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[in Japanese]
1973 Volume 21 Issue 5 Pages
907
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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[in Japanese]
1973 Volume 21 Issue 5 Pages
908-914
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
JOURNAL
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[in Japanese]
1973 Volume 21 Issue 5 Pages
915-919
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
JOURNAL
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[in Japanese]
1973 Volume 21 Issue 5 Pages
920-924
Published: July 25, 1973
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[in Japanese], [in Japanese]
1973 Volume 21 Issue 5 Pages
925-931
Published: July 25, 1973
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[in Japanese]
1973 Volume 21 Issue 5 Pages
932-941
Published: July 25, 1973
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[in Japanese]
1973 Volume 21 Issue 5 Pages
942-952
Published: July 25, 1973
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[in Japanese]
1973 Volume 21 Issue 5 Pages
953-958
Published: July 25, 1973
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HIROSHI OSHIMA, TOYOJI OKUBO, NARUMI FUSE, HARUHIDE KAWABE, MATSUHISA ...
1973 Volume 21 Issue 5 Pages
959-963
Published: July 25, 1973
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Antibacterial activity of propionylmaridomycin was investigated by using
Staphylococcus aureus and gram-negative enteric bacteria which were isolated from clinical specimens. The results are summarized as follows :
1. Propionylmaridomycin is ineffective against gram-negative enteric bacteria including
Escherichia coli, Proteus, Klebsiella-Aerobacter group, and
Pseudomonas aeruginosa.
2. Propionylmaridomycin was not an active inducer for macrolide (Mac) inducible strains of staphylococci. Therefore, this agent was effective against both Mac-sensitive and Mac-inducible strains of staphylococci.
3. The staphylococcal strains carrying Mac-constitutive resistance were resistant to propionylmaridomycin.
4. Mac-inducers such as erythromycin and oleandomycin exhibited to be ineffective against mouse infected with staphylococcal strain carrying Mac-inducible resistance, and the microorganisms in the organs of animals treated with Mac-inducers, were found to acquire resistance to both Mac antibiotics and lincomycin. In contrast to this, propionylmaridomycin did not induce
in vivo Mac-resistance when mice infected with a staphylococcal strain carrying Mac-inducible resistance were treated with the drug.
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SHYOZO NAKAZAWA, HISAKO ONO, MASAKO OTSUKI, TAKESHI NISHINO, MASAFUMI ...
1973 Volume 21 Issue 5 Pages
964-974
Published: July 25, 1973
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Biological evaluation was made on propionylmaridomycin which was provided by the Research Laboratories of Takeda Chemical Industries, Ltd.
1) The antibacterial activity of this macrolide antibiotic was similar to that of the known macrolide antibiotics such as leucomycin or josamycin.
2) The components and metabolites of this macrolide antibiotic showed
in vitro and
in vivo antibacterial activity.
3) The susceptibity distribution of this macrolide antibiotic against clinical isolates of
Staphylococcus showed similar patterns as that of leucomycin or josamycin.
4) The vulnerability to the influences of the pH value, human serum concentration and inoculum size
in vitro antibacterial activity of this macrolide antibiotic was also similar to the known macrolide antibiotics.
5)
In vitro antibacterial effect of this macrolide was bacteriostatic at the MIC and it was bactericidal at the concentration higher than MIC.
6) By the electron microscopic observation of the antibacterial effect of this macrolide antibiotic against
Staphylococcus, degeneration and lysis of the cytoplasma and the remarkable thickness of the cell wall were recognized.
7) Propionylmaridomycin acquired resistance stepwise like that of the other known macrolide antibiotics
in vitro. The complete cross resistance was observed among the known macrolide antibiotics against artificial resistant strains.
There were three types of resistance in the clinical isolates,
i. e.,
1) against erythromycin alone, 2) against erythromycin and oleandomycin, and 3) against erythromycin, oleandomycin, leucomycin, josamycin, propionylmaridomycin and spiramycin.
8) Propionylmaridomycin did not induce resistance.
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TAKETOSHI ARAI
1973 Volume 21 Issue 5 Pages
975-981
Published: July 25, 1973
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The chemical and bacteriological studies on a new macrolide antibiotic, propionylmaridomycin, were performed in comparison with the other macrolide antibiotics, and the following results were obtained.
1) The chemical structure of propionylmaridomycin was closely related to kitasamycin, josamycin and spiramycin, but the difference between structures of propionylmaridomycin and other macrolide antibiotics was clearly confirmed by TLC, IR, NMR and UV spectrum.
2) The sensitivities to propionylmaridomycin of 42 clinical isolates of
Staph. aureus were measured by the plate dilution method. The sensitivity distribution curve of
Staph. aureus showed bimodal pattern with peaks at 3.1 mcg/ml and more than 200 mcg/ml, respectively. Comparatively speaking, mean MIC of propionylmaridomycin tends to be greater than that of EM, LM and JM, less than SPM, and nearly the same as OM.
3) Cross resistance was observed between propionylmaridomycin and other macrolide antibiotics, but some strains of EM resistant organisms showed to be sensitive to propionylmaridomycin.
4) The antibacterial activity of propionylmaridomycin showed to be more potent at the alkaline side of culture medium pH.
5) The inoculum size did not show any influence on antibacterial activity of propionylmaridomycin.
6) The difference was observed among antibacterial activities of the 6 components of propionylmaridomycin complex. Presence of acetate at the 4″-position of the mycarose showed lower antibacterial activity than propionate or isovalerate at the same position.
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KEIU NINOMIYA, ETSUKO TANI, KUNITOMO WATANABE, TSUTOMU USHIZIMA, KAZUE ...
1973 Volume 21 Issue 5 Pages
982-988
Published: July 25, 1973
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Antibacterial activities of propionylmaridomycin and other macrolide antibiotics were investigated
in vitro. Strains used are strict anaerobes isolated lately from clinical materials (
Peptococcus 37 strains,
Peptostreptococcus 14 strains,
Veillonella 22 strains,
Bacteroides 89 strains and
Fusobacterium 47 strains).
