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KOJI SERA, NOBUHARU TAGASHIRA, AKIRA NAGASAWA, TOSHITADA SAKAI, YASUO ...
1986 Volume 39 Issue 3 Pages
661-666
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Two tenths ml of 5% fosfomycin sodium solution (10mg) was injected into the tympanic cavity of guinea pigs once a day for 7 days. Auditory brain stem response (ABR) was performed to examine the effect of the drug on the experimental animals. Additionally, a scanning electron microscopic study was also performed to observe the effect of the drug on outer hair cells of the organ of CORTI and on vestibular sensory epithelia.
No degenerative changes were observed in outer hair cell cilia of the organ of CORTI and the vestibular sensory cilia at 1 day, 7 days, 14 days and 1 month after injection. No changes of the threshold of ABR were also noticed.
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TOSHIAKI KUBOYA, HIROSHI TAKARADA, TAKAO KINEBUCHI, EIJI NISHIKAWA, TA ...
1986 Volume 39 Issue 3 Pages
667-678
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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In this study, the clinical efficacy of fosfomycin (FOM) for various types of orofacial infections was evaluated in 40 patients, 27 males and 13 females, ranging in age from 16 to 71 years. All but 1 patients were treated orally with FOM at 500mg 4 times daily. The total duration of treatment varied from 3 to 31 days.
Basically, clinical effectiveness was determined by the criteria of Japanese Society of Oral and Maxillofacial Surgeons. Two cases, in which the final therapeutic evaluation could not be obtained because of side effects, were excluded from the analysis. The results were rated as excellent in 7, good in 26 and poor in 5 out of 38 evaluable cases, with an efficacy rate reaching 86.8%. From the clinical standpoint, the differences of efficacy were further discussed in terms of phase, type and intensity of infections respectively.
In 9 (10 times) of 40 cases, the bacteriological analyses could be made. The identification of organisms obtained from abscess in each case demonstrated mixed infections caused by both aerobic and anaerobic organisms in more than half cases. From their sensitivity tests, it should be pointed out that FOM was efficiently active against aerobic and anaerobic Gram-positive organisms, while it was ineffective for the anaerobic Gram-negative organism, Bacteroides, although the role of the latter generally remained still obscure in orofacial infection.
No serious side effects were observed except for mild diarrhea in 3 patients and a slight elevation of serum glutamic oxaloacetic transamirase (GOT) level in 1 patient.
This study conclusively demonstrated that FOM was a useful and safe antibiotic in the treatment of patients with various orofacial infections.
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SHINJI MOTOJIMA, TOSHIO NUMAO, SHIGEO WATANABE, NAOHIKO ANDO, HIROSHI ...
1986 Volume 39 Issue 3 Pages
679-685
Published: March 25, 1986
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Respiratory infections of 19 subjects of advanced age and/or with underlying respiratory diseases were treated with cefoperazone (CPZ) and its clinical effects were studied. Sixteen subjects suffered from respiratory tract infection and 3 subjects had pneumonia. The age of the subjects ranged from 39 to 77 years with the mean of 63.8, 7 of them being more than 70 years of age. The underlying respiratory diseases included chronic pulmonary emphysema in 6 subjects, diffuse panbronchiolitis in 3, bronchiectasis in 3, silicosis in 2 and one each of chronic bronchitis, pulmonary fibrosis, lung cancer and old pulmonary tuberculosis. One case, 75 years of age, had renal insufficiency. The daily dose of CPZ was 4 grams in 18 of the 19 subjects and the duration of administration ranged 5 to 22 days. The remaining 1 subject received 2 g of CPZ daily for 6 days. Clinical effects were judged from the changes in fever, cough, amount of sputum, dyspnea, rales, cyanosis, chest X-ray, white blood cell counts, CRP, erythrocyte sedimentation rates and results of sputum culture. Clinical effects were good in 16 subjects, fair in 1, and poor in 2. Bacteriological follow-up was carried out in 13 subjects. Infecting bacteria were eliminated from 5 subjects, reduced in 2 and, in 4 subjects, they were replaced by other bacteria. In 1 subject,
P. aeruginosa was isolated from sputum even after the treatment with CPZ, and in another subject
H. influenzae relapsed immediately after the cessation of the CPZ treatment. No side effects were observed except in 1 subject with eosinophilia. No difference in the effect of CPZ was found between subjects more than from 60 years of age and those less than 59. We conclude that CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.
