Fates of sulfobenzylpenicillin (SB-PC)(distribution, permeability, binding to serum and liver protein, and partition coefficient), and effects of serratiopeptidase (TSP) on them were investigated.
1) Peak concentration of SB-PC in plasma and tissues reached 30 minutes after subcutaneous injection of SB-PC in the rat and then gradually decreased. Its transfer to kidney and liver waslarger than that to serum. Combined use of TSP increased tissue concentrations of SB-PC. This effect was considered to be partly due to increased level in plasma.
2) Transfer rate of SB-PC to rat fetus (at 18th-21st days of pregnancy) was 9.24-10.15%.
3) Equilibrium of permeability of SB-PC to rabbit intestine was established after 60 minutes, and its rates were calculated 34.44-47.70%. This permeability was increased by combined use of TSP.
4) Binding rates of SB-PC to bovine serum and albumin were more than 90%, and approximately half of them was inactivation rate. Inactivation rate was lowered with increased protein content and/or increased concentration of SB-PC. Binding rates of SB-PC to rat liver homogenateand microsome were less than 50%, and binding rate to liver microsome was slightly lower than that to liver homogenate.
5) Partition coefficients of SB-PC in chloroform over phosphate buffer were 0.263-0.66, which was independent upon pH, and those in lipid over phosphate buffer were 0.02-0.783, which were larger at neutral and alkaline pH than at acidic pH.

View full abstract

[in Japanese]

View full abstract

We studied on the changes of antibiotic susceptibility of anaerobes isolated from various-clinical materials between two periods, October 1965-May 1967 and January 1972-May 1973. Antibiotics we used are benzylpenicillin (PC-G), ampicillin (AB-PC), cephaloridine (CER), erythromycin (EM), oleandomycin (OLM), josamycin (JM), lincomycin (LCM), chloramphenicol (CP), tetracycline (TC) and streptomycin (SM).
Almost all strains of anaerobes excluding Gram-negative bacilli were inhibited by 12.5 mcg/ml of PC-G, AB-PC or CER. Numbers of strains of Bacteroides, Clostridium or non-spore-forming Gram-positive bacilli resistant' to one of these antibiotics (not inhibited by 12.5 mcg/ml) increased slightly.
Among three macrolides, EM, JM and OLM, antibacterial activity of OLM was weakest. Many strains of Fusobacterium and Veillonella were not inhibited by 12.5 mcg/ml of EM or JM. LCM showed the similar antibacterial activity to EM, but has the stronger antibacterial activity for Veillonella, and strains which were not inhibited by 12.5 mcg/ml were rather few excluding Fusobacterium. Changes of susceptibility of anaerobes to macrolides and LCM were not so remarkable.
Almost all strains tested were inhibited by 12.5 mcg/ml of CP and we could not recognize the increase of resistant strains, but many TC-resistant strains were observed among all genus tested except Fusobacterium. The increase of resistant strains was recognized among following genus, Peptostreptococcus, Veillonella, Clostridium, non-spore-forming Gram-positive bacilli and Bacteroides.
Antibacterial activity of SM against anaerobes is very weak. More than fifty per cent of strains excluding Veillonella and non-spore-forming Gram-positive bacilli were not inhibited by 100 mcg/ ml of SM and the increase in strains resistant to 100 mcg/ml were recognized among Bacteroides.

View full abstract

The ability of antibiotics to bind to serum proteins was studied. The extent of binding of cefazolin depends on the species of animals used: about 90% with the sera from man, rabbits or rats, and less in degree with the sera from horses, calves or dogs.
In cefazolin, the binding was characterized by its considerably high extent and easy reversibility. Antibiotics which can bind with proteins to a great extent are generally said to cause high total concentrations in the serum when given parenterally, and this applies to cefazolin. In the superposition method and disc method, the presence of serum interferred with the diffusion of cefazolin into agar medium.
The laboratory evaluation of cefazolin was reported in previous papers1-4), and the proteinbinding property of this new antibiotic was indicated therein. The present paper reports the results from further investigations verifying the extent of binding to serum proteins, a feature which is somewhat different from that of other antibiotics.