Many strains of
Peptococcus,
Peptostreptococcus and
Bacteroides were inhibited by 12.5 mcg/ml of propionylmaridomycin, while concentrations as high as 500 mcg/ml of propionylmaridomycin were without antibacterial effect on
Fusobacterium including
Sphaerophorus.
Strains of
Peptococcus,
Peptostreptococcus and
Bacteroides were as sensitive to EM, LM, JM, SPM and mydecamycin as to propionylmaridomycin and more sensitive to LCM, CLM and RFP than it.
For the purpose of differentiating Genus
Bacteroides from Genus
Fusobacterium, the plate or disk containing 500 mcg/ml of propionylmaridomycin would be useful.
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TAKESHI FUGONO, YASUO KITA, KEN'ICHI MAEDA
1973 Volume 21 Issue 5 Pages
989-995
Published: July 25, 1973
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Assay methods for propionylmaridomycin and its metabolites were studied.
1. For determination of total activity, a cup-plate method, using
Sarcina lutea ATCC 9341 as test organism, was established (Table 1). Sensitivity by this method for propionylmaridomycin in human plasma was 0.3mcg/ml.
2. For extraction of the metabolites from body fluids, extraction with ethyl acetate resulted the highest recovery rate (90% or more).
3. For differential assay of the metabolites, a thin layer chromatography-bioautography system was devised with best results under following conditions;
i) Silica gel plate : “Spotfilm” (Tokyo Chemical Industry Co., Ltd.)
ii) Developing solvent system : CHCl
3·MeOH·NH
4OH (40 : 3 : 20)
iii) Test organism :
Sarcina lutea ATCC 9341.
iv) Assay range : 0.2-2.0mcg (Fig 5).
4. As example for application of the differential assay method, propionylmaridomycin and its metabolites in human body fluids (plasma, urine and bile) after oral administration were analyzed.
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KEIMEI MASHIMO, YASUMICHI KATO, AKIRA SAITO, OSAMU YAZIMA
1973 Volume 21 Issue 5 Pages
996-1000
Published: July 25, 1973
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The laboratory investigation was carried out on propionylmaridomycin, a new macrolide antibiotic, and the results obtained are as follows;
1. In the susceptibility test of 59 strains of
Staphylococcus aureus using plate dilution method, similar results were obtained from propionylmaridomycin and kitasamycin, and 70% of strains was distributed below 3.2mcg/ml, although 30% was resistant to 100mcg/ml of the antibiotics.
The antibacterial activity of a metabolite, 4″-deacyl-propionylmaridomycin was 1/2-1/4 of original substance.
The effect of alkalization of media was not prominent on the susceptibility of
S. aureus, Escherichia coli and
Klebsiella species.
2. The investigation of
in vitro and
in vivo metabolism of the substance was carried out using thin layer chromatography.
The degradation to 4″-deacyl-propionylmaridomycin fellowing incubation with serum of the rat was demonstrated but not with Monitrol I.
The antibiotic was degraded by the acidification of solution but not by alkalization.
The antibiotic was changed to 4″-deacyl-propionylmaridomycin following incubation both with liver homogenate of healthy rat and with that of premedicated with carbon tetrachloride.
These changes were inhibited by pretreatment of liver homogenate with acetone.
In analysis of human urine, 4″-deacyl-propionylmaridomycin, maridomycin and other unknown metabolites were detected following oral medication.
3. In pretein binding study of the substance, over 90% of binding rate was found with Monitrol I serum using ultrafiltration method.
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KEIZO MATSUMOTO, KOICHI YOKOYAMA, KIYO NISHIOKA, YUKIO NOGUCHI, YOSHIO ...
1973 Volume 21 Issue 5 Pages
1001-1007
Published: July 25, 1973
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(1) Propionylmaridomycin (PMDM) is a new macrolide antibiotic developed by the Takeda Chemical Industries, Ltd.
(2) The concentration of PMDM in tonsils extirpated two hours after a single oral administration of 400mg of PMDM in ten cases was extremely small by our biological assay method.
(3) Oral administration of 1200mg of PMDM in three divided doses daily for 7 days in 15 cases of acute bronchitis and 9 cases of acute purulent tonsillitis and 1600mg in 4 divided doses daily for14 days in 10 cases of acute pneumonia, was effective in 22 of the total of 34 cases (64.7%).
(4) Mild side effects, chiefly gastrointestinal disturbance, were observed in 6 cases.
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KAZUO SATO, MASAKO SASAKI, YUSHI NAKAI, KENKICHI KURITA
1973 Volume 21 Issue 5 Pages
1008-1016
Published: July 25, 1973
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Laboratory and clinical investigations were carried out on a new macrolide antibiotic, propionylmaridomycin, and the following results were obtained.
1) Among 34 bacterial strains isolated from the clinical material in our hospital, gram-positive cocci except
Staphylococcus epidermidis were sensitive, but all gram-negative strains were not sensitive to propionylmaridomycin.
2) Its minimum inhibitory concentrations were nearly comparable to josamycin and leucomycin, while rather inferior to erythromycin.
3) Propionylmaridomycin was administered orally to 15 patients with respiratory infection in the range of 1.2 to 2.4 g daily for 5 to 50 days. Results of this treatment were excellent in 2 lung abscess and 4 pneumonia cases, good in 2 pneumonia and 2 tonsillitis cases, poorly responsive in one pneumonia case. No severe side effect was observed except in one case who developed a measles like exanthema. Thus, it was concluded that propionylmaridomycin would be promising for the treatment of respiratory infection.
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KIHACHIRO SHIMIZU, OTSUHIKO KUNII, KAORU SHIMADA
1973 Volume 21 Issue 5 Pages
1017-1019
Published: July 25, 1973
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1) Blood level and urinary excretion of propionylmaridomycin were studied.