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SHIRO NOZAWA, DU-ZEN TSAI, CHENG-HUE JENG, MASAHIKO KOJIMA, FUMIO TSUT ...
1986 Volume 39 Issue 3 Pages
686-692
Published: March 25, 1986
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The purpose of the study was to examine the penetration of cefoperazone (CPZ) into the exudate of retroperitoneal space after (semi-) radical hysterectomy in patients with uterine carcinoma and to evaluate the suitability of its prophylactic use. Two grams of CPZ was administered by intravenous infusion over 1 hour just after the operation and the same dose was repeated every 12 hours for 3 consecutive days. The exudate was collected from the abdominal drainage for every 3 hours for measurements of hemoglobin, total protein and CPZ levels.
Concentrations of CPZ in exudate samples were found to remain above the MICs for major causative organisms of the inflammation in both groups of patients of radical (14 cases) and semiradical (5 cases) hysterectomy. On the operative and 1st days, exudate CPZ level in the group of semiradical hysterectomy patients showed higher than that in the group of radical hysterectomy patients. But on the 2nd day, there was no significant difference in exudate CPZ level between these 2 groups.
The above results indicated that the presence of blood in the retroperitoneal space might affect the concentration of the antibiotic in the exudate.
From these findings, it is concluded that the present dosage regimen is efficient to prevent the postoperative infection after (semi-) radical hysterectomy.
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HISASHI NAKAHATA, YUICHI HIRAI, YOSHIHIRO KUMASAKA, TADASHI MIYAZAWA, ...
1986 Volume 39 Issue 3 Pages
693-700
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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The disulfiram-like reactions following the treatment of cephem antibiotics with methyltetrazolethiol moiety (latamoxef (LMOX) and cefoperazone (CPZ)) was studied by using large (500mg/kg) and small (50mg/kg) doses of the drugs.
Normal and fatty liver rats were injected intraperitoneally with the cephem antibiotics.
After overnight fasting blood samples were obtained following an administration of 20% ethanol (2g/kg).
Blood ethanol and acetaldehyde concentrations, and liver acetaldehyde dehydrogenase activity were determined. Blood ethanol concentration upon the small dose was similar to that obtained upon the large dose in both groups of normal and fatty liver rats. Blood acetaldehyde concentration upon the large dose was higher than that upon the small dose; 2-fold increase in normal rats and 2.6-4.7-fold increase in fatty liver rats were observed after administering LMOX, while 3.7-fold increase in normal rats and 5-5.7-fold increase in fatty liver rats upon administering CPZ.
Additionally, liver acetaldehyde dehydrogenase activity (Enzyme 1) observed upon the large dose was lower than that observed upon the small dose; the degree of reduction was 33% in normal and 19% in fatty liver rats upon the administration of LMOX, while 37% in normal and 45% in fatty liver rats upon the administration of CPZ.
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MITSUO KOZURU, TAKAO KURATA, NAOKUNI UIKE, YOSHIYUKI NIHO, TSUNEFUMI S ...
1986 Volume 39 Issue 3 Pages
701-712
Published: March 25, 1986
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Therapeutic effects of cefmenoxime hemihydrochloride (CMX, Bestcall®), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; HODGKIN'S disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases.
By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.
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NOBUYUKI MINAMI, NOBUO UNO, SHIGERU SHIRAKAWA, RYUZO OHNO, MASAO OKUMU ...
1986 Volume 39 Issue 3 Pages
713-720
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Infected patients with hematological disorders were treated with the combination of cefmenoxime (CMX) and cefsulodin (CFS). This therapy was done on 74 patients, of whom 38 (51%) had acute myelocytic leukemia, 14 (19%) malignant lymphoma, 7 (9%) acute lymphocytic leukemia, 5 aplastic anemia, 4 adult T cell leukemia, 4 chronic myelocytic leukemia, 1 multiple myeloma and 1 histiocytic medullary reticulosis.
