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MIDORI ISONO, MAKOTO AOKI, TOYOKO KOBAYASHI, TOSHINORI MARUI, HISASHI ...
1981 Volume 34 Issue 5 Pages
647-650
Published: May 25, 1981
Released on J-STAGE: May 17, 2013
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Synergistic effect of thiamphenicol (TP) and cephalothin (CET) on
Bacteroides fragilis was proved
in vitro. Especially its effect was much clear on
B. fragilis which is possible to produce β-lactamase.
Synergistic bactericidal effect of TP and CET was proved.
Chemotherapeutic effect of TP and CET against experimental mixed infectious mouse due to
E. coli (β-lactamase-) and
B. fragilis (β-lactamase +) was proved.
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YOSHIKI TAKASHIMA, TAMEO HATANO, NOBUO TAUCHI, TAKAKO MAKI, KIMIEKO UO ...
1981 Volume 34 Issue 5 Pages
651-654
Published: May 25, 1981
Released on J-STAGE: May 17, 2013
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A clinical study on cefotiam (CTM) was performed in the field of pediatric infection, and the following results were obtained:
The number of cases studied were six including 2 cases of U.T.I., 1 case of vaginitis and vulvitis, 1 cervical lymphadenitis, 1 abscess of thigh and coxitis. Clinical responses to CTM were excellent in 3 cases, good in 1 cases but there was 1 exception who dropped out because of concurrent use of other antibiotics.
As for bacteriological responses, CTM eliminated the pathogens
E. coli and
P. mirabilis from U.T.I.,
Staph. epidermidis and
P. morganii, from vaginitis and vulvitis,
H. influenzae and
Str. pneumoniae from cervical lymphadenitis and
Staph. aureus from abscess of thigh.
No side effect was observed except 1 case who showed an elevation of GOT, GPT and LDH. It is uncertain, however, wether this abnormality was resulted from the use of CTM or not, because the other antibiotics were used also.
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TOMONOBU TOKIWA, KOHJI MIYOSHI, TOYOMI TAKAHASHI, FUMIAKI UDA, TOMOKO ...
1981 Volume 34 Issue 5 Pages
655-662
Published: May 25, 1981
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A subacute (5-week) subcutaneous toxicity study of cefotiam (CTM) was carried out using 9 threeweek old Beagle puppies. The puppies were assigned to one of three groups, each containing three. Puppies in group I (control) were given physiological saline; puppies in group II and III were given 300mg/kg/day of CTM and cefazolin (CEZ), respectively.
No behavioral abnormalities were seen in puppies in each group. The changes, considered to be drug-related, were histopathological changes at the sites of injection, which consisted inflammatory cellular infiltration, hemorrhage and hyperplasia of fibroblast in connective tissue of skin and skeletal muscle. In terms of severity, CTM was rather more irritating than CEZ. Except the histopathological changes described above, there observed no abnormalities which were considered to be related to CTM.
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MIKIO MINAMITANI, KEI HACHIMORI, HIDEO NAKAZAWA, NORIKO TOMORI
1981 Volume 34 Issue 5 Pages
663-669
Published: May 25, 1981
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The therapeutic effects of cefotiam (CTM) in the pediatric field were studied, and the following results were obtained:
1.Absorption and excretion:
After 30minutes intravenous dripinfusion of 250mg (14.7mg/kg) of CTM to a 5-year old child weighing 17kg, the serum levels and urinary excretion were measured. The serum levels were 47.8mcg/ml at 30minutes after administration, 23.9mcg/ml after 1hour, 12.5mcg/ml after 1hour and 30minutes, 5.2mcg/ml after 2hours and 30minutes, 0.3mcg/ml after 6 hours and 30 minutes. Excretion rate in the urine was 48.8% at 6hours after administration.
2.Clinical results:
CTM was administered at a daily dose of 35 to 91mg/kg b.i.d. to q.i.d. by intravenous or intraveous drip injection for 2 to 6.5days to six patients
i.e. two with bronchopneumonia, one with acute bronchitis, one with acute enteritis, one with impetigo and atopic dermatitis one with acute tonsillitis a nd acute cervical lymphadenitis. The responses were excellent in 2 cases and good in 4 cases. The response e was 100%. No side effect was observed.