By the cup method with
Sarcina lutea PCI 1001 as a standard organism, it was possible to measure the body fluid concentration of 0.4 mcg/ml, which proving was more sensitive than by the double layer method with
Streptococcus hemolyticus Cook as a standard organism.
2) After oral administration of the usual single dose (400 mg) of propionylmaridomycin in three healthy adults the blood level was undetectable in two cases, after one, three and five hours, while 0.4 mcg/ml and 0.6 mcg/ml were measured in the other one case after one and three hours respectively.
3) Urinary excretion of active propionylmaridomycin was as low as 0.4-2.9%.
4) Seven patients were treated with propionylmaridomycin. The drug was effective in 4 of 5 PAP patients. Adverse reactions were observed in two patients : one was rash, and the other was nausea.
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KAZUFUTO FUKAYA, SHOJI NAKAMURA, KATSUMASA HARANAKA, OSAMU KITAMOTO
1973 Volume 21 Issue 5 Pages
1020-1025
Published: July 25, 1973
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On a new macrolide antibiotic, propionylmaridomycin (abbreviated as PMDM), produced in Japan, several laboratory experiments were performed along with clinical evaluation and the following results were obtained.
1. The susceptibility of
Staphylococcus aureus of clinical isolates was the same grade as that of other macrolide antibiotics such as kitasamycin or mydecamycin. Two metabolites of PMDM were also tested for the antibacterial activity to
Staphylococcus. Against
Mycoplasma pneumoniae, the activity of PMDM was also the same as other macrolide antibiotics.
2. The therapeutic effect of PMDM against experimental subcutaneous infection of
Staphylococcus in mice was superior to that of mydecamycin.
3. Both of the serum protein binding rate and the adsorption rate to red blood cells proved to be low.
4. After oral administration of PMDM to a rabbit, the biliary level reached 40 to 50 fold higher than the serum level at the peak value, the urinary level reaching near 100 fold.
5. After oral administration of PMDM to mice, the organ level exceeded the serum level in the liver at the peak value, being followed by that of the lungs. By mixing the homogenate of each mouse organ with PMDM solution, considerable reduction of PMDM activity was observed in general.
6. Five cases of respiratory infections were treated and good results were obtained in 4 of them. In a case of latent lues and 5 cases of bacillary dysentery, PMDM showed also good effect. The transient rise of GOT and GPT was recorded in one case with pneumonia during the course of PMDM treatment.
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KEIICHI NAKAGAWA, JUNZABURO KABE, KENTARO WATANABE, MITSUHIRO YOKOZAWA
1973 Volume 21 Issue 5 Pages
1026-1029
Published: July 25, 1973
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1) Forty five strains of
Staphylococcus aureus cultured from clinical specimens were tested for susceptibility to propionylmaridomycin and erythromycin. Most of the strains were inhibited in 1.56 mcg/ml of propionylmaridomycin and in <0.20 mcg/ml of erythromycin. However, 4 strains showed more than 100 mcg/ml of MIC to both propionylmaridomycin and erythromycin.
2) Blood level of propionylmaridomycin after a single oral administration of 1000 mg in healthy volunteers were very low (0 to 0.50mcg/ml at one hour after administration). Urinary excretion rate was 1.24% in mean value of 6 cases during 8 hours after a single oral administration of 1000mg propionylmaridomycin.
3) Clinical results of propionylmaridomycin in 17 cases of respiratory infectious diseases were good (good 13, failed 4). No side effects were seen in all patients.
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MASATAKA KATSU, IPPEI FUJIMORI, SACHU SHIMADA, FUYUHIKO HIGASHI, TOSHI ...
1973 Volume 21 Issue 5 Pages
1030-1034
Published: July 25, 1973
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Purpose of this paper is to describe clinical evaluation of propionylmaridomycin prescribed to 33 patients with respiratory infectious diseases.
Patients treated were 9 of tonsillitis, 21 of bronchitis, each one of pneumonia and abscess of the lung.
Patients were consisted of 17 males and 16 females and age of patients ranged from 19 to 76 year-old.
Clinical efficacy of propionylmaridomycin in pneumonia, abscess of the lung and tonsillitis was excellent and it was 41% in bronchitis.
Dosage of propionylmaridomycin in tonsillitis, bronchitis and pneumonia was 1, 200 mg t. i. d., and duration was varied from case to case. They were from 3 to 27 days.
Abscess of the lung was treated with propionylmaridomycin 1, 600 mg four times daily for 47 days.
No serious side effects were noted except stomatitis and increased gurgling in 2 cases of bronchitis.
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HIROSHI OKUBO, YURUKO OKAMOTO, KYOSHU GO, JUNKO MAKINO
1973 Volume 21 Issue 5 Pages
1035-1043
Published: July 25, 1973
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1)
In vitro sensitivity of clinically isolated strains : Sensitivity of staphylococci (58 strains) againstpropionylmaridomycin was similar to those against leucomycin and josamycin. Thirteen out of erythromycin-resistant strains were sensitive to propionylmaridomycin (MIC<3.1 mcg/ml).
Proteus,
Klebsiella and
E. coli were resistant to this antibiotic.
2) Basic studies on the assay method for serum concentrations : Comparative studies on the length of inhibition zones produced by propionylmaridomycin, propionylmaridomycin III (main component of propionylmaridomycin) or 4″-deacyl-propionylmaridomycin (main metabolite of propionylmaridmycin), each dissolved in human serum or in buffer solution (pH 7.2), revealed that no significant differences may occur which-ever of those three substances is used as the standard for biological assay, as far as they are dissolved in human serum and
Sarcina lutea is used as the test organism.
3) Serum concentrations in humans after oral administration of 1 g propionylmaridomycin were low (≤1 mcg/ml). Average urinary recovery was 1.10% in 8 hours.