Complicated infections included 5 cases of septicemia, 41 cases of suspected septicemia, 19 cases of respiratory tract infection, 2 with anal abscess, 1 with urinary tract infection and others.
The obtained results were as follows:
1. Clinical effectiveness of the combination therapy was excellent in 17 cases (23.0%), good in 24 (32.4%) and poor in 33 (44.6%). Total clinical efficacy rate was 55.4%.
2. Clinical efficacy rate was 40% against septicemias, 51.2% against suspected septicemias and 57.9% against respiratory tract infections.
3. Causative pathogens were isolated in only 21 cases (28.4%): Gram-positive bacteria in 9 cases, Gram-negative bacteria in 11 and fungus in 1. About half of the Gram-negative bacteria belonged to
Pseudomonas sp.
4. The efficacy rate of this combination therapy against Gram-negative bacterial infections was 72.7% but the rate against Gram-positive bacterial infections were only 33.3%.
5. Only in 1 case, this combination therapy was discontinued because of drug eruption. Abnormal laboratory findings were observed in 5 cases: Elevation of BUN in 3, GOT and GPT in 1 and prolongation of activated partial thromboplastin time in 1.
In conclusion, this combination therapy of CMX and CFS is useful and safe against infections complicated by hematological disorders.
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KAZUHISA FUJITA, MICHIAKI YOKOYAMA
1986 Volume 39 Issue 3 Pages
721-725
Published: March 25, 1986
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Concentrations of cefmenoxime (CMX) in serum and tissue were determined in surgical patients with chronic sinusitis, maxillary cyst or chronic tonsillitis. CMX was intravenously administered in a dose of 1 gram. Thirty minutes after the administration, patients were operated under local anesthesia. Concentrations of CMX in tissues were determined 1 hour after administration, and were 15.8μg/g and 20.3μg/g in mucous membrane of maxillary sinus and maxillary cyst. CMX was not detectable in tonsils of 8 patients out of 11 examined. An examination of MIC against various bacteria isolated from sinus pus and pharyngeal swab indicated that CMX was effective enough to produce a prophylactic effect against otolaryngo-infections.
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TAKESHI MATSUOKA, HISAHIKO OTA, JUN TAKEDA, OSAMU TAKATANI
1986 Volume 39 Issue 3 Pages
726-732
Published: March 25, 1986
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The most frequently encountered infectious disease in the field of internal medicine is respiratory tract infections. One of the most important requirements for an antibiotic in the treatment of infections is that it must be efficiently transferred to the infected site to attain a high concentration there. In the case of respiratory tract infections, it is desirable for the drug concentration in the sputum to be higher than the MIC for the causative bacterium.
Cefotaxime (CTX) expresses potent antibacterial activity against
Haemophilus influenzae, Klebsiella pneumoniae and
Streptococcus pneumoniae, which are the major causative bacteria of respiratory tract infections. CTX also exerts antibacterial effects against a wide range of other bacteria. We administered CTX to patients with respiratory tract infections, then measured and compared the drug concentrations in the serum and sputum. The results are described below.
1. When 2g of CTX was drip-infused, the drug concentration in the serum was 113.0μg/ml at 5 minutes after the completion of infusion, 64.9μg/ml at 30 minutes, 38.7μg/ml at 1 hour, 19.0μg/ml at 2 hours, 8.9μg/ml at 4 hours and 3.8μg/ml at 6 hours.
2. The drug concentration in the sputum was 1.29μg/ml at 5 minutes after the completion of infusion, 1.54μg/ml at 5 to 30 minutes, 1.36μg/ml at 30 minutes to 1 hour, 1.47μg/ml at 1 to 2 hours, 1.12μg/ml at 2 to 4 hours and 1.35μg/ml at 4 to 6 hours.
The drug concentration in the serum was the highest at 5 minutes after completion of the dripinfusion, and then it gradually decreased. Even 6 hours after the infusion, however, a drug concentration as high as 3.8μg/ml was detected. The drug concentration in the sputum showed a different pattern from that in the blood: A nearly constant concentration (1.12-1.54μg/ml) was observed immediately after the completion of administration through 6 hours after the administration.