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SUSUMU NAKAZAWA, HAJIME SATO, KENJI NIINO, SHIN-ICHI NAKAZAWA, HIROYUK ...
1981 Volume 34 Issue 5 Pages
670-677
Published: May 25, 1981
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The studies on cefotiam (CTM) administered by intravenous or intravenous drip infusion in pediatric field made the following results:
1. The serum levels after administration of cefotiam 25mg/kg, 63mg/kg by intravenous was maintained high until 2 hours after and keeped to be able to measure after 5 hours, and the half life was 0.9-1.7 hours.
2. The drug transfered actively about 1/5 of serum level into the intrathoracic pus. The excretion rate in urine was about 80% of the drug administered.
3. The clinical effective rate after the administration of CTM 50-70mg/kg for 4 to 29days was 95% in 21 patients with different five diseases.
4. No side effect and abnormality in laboratory findings were observed.
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RYUZO AOYAMA, KISHIRO NAGATA, YUKIO IZUMI, TADAYUKI KURONUMA, NORIHISA ...
1981 Volume 34 Issue 5 Pages
678-681
Published: May 25, 1981
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Cefotiam is a new semisynthetic cephalosporin antibiotic.
The treatment with this drug was carried out in 12 cases of pediatric infection. The clinical response was observed in 92% of the cases. Cefotiam was found to be active against a variety of Gram-positive and Gram-negative bacteria.
Neither marked side effects nor laboratory abnormalities were found with this treatment.
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MASATOSHI TAKIMOTO, HAJIME YOSHIOKA, ICHIMEI NAGAMATSU, AIKO TAKASE
1981 Volume 34 Issue 5 Pages
682-685
Published: May 25, 1981
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We have administered cefotiam intravenously to 23 pediatric patients. The daily dose was 13-210mg/kg. The clinical responses were excellent and good in 20 cases. Excluding 1 case with infectious mononucleosis, the efficacy rate of 90.9% (20/22 cases) was achieved As for side effect, diarrhea and eosinophilia were observed one each in 2 cases. In 2 cases, half lives were 24 and 53minutes, urinary recovery rates were 88.3 and 91% over 6 hours.
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AKIRA KANAI, MASAKI MORI
1981 Volume 34 Issue 5 Pages
686-689
Published: May 25, 1981
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Cefotiam (CTM) were clinically applied to 6 cases and the following results were obtained:
1. The patients were aged 1 year in 5 cases and 7 years in 1 case. They comprised three cases of acute tonsillitis and 1 case each of phlegmon, bronchopneumonia and cervical abscess. CTM was administered in a daily dose of 50-115 mg/kg t.i.d. by an 1-hour intravenous drip infusion for 4 to 8 days.
2. The causative bacteria were
S. aureus in 3 cases and
H. parainfluenzae, K. pneumoniae and unknown pathogen in each 1 case. The organisms were eradicated in all cases except for only 1 case of
S. aureus.
3. Overall responses were good in 4 cases and fair in 2 cases.
4. As for the abnormal laboratory findings, slight increase of GOT and GPT was observed in 1 case. Any other side effects were not observed.
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YOSHIKIYO TOYONAGA, YOSHIIE KUROSU, MAKOTO HORI
1981 Volume 34 Issue 5 Pages
690-704
Published: May 25, 1981
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A new synthetic cephalosporin, cefotiam (CTM) was studied from the basic and clinical aspects, and the following results were obtained:
1. Bacteriological study:
The bacterial activities of CTM against the clinical isolates of
S. aureus, S. pyogenes, E. coli, Klebsiella sp. and
Proteussp. were compared with those of CEZ, CER, ABPC and GM.
(1) As for
S. aureus and
S. pyogenes, the antibacterial actions of the conventional cephalosporins were slightly more potent than those of CTM.
(2) However, CTM had the antibacterial actions which were most potent
Proteus sp. among the above 4 antibiotics and more potent against
E. coli and
Klebsiella sp. than the above 2 conventional cephalosprins.