4) Distribution into rat organs : The highest tissue concentration of the antibiotic was found in lungs (8×of blood concentration), followed by spleen, kidney and liver. This distribution pattern. was similar to that of josamycin, but the tissue levels of propionylmaridomycin were higher than those of the latter.
5) Twenty-eight clinical cases (most of them suffering from respiratory tract infections) were treated with oral propionylmaridomycin (1.2g daily) administration, which was effective in 17 cases. As the side effects abdominal distension, rash and stomatitis were complained by each one case.
Those findings suggest that this antibiotic should be valuable in the treatment of respiratory tract infections because of its high concentration in lungs as well as its effectiveness to a half of erythromycin-resistant staphylococcus strains.
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FUMIO MIKI, TATSUO OZAKI, MEGURU HADA, TOMOKAZU ASAI, MICHIHIDE KAWAI, ...
1973 Volume 21 Issue 5 Pages
1044-1049
Published: July 25, 1973
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Studies were done on a new macrolide antibiotic, propionylmaridomycin.
1) Antibacterial activity of propionylmaridomycin was compared with that of erythromycin against 32 clinical isolates of
Staphylococcus.
Twenty-eight strains were inhibited at 0.78-3.13mcg/ml of propionylmaridomycin. The peak distribution of the
Staphylococcus strains susceptible to propionylmaridomycin was at the MIC of 1.56mcg/ml, while that of erythromycin was at 0.2mcg/ml.
Four strains were resistant to the concentration lower than 100mcg/ml of propionylmaridomycin and erythromycin (Table 1, Fig.1).
2) Serum levels following oral administration of 1g of propionylmaridomycin in healthy adults atfasting were individually different and reached maximum of 1.0-7.0mcg/ml 1-4 hours after administration.
The urinary recovery within 6 hours was also different individually and was 0.8-14.7% (Table 2).
3) Eight patients with the respiratory tract infections (2 acute pharyngitis, 2 acute tonsilitis, 1 acute bronchitis, 1 bronchiectasis with infections, 1 bronchopneumonia and 1 lung abscess complicated with lung cancer) were treated with the daily dose of 6g of propionylmaridomycin. Therapeutic response was remarkable in 5, favourable in 1, negative in 1 and undecided in 1.
No noticeable adverse reactions were observed except anorexia and nausea in 1 patient.
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NATSUO NISHIZAWA, YUZO KAWAMORI
1973 Volume 21 Issue 5 Pages
1050-1055
Published: July 25, 1973
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The
in vitro test on susceptibility of
Staphylococcus aureus to propionylmaridomycin showed MIC between 0.78 and 1.56mcg/ml. MIC of josamycin was also between 0.78 and 1.56mcg/ml. The inhibitory action of propionylmaridomycin was thus found to be similar to that of JM against
Staphylococcus aureus.
The serum concentration of propionylmaridomycin showed a peak of 1.1-1.6 mcg/ml at two hours after the administration of 400mg.
Clear inhibition against
Staphylococcus aureus 209 P was observed at the 4 fold dilution of the serum sample and slight inhibition was observed even at the 32 fold dilution.
Propionylmaridomycin was effective in all cases with upper respiratory infections such as pharyngitis and bronchitis. The effect was similar to that of other macrolide antibiotics.
No noticeable side reactions but one anorexia were observed.
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HARUO NOTSUTE, SHOTA TOMIMATSU, KATSUMASA TOKUNAGA, RINZO SOEZIMA
1973 Volume 21 Issue 5 Pages
1056-1059
Published: July 25, 1973
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Antibacterial activities of propionylmaridomycin were examined in vitro against
Staphylococcus aureus.
Serum level was studied following a single oral administration of 400 mg or 600 mg of propionylmaridomycin in healthy human adults, and some clinical assessments also performed.
1) The MICs were 0.4-3.2 mcg/ml against 45 of the total 53 strains, and more than 50 mcg/ml against the remaining 8.
2) Following a single oral administration of propionylmaridomycin 400 mg, the serum level reached the maximum of 0.84 mcg/ml at 1 hour, decreasing unmeasurably at 6 hours.
3) Clinical trial : Eight of the nine patients with respiratory infection given propionylmaridomycin_showed favorable response to propionylmaridomycin, and no noticeable side reactions were encountered.
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I FUNDAMENTAL AND CLINICAL STUDIES
KOHEI HARA, ATSUSHI SAITO, YASUTAKA KATOH, MASARU NASU, TSUNEO TSUTSUM ...
1973 Volume 21 Issue 5 Pages
1060-1067
Published: July 25, 1973
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1. Two hundreds and ninety-one strains of gram positive cocci which were isolated from various clinical specimens were studied, and it revealed that erythromycin (EM) was the most active one, as far as the susceptibility of these organisms to the macrolide antibiotics is concerned. The susceptibility of these organisms to propionylmaridomycin was virtually comparable to that of josamycin (JM) and lincomycin (LCM). It was particularly noted that, 10 strains out of 35 which were resistant to EM, were significantly susceptible to propionylmaridomycin as well as JM and LCM. All of these 10 strains were demonstrated invariably to have inducible-drug-resistance, in one strain was induced by EM and OM, it was called Mac. B and in the other nine were only by EM, called Mac. C. The growth of
Mycoplasma pneumoniae was inhibited with the concentration of 0.05 mcg/ml of propionylmaridomycin.
2. The concentrations of propionylmaridomycin in the various organs of rats were determined by the method of cup-plate technique using
Sarcina lutea as the indicator organism. The rats were given 200 mg of propionylmaridomycin per kg of body weight by mouth (intragastric-administration), and sacrificed serially to take the organs, which were homogenized to determine the concentration of the drug. The peak of the concentrations in each organs were seen at 2 hours after administration. The lung showed always the highest concentration and liver, kidney and serum followed it. In all organs, the concentration to inhibit the microorganism remained for 6 hours after administration.
