We compared the in vitro and in vivo antibacterial activity of 7432-S with that of T-2525 (T-2588), cefixime (CFIX), cefuroxime (CXM-axetil), cefaclor (CCL) and cephalexin (CEX), and obtained the following results.
7432-S was potently active against a wide variety of Gram-negative bacteria and its antibacterial spectrum was almost the same as that of T-2525 and CFIX.
The antibacterial activity of 7432-S against Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Enterobacter cloacae and Serratia rnarcescens was more potent than those of the control antibiotics. It was, however, inactive against Preudomonas aeruginosa and methicillin resistant Staphylococcus aureus.
7432-S, like CFIX and T-2525, was highly stable to various types of β-lactamases produced by Gram-negative bacilli.
In the studies on mice, the therapeutic effect of oral 7432-S against infections due to β-lactamase producing bacteria was excellent and almost the same as that of CFIX and T-2588.

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7432-S is a new oral cephalosporin. The in vitro and in vivo antibacterial activity of 7432-S was evaluated and compared with that of cefixime, cephalexin, cefaclor and cefteram. The following results were obtaind.
7432-S showed much more potent antibacterial activity than cefixime and was superior to cefteram, cephalexin and cefaclor against Escherichia coli, Klebsiella pneurnoniae, laebsiella oxytoca, Salmonella spp., Providencia rettgeri, Proteus vulgaris.
7432-S was highly stable to various types of β-lactamase except for those of Xanthomonas maltophilia.
The therapeutic effects of 7432-S against infections with E. coli ML 4707 and Serratia marcescens GN14931 in mice were almost equal to that of cefixime, and were superior to those of reference compounds.

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7432-S is a new oral cephem antibiotic which is well absorbed from the intestinal mucosa. MIC₇₀s of 7432-S against 21-51 clinical isolates of Staphylococcus aureus, coagulase (-) staphylococci (CNS), β-streptococci, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Escherichia colt, Escherichia coli CS 2 carrying various R (bla) plasmids, Klebsiella pneamoniae, Proteus mirabilis, Proteus uulgaris, Morganella morganii, Providencia rettgeri, Citrobacter freundii, Serratia marcescens, Enterobacter cloacae, Pseudomonas cepacia, Xanthomonas maltophilia, Pseudomonas aeruginosa, ampicillin resistant Haemophilus influenzae and Bacteroides fragilis were >100., >100., 12.5, 6.25, >100., >100., 0.2, 0.2, 0.05, 0.025, 0.025, 0.78, 0.013, 1.56, 0.2, 3.13, 1.56, >100., >100., 0.1, and 100g/ml, respectively.
The binding affinity of 7432-S with PBP 3 and 1 bs of E. coli was found to be stronger than that of cefaclor, although 7432-S did not bind to PBP 2 and 3, both of which are essential murein-trans-peptidases, of S. aureus. The binding affinity of 7432-S with PBP 3 of P. uulgaris was much higher than that of cefaclor.
Synergy of bactericidal effect between 7432-S and the complement was moderate whereas the cells of E. coli NIHJ-JC 2 were well engulfed and rapidly digested in the presence of higher than ¼ MIC of 7432-S.

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We evaluated the in vitro and in vivo antibacterial activity of a new cephem, ceftibuten (CETB), against anaerobes and compared it with those of cefaclor (CCL), cefixime (CFIX), amoxycillin (AMPC) and others. CETB showed a relatively broad spectrum against Grampositive and -negative anaerobes except Bacteroides fragilis group and a few other species. CETB was less active than CCL and as active as CFIX against Gram positive and more active than CCL and as active as CFIX against Gram-negative species. CETB was hydrolyzed by β-lactamase derived from two strains of B.fragilis, but was more stable than CCL. In an in vivo xperimental infection in rat pouch, CETB 200 mg/kg had a slight effect against B. fragilis GAI-5562 the growth of which was inhibited by CETB at a concentration of 1.56 μg/ml (inoculum size, 10⁶CFU/ml). The pouch concentration level of CETB was 1.7-2.2μ/ml at 6 h after administration.
When CETB was given orally to mice at a dose of 100 mg/kg for 5 days, growth of Clostridium difficile was observed on days 1 and 7 after withdrawal of the drug, with a higher concentration on day 1.