View full abstract

The results of experimental studies on minocycline intravenous were summarized as follows:
1. The sensitivity of pathogenic staphylococci to intravenous infusion of minocycline was studied based on the MIC values. The MIC values of all the tested staphylococci were below 1.56 mcg/ml and 91% of them were below 0.2 mcg/ml.
2. The MIC values of this drug for strains of Hemophilus influenzae were distributed below 12.5 mcg/ml.
3. Standard curves of minocycline for the determination of blood level of the drug varied depending on solvents of the drug, phosphate buffer solution or pooled human serum.
4. Concentration of minocycline in blood determined immediately after the 2-hour continuous intravenous infusion of 200 mg minocycline dissolved in 5% glucose in healthy adult males was as high as 6.4 mcg/ml on average. The concentration was rapidly decreased to 2.8 mcg/ml for 2 hours after the termination of infusion but it was kept almost unchanged afterwards showing 2.6mcg/ml even 4 hours after the infusion.
5. Blood levels of minocycline in cases of chronic bronchiolitis and chronic, bronchitis complicated by bronchial asthma showed the similar tendency to those in volunteers. After one shot intravenous injection for 5 minutes of 100 mg minocycline dissolved in 40 ml of 20% glucose, the peak of blood level of 5.3 mcg/ml was observed 30 minutes after the injection and the high blood level of 2.0 rncg/ml was observed 6 hours after the injection.
6. High drug concentration in sputum was observed.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

Cephapirin was administered to 15 cases of acute infections in the otorhinolaryngology. To children, 500mg/day of cephapirin was intramuscularly injected, and to adults, 1,000-2,000mg/ day was intraveneously injected, or drop-infused in order to evaluate the therapeutic effects and side effect, if any. As the results, 6 remarkably effective, 6 effective and 3 non-effective cases, 80% of effectiveness, were observed. Only one case showed facial eruption or rash immediately after the administration of cephapirin, but no severe side effect was observed. No abnormality was found in the blood, liver, kidney and other functions in cases to which cephapirin was administered relatively long period. Therapeutic effect and side effect of cephapirin were not so different from other cepharosporin antibiotics, and it may be said that cephapirin is very effective and safe drug to acute infections.

View full abstract

Studies were done on antibacterial activity and clinical effect of amikacin (BB-K8).
1) Antibacterial activity was excellent against Pseudomonas aeruginosa and almost equivalent activity to kanamycin was observed in Escherichia coli, Klebsiella, Proteus and Staphylococcus aureus.
2) The effects of amikacin (BB-K8), kanamycin and 3', 4'-dideoxykanamycin B (DKB) on the growth curve of E. coli NIHJC-2 strains were examined by using biophotometer. The effect of amikacin was slightly better than kanamycin and 3', 4'-dideoxykanamycin B (DKB).
3) Twenty-eight cases with urinary tract infections and 8 cases for prophylaxis of postoperativeinfections were treated with amikacin. Of the 9 cases with acute urinary infections (cystitis 8 cases, pyelonephritis one case), response was excellent in 6 cases, good in 1 case h and negative in 2 cases.
Of the 19 cases with chronic complicated urinary tract infections (cystitis 15 cases, pyelonephritis 4 cases), effective response was seen in 14 cases and no response in 5 cases.
Good results were obtained in clinical use for prophylaxis of postoperative infections.
4) No adverse effects were observed.

View full abstract

[in Japanese]

View full abstract

Amikacin, a new semisynthetic aminoglycoside antibiotic, has been investigated with the following results.
In susceptibility test of 29 strains of Staphylococcus aureus and 17 strains of Escherichia coli using a plate-dilution method, gentamicin and dideoxykanamycin B showed low M. I. C.(minimum inhibitory concentration) values, whereas amikacin and kanamycin higher values. As for 12 strains of Pseudomonas aeruginosa, the antibacterial activity of amikacin was superior to kanamycin, but inferior to dideoxykanamycin B and gentamicin. No definite cross-resistance was found using correlogram.
In human subjects (Ccr: 64-72ml/min.) injected intramuscularly with 200 mg amikacin, peak serum level of 10.8mcg/ml in average was observed one hour after the injection, and about 50% of the injected dose was recovered from urine. In the study of protein binding, amikacin did not bind with Monitrol-1 plasma.
Two cases with respiratory infections and 9 with urinary tract infections were treated with amikacin. Clinical improvement was observed in 9 cases. One case complained of tinnitus, and another case vertigo. The treatment was discontinued in the latter case. An increase in alkaline phosphatase value with no fluctuation of transaminase was observed in an old female patient.