3. Clinical effect was excellent in 3, good in 8, moderate in 1 and poor in 2. The overall efficacy rate was 78.6%.
No adverse reactions due to the administration of the drug were observed.
The concentrations of CTX in the blood and sputum were much higher than the MIC
80 for the major causative bacteria of respiratory tract infections. Therefore, it can be concluded that CTX is an effective and safe antibiotic for the treatment of respiratory tract infections.
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HIROSHI IWAMORI, NAGAO ADACHI
1986 Volume 39 Issue 3 Pages
733-738
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Cefotaxime (CTX) was administered in a dose of 2g to 20 adult patients prior to orthopaedic surgery. Samples of the bone marrow blood and the forearm venous blood were collected at 30, 60, 90 and 120 minutes after the CTX administration, and the concentration of the drug in each sample was determined. The results are described below.
1. The mean concentration of CTX transferred into the bone marrow blood was 59.7, 28.9, 14.7 and 7.2μg/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively.
2. The mean concentration of CTX in the venous blood was 84.0, 39.1, 19.0 and 13.8μg/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively.
3. The mean ratio of the CTX concentration in the bone marrow blood to that in the venous blood was 73.9%, 71.0%, 75.1% and 51.6% at 30, 60, 90, 120 minutes after the CTX administration.
From the above results, CTX is considered to be a useful antibiotic if it is administered prior to orthopaedic surgery to prevent infections.
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MINORU SAKURAI, SHINJI SHIBUYA, JUN MIYAGISHIMA, EIKICHI WAKAMATSU
1986 Volume 39 Issue 3 Pages
739-745
Published: March 25, 1986
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Cefotaxime (CTX) was intravenously administered in an amount of 2.0g to each of 34 adult patients before the surgery mainly of the hip joint. Samples of the blood from the bone marrow around the trochanter were taken at the time of the operation. At the same time blood samples were taken from peripheral veins. The sample was centrifuged and the supernatant was analyzed for CTX and desacetyl-CTX. The concentration of CTX in the marrow blood was 150.9μg/ml and that in the blood was 182.5μg/ml in the earliest samples taken at 20 minutes after injection. In the 44 pairs of samples, the concentration of CTX in the marrow blood was lower than that in the peripheral blood in all the cases except 4. The concentration of desacetyl-CTX (Des-CTX), however, in the marrow blood was higher than in the peripheral blood in 33 of the 44 pairs of specimens.
Since the degradation of the drug progresses with time, the ratio of Des-CTX to CTX increased with time. This trend was particularly marked in the bone marrow blood and can be expressed as Y=113.0+0.32t, when Y is the ratio percentage (Des-CTX/CTX) and t is time after the injection of the drug in minute. Thus, CTX transferred into the bone marrow tends to remain there and transformed into the desacetyl form.
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KANKI KOMIYAMA, CLAUDE TRONQUET, YUMIKO HIROKAWA, SHINJI FUNAYAMA, OSA ...
1986 Volume 39 Issue 3 Pages
746-750
Published: March 25, 1986
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In the course of a search for novel antibiotics, an antiplatelet substance was isolated from the fermentation broth of
Streptomyces sp. No.82-85. Thereafter, the active substance was identified as pyrrole-2-carboxylic acid (P2C) by structural studies. The effects of P2C on adenosine diphosphate (ADP)-, arachidonic acid-, collagen-or tumor cell-induced platelet aggregation were examined
in vitro and
ex vivo. In
in vitro studies, P2C (25-100μg/ml) suppressed the aggregation of platelets of normal Wistar rats. The intraperitoneal administration of P2C (200mg/kg) to rats and rabbits suppressed platelet aggregation induced by ADP, arachidonic acidand collagen when examined for 0.5-3 hours after administration. The agent also suppressed platelet aggregation induced by both mouse syngenic tumors, Meth-A fibrosarcoma and IMC carcinoma
in vitro.
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WITH SPECIAL REFERENCE TO CEFOTIAM ANDCEFMENOXIME
HIDEO SHIOZAKI, SHOICHI AEBA, HIROSHI MATSUMOTO, RYU USUI, SHIGEO TOTS ...