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The in vitro and in vivo antibacterial activities of 7432-S, a new oral cephem antibiotic, were compared with those of cefixime (CFIX), cefaclor (CCL) and amoxicillin (AMPC).
7432-S had a broad antimicrobial spectrum against Gram-positive and Gram-negative bacteria, and was highly active against the latter including CCL-resistant enterobacteriaceae, but showed weak activity against staphylococci and Enterococcus faecalis.
The antibacterial activity of 7432-S was only slightly effected by the pH of medium, the addition of horse serum and inoculum size.
7432-S showed dose-related bactericidal action against Escherichia coli, Klebsiella pneumoniae and Serratia marcescens used in this study. The therapeutic effects of 7432-S against experimental intraperitoneal infections caused by E. coli, K. pneumoniae, Enterobacter cloacae, S. marcescens, Proteus mirabilis of Gram-negative bacteria in mice were superior to those of CFIX and CCL. It was, how ever, less active against the Gram-positive cocci of Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae than was CCL.
In addition, 7432-S exhibited the good activity against experimental local infections in mice. 7432-S showed a higher serum peak level and urinary recovery than did CFIX and CCL after a single oral administration in mice.

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Minimum inhibitory concentrations (MICs) of 7432-S, a newly developed oral cephalosporin, were determined against 136 strains of Shigella spp., 55 of Salmonella spp., 33 of Escherichia coli, 24 of Campylobacter spp., 12 of Vibrio parahaemolyticus and 10 of V. cholerae, and compared with those of cefixime (CFIX), enoxacin (ENX), and nalidixic acid (NA).
The MICs of 7432-S which inhibited 90% of the strains (MIC₉₀) were 0.20 μg/ml against Shigella spp., 0.10μg/ml against Salmonella spp., 0.39 μg/ml against E. coli, 50 μg/ml against Campylobacter spp., 0.78 μg/ml against V. parahaemolyticus, and 0.20 μg/ml against V. cholerae. These values were mostly half those of CFIX, another oral cephalosporin, except against Vibrios, for which the former was four times higher than the latter. MIC90s of 7432-S were mostly higher than those of ENX, except against Salmonella spp., which was one quarter that of ENX, and against Shigella spp., which was equal. MIC₉₀s of 7432-S were lower than those of NA, except against Campylobacter spp., for which those of cephalosporins were higher.
To 7432-S, more than 90% of the Campylobacter strains (MIC, ≥6.25 μg/ml) and one strain of Shigella sonnei (MIC, 25μg/ml) were moderately resistant.

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Phase 1 studies or 7432-S (general name: ceftibuten), a new oral cephem antibiotic, were conducted with 48 healthy male volunteers. 7432-S was orally administered in a single or multiple doses to evaluate its safety and tolerance as well as its pharmacokinetics.
The results obtained were as follows.
1. After single administration of 10, 20, 25, 50, 100 or 200mg or multiple administration of either 100mg twice a day for 14 days or 200mg twice a day for 7 days, nothing. remarkable possibly attributable to 74322-S was observed in subjective symptoms, objective signs, hematology, blood biochemistry or urinalysis.
2. Effects on the intestinal flora were examined in the volunteers allocated to the multiple administration groups.
Some aerobes were susceptible to 7432-S; for instance, Escherichia coli, Klebsiella sp., Enterobacter cloacae and Citrobacter freundii decreased during administration but recovered to the baseline after completion of administration. Little effect was observed on anaerobes.
3. After a single dose of 25, 50, 100 or 200mg in a fasting state, the mean plasma drug concentrations reached a peak at 3 h, being 1.30, 3.03, 4.57 and 10.48μg/ml, respectively, increasing linealy according to dose. The half-lives ranged between 1.5-2.1 h. Most of the drug was excreted unchanged into urine, but 7432-S-trans, the metabolite of 7432-S, was detected in plasma and urine. The urinary recovery, including 7432-S-trans, amounted to 78.6-79.9% in the first 24 hours.
4. The plasma Cmax and AUC were not affected by food intake, although Tmax was prolonged.
5. No evidence of accumulation was observed following multiple administration of 100mg twice a day for 14 days or 200mg twice a day for 7 days.
6. The percentage of serum protein binding was found to be almost constantly 65.2% on the average, up to 16μg/ml of 7432-S.

