The clinical effectiveness and safety of Cefoperazone (CPZ, T-1551) and Cefazolin (CEZ) were compared in this randomized, double-blind multi-clinical study of 239 patients with respiratory tract infections. Patients were assigned to treatment with either CPZ or CEZ by drip infusion for 7 to 14 days at a daily dose of 4 g.
The results obtained were as follows:
1. One hundred and eighty-eight patients were selected for evaluation by committee members. 90 of these patients were treated with CPZ and 98 were treated with CEZ. Each number of patients administered either CPZ or CEZ was 40 and 36 in bacterial pneumonia, 9 and 9 in mycoplasmal pneumonia and primary atypical pneumonia (PAP), and 31 and 27 in chronic respiratory tract infections, respectively.
2. On the other hand, one hundred and ninty-five patients were selected, excepting that was remarkably against the rule, the number of cases adopted as able as possible by doctors in charge. 95 of these patients were treated with CPZ and 100 were treated with ABPC.
3. The clinical efficacy rate (excellent and good results) in all cases adopted by committee members was 85.5% in CPZ group and 56.2% in CEZ group, respectively. The effectiveness in CPZ group was significantly superior to that of CEZ group.
4. The clinical efficacy of CPZ was significantly superior to that of CEZ in all cases adopted by doctors in charge.
5. CPZ showed an excellent effect for improvement of symptoms and findings of chest roentgenogram, property of sputum dyspnea and rales in bacterial pneumonia, and body temperature, property of sputum, WBC and CRP in chronic respiratory tract infections. The results obtained in CPZ group was significantly superior to that in CEZ group.
6. No significant difference was observed in the occurrence of side effect between both groups.
7. The utility of CPZ was significantly superior to that of CEZ. The results indicated thus that CPZ is more useful for therapy of respiratory tract infection than CEZ.

View full abstract

The clinical efficacy and safety of cefadroxil and L-cephalexin prolonged action granules were evaluated in patients with complicated urinary tract infections under a well-controlled clinical trial.
The dose for cefadroxil was 500 mg administered orally 3 times a day for 5 days while the dose for L-cephalexin was 1000 mg administered orally twice a day for 5 days.
A total of 237 patients were treated. Clinical efficacy was examined with 99 patients receiving cefadroxil and 91 patients receiving L-cephalexin from whomthe withdrawals and dropouts had been removed. Adverse reactions were investigated with 236 patients from whom 1 patient receiving cefadroxil had been removed.
Based on the criteria set by the UTI committee in Japan, the efficacy of cefadroxil was assessed excellent in 24 cases, moderate in 22 cases and poor in 53 cases resulting in an effectiveness rate of 46.5%, while that of L-cephalexin was assessed excellent in 22 cases, moderate in 19 cases and poor in 50 cases resulting in an effectiveness rate of 45.1%. No statistically significant difference was found between the 2 drugs.
Adverse reactions were reported in 1 patient receiving cefadroxil; abnormal velues for clinical laboratory tests in 7 patients receiving cefadroxil and in 10 patients receiving L-cephalexin demonstrating no statistically significant difference between the 2 drugs.
Utility judgment by attending physicians indicated 46.5% utility value for cefadroxil and 47.3% for L-cephalexin, once again exhibiting no statistically significant difference between the 2 drugs.
The results therefore indicate that cefadroxil is an effecttive, safe and highly useful drug in the treatment of complicated urinary tract infections.

View full abstract

The absorption, metabolism and excretion were studied, in a 6-subject crossover experiment, for 9, 3''-diacetylmidecamycin (MOM) and midecamycin (MDM). The dosing was made on fasting and postprandial condition at each interval of a week.
The serum was analyzed for each case by the conventional agar-plate diffusion cup method, using M. luteus as the test organism; the blood and urine were analyzed for the metabolites by a TLCdensitometric method. The peak serum concentration, peak time, biological half-life, and area under the curve were evaluated. It has been demontrated that MOM was rapidly absorbed; the rate of absorption was found to be similar for two types of dose conditions, fasting and postprandial.
The serum profile parmeters of MOM were 30min, 2. 38±0. 33μg/ml (fasting) and 30 min, 1.87±0.45μg/ml (postprandial), respectively, for the peak time and the peak concentration. On the other hand, significant differences were observed for the case of MDM, between these two conditions, 30 min, 0.97±0.33 μg/ml (fasting), 3 hr, 0.17±0.05 μg/ml (postprandial) were observed. A higher absorption has been shown to occur in the fasting condition. The blood metabolites concentrations were evaluated and the results obtained for MOM and MDM were compared.
The principal route for the MOM metabolism in humans has been found to be: MOM→Mb-1→Mb-12→Mb-6→Mb-9a: the other pathways were: MOM→Mb-1→Mb-2→Mb-3 (or Mb-5)→Mb-9a (or Mb-9b). While non-metabolized MDM, M1 (=Mb-6) and M2 (=Mb-9a) were found in blood and urine after dosing of MDM. The ratios Mb-6/Mb-12 (for MOM metabolism) and Ml/MDM (for MDM metabolism) in blood have been shown to differ substantially; this demonstrates that Mb-12 is metabolized much slower relative to MDM.
The urinary excretions of total metabolites were evaluated by the pharmacokinetics and the results were compared among four formulations, MOM-fasting, MDM-fasting, MOM-postprandial and MDMpostprandial. The scatters observed in the urinary excretion data were ascribed to the intrinsic differences of the intestinal absorption of these antibiotics attributable to the individual subjects.