3. The satisfactory therapeutic effect was recognized in nine cases out of eleven respiratory tract infections treated with propionylmaridomycin. The main side effect was nausea, seen in only one case though it was not necessary to discontinue the drug.
In all cases no significant changes were noted in the liver function tests and hematologic or biochemical examinations.
One case of pneumonia caused by
Mycoplasma pneumoniae was treated with this antibiotic and improved satisfactorily after 14 days.
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II THE CONCENTRATION AND METABOLISM OF PROPIONYLMARIDOMYCIN IN MAN
KOHEI HARA, YASUTAKA KATOH, ATSUSHI SAITO, MASARU NASU, TSUNETOSHI KOT ...
1973 Volume 21 Issue 5 Pages
1068-1077
Published: July 25, 1973
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Following a single oral administration of 1000 mg propionylmaridomycin the blood level reached peak at one hour and then was diminished until 4 hours. The average value of blood peak level was 0.7mcg/ml. The administered propionylmaridomycin was metabolized completely and maridomycin, 4″-deacyl-maridomycin and unknown metabolites were observed. In the viewpoint of the antimicrobial-activity, however, propionylmaridomycin acted as a form of maridomycin. Urinary recovery was 0.8% in 6 hours after administration and urine contained 4″-deacyl-propionylmaridomycin, maridomycin, 4″-deacyl-maridomycin, unknown metabolites and trace of propionylmaridomycin.
The biliary level was predominantly higher than the blood level. In the bile, 4″-deacyl-propionyl-maridomycin, maridomycin, 4″-deacyl-maridomycin and unknown metabolites were revealed. These unknown metabolites in blood, urine and bile had each different Rf value on TLC. The unknown metabolites in blood were readily excreted into urine.
In the lung tissues the antibacterial activity was observed even if the blood antibacterial activity was not observed, and only maridomycin was observed as a metabolite of propionylmaridomycin. In the patient with liver cirrhosis the blood antibacterial activity was observed more prolonged than in normal persons. It seemed that the deacylation of 4″ was inhibited and so maridomycin was accumulated.
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SUSUMU NAKAZAWA, HAJIME SATO, OSAMU WATANABE, NAOMICHI FUJII, SYU OKA, ...
1973 Volume 21 Issue 5 Pages
1078-1084
Published: July 25, 1973
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1) Seventy-two percent of the clinical isolates of
Staphylococcus aureus was susceptible at the MIC of 0.78-1.5mcg/ml and a few strains were susceptible at the concentration of 100 mcg/ml of propionylmaridomycin showing similar susceptibility to that of josamycin and mydecamycin.
2) MIC of propionylmaridomycin was 0.39-0.78mcg/ml against A-group
Streptococcus.
3) Peak serum concentration was 1.32mcg/ml and 1.9mcg/ml at one hour after oral administration at dose of 600 mg and 1, 000 mg respectively.
In the latter case measurable concentration sustained for six hours.
Urinary excretion for six hours was 1.08% and 0.54% after 600 mg and 1, 000 mg doses, respectively.
4) Propionylmaridomycin was administered to 40 cases of five kinds of upper and lower respiratory infectious diseases in children.
Efficacy against upper respiratory infections at dose of 20-30mg/kg was unfavourable. However, clinical response was good against bronchial asthma and bronchopneumonia, which may be due to the long dosage period.
5) No untoward findings were observed in liver and kidney functions and hematology.
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TADAFUMI NISHIMURA, YASUSHI KOTANI, YASUNORI ASATANI
1973 Volume 21 Issue 5 Pages
1085-1089
Published: July 25, 1973
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The authors have carried out the laboratory and clinical studies of propionylmaridomycin. The results were as follows;
The sensitivity was measured by the plate dilution method with 25 strains of coagulase positive staphylococci. The peak distribution of staphylococci susceptible to propionylmaridomycin was 1.56 mcg/ml and the growth of 68.0% of these was inhibited in concentration of less than 1.56mcg/ml.
The antibacterial activity of propionylmaridomycin to
Staphylococcus was equal to LM and SPM, while it was slightly inferior to EM.
Propionylmaridomycin was given a single oral dose of 20 mg per kg b. w. to 3 children.
The blood levels of propionylmaridomycin in these were low. The maximum blood level was reached at 1 hour after administration, was 2.2mcg/ml and the blood level was not determined at 6 hours. But the blood level of another cases was not determined.
The excretion rates of propionylmaridomycin in the urine after a single oral dosing were 1.8%, 2.6% and 5.6% respectively up to 8 hours.
Propionylmaridomycin was effective in 4 of 8 cases with the infection of respiratory tract.
No side effects were observed except diarrhea in one case of pneumonia.
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YASUZO NAKAMIZO, MASAHIRO TSUJI, AKIRA HIRAYAMA, HAJIME ISOGAI, SHUTAR ...
1973 Volume 21 Issue 5 Pages
1090-1098
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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1)
In vitro antibacterial activities of propionylmaridomycin, leucomycin and erythromycin against clinical isolates of A-group Streptococcus obtained from the scarlet fever patients in 1969-1971 were studied.
Some strains obtained in Hokkaido and Tokyo in 1969 and 1970 were already resistant to propionylmaridomycin and leucomycin of which MIC was 25 mcg/ml or higher.
Most clinical isolates, however, were susceptible at the MIC of 6.25-1.56 mcg/ml and 0.78-0.39 mcg/ml to propionylmaridomycin and leucomycin, respectively. On the other hand, the MICs of clinically isolated strains in 1971 were almost distributed between 0.39 mcg/ml and 1.56 mcg/ml, and only one strain, the MIC was over 100 mcg/ml.
2) Clinical effects of propionylmaridomycin observed in terms of days of pyretolysis from the start of administration, disappearance of skin rash and bacterial elimination seemed a little inferior to those of erythromycin.
Much more favourable effects were obtained when the dose of propionylmaridomycin was increased twice as large as the usual dosage.
