The bactericidal activity of cefbuperazone (CBPZ) against Escherichia coli TK-16 R and Serratia marcescens IID 620 was compared with cefotaxime (CTX) and latamoxef (LMOX) using the mixed cultures and experimental mixed infections with Bacteroides fragilis strains.
The stability of cephems to β-lactamase produced by B. fragilis varied with the type of the enzyme. CBPZ and LMOX were more stable than CTX to the β-lactamases produced by B. fragilis G-210 and G-242. Moreover, CBPZ showed the high stability to the β-lactamase produced by B. fragilis G-237. The bactericidal activities of CBPZ and LMOX against E. coli TK-16 R and S. marcescens IID 620 were more potent than those of CTX in the mixed cultures with each of B. fragilis G-210 and G-242. In the case of the mixed culture with B. fragilis G-237, CBPZ showed potent bactericidal activities against E. coli TK-16 R and S. marcescens HD 620 in the mixed cultures with B. fragilis G-210 and G-242. However, the bactericidal activities of CTX and LMOX were inferior to those in the mixed cultures with B. fragilis G-210 and G-242. The results on the experimental mixed infections with B. fragilis and E. coli TK-16 R or S. marcescens IID 620 were well coincided with in vitro results.
These results show that the bactericidal activities of these three drugs against E. coli TK-16 R and S. marcescens IID 620 in the mixed cultures and mixed infections with B. fragilis bear a close parallelto their stabilities to β-lactamases produced by B. fragilis strains.

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A series of experiments was performed to investigate the synergy of bactericidal effect between mouse leukocytes and cephem antibiotics.
Cefbuperazone (CBPZ) enhanced phagocytosis of E. coli by polymorphonuclear leukocytes (PMNs) in the presence of 1.25% fresh normal mouse serum, this synergy, however, was diminished in the absence of the fresh serum, or in the presence of heat inactivated or Mg-EGTA treated mouse serum. The cells of E. coli preincubated with sub-MIC of CBPZ were more susceptible to phagocytosis by PMNs.
The synergy of bactericidal effect between PMNs and 6 cephem antibiotics was also compared. The synergy of bactericidal effect was confirmed with PMNs and up to 1/8 MIC of CBPZ, 1/4 MIC of ceftizoxime, latamoxef, cefotaxime and cefotetan, and 1 MIC of cefmetazole.
When macrophages were employed for phagocytosis, cells of E. coli were engulfed and digested well even in the absence of the fresh serum and in the presence of the heat inactivated mouse serum. The subinhibitory concentrations of CBPZ helped phagocytic and bactericidal effects of macrophages against E. coli. However more clear phagocytosis was observed in the presence of and E. coli mouse serum than with the heat inactivated mouse serum.

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The effects of intravenous injection of three new nalidixic acid analogues on gastrointestinal contractile activity in conscious dogs were studied to find possible side-effects on the gastrointestinal tract.
It was found that OPC-7241, 9-Fluoro-5-methyl-8-(4-methyl-1-piperazinyl)-6, 7-dihydro-1-oxo-1 H, 5 H-benzo (ij) quinolizine-2-carboxylic acid, induced retrograde migrating contractions followed by nausea and vomiting in doses of 20 and 40mg/kg of body weight. The incidence of nausea and vomiting was 100% at a dose of 40mg/kg, while that of nausea was 67% and of vomiting 27% at 20mg/kg. It was concluded that OPC-7241 may have reverse effects on the gastrointestinal tract when given to humans.

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The serially determined concentrations of CTT in human serum after 1g of its intravenous administration revealed very high level of CTT and was persistent in character. They were 155.0μg/ml (30 min.), 114.6μg/ml (60 min.), 112.0μg/ml (90 min.), 93.5μg/ml (120 min.) and 72.0μg/ml (180 min.), respectively. And the concentrations of CTT in the lung tissue were also observed to be high and persistent as comparable to the concentration in the serum noted in the present studies. They were 40.7μg/g (30 min.), 38.7μg/g (60 min.) and 27.9μg/g (120 min.).
The clinical study of 7 cases where CTT was used for the prevention of postoperative infection showed very favorable results without causing any postoperative complication to the lung. Besides this, there were 4 other cases CTT was clinically used. In 2 cases of primary lobar pneumonia, good antibacterial effects were obtained with CTT, while one of them did not respond to CTX and GM, but indicated and excellent antibacterial effects of CTT. In the remaining 2 cases of emphysema with mixed infection, fairly good antibacterial response was obtained.

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Complicated urinary tract infection (UTI) in outpatients and that in inpatients were compared in terms of background characteristics of the patients and clinical efficacy of chemotherapy with oral β-lactam antibiotics. A total of 366 patients with complicated UTI (247 outpatients and 119 inpatients) were treated with 1, 125mg of sultamicillin, 300mg of T-2588 or 750mg of cefadroxil a day in 3 divided doses for 5 days by oral administration. All patients had pyuria of at least 5 WBCs per high power field, bacteriuria of at least 10⁴ bacteria per ml of urine and identifiable underlying urinary tract disease. Overall clinical efficacy of the treatment was evaluated by the criteria proposed by the UTI Committee in Japan as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria.
Complicated UTI in inpatients were shown to have following characteristics when compared to that in outpatients; patients with higher age and male patients were prevalent, as a type of infection, Group 1, 2 and 5 which are regarded to be difficult to treat were more frequent, Citrobacter, Enterobacter, Serratia and glucose non-fermenting gram-negative bacilli other than P. aeruginosa were isolated more frequently as an infecting organism, β-lactamase producing bacteria were prevalent, MICs of sultamicillin, T-2525 and cefadroxil for infecting organisms were generally higher.
Due to these differences in background factors between outpatients and inpatients with complicated UTI, clinical efficacy of chemotherapy with oral β-lactam antibiotics was significantly lower in complicated UTI in inpatients than that in outpatients.
From the results obtained in this study, distinction between outpatients and inpatients seemed to be important as a background factor in the evaluation of clinical efficacy of chemotherapy on complicated UTI.