View full abstract

[in Japanese]

View full abstract

Studies were made on BB-K8 (amikacin), a new semisynthetic derivative of kanamycin developed in Japan. The results obtained are as follows:
1) The M. I. C. of amikacin against 18 strains of Staphylococcus aureus isolated from human infection foci were between 0.1 and 12.5mcg/ml, and those against Pseudomonas aeruginosa between 0.8 and 25mcg/ml.
2) The average serum peak level of 5.7mcg/ml was obtained in normal human adults 30 minutes after single intramuscular injection of 100mg amikacin, while 200mg injection yielded a peak level up to 14.9mcg/ml. The average urinary recovery of the drug in 8 hours was 72.5% of the dose.
3) Distribution into organs (rats): The highest tissue concentration of the antibiotic was found in kidney, followed by serum, lung, spleen and liver. This distribution pattern was similar to those of other aminoglycoside antibiotics.
4) Excretion into bile (rabbits): Concentration of the drug in rabbit bile obtained from choledochus canule after intravenous injection was usually 1/3-1/5 of the blood level, similarly to other aminoglycosides.
5) Clinical trials: Ten patients (bronchopneumonia 5, urinary tract infections 5) were treated with intramuscular injections of amikacin (200-400mg daily), which were effective in nine cases, excepting one pneumonia case.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

1. A single intramuscular administration of 125 mg of BB-K8 to a 10-years-old boy (body weight 32.0 kg) yielded a maximum serum level of 10.6mcg/ml at one hour, and of 200 mg to a 7-years-old boy (20.0kg) 15.0mcg/ml at 30 minutes. The serum level declined thereafter and the half-life was determined to be 1.39 and 1.84 hours, respectively. In the first patient 37.44% of given dose was excreted into urine within 2 hours and urinary concentration in this period averaged 780 mcg/ml. Urinary recovery within 8 hours was 58.69%. In the second patient 70.2% of the given dose was recovered in urine in the course of 24 hours following injection.
2. Twenty children with acute infections, including pneumonia, urinary tract infection, enterocolitis and furunclosis were treated with BB-K8 of 7.5-10mg/kg/day. In three patients the result was excellent and in 9 it was satisfactory. The overall clinical effectiveness was thus estimated to be 60.0%.
No adverse effects were observed during and after the BB-K8 treatment, including abnormalities in laboratory examinations.

View full abstract

[in Japanese]

View full abstract

Ten infants and children with bacterial infections were treated with amikacin (BB-K8), a new semisynthetic aminoglycosidic antibiotic. The patients ranged in age from 10 days to 8 years. Their clinical categories were as follows: 6 urinary tract infections, 2 pulmonary infections, one bacterial meningitis due to Proteus mirabilis, and one subcutaneous abscess of the head due to Pseudomonas aeruginosa. The causative organisms of the urinary tract infections were Pseudomonas aeruginosa in three, Proteus mirabilis in one, and Escherichia coli in two cases, respectively.
Amikacin was administered intramuscularly in doses of 12-18mg/kg per day to 7 patients every 12 hours, and 9-10mg/kg per day to 2 patients every 24 hours. The case of subcutaneous abscess was treated exclusively by topical irrigation with 10mg/ml solution of amikacin. Duration of treatment varied from 5 to 21 days.
The response of therapy for 6 urinary tract infections was excellent in 5 cases, and good in one, respectively. The response was good in a case of pulmonary suppuration. The response to topical therapy was excellent in a case of subcutaneous abscess. Two therapeutic failures were observed in a child with pneumonia and in an infant with bacterial meningitis, respectively. The overall effectiveness was 80%.
An elevation of serum transaminase (GOT 182, GPT 127) was observed in a case and was transient; the values returned to normal levels when treatment discontinued. Auditory function evaluated by audiometer was unchanged in two cases.
On the basis of these clinical studies, amikacin (BB-K8) was shown to be a useful and relatively safe antibiotic in the treatment of bacterial infections, especially of the urinary tract.

View full abstract

[in Japanese]

View full abstract