2. Pharmacokinetic study:
The peak serum levels of CTM were comparativelly low with 19.30±1.66 mcg/ml 30 minutes after a bolus injection of 20 mg/kg and 25.854±4.32 mcg/ml just after a drip infusion of 20 mg/kg.
The half-life of the serum levels was 0.98 hrs. and 0.87 hrs., respectively.
The 4 hours urinary excretions in six patients ranged from 38.6 to 64.9%, showing a slightly wide variance.
3. Clinical study:
The clinical response was good in 23 out of total 25 cases,
i. e. 14 cases with respiratory tract infection, 7 with urinary tract infection and 4 with skin and soft tissue infection.
The response rate was 92%.
Also, neither side effects nor abnormal laboratory findings was observed.
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KOJI YANAGISAWA, HARUO ICHIHASHI
1981 Volume 34 Issue 5 Pages
705-710
Published: May 25, 1981
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Cefotiam, one of the new cephem antibiotics, was used in 14 cases with pediatric infections: (10 cases with respiratory tract infections, 2 with urinary tract infections, each 1 with purulent meningitis+sepsis and acute appendicitis).
The patients were aged between 15 days and 9 years old. The drug was, as a rule, given at a daily dose of 50mg/kg to 100mg/kg q. i. d. by bolus intravenous injection. The duration of treatment was between 3 and 38 days.
The treatment produced the following clinical responses: Out of the 10 cases, good response in 7 with respiratory tract infections, fair in 1 and poor in the remaining 2. The responses in urinary tract infections were excellent in 1 and good in the other case. An apparently clear response was obtained in 1 case with purulent meningitis+sepsis due to
K. pneumoniae. Also, an excellent response was seen in 1 case with acute appendicitis. The response rate including fair response was 85.7%. The suspected pathogens isolated from 5 cases (
S. aureus: 1 strain,
H. influenzae: 1,
K. neumoniae 2,
E. coli: 1) were eliminated after CTM administration. Good clinical responses were also obtained in these cases.
No side effect was observed. Mild elevation of GOT and GPT was noted during the treatment in 1 case. It is unclear, however, if CTM was associated with this side effect or not.
P. aeruginosa, Serratia appeared after superinfection in 1 case.
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HIDENORI MEGURO, JIN MASHIKO, SHIN-ICHI OZAWA, YORIKO MATSUEDA, RYOCHI ...
1981 Volume 34 Issue 5 Pages
711-718
Published: May 25, 1981
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Cefotiam (CTM) was evaluated for its safety and efficacy in children. Twenty-six patients were treated with 40 to 200 mg/kg per day of CTM by intravenous administrations. The diagnosis of the patients were acute pharyngitis (2), acute bronchitis (1), pneumonia (4), empyema (2), urinary tract infection (2), typhoid fever (1), acute enterocolitis (2), partially-treated purulent meningitis (1), and suspected septicemia in neuroblastoma (1); and the remaining ten patients were considered to have nonbacterial infections. The pathogens recovered were
Streptococcus pyogenes(1),
Streptococcus pneumoniae(1),
Staphylococcus aureus(4),
Haemophilus influenzae(4),
Escherichia coli(1) enteropathogenic
Escherichia coli(1),
Salmonella typhi(1) and
Campylobacter jejuni(1). All but two patients of bacterial infections were cured after the CTM therapy, and the rate of efficacy was 87.5%.
Diarrhea (3), urticaria (1), transient elevation of GOT and GPT (1), and transient eosinophilia (3) were found to be associated with the CTM therapy. However, no severe adverse reactions were encountered.
Half life of the serum CTM level was 0.93±0.13 hours, and excretion into the urine was rapid. CSF concentration obtained 1 hour after an intravenous injection of 21 mg/kg of CTM in a case with inflamed meninges was 1.5 mcg/ml, and the CSF/serum ratio was 9.0%.