1986 Volume 39 Issue 3 Pages
751-760
Published: March 25, 1986
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Cefotiam (CTM) and cefmenoxime (CMX) were studied for their serum concentrations and transference into bile in patients with PTCD or T-tube. One gram of CTM or either 1g or 2g of CMX was administered by an intravenous drip infusion for over 30 minutes. These drugs were also studied for their serum concentrations, bile concentrations, and tissue concentrations in the walls of the gallbladder of patients operated on for cholelithiasis. Intravenous drip infusion (over 30 minutes) was used to administer 1g of CTM or 1g or 2g CMX immediately before surgery.
1. Both CTM and CMX were readily transferred into bile. Their bile concentrations, however, varied greatly among patients, and extremely low levels were detected in some patients.
2. A crossover analysis of concentrations of CMX in bile of patients given doses of 1g and 2g revealed a dose-response relationship.
3. The crossover analysis of drug concentrations in bile of patients given CTM and CMX showed that CMX is transferred more readily to bile.
4. The relationship between liver functions and drug transfer to bile was examined by plotting the total bilirubin level against drug concentrations in bile. The plots formed an exponential curve with a correlationcoefficient (r) being-0.52 in cases when each subjects received 1g of CTM and-0.72 in cases when each subjects received 1g of CMX. A study of 3 patients given CMX at a dose of 1g suggested that bile levels of CMX may be correlated to ICG.
5. Concentrations of CTM and CMX in tissues of the gallbladder wall were fairly high, with unexpectedly small variance among patients. Even in patients with low bile concentrations of these drugs, drug levels in the tissues of the gallbladder wall were high. Drug levels in the noninflammatory tissues were higher than those in inflammatory lesions.
The above findings suggest that CTM should be the antibiotic of choice for patients with ordinary biliary tract infections and after the surgery of the liver and biliary tract system, while CMX should be the antibiotic of choice for patients with severe biliary tract infections, and for compromised hosts after the surgery of the liver and biliary tract system.
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AKIRA KOYAMA, JUNICHI MORI, HITOSHI TOKUDA, MUNEAKI WAKU, HIROSHI ANNO ...
1986 Volume 39 Issue 3 Pages
761-771
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Cefotiam (CTM) is a new cephalosporin with a broad spectrum of activity against both Gram-positive and Gram-negative microorganisms. Cephalosporins are widely used for prophylaxis of infections in patients undergoing thoracotomy. Augmentation by serrapeptase on tissue permeation of CTM was examined in 35 thoracotomy patients with lung cancer. The subjects were divided into two groups according to the method of the administration of CTM. Group I consisted of 17 subjects, each of whom received a single dose of 2g of CTM alone by an instillation for 30 minutes. Group II consisted of 18 subjects, each of whom received a combination of CTM and serrapeptase; serrapeptase was given 2 tablets(10mg) each time for three times/day until the day before surgery, and then CTM was administered by the same procedure. The following results were obtained:
1. Individual difference was observed for the permeation of CTM into tissues. Pathologic differences also affected the permeation. Nevertheless, the CTM levels in pulmonary tissues reached about a half of those in the blood in both the single dose group and the combination group, hence sufficient concentrations exceeding MIC
80 for main microorganisms that caused infections in the lung were obtained.
2. The concentrations of CTM in inflammatory tissues have showed lower levels than those of normal tissues in both CTM single dose and the combination groups. Decrease of blood flow volume may have contributed to the reduction in levels of CTM in the inflammatory tissues. The ratio of the concentration of the drug in pulmonary tissues to that in the blood was 29.1±2.5% in the single dose group, and 44.2±6.0% in the combination group, the latter showing quite a significant increase (P<0.05).
Combined administrations of CTM and serrapeptase deserves more trials in the case when surgical treatments of the lung are performed. An antiinflammatory effect of serrapeptase in the respiratory system is expected, and in addition, the combined use of CTM and serrapeptase should stimulate permeation of the antibiotic into tissues.
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MASAKO OTSUKI, MAYUMI TANAKA, YUMIKO SAJI, TAKESHI NISHINO, TERUO TANI ...