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Using high pressure liquid chromatography (HPLC), we measured the serum and urinary concentrations after administration of a new oral cephem antibiotic, 7432-S, at a dose of 100mg to 5 healthy volunteers.
The mean peak serum concentration was 4.29μg/ml at 3 h after treatment.
The level declined with time to 0.06-0.23μg/ml (mean concentration: 0.17μg/ml) at 12 h, of the Cmax, Tmax, T1/2 (β) and AUCs were 4.95±1.02μg/ml, 1.99±0.58 h. 2.23±0.89 h. and 22.4± 3.7μ·h/ml, respectively.
The results suggest that 7432-S reaches high concentrations in serum and urine and is therefore a useful drug in various mild infections.

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The new oral cephem antibiotic, 7432-S, which is highly active against Gram-negative bacilli and resistant to β-lactamase, has great therapeutic promise in the treatment of various infections.
We clarified the kinetic profile of 7432-S in biliary tract diseases.
1) When 100 mg of 7432-S was given orally to three patients, the mean blood concentration reached 2.8±1.0μg/ml at 3 to 4 h after administration. The concentration in gallbladder bile was 0.4-2.4μg/ml, and in gallbladder tissue 33.6μg/g in one case but as low as 0.3 and 1.1μg/g in the 2 other cases. In one patient given 200mg, the concentration in blood was 5.7μg/ml at 4 h after administration, while that in gallbladder bile was 2.3μμg/ml and in the gallbladder tissue 2.7μg/ml.
2) Comparison of bile concentrations at doses of 100 mg and 300mg in patients with T-tube showed that the peak bile levels were 8.2 and 18.9μg/ml, and AUCs were 29.9 and 103.7 μg·h/ml, clearly indicating dose dependency.
3) Comparing 7432-S 200 mg with 7432-S 200mg plus UDCA 300 mg, the peak bile concentration was 36.2μg/ml vs. 142μg/ml and AUC_0-12 was 194.0 μg·h/ml vs. 577.8μg·h/ml in a first case. Thus the values for the combination treatment were about 3 times higher. In a second case, the peak bile concentration was 3.2μg/ml vs. 5.5 μg/ml and AUC0-10 was 6.1μg·h/ml vs. 13.3μg·h/ml, the values for the combination treatment being twice as high.
None of the patients given 7432-S showed side effects or abnormal laboratory values attributable to the antibiotic.

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We clinically evaluated 7432-S, a new oral cephem antibiotic, and investigated its antimicrobial activity, pharmacokinetic and clinical evaluation.
The peak MICs of 7432-S against 180 strains of clinical isolates, using the plate dilution method, were 0.1 μg/ml against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii and Serratia marcescens. 7432-S had activity superior to that of cefaclor, cefixime and CS-807 against these organisms, but it was not sensitive to Paeudomonas aeruginosa and Staphylococcus aureus.
The pharmacokinetics of 7432-S were studied in 6 healthy male volunteers after a single oral administration of 200 mg in a fasting state. Plasma and urinary levels of 7432-S were measured by bioassay and HPLC. Using a one-conpartment open model, the pharmacokinetic parameters of 7432-S were calculated as follows: Cmax 9.33μg/ml, Tmax 2.59h, T1/2 1.79h and AUC 40.6 μgh/ml by bioassay, and 9. 37, 2.60, 1.84 and 40.7 by HPLC, respectively.
The urinary excretion rate of 7432-S within 12h was over 70% by bioassay and HPLC. HPLC revealed 10-20% of 7432-S-trans for metabolites in blood and urine.
Twenty-two patients with bacterial infection (7 cases of respiratory and 15 of urinary tract infection) were treated with 7432-S at 300 mg t. i. d. for 3-10 days. The clinical effect was excellent in 10 cases, good in 7, fair in 4 and poor in one. The clinical efficacy rate was 77.3%. No side effects and abnormal laboratory findings were observed.

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We performed clinical studies on 7432-S, a new oral cephem antibiotic, and obtained the following results.
Fourteen patients with respiratory tract infection (11 of chronic bronchitis and one each of diffuse panbronchiolitis, bronchiectasis and acute pneumonia) were treated with 7432-S. The clinical effect was good in 12 and fair in 2 patients. The efficacy rate was calculated as 85.7%.
No side effects or abnormal laboratory findings were recognized.

