaxime (CTX) was compared with other cephems concerning stability to β-lactamases and affinity to penicillin-binding proteins of
Escherichia coli JE1011.
The results are summarized as follows.
1. CTX showed potent activity against bacteria whose resistance is mediated by plasmids on chromosomal genes.
2. The antibacterial activity of CTX was not influenced by the transfer of 25 different plasmids to
E. coli ML1410.
3. CTX was stable to typical cephalosporinases (CSases). This compound was slightly hydrolyzed by cefuroximases (CXases).
4. There was no difference between CTX and other cephems in the affinity to β-lactamases.
5. CTX showed high affinity to the 1A, 1Bs and 3 fractions of penicillin-binding proteins of
E. coli JE1011.
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YOSHIAKI SAKAGUCHI, KENJIRO MURATA, MASAHIDE KIMURA, USAMI YAMANOSHITA ...
1983 Volume 36 Issue 1 Pages
124-128
Published: January 25, 1983
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Cefotaxime (CTX) disks and ampicillin (ABPC) disks exhibited synergism against 24 strains of
Streptococcus D group isolated from various sources in our hospital.
We were interested in these synergism effec ts and compared them with the combination index.
Twenty-two out of the 24 strains examined exhibited synergism, and were identified as
Streptococcus faecalis by the API strep system.
We divided th em into 4 groups (combination index: 19, 15, 11, 9) according to the degree of synergism. Another 2 strains showed additive effects (combination index: 1), and were identified as
Streptococcus faecium.
Among these 24 strains,β-lactamases were produced by only 1. There was no direct connection between β-lactamase production and synergism. The mechanism of synergism between CTX and ABPC has not yet been studied.
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MITSUO OHKAWA, SHOJI HIRANO, TAKAO NAKASHIMA, SHUJI TOKUNAGA, ISAMU MO ...
1983 Volume 36 Issue 1 Pages
129-149
Published: January 25, 1983
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We conducted a randomized double blind comparison of cefamandole (CMD) and cefmetazole (CMZ) in the treatment of 193 patients with complicated urinary tract infections. The patients received 1 gram of CMD or CMZ twice a day intravenously by drip infusion over 1 hour for 5 days. Pretreatment urinary leukocyte counts and urinary bacterial counts were at least 5 cells/hpf and 10
4bacteria/ml, respectively. Each patient was randomly allocated either to CMD or CMZ group. There were 93 patients in CMD group and 100 patients in CMZ group. Clinical efficacy was evalutated based on the effect of treatment on bacteriuria and pyuria according to the criteria set by the UTI Committee, Japan. The response to CMD treatment was excellent in 18 cases (19.4%), moderate in 38 cases (40.9%) and poor in 37 cases (39.8%) with an overall effectiveness of 60.2%, whereas the response to CMZ was excellent in 19 cases (19.0%), moderate in 40 cases (40.0%) and poor in 41 cases (41.0%) with an overall effectiveness of 59.0%. No statistical significant difference was found between 2 treatment groups. Comparison of the bacteriological response between 2 groups showed that the eradication rate for strains of Gram-positive cocci were significantly higher in those patients treated with CMD. Gramnegative rods were eradicated from 68.4% of cases treated with CMD, and 78.0% of those with CMZ, but the difference was not significant. Adverse reactions were observed in 3 patients receiving CMD 1 case each of diarrhea, eruption and epigastric pain. Abnormality in labolatory tests was found in 6 patients in each treatment group. The results indicate that CMD is effective, safe and useful in the treatment of patients with complicated urinary tract infections, and its efficacy, safety and usefulness are comparable with those of CMZ.
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SUBACUTE AND CHRONIC T O XICITY IN DOGS
TAKUJI HARA, SATOSHI NISHIKAWA, HIDEHARU MIYAZAKI, YUJI OHGURO
1983 Volume 36 Issue 1 Pages
150-173
Published: January 25, 1983
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Micronomicin (MCR) is a new aminoglycoside antibiotic produced by
Micromonospora sagamiensis var.
nonreducans which was isolated from soil collected at Sagamihara by NARA et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties.