1986 Volume 39 Issue 3 Pages
772-782
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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In vitro susceptibilities of bacterial pathogens to β-lactam antibiotics were determined. Bacterial pathogens examined included various isolates from the patients of respiratory tract infections at the hospitals of Kyoto-Shiga area in 1981 and 1983. Major organisms isolated from clinical specimens were
Haemophilus spp.,
Klebsiella spp.,
Pseudomonas spp.,
S. aureus and
Streptococcus spp. An increase in the isolation frequency of
P. aeruginosa, a decrease in the isolation frequency of
H. influenzae and no change in the isolation frequency of the other organisms were observed between the years 1981 and 1983.
Data from susceptibility tests of clinical isolates confirmed that cefazolin (CEZ) and cefotiam (CTM) showed good antibacterial activity against
S. aureus and cefmenoxime (CMX) was highly effective on
Streptococcus spp., but that the susceptibilities of both organisms to CEZ, CTM, and cefmetazole (CMZ) in 1983 were lower than in 1981. Although CMX also showed good antibacterial activity against
Klebsiella. spp., there were no changes in the effectiveness of CTM, CMZ, and CEZ between the years 1981 and 1983. The
in vitro antibacterial activities of CMX and cefoperazone against
Haemophilus spp. were superior to those of the other β-lactams tested, but there was a decline in the efficacy for CEZ. Although cefsulodin and piperacillin were highly active against
Pseudomonas spp., declines in their effectiveness was observed between the years 1981 and 1983.
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YEARLY CHANGES IN ISOLATION FREQUENCIES FROM CLINICAL SPECIMENS, SERO-TYPE DISTRIBUTIONS AND DRUG-SUSCEPTIBILITIES, ESPECIALLY THOSE OF β-LACTAM-RESISTANT STRAINS
TOYOKO OGURI
1986 Volume 39 Issue 3 Pages
783-806
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Although chemotherapeutics have markedly reduced the mortalities of infectious diseases caused by
Streptococcus pneumoniae, it has recently been recognized that
S. pneumoniae is still clinically significant for the infants, highly-aged and high-risk patients.
This work was planned to examine the isolation frequency of
S. pneumoniae from clinical specimens and its drug-susceptibilities, especially to β-lactam antibiotics. The strains were obtained from in-and out-patients in Main and Branch Hospitals of Juntendo University from 1961 to 1985. Drug-susceptibility tests were carried out against 39 different drugs including 10 penicillins, 16 cephalosporins, 3 tetracyclines, 3 macrolides, chloramphenicol, gentamicin, vancomycin, 3 pyridone carboxylic acids and sulfamethoxazole-trimethoprim using agar dilution method. The sero-typing of the isolates was made by the QUELLUNG technique using Diagnostic Pneumococcal Anti-Sera (Statens Seruminstitut, Copenhagen).
The following results were obtained: (1)
S. pneumoniae was isolated mostly from sputum and throat swabs, but rarely from the blood and cerebrospinal fluid.
S. pneumoniae was also isolated from the pus and discharges of ears, sinuses and eyes.(2) The isolation frequency of
S. pneumoniae was higher in Branch Hospital where subjects were mostly out-patients than in the Main Hospital.(3) Frequent sero-types of
S. pneumoniae were groups 23, 6, 19, and type 3, regardless of clinical specimens and years.(4) Against tetracycline and chloramphenicol, approximately 40 to 70% of the strains were resistant, while against maclorides, resistant strains were few. Resistant strains were still fewer against βlactam antibiotics.(5) Tetracycline-and chloramphenicol-resistant strains are recently decreasing, while macrolidesand β-lactam-resistant strains are somewhat increasing.(6) Nine β-lactam-resistant strains of
S. pneumoniae were isolated from sputum and throat swabs, with benzylpenicillin-MICs ranging from 0.39 to 3.13μg/ml. Three (2 of 23F and 1 of 23A) out of the 9 strains were resistant to β-lactams, tetracycline, chloramphenicol, erythromycin and lincomycin. Four strains (3 of 23F and 1 of group 23) were resistant to β-lactams, tetracycline, erythromycin and lincomycin. One strain (type 45) was resistant to β-lactams, tetracycline and chloramphenicol. One strain (23A) was resistant to β-lactams only. Those 9 β-lactam-resistant strains were isolated mostly from children. Most of the patients had been given β-lactam antibiotics before those resistant strains were isolated. The PBP (penicillin-binding protein) patterns were different in β-lactam-resistant strain from those of susceptible strains.