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We studied the in vitro antimicrobial activity of 7432-S, a new cephem antibiotic for oral use, and evaluated its therapeutic efficacy in chronic respiratory tract infections.
The minimum inhibitory concentrations (MICs) of 7432-S, cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC) against 20 strains each of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa were determinedby a microbroth dilution method using the Dynatech MIC-2000 system. The results showed that 7432-S was less active than other antibiotics against S. aureus, was as active as cefixime and more active than cefaclor and amoxicillin against E. coli, K. pneumoniae, E. cloacae and S. marcescens. 7432-S was not as potent as the other agents against P. aeruginosa.
A daily dose of 300 mg of 7432-S was given orally to 11 patients: 2 with infected bronchiectasis, 6 with chronic bronchitis, 1 with diffuse panbronchiolitis and 1 each with infection superimposed on pulmonary fibrosis and lung cancer. The clinical effect was good in 7, fair in 1 and poor in 3.
Eleven strains were identified as causative organisms.
Eight of these were eradicated by 7432-S. Eosinophilia was observed in 2 patients. A transient elevation of s-GOT and s-GPT values was observed in one patient. The adverse reactions disappeared after completion of the therapy.
From the above results, we concluded that 7432-S is a most useful first choice antibiotic for oral use in chronic respiratory tract infections.

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We clinically evaluated 7432-S in 14 patients, six males and eight females from 31 to 85 years old, with chronic respiratory tract infection.
7432-S was given orally in daily doses of 300 or 400mg in two or three divided portions for 4 to 28 days.
A total of 12 strains comprising 3 of Haemophilus influenzae, 3 of Streptococcus pneumoniae, 3 of Branhamella catarrhalis and one strain each of Staphylococcus epidermidis, Streptococcus pyogenes and Escherichia coli were identified from sputum before administration. Two strains each of H. influenzae, S. pneumoniae and B. catarrhalis and one strain each of S. epidermidis, S. pyogenes and E. coli, were eradicated; but one strain each of H. influenzae, S. pneumoniae and B. catarrhalis were diminished, and one strain of H. influenzae appeared after the treatment (erradication ratio=75%).
The clinical efficacy rate was 92.9%: excellent in 4 cases, good in 9 and fair in I case.
There were two incidences of side effect: one of nausea and the other itching, but neither was severe.
One patient showed slight elevation of GOT·GPT values.
From the above results, we concluded that 7432-S is an effective, safe and useful new oral cephem in chronic respiratory tract infections.

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We performed basic studies on 7432-S with the following results.
1) 7432-S was administrated orally in a dose of 200 mg to 8 patients with various renal functions.
By bioassay method, in patients with normal renal function (Ccr.: 90 ml/min.<), Tmax, Cmax, T_1/2 (β) and AUCs were 0.76-3.25 h, 9.14-13.76μ g/ml, 1.17-1.93 h, 38.70-45.63μg ·h/ml, respectively. The comulative urinary recovery rate within the first 12 h was 50-72%. In patients with moderate renal dysfunction (Ccr.: 30-60), they were 3. 71-6. 76 h, 6.67-11.82μg/ml, 3.54-6.88 h, 101.07-117.70μg μ h/ml. Urinary excretion (0-12h) was 6.1-39.0%. In patientswith renal failure (Ccr.:<10), they were 2.53-3.70 h, 8.37-13.01μg/ml, 18.24-28.88 h, 324.54-586.14μg · h/ml. Urinary excretion (0-12h) was 2.0-8.1%. In patients with continuousambulatory peritoneal (CAPD), they were 0.89 h, 16.93μg/ml, 16.12 h, 423. 84 μg μ h/ml. PD excretion (0-12 h) was 7.5%.
By HPLC method, in patients with normal renal function, they were 0.66-3.28 h, 8. 02-15.92μg/ml, 1.25-1.85h, and 40. 50-41. 20μgμh/ml. Urinary excretion (0-12h) was 51.5%-79.5%. In patients with moderate renal dysfunction, they were 3.72-6.37 h, 6.91-11.82 μg/ml, 3.54-8.44 h, and 97.07-133.64μg · h/ml. Urinary excretion (0-12h) was 6.1-41.0%. In patients with renal failure (Ccr.:<10), they were 0.86-3. 74 h, 9.03-15.66μg/ml, 13.33-30.13 h, and 296.16-702.22μgh/ml. Urinary excretion (0-12 h) was 1.9-7.6%. With CAPD, they were 0.48 h, 18.18μg/ml, 13.08 h, 407.88μgμh/ml. PD excretion (0-12h) was 7.8%.
2) 7432-S was given to 8 patients with respiratory tract infections for 7-21 days at a dose of 300-400mg/day.
Clinical effect was good in all cases. As for abnormal laboratory findings possibly related to this drug, in one case GPT was elevated. But no side effects were found.