The antibacterial activity of MCR is broad-spectrum and almo st equal to that of gentamicin C complex. MCR exhibits particularly high activity against
Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some
Pseudomonas aeruginosa strains resistant to gentamicin C
1a.
Toxicological studies of MCR in dogs were carried out by intravenous injection fo r safety evaluation.
1. Study on subacute toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 4, 10, 25, 63 mg/kg and 100 mg/kg for 30 days.
2. Study on chronic toxicity: Beagl e dogs were injected intravenously with MCR at the dose levels of 1.6, 4 mg/kg and 10 mg/kg for 180 days.
The results of the studies are as follows:
1. In the subacute toxicity stud y, animals died at the dose level of 100 mg/kg (3 out of 6 animals). Main changes observed were renal disorders and ataxia which showed a close similarity to those seen during intramuscular toxicity studies in dogs. The renal histological disorders occurred at the dose levels of 10 mg/kg and over, but they were slight at the dose levels of 10 mg/kg and 25 mg/kg. Ataxia was observed at the dose levels of 63 mg/kg and over, but its grade was slight at the dose level of 63 mg/kg.
2. In the chronic toxicity study, animals did not die at any do se. Renal disorders occurred; they were almost similar to those observed in the subacute toxicity study and were slight at the dose level of 10 mg/kg. Ataxia was not observed at any dose.
3. The maximum safety d ose was equal to in the subacute toxicity and chronic toxicity study (4 mg/kg). Therefore, cumulative toxicity by intravenous injection seemed very slight.
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IRRITATION BY REPEATED INTRAVE N OUS INJECTION IN DOGS
TAKUJI HARA, SATOSHI NISHIKAWA, HIDEHARU MIYAZAKI, YUJI OHGURO
1983 Volume 36 Issue 1 Pages
174-176
Published: January 25, 1983
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Micronomicin (MCR) is a new aminoglycoside antibiotic prod uced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by NARA et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties.
The antibacterial activity of MCR is broad-spectrum and almo st equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a.
A study on the irritation by repeated intravenous injection in dogs was carrie d out for safety evaluation (Doses: 4, 10, 25, 63 mg/kg and 100 mg/kg). Bleeding, edema, vasculitis and perivasculitis were ob served at injection sites both in physiological saline-treated controls and MCR-treated groups. But irritation attributable to MCR was not observed at any dose.
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TERATOGENICITY STUDIES IN RATS
TAKUJI HARA, SATOSHI NISHIKAWA, HIDEHARU MIYAZAKI, YUJI OHGURO
1983 Volume 36 Issue 1 Pages
177-181
Published: January 25, 1983
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Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by NARA et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties.
The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin Cla.
Teratogenicity studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50mg/kg and 75mg/kg). The results of studies are as follows.
1. Fetal malformation attributable to MCR was not ob served at any dose.
2. Suppression of maternal weight gain was observed at the dose levels of 50 mg/kg and over.
3. There was no adverse effect on new borns at any dose.
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MASATOYO AKIYOSHI, TETSUJI NARA, TAKUJI HARA
1983 Volume 36 Issue 1 Pages
182-188
Published: January 25, 1983
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The present experiment was made to clarify the effect of intravenous adm inistration of micronomicin (sagamicin®MCR) on the inner ear of guinea pigs (300-350g). MCR was given to the animals intravenously at dose of 25, 50mg/kg and 100mg/kg, respectively for 28 days. Pinna reflex test in frequency range from 20 kHz to 0.5 kHz was performed before, during and after the administration. The temporal bones were removed after intravital perfusion of the inner ears with neutral formation after the end of the administration. Histopathological examination was performed on the serial celloidin sections of the inner ears which had been stained with hematoxylin eosin. The following results were obtained.
1. MCR had a mild corti toxicity, which did not show remarkable dose dependent increase.
2. MCR had more affinity for the vestibular organs than for the organ of corti. The affinity for the vestibular organ increased with increase in dose.