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YOSHIAKI MORIYAMA, AKIRA SHIBATA, MASAKAZU ITO, TOSHIO IIZUMI, TORU WA ...
1986 Volume 39 Issue 3 Pages
807-814
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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Seventy-one patients with severe infections associated with hematologic disorders including leukemia, lymphoma and aplastic anemia were treated with ceftizoxime (CZX) in daily doses of 4-6g for an average of 20.1 days.
Infections associated with hematologic disorders consisted of sepsis and pneumonia, and most of the causative organisms appeared to be Gram-negative bacteria. Of the 64 patients who completed the trial, excellent response was observed in 16 and moderate response in 26. The rate of clinical effectiveness was 65.6%.
Side effects observed during the treatment included skin rash in only 1 patient, and hepatic disorders in 6 patients. However, the relationship between CZX and these abnormal findings was not established.
These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections associated with hematologic disorders.
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COMPARATIVE STUDY WITH NEOCARZINOSTATIN
SATOKO HIRAYAMA, FUMIO SATO, TATSUYA ODA, HIROSHI MAEDA
1986 Volume 39 Issue 3 Pages
815-822
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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SMANCS is a conjugate protein of copolymer of styrene-maleic acid [SMA] (molecular weight: 1,500) and an antitumor protein neocarzinostatin [NCS] (molecular weight: 11,700). It has an approximate molecular weight of 15,000. We report here stability of SMANCS in oil and in water, and NCS in water, under various physical conditions such as exposure to heat, UV, pH, and ultrasonic treatment. Then, we carried out an experiment of transfer of SMANCS in lipid contrast medium [lipiodol] (oil phase) to water phase (blood and physiological saline)
in vitro. Results are summarized as follows:
1. In aqueous condition, SMANCS is far more stable than NCS against the exposure to heat and UV, though it is inactivated by excessive exposures.
2. SMANCS in an oily medium was found much more stable even at higher temperatures than in the aqueous phase.
3. Both SMANCS and NCS are the most stable at pH 4.9-6.0.
4. SMANCS dissolved in oil transferred to water phase slowly, having T1/10 of 24 hours (in case of lipiodol). This helps maintaining the anticancer effect of the drug
in vivo for a long period of time.
5. SMANCS in lipiodol was found to exert its action against cultured tumor cells as in an aqueous solution.
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YUTAKA KANAZAWA, KAZUKO SHIGENO, TOSHIO KURAMATA
1986 Volume 39 Issue 3 Pages
823-841
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
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The effect of antibacterial chemotherapy is influenced by the drug-susceptibility (minimum inhibitory concentration: MIC or minimum bactericidal concentration: MBC) of a bacterium and the drug concentration in an infected focus. An intracellular drug-inactivating activity is reflected generally by the value of MIC, while an extracellular inactivating activity, which may affect focal drug-concentrations, is usually overlooked.
β-Lactamase, an inactivating enzyme, is usually detected using benzylpenicillin1, 2) or chromogenic cephalosporin3, 4) as a substrate. From the clinical point of view, however, it seems more appropriate to observe the direct reactionship between the isolated causative organism and the drug used.
No readily-applied simple method has been reported in any combination between bacteria and drugs for such a direct observation. In this paper, we intend to present a simple and routine method for the determination of the drug-inactivating activity of living cells.
We have studied a simple method which we call “the cell-disc system” that satisfies the above requirements and permits an easy measurement of the extracellular drug-inactivating activity of any bacteria against any drugs using ordinary sensitivity discs containing the drugs in question. KANAZAWA et al. 5) have previously reported a method which permits classification of degrees of drug inactivation by comparing the sizes of inhibition zones produced by sensitivity discs on preinoculated agar plates and uninoculated plates. TOMIOKA et al. 6) reported a “double disc technique” for a semiquantitative assay for β-lactamase production by Gram-negative bacteria. Recently, Tsun et al.7) presented an assay technique for β-lactamase substrate-profiles using an agar plate consisting of a base-layer containing crude enzyme, sensitivity discs and a top-layer inoculated with an indicative organism.