3) In some cases, bacteria relapsed not only in the usual-dose group of propionylmaridomycin but also in the double-dose group of propionylmaridomycin, and in the leucomycin group.
One patient given 117.7 mg/kg of propionylmaridomycin showed no recurrence of bacteria that is noteworthy because it indicates the efficacy at increased doses.
4) No noticeable adverse reactions such as skin rash and gastrointestinal disorders were observed unlike in the case of aminobenzylpenicillin.
These findings suggest that further clinical trials with this antibiotic at 100 mg/kg and higher would be worthy to be carried out.
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KIYOHITO SHIBATA, TADAO ITO, MICHITERU FUJII, NAGAO SHINAGAWA, HIDEKI ...
1973 Volume 21 Issue 5 Pages
1099-1106
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Studies were done on basic and clinical studies on propionylmaridomycin.
1) Blood level and urinary excretion
The peak blood level of propionylmaridomycin reached about 0.4 mcg/ml one hour after oral administration of 600 mg.
As low as 0.8% of the activity was excreted in urine for 6 hours.
2) Concentration in bile Biliary concentration of this macrolide antibiotic revealed comparatively high level of 275 mcg/ml in healthy adults, while that of patients with renal impairment revealed somewhat low level.
The metabolites mostly consisted of 4″-deacylmaridomycin and unknown substances. The unknown substances increased in the patients with malfunction of biliary excretion.
3) Concentration in pus
The concentration of the activity in pus was about the same as that in the blood. 4″-Deacylmaridomycin was the main metabolite in pus.
4) Antibacterial activity
The susceptibility pattern of 26 strains of
Staphylococcus aureus to this macrolide antibiotic revealed two peaks.
Nineteen strains (73%) were susceptible to the antibiotic at MIC of 6.3mcg/ml or less.
5) Clinical trials
Of the 20 patients of superficial infectious diseases mainly, 2 showed excellent response, 12 good. 2 unidentified and 4 failed to respond to it.
No adverse reactions were observed but one numbness at the upper limb.
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YAEMON SHIRAHA, JUNICHI NAKAO
1973 Volume 21 Issue 5 Pages
1107-1110
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Seventeen cases of infections in the field of surgery were placed on trial of oral propionylmaridomycin preparations, and the results obtained are summarized as follows :
1. There were noticed good responses on 12 cases, effectiveness accounting for 70.7 per cent.
2. The shorter the interval period following onset of the signs of an infection, the better the responses to the preparations.
3. The antibiotic was given orally to 17 patients on the trial, and untoward side effects experienced as dyspeptic complaints on 2 cases were slight to complete the full dose.
4. It is present impression of the authors that the propionylmaridomycin seems to be a promising oral antibiotic for infections in the field of surgery because of its effectiveness without severe side effects.
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YASUTO ITAMI, TERUYA OTO, MUNEHIKO YOSHIDA, HIROSHI UENO, MASATO NISHI ...
1973 Volume 21 Issue 5 Pages
1111-1115
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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On propionylmaridomycin, a new macrolide antibiotic developed in Japan, we performed laboratory and clinical studies in the orthopedic infectious disease.
With 60 strains of
Staph. aureus isolated from the patients of osteomyelitis, the sensitivities to propionylmaridomycin, LM and EM were measured by the plate dilution method.
The MIC values of propionylmaridomycin were 0.78mcg/ml to 100mcg/ml (peak 1.56mcg/ml) and propionylmaridomycin had cross resistance with LM.
A serum level and a synovial fluid level showed similar results to another macrolide antibiotics.
Nine cases of orthopedic infectious disease were treated with propionylmaridomycin.
The results were good in seven cases, no effect in one case and unknown in one case.
No side effect was found in all cases.
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SHIGEMITSU MIZUNO, SEIJI MATSUDA, SOSHICHIRO MORI, SHINICHI SANO
1973 Volume 21 Issue 5 Pages
1116-1120
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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The antibacterial activity of propionylmaridomycin was almost equivalent to those of known macrolide antibiotics showing the MIC of 3.12 mcg/ml against
Staphylococcus aureus.
Blood level was 0.5 mcg/ml and 1.8 mcg/ml 1-2 hours after the oral administration of 400 mg and 1000mg, respectively. The level then rapidly decreased.
This macrolide antibiotic was excreted 1.5% and 3.6% in urine for six hours after the oral administration of 400 mg and 1000 mg, respectively.
The level of the activity in the umbilical blood was 1/3 and 1/2 the maternal blood level after the 400 mg and 1000 mg of oral administration respectively, while it was hardly detected in amniotic fluid and milk.
Clinically, the efficacy rate was 85.7% in the 14 patients of adnexitis, endometritis, puerperal mastitis and infections of external privates. Therapy on puerperal mastitis seemed most promising. No adverse reactions were observed.
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KANJI SEIGA, MASAO MINAGAWA, KUNIHIKO YAMAJI, YOKO SUGIYAMA
1973 Volume 21 Issue 5 Pages
1121-1125
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Propionylmaridomycin was examined as to
in vitro antibacterial activity, absorption and clinical effects.
1) Propionylmaridomycin showed excellent antibacterial activity against 148 clinical isolates obtained in the field of obstetrics and gynecology.
MICs of this macrolide antibiotic were 1.56-3.12 mcg/ml against
Staphylococcus aureus, 0.39-0.78 mcg/ml against
Streptococcus pyogenes, ≤0.39 mcg/ml against
Diplococcus pneumoniae and 1.56-3.12 mcg/ml against
Peptostreptococcus anaerobius.
2) Distribution of the MIC of propionylmaridomycin against the clinical isolates showed a large peak at 1.56-3.12 mcg/ml and a small peak at >100 mcg/ml. The susceptibility pattern was similar to those of josamycin and leucomycin.
3) Blood level of propionylmaridomycin in 5 healthy women given a single oral dose of 1g demonstrated a peak level of 0.9 mcg/ml an hour after administration. The antibiotic was detectable after six hours (0.2 mcg/ml).