3. MCR showed less increase in cort i toxicity in intravenous administration than in intramuscular injection. However, the affinity of MCR for the vestibular organ showed little more increase in the intravenous administration than in the intramuscular injection.
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KINYA YAMASHITA, HARUSHIGE MINAGAWA, KIYOSHI SATO, KOZO KITAURA, RYO O ...
1983 Volume 36 Issue 1 Pages
189-193
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
JOURNAL
FREE ACCESS
Micronomicin (MCR, sagamicin & reg;) exhibited bactericidal enects at the lowest concentration among the tested aminoglycoside antibiotics, those were all bactericidal at lower concentrations than that of cefoperazone.
When MCR was combined with cefoperazone (CPZ) or piperacillin (PIPC), they showed synergistic activity on checker-board method against
Pseudomonas aeruginosa, and they were also synergistic against
Escherichia coli when MCR was combined with cefmetazole (CMZ) and cefoxitin (CFX).
MCR was synergistic against 40.7% and 44.4% of clinically is olated
P. aeruginosa at the fractionary inhibitory concentration (FIC) index 0.5 or less in combination with PIPC and CPZ, respectively. All of the remaining strains of P. aeruginosa were included in the partially synergistic range of FIC index 0.5 to 1.
Between MCR and CFX or CMZ, synergy was observed against 63.0% and 88.9% of clinical i solates of
E. coli at the FIC index less than 1.
Combined effects of MCR and PIPC or CPZ were observed investigating the growing curve of
P. aeruginosa, too.
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KIYOSHI SATO, TSUKASA KURIMOTO, RYO OKACHI
1983 Volume 36 Issue 1 Pages
194-198
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
JOURNAL
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Minimal inhibitory concentrations (MIC) of micronomicin (MCR) and gentamicin (GM) against clinically isolated Pseudomonas aeruginosa F 4150 were 1.56mcg/ml and 6.25mcg/ml, respectively.
Sisomicin, dibekacin, amikacin, netilmicin, tobramycin ribostamycin and kanamycin did not inhibit the strain at the concentrations less than 25mcg/ml.
Each aminoglycoside antibiotic was incubated in Tris-HC1 buffer solutions (pH 7.8) containing cell free crude enzyme preparations obtained by sonic oscillation of intact cells of P. aeruginosa F 4150, coenzyme A and adenosine-5'-triphosphate.
The residual activity at 3 hours of incubation at 37 & deg;C was 88% for MCR and 33.6% for GM, while all of the other aminoglycoside antibiotics tested were completely inactivated under this condition.
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NORIE YAMADA, MIDORI ISONO, KUNITOMO WATANABE, KAZUE UENO
1983 Volume 36 Issue 1 Pages
199-204
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
JOURNAL
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The antibacterial activity of micronomicin (MCR) as studied comparatively w ith that of AMK, GM, CMZ and CFX against 346 strains of
E. coli, K. pneumoniae, S. marcescens, P. mirabilis, P. rettgeri, P. vulgaris, M.morganii, E. cloacae, P. aeruginosa, S. aureus and
S. epidermidis isolated from patients with urinary tract infections on a nation-wide scale from January to July, 1981.
MCR was as high as GM in antibacterial activity against all of strains tested, especially very potent against
E. coif and
P. mirabilis. On the other hand, AMK showed a tendency to be a little lower in antibacterial activity than MCR and GM, CMZ and CFX were weaker in antibacterial activity against the strains tested in this study than MCR, AMK and GM.
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TAKASHI HIRAYAMA, KANEO KIKUCHI, KAZUO CHIBA
1983 Volume 36 Issue 1 Pages
205-208
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
JOURNAL
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The clinical effects of micronomicin (MCR, Sagamicin®) treatment for 10 patients with surgical infections were investigated and following results were obtained.
1. Clinical effectiveness Of 10 patients treated with MCR, the results were good in 7 cases, poor in 3 cases.
2. Side effects of MCR No significant side effects were observed in 10 patients treated with MCR.
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1983 Volume 36 Issue 1 Pages
209-212
Published: January 25, 1983
Released on J-STAGE: May 17, 2013
JOURNAL
FREE ACCESS