View full abstract

Studies on the efficacy of chemotherapy of experimental Klebsiella pneumonia were made on mice with lung injury (the mice transnasally instilled with one percent formaldehyde) as an experimental model of intractable respiratory infections.
In the investigation that pneumonia was treated with a single injection of Cefotaxime (CTX) or and Gentamicin (GM), the following result was obtained. Viable counts of bacteria in murine lung decreased more rapidly and regrowth time was prolonged much more when treated with a combination of CTX and GM than when treated with CTX or GM alone.
As for pneumonia treated with a repeated injection of CTX or/and GM, it was not cured even Studies on the efficacy of chemotherapy of experimental Klebsiella pneumonia were made on mice with lung injury (the mice transnasally instilled with one percent formaldehyde) as an experimental model of intractable respiratory infections. In the investigation that pneumonia was treated with a single injection of Cefotaxime (CTX) or and Gentamicin (GM), the following result was obtained. Viable counts of bacteria in murine lung decreased more rapidly and regrowth time was prolonged much more when treated with a combination of CTX and GM than when treated with CTX or GM alone.
As for pneumonia treated with a repeated injection of CTX or/and GM, it was not cured even when viable counts of bacteria in murine lung had decreased less than 10 CFU/lung. It was necessary to continue the treatment for more than 24 hours to cure pneumonia in controlled mice, and for more than 48 hours in mice with lung injury. When viable counts of bacteria in murine lung decreased more rapidly within 12 hours, duration of less than 10 CFU/lung persisted longer, especially treated with a combination of CTX and GM.
For the survival of mice with pneumonia treated with CTX or/and GM, the following results were obtained. Pneumonia in controlled mice was cured with a treatment of CTX or GM alone. But pneumonia in mice with lung injury was not cured with the treatment of either CTX of GM. It was necessary for these mice to be treated with a combination of CTX and GM, which decreased viable counts of bacteria in murine lung more rapidly, necessiating yet longer duration of therapy.
These results suggested that initial intensive chemotherapy was more important for the treatment of pneumonia in mice with lung injury and long duration of therapy was necessary. Experimental studies should be contiuea on more intensive chemotherapy for pneumonia in animals with decreased lung defense.

View full abstract

The results of a preoperative antibiotic preparation in colon surgery are presented. Tobramycin, mainly combined with clindamycin given by mouth for 2 days prior to operation reduced significantly postoperative infection as compared to kanamycin (<0.01) or fradiomycin (<0.05).
Cultures taken of the bowel before preparation and at the time of surgery showed a significant reduction of the flora with the elimination of E. coli and Klebsiella.
After oral administration of tobramycin, no detectable concentration in serum and high concentration in stool were noted.
It was concluded that the bowel preparation of tobramycin can be used effectively and safely.

View full abstract

Rifampicin (RFP) or gentamicin (GM) was added to cefotiiim (CTM), and antibacterial effects of combined use were examined on Enterobacter cloacae strain No.391 and Strratia.marcescens strain No.240 which were highly resistant to CTM. The combination of CTM and RFP was more effectivethan that of CTM and GM in the viewpoints of fractional inhibitory concentration and bactericidal effects in broth. Both strains produced beta-lactamase in significant amount, and it additionally increased under the presence of CTM. The production of beta-lactamase was markedly inhibited by low concentration of RFP in the broth, while not inhibited at all by GM.

View full abstract

Gentamicin (GM) was examined in the following points of view. 1) Antibacterial pattern against gram-negative rods (GNR). 2) Influence of pH to the antibacterial activity. 3) Effect of combination with Cefotiam (CTM).
Antibacterial pattern was examined in the broth culture which contained 4×MIC of GM. The initial number of the organisms was 10⁶-10⁷/ml. Enterobacter cloacae was rapidly killed, while Escherichia coli was not killed through the viable cell count increased. The growth curves or the killing curves of the other GNRs were variable between those of the upper two organisms.
The pH of the media significantly influenced the antibacterial activity of GM. The higher pH was, the stronger activity was against Escherichia coli, Enterbacter cloacae, Klebsiella pneumoniae and Proteus morganii. However, the activity of GM against Pseudomonas aeruginosa was rather weakened when the pH was high.
Fractional inhibitory concentration (FIC) and bactericidal effects of GM plus CTM combination were examined against 5 strains of Escherichia coli. FIC index revealed 0.500, 0.503, 0.625, 0.625 and 0.750 in each strain. These results were not always coincident with the bactericidal synergisms.

View full abstract