From these data, CTM appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections.
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SUSUMU IWAKI, KAZUYA HONKE, HITOSHI OHI, NAOMI NISHIDA, NOBORU TANIGUC ...
1981 Volume 34 Issue 5 Pages
719-722
Published: May 25, 1981
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The influence on bowel flora of CTM was studied in 5 children who were taking a normal diet.
1) In the cases following no diarrhea, administration of CTM caused no significant changes in bowel flora. In the cases following diarrhea, administration of CTM caused a fall in coliform, BEP* group,
Lactobacillus and
Peptostreptococcus. However, after the administration was discontinued, thereduced bowel flora was returned to the normal range within a few days.
2) No overgrowth of bowel flora by
Pseudomonas, Clostridium difficile or
Candida was observed.
3) One strain of nontoxigenic
Clostridium difficile was observed in the case of following no diarrea.
4) As for the side effects, diarrhea was observed in 2 cases. *BEP group: Nonspore making anaerobic Gram positive rods of
Bifidobacterium, Eubacterium, Propionibacterium.
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HIRONOBU AKITA, YUKIO IWASAKI, SATOSHI IWATA, TAKEFUMI KANEMITSU, HARU ...
1981 Volume 34 Issue 5 Pages
723-728
Published: May 25, 1981
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The fundamental and clinical studies on cefotiam (CTM) were performed in the field of pediatrics, and the following results were obtained:
.1. The peak MICs of CTM against Gram negative rods such as
E. coli, Klebsiella, Salmonella, Proteus were 1.56mcg/ml.
The MIC distribution against
S. aureus was almost equal to the conventional cephalosporin antibiotics.
The MICs against
P. seudomonas and
Serratia were over 400mcg/ml.
2. The mean serum levels of CTM after bolus intravenous injection of 25mg/kg were 59.9mg/ml after 15 min., 30.0mcg/ml after 30min., 15.6mcg/ml after 1 hour.
3. Administration of CTM to 6 pediatric patients produced the clinical responses which were good in all 6 cases and the bacterial effects of eradication in 3 cases and superinfection in the 2 cases in the 5 cases from whom the organism were isolated.
No side effect was observed. From the above results, it is considered that a bolus injection of CTM 25 mg/kgt. i. d. to q. i. d. is a safe and useful treatment for pediatric cases.
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1981 Volume 34 Issue 5 Pages
729-733
Published: May 25, 1981
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1. EFFECTS ON THE CENTRAL NERVOUS SYSTEM
UICHI SHIBATA, YOSHIO YAMAKI, HIROYASU ASAOKA, SHIRO SUGIYAMA, UETO TA ...
1981 Volume 34 Issue 5 Pages
734-746
Published: May 25, 1981
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Behavioral and electroencephalographic (EEG) effects on a new macrolide antibiotic miokamycin (MOM), 9, 3 diacetylmidecamycin, were investigated in mice, rats and rabbits after oral administration.
MOM caused a decrease in the spontaneous motor activity, a slight increase in the effect of megibal seizure at a dose of 1,000mg (Potency) /kg, and an increase in the number of deaths on the maximal electroshock seizure after administration of doses more than 100mg (Potency) /kg. Even at a dose of 1,000mg (Potency) /kg, however, MOM showed no effects on general behavior, rectal temperature, traction test, inclined screen test, rotarod performance, thiopental-induced sleep, pentetrazol seizure, fighting behavior induced by electric stimulation and conditioned avoidance response.
EEG effects in unanesthetized rabbits with permanent electrode implants were studied. MOM showed no effects on spontaneous EEG, arousal response to mesencephalic reticular stimulation, photic driving response, evoked cortical respo se by ventralis posterolateralis stimulation and afterdischarge elicited by hippocampal stimulation at a dose of 1,000mg (Potency) /kg.
Consequently, it can be concluded that MOM has no specific pharmacological effects on the central nervous system.
Behavior effects of MOM metabolisms, Mb-1, Mb-2, Mb-6 and Mb-12, were almost the same as those of MOM in the mode of action.
