1. When gentamicin (GM) and sulbenicillin (SBPC) or cephacetrile (CEC), in combination with pre- or post-treatment, were injected intravenously to the rat, their pharmacokinetics were investigated.
2. The antibiotics in the samples were separated by paper electrophoretic technique and their concentrations were determined by cup thin layer plate method using Bacillus subtilis as the test organism.
3. The biological half-life of SBPC in the serum was shortened in pretreatment with GM and prolonged in posttreatment with GM, while that of GM did not vary in pre- or post-treatment with SBPC.
4. The half-life of CEC was prolonged in treatment with GM, while that of GM did not vary.
5. These phenomena may be considered to be produced as the results of a concentration ratio of SBPC and GM or of CEC and GM, and protein binding of these antibiotics, as far as plasma initial levels, tissue distribution, urinary excretion and protein binding of these antibiotics are concerned.

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For the purpose of measuring concentrations of gentamicin (GM) into body fluids (pancreatic juice, abdominal cavity, and bile) after intramuscular injection, the authors conducted experiments using adult mongrel dogs with following results.
1) The highest concentration in pancreatic juice was observed 1-1.5 hours after single intramuscular administration of 4mg/kg. The highest concentration was 51.3% of that in blood.
2) The highest concentration in bile was observed 30 minutes -1 hour after single intramuscular administration of GM. The concentration was about 50% of that in blood.
3) The diffusion of GM into the abdominal cavity was good after single intramuscular administration.
4) The rate of urinary excretion was high as is generally known.

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[in Japanese]

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[in Japanese]

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In order to elucidate the usefulness of cephacetrile (CEC), comparative trials with cefazolin (CEZ) were carried out in the patients with complicated infections of the urinary tract, and the following results were obtained:
1. There were no statistically significant differences or tendencies observed between the groups given CEC and CEZ in either of the global effects, bacteriological effects, rate of superinfection, relapse, relapse with bacterial alternation, drug usefulness, rate of improvements in symptoms and findings in all the cases.
2. According to a result of stratified analyses, there were statistically significant differences observed, showing more inferior results of CEC than CEZ in either stratum of “below 50” in the age, “acute” in the disease phase,“infections of the upper urinary tract” in the disease pattern, and “E. coli including mixed infections with gram-positive organisms” in the pathogenic strains. However, it should be taken into consideration that certain background factors influence greatly in the effects and there were some problems on deviated backgrounds in these strata.
On the other hand, CEC displayed better bacteriological effects than those of CEZ in higher stratum of “chronic” in the disease phase and “Klebsiella, Proteus, Citrobacter, Enterobacter including mixed infections” in the pathogenic strains, and statistically significant differences were not observed.
3. In consequence of bacteriological studies, CEC showed stronger resistance than CEZ against β-lactamase produced in all the strains of gram-negative bacilli. Particularly there were significant differences or tendencies observed in those ofProteus, Citrobacter, and Enterobacter, and at the same time there were great differences in the activity of β-lactamase between CEC and CEZ as the substrate.
4. In correlation of the MIC and effects, CEC showed weaker actions than CEZ against susceptible organisms, but slightly stronger actions against moderately or highly resistant strains.
A study of the relationship between the MIC of pathogenic strains, β-lactamase, and bacteriological effects, showed possibilities that even the high activity of β-lactamase results in remarkable effects in susceptible strains and the drugs with stronger resistance against β-lactamase given better results in moderately or highly resistant organisms.
5. The incidence rate of adverse reactions was 2 out of 51 cases in the CEC group (3.9%) and 3 out of 50 cases in the CEZ group (6.0%), showing no significant difference, and those symptoms were similar.
In conclusion, when the usefulness of CEC in complicated infections of the urinary tract is compared with that of CEZ, the former is said to be equal to the latter without significant difference as a whole.
However, in consideration of the characteristics of both drugs, it seems that CEC is less effective than CEZ in the infections with cephalosporin susceptible gram-negative bacilli which are isolated in relatively great numbers from acute patients and have less strains producing β-lactamase, while CEC may be useful in the infections with moderately or highly cephalosporinresistant gram-negative bacilli which are isolated in relatively great numbers from chronic patients and have more strains producing β-lactamase.

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The therapeutic efficacy of cephacetrile (CEC) in bacterial pneumonia was evaluated in contrast with that of cefazolin (CEZ) by a double blind method. Both drugs were administered via intravenous route at a dose of 1 g twice daily for 14 days.
1) Of 81 patients, each 2 from both groups were eliminated from the study because of unknown results. In CEC group, 36 out of 38 obtained a slightly effective or better results (94.7% of effectiveness). In CEZ group, 31 out of 39 showed a similar result and there was no significant difference between the two groups.
2) In more detail, CEC achieved significantly better results in AaDo₂ and cardiac insufficiency than CEZ, and this trend was also seen in dyspnea.
3) Regarding background factors, pretreatment severity was slightly in favor of CEC. However, so long as supplementary analysis is concerned, we could not find any relation between the pretreatment severity of symptom and drug efficacy or improvement of symptom.
4) Since there was a slight bias in the background factors, it is difficult to conclude that CEC is better than CEZ in terms of effectiveness. However, we consider CEC is superior to CEZ if compared in details.
5) Both drugs had the same incidence of side effect (6.25%, 3/48 in both groups).
When clinical efficacy of CEC in bacterial pneumonia is evaluated together with the incidence of side effect, we may consider that CEC is an effective antibiotic agent equal to or better than CEZ.

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[in Japanese]

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Effects of schizophyllan (SPG) and several antibiotics in combination against experimental Pseudomonas aeruginosa infection were examined.
(1) Whereas the increase in protective effect of SPG was not observed in combination with carbenicillin or sulbenicillin, remarkable effects could be recognized in combination with dibekacin or gentamicin (GM). The combined therapy with SPG and GM proved to be most excellent.
(2) The time course for changes of viable number of Ps. aeruginosa in various organs of mice revealed that the multiplication of the infected bacteria was more markedly inhibited in mice treated with SPG and GM in combination than those treated with each alone.
(3) The increase in bactericidal activity of the peritoneal exudate cells was more remarkablydemonstrated in the combined treatment with SPG and GM than with each alone, showing the rapid clearance of bacteria from the peritoneal cavity in the former.
(4) The microscopic estimation demonstrated that the increase in both phagocytic index and intracellular digestion of bacteria by cultivated macrophages was larger in combination of SPG and GM than each alone.
(5) The measurement of viable number of bacteria in cultivated macrophages by the platecount method also showed that the ingestion and bactericidal activity within the cells were much higher in combined treatment with SPG and GM than each alone.

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The serum and urinary levels and urinary recovery of cephaloridine during and after two-hour drip infusion of 1 or 2 grams of cephaloridine dissolved in 500ml of physiological saline solution were determined in four healthy volunteers in cross-over fashion.
Using the values of serum levels obtained from this experiment, pharmacokinetic parameters were calculated and simulation curves of serum levels for various doses and durations of cephaloridine drip infusion were drawn.

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