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Ceftizoxime suppository (CZX-S), a newly developed antibiotic preparation containing in each suppository 500mg of CZX, was evaluated for pharmacokinetics and therapeutic effectiveness and safety in aged patients with urinary tract infection (UTI). The results are summarized as follows.
1. The average serum concentrations of CZX 30 minutes, 1 hour, and 6 hours after administration of one suppository (500 mg), were 0.93μg/ml, 1.31μg/ml, and 0.40μg/ml, respectively. The serum half-life was 3.02 hours. The average urinary concentrations of CZX in three successive collections of 0-2 hours, 2-4 hours, and 4-6 hours were 37.9μg/ml, 86.8μg/ml, and 43.0μg/ml. The average urinary recovery rate up to 6 hours was 2.15%.
2. Therapeutic effectiveness was “good” in 9 patients and “fair” in 2, with an effectiveness rate of 81.8%.
3. Bacteriological effectiveness against the 13 causative strains was “eradicated” in 7 patients, “reduced” in 1, and “replaced by other bacterial flora” in 5, with a bacterial elimination rate of 92.3%.
4. No side effects were observed in any patient. Abnormal laboratory findings were eosinophilia in 2 patients.

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The clinical effectiveness, safety and utility of ciprofloxacin (CPFX) in the treatment of chronic respiratory tract infections were compared with those of cefaclor (CCL) by a double dummy fashion.
The following diseases were studied in this trial;i. e. infectious exacerbation of chronic bronchitis, diffuse parIbronchiolitis and other respiratory diseases, such as bronchiectasis, bronchial asthma, pulmonary emphysema, pulmonary fibrosis.
Patients were orally administered with either 200mg of CPFX or 250mg of CCL three times a day for 14 days in principle. Out of all 230 patients, CPFX was given to 111 patients and CCL to 119 patients. Clinical effectiveness, safety and utility were evaluated on the basis of committee judgement and the results obtained were as follows.
1) The clinical effectiveness rate was 84.5%(87/103) in CPFX group and 61.9%(60/97) in CCL group, respectively. Statistically significant difference was observed between the two groups (P<0.001).
2) Bacteriologically, the eradication rate of 75.0%(45/60) was observed in CPFX group, and that in CCL group was 52.6%(30/57)(P<0.05). The eradication rate of H. influenzae was 90.0% in CPFX group, which was significantly higher than that of the CCL group (P<0.05).
3) Side effects were noted in 5.6% among 107 patients of CPFX group and 6.1% among 114 patients of CCL group. Abnormal changes in laboratory findings after administration were noted in 11.5% of CPFX cases group and in 11.4% of CCL cases. There was no significant difference between the rates of two groups.
4) The utility rate in CPFX group was 83.5%(86/103), which was higher than that in CCL group (P<0.001).
From the above results, CPFX is assessed to be more useful in clinical use than CCL specifically in the treatment of chronic bronchitis, diffuse panbronchiolitis and other chronic complicated or intractable respiratory tract infectious diseases.

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The clinical efficacy, side effects and clinical usefulness of T-2588 were compared with dose of bacampicillin (BAPC) by a double-blind method in the treatment of obstetrical and gynecological infections. As the test compounds are oral antibacterial agents, the target diseases were limited to intra-uterine infection, adnexitis, Bartholinitis and Bartholin's abscess. T-2588 was administered for 7 days at the daily dose of 300mg (divided into 3 times a day) and BAPC was administered for 7 days at the daily dose of 1, 000mg (divided into 4 times a day).
162 out of 226 patients administered test compound were selected for evaluation by committee members. 75 of these patients were treated with T-2588 and 87 patients treated with BAPC. Number of patients administered either T-2588 or BAPC was 49 and 54 in intra-uterine infection or adnexitis (A-group disease), and 26 and 33 in Bartholinitis or Bartholin's abscess (B-group disease), respectively. Following results were obtained.
1) Clinical efficacy (judgement by the committee members): 75 patients of T-2588-group and 87 of BAPC-group were evaluated for clinical efficacy. The efficacy rate (Excellent and Good) of T-2588 and BAPC was 74.2% and 65.5%, respectively. As to A-group disease, clinical efficacy rate of T-2588 and BAPC-group was 77.6% and 66.7%, respectively. As to B-group disease, clinical efficacy rate of T-2588 and BA PC-group was 69.2% and 63.6%, respectively. No significant difference was observed between T-2588-group and BA PC-group.
2) Clinical improvement (judgement by the doctors in charge): Clinical improvement rate (Markedly improved and improved) was 82.7% in T-2588 group and 70.1% in BAPC-group. As to A-group disease, clinical improvement rate of T-2588 and BAPC-group was 83.7% and 64.8%, respectively. No significant difference was observed between T-2588 and BAPC-group.
3) Bacteriological effect: 41 and 55 patients of T-2588 and BAPC-group were evaluated for bacteriological effect. Eradication rate (Eradicated) of T-2588 and BAPC-group was 85.4% and 58.2%, respectively. T-2588 was superior to BAPC with a statistical significance (x²-test: P<0.01).
4) Side effects were noted in 6 cases out of 106 patients with T-2588 and 7 out of 118 patients with BAPC, and abnormal laboratory findings were noted in 2 out of 102 patients with T-2588 and 4 out of 114 patients with BAPC-group. there was no significant difference between T-2588-group and BAPC-group.
From these results, it is concluded that T-2588 is useful agent in the treatment of obstetrical and gynecological infections.

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