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ITARU TERASHIMA, AKIRA NAKAMURA, URI OKIMOTO, NAOKO SUGAYA, TOMOMICHI ...
1981 Volume 34 Issue 5 Pages
747-756
Published: May 25, 1981
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KOJI YANAGISAWA, KEIKO IDE, HIROKI HOSHINA, HARUO ICHIHASHI
1981 Volume 34 Issue 5 Pages
757-763
Published: May 25, 1981
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YOSHIKIYO TOYONAGA, MORIMASA SUGITA, YOSHIIE KUROSU, KOMEI KUMAGAI, MA ...
1981 Volume 34 Issue 5 Pages
764-781
Published: May 25, 1981
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Experimental and clinical studies in the pediatric field on 6059-S a newly synthesized broad spectrum parenteral antibiotics, were carried out, and the following results were obtained.
Antibacterial activities of 6059-S against
S. pyogenes, S. aureus E. coli and P. aeruginosa, recently isolated from patients, 50 strains respectively was compared with that of cefazolin (CEZ), cefmetazole (CMZ), ceftizoxime (CZX), cefotiam (CTM) and ticarcillin (TIPC).
6059-S was less active than the other compound against
S. aureus and
S. pyogenes, but was about 1-5 times more active than other CEZ CTM, CMZ and CZX against
E. coli, and 6059-S had a activity against
P. aeruginosa. It was equar or slightly more activity than that of TIPC.
Serum concentrations were measured in 14 infants (3y 3m-12y) by one shot or intravenous drip infusion with 10mg/kg or 20mg/kg.
By one shot intravenous infusion the peak of serum concentrations of 6059-S with 10 mg/kg and 20 mg/kg were 40.4-44.2mcg/ml, 79.1-90.8 mcg/ml at 30 minutes after administration respectively and that's half life were 1.5, 1.4 hours.
By intravenous drip infusion, the peak of serum concentration was 899 mcg/ml at the end of administration, 13.7 mcg/ml at 5 hours after administration and half life was 1.5 hours.
The urinary recovery rate of 6059-S were 974, 67.4% during 6 hours in 2 cases.
The cerebrospinal fluid concentration of 6059-S were 24-3.6 mcg/ml at 90 minutes after intravenous infusion administration, and the CSF/serum ratio were about 7-8%.
Clinical studies of 6059-S was performed in total of 27 cases (25 patients); 8 cases of urinary tract infection, 15 cases of respiratory tract infection 1 case of staphylococcal scalded skin syndrome, 1 case of peritonitis, 2 cases of purulent meningitis, with the dose of 6059-S 150 mg/kg/day in purulent meningitis 40-80mg/kg/day in other disease. That's efficacy rate was 852%. Side effect observed in this therapy were 2 cases (exanthema 1 diarrhea 1), and 2 cases of rise of GOT, GPT.
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NAOICHI IWAI, AKIRA SASAKI, YOICHI TANEDA, TAMIKO OSUGA, KAZUYO INOKUM ...
1981 Volume 34 Issue 5 Pages
782-799
Published: May 25, 1981
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Laboratory and clinical studies were performed on 6059-S in the field of pediatrics, a new semisynthetic 1-oxacephem antibiotic, and results were as follows.
1. MICs of 6059-S were compared with those of cefazolin (CEZ) and cefmetazole (CMZ) on 31strains of S. aureus, 29 strains of E. coli, 30 strains of
K.peneumoniae and 16 strains of
P. aeruginosa. With the inoculum size of 10
8 cells/ml and 10
6 cells/ml, the peak of distribution of MICs were
S. aureus 6.25, 3.13 μg/ml,
E. coli 0.2, 0.1 μg/ml,
K. pneumoniae 0.2, 0.05 μ/ml and
P. aeruginosa 12.5, 6.25 μ/ml, respectively. MICs of 6059-S against
S. aureus was more less 2 to 3 tubes than CEZ and CMZ, but against
E. coli and
K.peneumoniae were more higher 3 to 4 tubes than CEZ and CMZ.
