Streptomycin (SM)-inactivating enzymes from SM-resistant strains in clinical isolates have been assayed by using crude enzyme solution. In this paper, SM was inactivated by ATP with living cells of Pseudomonas aeruginosa K-Ps 94 producing APH (3''). Optimum pH and ATP concentration of this reaction were 7.8-8.4 and 32mM, respectively, and optimum temperature was 45°C. From the results of applications to P.aeruginosa clinically isolated, it was demonstrated that this simple method was useful for detection of SM-phosphotransferase-producing strains.

View full abstract

After d. i. administration of cephems (cefazolin, cefoperazone, cefotetan, cefsulodin) alone or combined with piperacillin consecutively to normal volunteers, the course of serum levels and urinary recovery were assessed.
When PIPC was combined with CEZ or CTT, the elevation of serum levels and reduced urinary recovery of CEZ and CTT were observed comparing to those of each alone.
When PIPC was combined with CPZ, the elevation of serum levels of CPZ was observed comparingto those of CPZ alone. However, urinary recovery of CPZ was not affected by PIPC.
When PIPC was combined with CFS, the serum levels and urinary recovery of CFS were not affected by PIPC.
With the combination of probenecid, the serum levels of PIPC and CEZ were elevated and urinary recovery of PIPC and CEZ was reduced by probenecid. However, the serum levels and urinary recovery of CPZ were not affected by probenecid. CEZ was much more affected than PIPC was.
These results indicate that PIPC influences the pharmacokinetics of CEZ and CTT causing by competitively inhibiting tubular secretion and those of CPZ causing by competitively inhibiting hepatic excretion. Inhibition of hepatic excretion of CTT was supposed to be another cause of elevated serum levels of CTT.
Because of its glomerular excretion, the serum levels and urinary recovery of CFS were not affected by PIPC.
These effects of PIPC were supposed to be specific for its own. Because another penicillin, ampicillin, did not affect the pharmacokinetics of CEZ.

View full abstract

The in vitro combined activities of TOB+CFS+FOM, TOB+PIPC+FOM, TOB+CPZ+FOM and TOB+CFS against fresh clinical isolates of P. aeruginosa were investigated by use of Microdilution Broth Method.
1) The MICs₈₀ of TOB, CFS, CPZ, PIPC and FOM against 201 freshly isolated P.aeruginosa were 4μg/ml, 32μg/ml, 64μg/ml, 128μg/ml and 128μg/ml, respectively.The percentage of resistant strains of TOB, CFS, PIPC, CPZ and FOM were 20%, 30%, 33.5%, 37.5% and 72.5%, respectively.
2) In comparison to the combined effects in TOB+CFS+FOM, TOB+PIPC+FOM and TOB+CPZ+FOM against P.aeruginosa, TOB+CFS+FOM was superior to TOB+PIPC+FOM and TOB+CPZ+FOM, 19% of the strains showed FIC index≤0.5.
3) Synergistic effect (FIC index≤0.5) of TOB+CFS was observed for 46% of the strains and the mean FIC index was 0.67.The mean FIC indices of addition of FOM 8 μg/ml or FOM 32μg/ml to TOB+CFS were 0.64 and 0.52, respectively.The synergism of TOB+CFS was enhanced by the addition of FOM 32 μg/ml.
The combined therapy of TOB+CFS+FOM may be useful for serious Pseudomonas infections. The strains used in this study showed the difference of synergistic effect.To use the combination of antibiotics for the clinical field, to measure MICs of each antipseudomonas antibiotics and the synergistic effects (FIC index) may be important in routine susceptibility testing.

View full abstract

Chlon A, an acidic polysaccharide purified from the hot water extract of Chlorella pyrenoidosa, possessed antitumor activity against transplantable murine tumors in vivo. In allogeneic systems, Chlon A showed remarkable life prolongation effects in mice bearing Sarcoma 180 with a broad optimal dose range. Chlon A was also active in syngeneic systems such as IMC carcinoma, Meth-A fibrosarcoma, B 16 melanoma and Lewis lung carcinoma growing in the intraperitoneal cavity. When Meth-A cells were admixed with Chlon A and inoculated Sc, remarkable growth inhibition of tumor cells was observed. Chlon A enhanced cytotocicity of mice macrophages for EL-4 tumor cells in vivo, lymphoproliferative effects in vitro, and carbon clearance activity (reticuloendothelial system) in vivo. The electrophoretic pattern showed that L_A (ceruloplasmin) and/or L_B (hemopexin)-like components rapidly appeared in serum proteins of mice receiving Chlon A. These findings indicate that Chlon A is a potent modifier of some biological responses.

View full abstract

Cefuroxime was investigated on its distribution after a continuous intravenous drip infusion of 3.0g for 30 min in humans, and its serum levels and cerebrospinal fluid levels were pharmacokinetically analyzed.
1. The distribution volume and the half-life of CXM in humans according to the one-compartment open model were 12.3 L/body and 0.67 hours, respectively.
2. The mean concentration of CXM in cerebrospinal fluid were 0.6 μg/ml respectively 2.0 to 3.0 hour after the injection, and the half-life were about 10 hours.
3. It was expected that the concentrations of CXM in normal cerebrospinal fluid can be simulated using the pharmacokinetic parameters.