In this paper we describe 2 simple systems based on the measurement of clear inhibition zones around ordinary sensitivity discs to quantitatively determine degrees of drug-inactivation caused by test bacteria.
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KOICHI DEGUCHI, SHIGEMI FUKAYAMA, YUKIKO NISHIMURA, NOZOMI YOKOTA, SET ...
1986 Volume 39 Issue 3 Pages
842-852
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
JOURNAL
FREE ACCESS
The
in vitro susceptibilities of various causative organisms recently isolated from patients with genital infections to BRL 25000 (a formulation with 2 parts of amoxicillin and 1 part of potassium clavulanate), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined. β-Lactamase-producing strains were detected by the nitrocefin disc method.
1. Frequencies of isolation of β-lact a ma se producing strains of
E. coli, K. pneumoniae and B. fragilis were 36%, 96% and 100%, respectively.
2. The activity of BRL 25000 against
S. agalactiae and anaerobic GPC (anaerobic Streptococci, Peptostreptococcus spp.) was slightly less than that of AMPC but was 2-to 4-fold higher than CCL and 8-to 16-fold higher than CEX, CDX and CXD.
3. Against
E. coli and
K. pneumoniae, the activity of BRL 25000 was superior to that of AMPC and approximately equal to CEX, CDX and CXD but 2-fold less than CCL.
4. Against the
B. fragilis group, BRL 25000 was much more active than AMPC or any of the cephalosporins tested, clearly demonstrating the β-lactamase inhibitory properties of the clavulanic acid in BRL 25000.
5. At inocula of 106 CFU/ml, MIC values of BRL 25000 were 12.5-50μg/ml against some strains of
E. coli,
K. pneumoniae and
B. fragilis. A mechanism of resistance other than β-lactamase production is obviously prevalent in these strains. It is speculated that the resistance may be due to a low affinity of the drug to target proteins.
6. Mixed infections of
B. fragilis and
E. coli or
K. pneumoniae are commonly found in the obstetric and gynecological patients. BRL 25000 shows activity against these strains and also against both aerobic and anaerobic GPC. Therefore, BRL 25000 is considered useful for the treatment of genital infections.
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
1986 Volume 39 Issue 3 Pages
853-886
Published: March 25, 1986
Released on J-STAGE: May 17, 2013
JOURNAL
FREE ACCESS
The S6472 is a 4: 6 mixture of 2 types of granules of cefaclor (CCL) coated with different films; one type of granules is soluble at low pH's and absorbed in the stomach while the other type is soluble at high pH's and absorbed in the intestine. The difference in absorption sites makes it possible to maintain blood concentrations of the drug at clinically efficient levels for a longer period of time compared with ordinary CCL.
The efficacy, safety and usefulness of S6472 in the treatment of bacterial pneumonia was compared with those of ordinary CCL and of amoxicillin (AMPC) by the blind method.
The patients entered in this trial were those who had bacterial pneumonia or lung abscess and were 16 years or above of age.
The S6472 was given orally for 14 days at a daily dose of 1,500mg (750mg each after breakfast and supper), CCL was given at a daily dose of 1,500mg (500mg each after every meal), and AMPC at 2,000mg (500mg each after every meal and at the bedtime). To make the study blind, placeboes were matched with the test drug so that patients in every treatment group took 4 doses per day.
Out of a total of 195 patients thus treated, 179 patients (55 in S6472 group, 62 in CCL group and 62 in AMPC group) were adopted for the evaluation by committee members while 185 patients (58 in S6472 group, 63 in CCL group and 64 in AMPC group) by controllers.
When clinical results of the 3 treatment groups were compared, no statistically significant differences were observed in efficacy rates (cure rates), incidences of side effects nor abnormal findings of laboratory tests.
From these results of this trial, it is concluded that oral administration of 750mg of S6472 twice a day (1,500mg per day) is as effective and useful as that of 500mg of ordinary CCL 3 times a day (1,500mg per day) or 500mg of AMPC 4 times a day (2,000mg per day) in the treatment of bacterial pneumonia or lung abscess.
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