2. The serum concentrations and urinary recovery rate of 6059-S were measured in 5 pediatric patients. 6059-S was given 20 mg/kg by an intravenous injection to 2 cases or a 30 minutes intravenous drip infusion to 3 cases. The mean concentration of the former were 64.3, 44.3, 26.8, 11.7 and 5.0 μ/ml at 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.51 hours. The urinary recovery rates was 75.0%within 6 hours after the injection. The mean concentration of the latter were 65.3, 86.3, 63.0, 40.3, 17.8 and 8.9 μ/ml at 0.25, 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.63 hours. The urinary recovery rates was 52.1% within 6 hours after the injection.
3. Eleven cases with acute pneumonia, 1 case with acute bronchitis, 3 cases with acute purulent tonsillitis, 1 case with acute purulent parotitis and 1 case subcutaneous abscess were treated with 6059-Sby intravenous injection. All cases were above effective clinically. Five strains of
H. influenzae, 3strains of
S. pneumoniae, 2 strains of
S. pyogenes and 1 strain of
S. aureus were eradicated in all strains.
No clinical adverse reaction and abnormal laboratory findings were noted.
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TADAFUMI NISHIMURA, KENJI HIROMATSU, TOSHIO TAKASHIMA, KAZUO TABUKI, M ...
1981 Volume 34 Issue 5 Pages
800-816
Published: May 25, 1981
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The authors have carried out the laboratory and clinical studies of 6059-S The results were asfollows:
The sensitivity was estimated by the plate dilution method on 27 strains of S. aureus, 26 strains of
E. coil, K. pneumoniae and
P. aeruginosa, 21 strains of
Salmonella sp. and 9 strains of GM resistant
P.aeruginosa isolated from patients.
The distribution of sensitivity of
S. aureus was 6.25-12.5 μg/ml and the peak of distribution was 6.25 μg/ml. The growth of 80.8% of
E. coil was inhibited at concentration of less than 0.1 μg/ml. The growth of 88.5% of
K. pneumoniae was inhibited at concentration of less than 0.2 μg/ml. The growth of 81.0% of
Salmonella sp. was inhibited at concentration of less than 1.56 μg/ml. The distribution of sensitivity of
P. aeruginosa was 12.5-> 100 μg/ml and the peak of distribution was 25.0 μg/ml. The distribution of sensitivity of GM-resistance
P. aeruginosa(≥25 μg/ml) was 12.5-50 μg/ml and 5 of 8 strains were inhibited at concentration of less taan 25 μg/ml.
Phagocytosis was determined by QuIE's method. Phagocytosis of
E. coli, K. pneumoniae, Proteus vulgaris and Enterobacter cloacae by human polymorphonuclear neutrophil was more enhanced in the presence of 1 MIC and 1/2 MIC for 6059-S than for cefazolin at 4 and 6 hours after incubation. But phagocytosis of
S. aureus did not enhanced in the presence of 6059-S.
6059-S was given by intravenous administration for 5 minutes and drip infusion for one hour at a single dose of 10 mg/kg of 6059-S to 3 and 4 children respectively. After intravenous administration of 6059-S, the mean peak serum level was 76.0±2.0 μg/ml at 15 minutes, 36.0±2.8 μg/ml at one hour, 1.5±0.4 μg/ml at 6 hours respectively. Half-life time was 1.3 hours.
And after drip infusion of 6059-S was 39.9±9.7μg/ml at one hour, 11.7±4.8 μg/ml at 3 hours and 1.8±1.4μg/ml at 7 hours respectively. Half-life time was 1.4 hours.
The mean urinary excretion rate was 90.4±6.1%, 76.5±16.0% up to 6 hous after intravenous administration and drip infusion respectively.
6059-S was effective in 17 cases out of 18 cases with bacterial infections. No side effects were observed except for 4 cases with elevation of serum transaminase, each one case of eosinophilia and of anemia.
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1981 Volume 34 Issue 5 Pages
817-818
Published: May 25, 1981
Released on J-STAGE: May 17, 2013
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