The cumulative urinary recovery of propionylmaridomycin was 0.92% after 8 hours which was very low as in the case of other macrolide antibiotics.
Transition to embryonic blood was 1/4-2/3 of the blood level of the mother.
It was also detectable in the amniotic fluid.
4) Ten patients with puerperal mastitis, external vulval furuncle and adnexitis uteri were given the drug in daily dose of 1, 600 mg for 4-10 days. Seven of the 10 cases responded to the therapy. No noticeable adverse reactions were observed.
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HISASHI TAKAHASHI, KAZUKO TANABE, KENRYU SATO, REIKO MURAYAMA
1973 Volume 21 Issue 5 Pages
1126-1128
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Serum and skin concentrations of propionylmaridomycin were studied in rabbits.
After the oral administration of propionylmaridomycin at dose of 600 mg, the peak concentration in skin was about half the serum concentration and the peak in skin appeared after little lag of time than the peak in blood.
In vitro antibacterial activity studies on 50 clinical isolates and the clinical studies were also performed.
Most Staphylococci of the 50 clinical isolates were susceptible to propionylmaridomycin with MIC of 1.56 mcg/ml. The antibiotic susceptibility of
Staphylococcus aureus 209 P was 0.78 mcg/ml of MIC.
Propionylmaridomycin demonstrated favourable effects against frunkles, MIC of which causative organism was 1.56mcg/ml or so.
However, it revealed negative effects against two folliculitis patients irrespective of the MIC of the causal organisms.
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YASUO ASADA, [in Japanese], [in Japanese], [in Japanese], [in Japanese ...
1973 Volume 21 Issue 5 Pages
1129-1132
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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The effect of propionylmaridomycin, a new antibiotic belonging to macroloide group, against 45 cases of various pyoderma including impetigo (1 case) furuncles (14 cases), furunculosis (8 cases), carbuncles (3 cases), cellulitis (4 cases), panaritium (4 cases), erysipelas (1 case), abscess (1 case), hidradenitis suppurativa (1 case), infected atheromas (5 cases) and lymphadenitis (3 cases), were reported.
The effect was classified as “excellent”, “good”, “fair” and “none”. Percentage of effectiveness in “excellent” to “good” was 80%. No side effects were observed in all cases tested.
The MIC of this antibiotic against 33 strains of staphylococci was 1.56 mcg/ml in 14 strains, 3.12 mcg/ml in 5 strains, 25 mcg/ml in 1 strain and 100 mcg/ml in 13 strains respectively. This result showed very similar pattern to that of leucomycin showing 0.78 mcg/ml in 1 strain, 1.56 mcg/ml in 13 strains, 3.12 mcg/ml in 5 strains, 12.5 mcg/ml in 1 strain and 100 mcg/ml in 13 strains.
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JIRO ARATA, KIHEI TANIOKU
1973 Volume 21 Issue 5 Pages
1133-1136
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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1) Antistaphylococcal activities of propionylmaridomycin were examined by the agar dilution method, using 19 strains of staphylococci separated from pyoderma lesions. Minimum inhibitory concentrations were 0.8 mcg/ml in 1 strain, 1.56 in 6, 3.13 in 8 and more than 100 mcg/ml in 4 strains. The resistant strains were also resistant to erythromycin.
2) Propionylmaridomycin were used in 7 acute skin infections. Good responses were obtained in 2 cases. Two cases improved and 1 case improved symptomatically. No change was obtained in 2 cases. The dosis was 1200 mg per day at three divided dosis.
3) Four acne patients were treated with propionylmaridomycin at the dosis of 1200 mg per day for 7 to 21 days. All patients showed some improvement.
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MASAYASU GOTO, MUNEO FUKAGAWA
1973 Volume 21 Issue 5 Pages
1137-1142
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Propionylmaridomycin, 800 to 1200 mg daily, was given orally to 25 cases of skin infectious diseases. In 12 cases, considerable improvement was apparent on the 7 th day of the treatment. Moderate effects were observed in other 6 cases.
Antibacterial activity of this drug was studied on the strains isolated from lesions in this clinical investigation. The MIC distribution of 13 gram-positive cocci showed the bimodal pattern with the peaks of 1.56 mcg/ml and more than 100 mcg/ml. The growth of gram-negative rods was not inhibited even with high concentration of 100 mcg/ml.
The comparison between clinical results and sensitivity of causative microorganisms against this drug showed that fair clinical results were obtained in 75% of the cases in which sensitive strains were isolated.
In acne cases 3 of 6 were considerably improved.
This result may suggest the drug is excreted via sebaceous gland.
There were no noticeable side effects.
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TOSHIHIKO MITA, AKIO KATAOKA, SHINJI HARA, JOJI ISHIGAMI
1973 Volume 21 Issue 5 Pages
1143-1147
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Laboratory and clinical studies on propionylmaridomycin were made.
Peak serum level of 0.35 mcg/ml was observed one hour after the oral administration of propionylmaridomycin at dose of 400 mg. The antibiotic was undetectable in serum six hours after administration.
Urinary recovery of this macrolide antibiotic was 0.72% on the average for six hours after administration.
Seven out of twenty-two patients (16 simple urinary tract infections and 6 complicated ones) showed excellent response, 8 good and 7 poor.
No adverse effects were observed.
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BUEMON SAMBE, HARUKO MURAKAMI, KEIKO KOBAYASHI, KEIICHIRO JO
1973 Volume 21 Issue 5 Pages
1148-1155
Published: July 25, 1973
Released on J-STAGE: August 17, 2011
JOURNAL
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From the laboratory and clinical studies on propionylmaridomycin, a new antibiotic of macrolides, the following results were obtained.