View full abstract

The concentration of latamoxef (LMOX) into the fluid of simple renal cyst after one gram of intravenous administration was investigated in five patients. The bilateral renal function in all patients was normal on intravenous pyelography. The fluid of the cyst was aspirated percutaneously at 20 to 40 minutes after a bolus injection of the drug, serum and urine specimen a were got at the same time. The chemical analysis showed that the components of the cyst was nearly equal to that of the serum. The concentration of LMOX bioassayed using E. coli 7437 strain as a test organism revealed 0.46±0.154 μg/ml (mean±S. D.) in the fluid, 43±10.2 in serum, and 4, 100±2, 160 in urine. These results suggest, because of very low level of LMOX detected in the simple cyst, intravenous administration of antibiotics may not be effective to treatment for the patients with the disease.

View full abstract

This report deals with the evaluation of the efficacy of chemotherapy in patients with chronic respiratory tract infections (CRTIs), i. e. chronic bronchitis, bronchiectasis, diffuse pan-bronchiolitis, and chronic pulmonary emphysema.
The five evaluable items were selected for judgement of the efficacy of antimicrobial agents. These items include bacteriological effect, improvement and/or normalization of sputum findings, and those of body temperature, WBC, and CRP. The most important item was the bacteriological effect, and the next was normalization and/or improvement of sputum findings, in these five items mentioned above.
Three days after the start of chemotherapy, the first judgement of the efficacy was done by using two items consisted of normalization and/or improvement of body temperature and those of sputum findings. Seven days after the start of chemotherapy, the final judgement was done by using all of five items.
One hundred and sixty six randomly selected infectious episodes with CRTI were studied from 1977 to 1985. The rate of correspondence between the judgement by doctors in charge and the judgement by the criteria determined in the present study was 77.1%(74/96) in chronic bronchitis, 76.9%(20/26) in bronchiectasis, 58.8%(20/34) in diffuse pan-bronchiolitis, 70.0%(7/10) in chronic pulmonary emphysema, and 72.9%(121/166) in all infectious episodes evaluable in this study.

View full abstract

A well-controlled comparative study was performed using ceftizoxime (CZX) as the control drug to objectively evaluate the efficacy, safety and usefulness of cefotaxime (CTX) in postoperative infections. Both antibiotics were administered intravenously by drip infusion at 2g/day in two divided doses, and the following results were obtained.
1. Overall clinical efficacy rates, based on assessment by the Efficacy Evaluation Committee, were 84.5%(60/71) in the CTX group and 75.7%(56/74) in the CZX group in postoperative wound infections (Trial A), and 73.7%(42/57) in the CTX group and 68.4%(39/57) in the CZX group in postoperative abdominal cavity infections and postoperative dead space infections (Trial B). No significant difference was found between the two treatment groups in either Trial A or Trial B.
2. Final overall improvement rates evaluated by the surgeons were 76.1%(54/71) in the CTX group and 74.3%(55/74) in the CZX group in Trial A, and 64.9%(37/57) in the CTX group and 57.9%(33/57) in the CZX group in Trial B. No significant difference was found between the two treatment groups in either Trial A or Trial B.
3. Bacteriological effectiveness was judged by the Efficacy Evaluation Committee. Pathogen eradication rates by case were 69.5%(41/59) in the CTX group and 52.6%(30/57) in the CZX group in Trial A, with CTX tending to be more effective. In Trial B, however, the rates were 52.2%(24/46) in the CTX group and 42.6%(20/47) in the CZX group, with no significant difference between the two treatment groups.
The eradication rate by bacterial species based on the growth and decline of the bacteria clinically isolated before administration was 73.3%(66/90) in the CTX group and 56.8%(54/95) in the CZX group in Trial A, while, in Trial B, the rates were 51.4%(37/72) in the CTX group and 33.0%(31/94) the CZX group, the CTX group exhibiting statistically significant better results in both Trials A and B (P<0.05).
4. Side effects were not observed in the CTX group but were reported in 4 out of 150 cases (2.7%) in the CZX group. Abnormal laboratory findings were observed in 1.4%(2/144) of the cases in the CTX group and in 4.1%(6/147) of the cases in the CZX group. However, no significant differences were found between the two treatment groups either in side effects or abnormal laboratory findings.
5. The usefulness was judged by the surgeons to be 66.7%(46/71) in the CTX group and 58.3%(42/74) in the CZX group in Trial A, and 54.5%(30/55) in the CTX group and 42.3%(22/52) in the CZX group in Trial B, with no significant difference between the two treatment groups in either Trial A or Trial B.
From the above results, CTX may be considered to be at least as highly useful as CZX in the treatment of postoperative infections.

View full abstract