1. Anti-staphylococcal activity
a) MIC of propionylmaridomycin, LM and mydecamycin against 48 patient strains of
Staph. aureus were compared, and well correlated titers were demonstrated among these three drugs, though some differences were observed among 7 strains which were resistant against propionylmaridomycin and mydecamycin.
b) MICs of propionylmaridomycin and its metabolites, 4″-deacyl-propionylmaridomycin and maridomycin, against 27 strains of
Staph. aureus were compared. MIC of 4″-deacyl-propionylmaridomycin was shown to be 2 to 8 times higher than those of propionylmaridomycin and maridomycin. Concerning about the MIC of the latter two drugs no notable differences were observed.
c) The effect of propionylmaridomycin and its metabolites on the growth curve of
Staph. aureus 209P strain was observed by using biophotometer.
Complete inhibition by 0.5 mcg/ml of propionylmaridomycin or maridomycin, and partial inhibition by 0.5 mcg/ml of 4″-deacyl-propionylmaridomycin or by 0.25 mcg/ml of propionylmaridomycin with 0.25 mcg/ml of 4″-deacyl-propionylmaridomycin were observed.
2. Anti-streptococcal activity
a) MICs of propionylmaridomycin, LM and EM against 17 strains of
Strept. pyogenes (group A) were compared. Though a little high titer was obtained for propionylmaridomycin than others, all showed MIC less than 6.25 mcg/ml.
b) The effect on the growth curve of patient strain “Murakami” of
Strept. pyogenes was followed up using biophotometer.
Complete inhibition by 0.5 mcg/ml and incomplete inhibition by 0.25 mcg/ml and of propionylmaridomycin were observed. Partial inhibition by 0.25 mcg/ml of LM was observed.
3. As a whole, propionylmaridomycin showed moderate clinical effects in practical use, but a little less activity than initially expected.
The reason would be considered to be due to the less activity of propionylmaridomycin metabolite, such as 4″-deacyl-propionylmaridomycin which would be found mainly in tissue soon after administration of propionylmaridomycin.
4. Propionylmaridomycin was clinically applied to 50 patients of ear, nose and throat infections and the results were as follows : remarkable effect in 21 cases (42%), moderate in 20 cases (40%) and ineffective in 8 cases (16%). The effectiveness ratio was 82%.
5. As for the side effect, eruption was encountered in one case out of the 50 cases.
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MASAO OISHI, MASAO IMAI, TAKETOYO NAKATSUE, TAKAKO TAKAHASHI, HAJIME T ...
1973 Volume 21 Issue 5 Pages
1156-1163
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Bacterial and clinical experiments concerning ophthalmic use of propionylmaridomycin revealed following results.
1) The minimum growth inhibitory concentrations of propionylmaridomycin were 0.39-0.78 mcg/ml for Koch-Weeks
bacillus, 6.25-12.5 mcg/ml for Morax-Axenfeld
bacillus, 0.39-3.13 mcg/ml. for
Pneumococcus, 0.39-3.13 mcg/ml for
Corynebact. diphtheriae, 1.56 mcg/ml for
Gonococcus, 0.78-3.13 mcg/ml for
Streptococcus, 0.78-6.25 mcg/ml for
Staphylococcus and>100 mcg/ml for
Ps. aeruginosa.2) The distributions of sensitivity for 50 strains of
Staph. aureus were in the range of 0.78-≥100 mcg/ml, and 34 strains (68%) of them were in 3.13 mcg/ml.
3) Cross resistance was recognized between propionylmaridomycin and the other macrolide antibiotics EM, JM, OM and SPM.
4) The blood concentration by oral administration of 1000 mg propionylmaridomycin at a single dose reached the highest level after 2 hours (1.11 mcg/ml), and decreased gradually until 6 hours.
5) After instillation of 1% propionylmaridomycin solution, the ocular tissue level was proved merely in outer parts of the eye. Particularly, the concentration in cornea was remarkably high at one hour after instillation.
After subconjunctival injection of 5 mg/0.5 ml propionylmaridomycin, the tissue level at 1/2 hour was high in extraocular muscles, sclera, cornea, bulbar conjunctiva and lid. Moreover, in the inner parts of the eye, such as iris and ciliary body, vitreous body and retina and chorioid, the relatively high concentration was recognized.
After oral administration of 200 mg/kg propionylmaridomycin, the tissue concentration was found not only in the outer parts of the eye, but also in the inner parts of the eye.
Compared with that local and systemic application, the tissue levels in the outer parts of the eye were as follows in the decreasing order : subconjunctival injection>oral administration>instillation. In the inner parts of the eye, the tissue level was in the order of : subconjunctival injection≥oral administration>instillation.
6) The influence of the ocular tissue and fluids on the potency of propionylmaridomycin and its metabolite were examined. The potencies of both of them were slightly reduced by the ocular tissues and the aqueous humor.
7) The oral application of propionylmaridomycin against suppurative ocular infection revealed excellent effects on 7 cases of external hordeolum, 2 cases of internal hordeolum, a case of chronic dacryocystitis, 2 cases of corneal ulcer and a case of orbital abscess.
8) Side effects : 2 cases out of all 22 cases complained anorexia, but any other serious one was not noticed.
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HIROSHI TAKAI, SHIGEYUKI HYUGA, HARUYUKI MIKOSHIBA, MASAO MURASE
1973 Volume 21 Issue 5 Pages
1164-1170
Published: July 25, 1973
Released on J-STAGE: March 08, 2011
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Propionylmaridomycin was examined in acute infectious diseases of oral and maxillary field.
1) Fifty-seven percent of 14 clinical isolates of pathogenic
Staphylococcus newly obtained from oro-maxillary infections was susceptible to 6.25 mcg/ml and less of propionylmaridomycin and 29% was resistant showing MIC of 100 mcg/ml or above.
2) Cross resistance was observed between propionylmaridomycin and erythromycin, leucomycin and josamycin.
3) Clinically, 78% of 20 cases with acute infections of oral and maxillary field responded to propionylmaridomycin therapy.
4) No noticeable adverse reactions were observed but one mild diarrhea.
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