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We used a new oral cephem antibiotic, 7432-S, to treat 16 patients with respiratory tract infection, and to evaluate its efficacy and safety. The study was carried out from April to July 1986. The patients consisted of 10 males and 6 females, aged 411-87 years, the mean age being 65.9.
7432-S was given two or three times a day at a dose of 100mg or 200mg. Therapy lasted from 5-21 days and the total dose was 1.3-6.3g.
The therapeutic effect was excellent in 1 patient, good in 11, fair in 2, and poor in 2, with a high efficacy rate of 75.0%. Laboratory tests revealed the elevation of transaminases in two cases and eosinophilia in another case. These findings were slight, however, and alleviated immediately after withdrawal of the drug.

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Basic and clinical studeis on 7432-S, a new oral cephem antibiotic, were carried out and the following results obtained.
The in vitro antibacterial activity of 7432-S was tested against 135 clinical isolates of 9 species and compared with that of cefaclor, T-2525, cefixime, ampicillin, imipenam, ofloxacin and minocycline. 7432-S was more effective against Gram-negative bacteria (Escherichia coli, Klebsiella pneum.oniae, Proteus vulgaris, Providencia rettgeri, Morganella morganii, Enterobacter cloacae, Serratia marcescens and Haemophilus influenzae) than any other antibiotic tested, but less active against Gram-positive cocci (Streptococcus pyogenes).
We administered 7432-S to 6 patients with respiratory and 2 with urinary tract infection at a dose of 300-400mg daily in 2 or 3 divided doses for 7-15 days.
The clinical efficacy rate was 71.4% in all 7 cases except one, which was unknown.
The organisms isolated from 3 cases, 2 strains of Streptococcus agalactiae and 1 of Enterococcus faecalis, were eradicated except E. faecalis.
There were no side effects or abnormal laboratory findings.

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7432-S is a new cephem antibiotic for oral use. We examined its effect on phagocytic cell function, its antibiotic action against clinically isolated strains and clinical efficacy.
1) The sensitivity of 7432-S, cefaclor (CCL), and amoxicillin (AMPC) against clinically isolated Escherichia coli (19 strains), Klebsiella pneumoniae (20), Pseudomonas aeruginosa (15) and Staphylococcus aureus (19) was examined. Against E. coli and K. pneumoniae, most MICs of 7432-S were less than 0.1μg/ml, which were superior to those of CCL and AMPC. Most strains of P. aeruginosa were highly resistant to 7432-S as well as CCL and AMPC. Against S. aureus, 7432-S was inactive, inferior to AMPC and slightly inferior to CCL.
2) After 3 h of exposure to subinhibitory concentrations (1/2, 1/4, 1/8 MIC) of 7432-S in a shaking water bath at 37°C, E. coli NIHJ JC-2 showed filamentous formation.
3) A whole blood chemiluminescence (CL) test of E. coli NIHJ JC-2 treated with sub-MIC (1/4 MIC) of 7432-S revealed a value 1.36 times higher than that of bacteria untreated with the drug (p<0.05).
4) The CL peak time of 7432-S treated bacteria was significantly short (p<0.05) as compared with that of the untreated control. This result suggests that serum opsonic activity is increased in bacteria pretreated with this drug.
5) Polymorphonuclear leukocytes (PMNs)-CL responses by drug treated bacteria were induced 1.31 times higher than those by control (p<0.05). Monocytes (Mo)-CL responses by drug treated bacteria also showed 1.18 times higher activities, but not significant.
6) Clinically 7432-S was given orally to 5 patients with urinary tract infection and 2 with pneumonia, at a dose of 100 mg three times a day for 5-21 days. The results were markedly effective in 3 cases, effective in 3 and slightly effective in 1 case.
No side effects were observed, but in 2 cases some laboratory abnormalities were detected which had no clear causal relationship with drug administration. One was a rise in GOT, GPT values and another was a decrease in Hb. Both were, however, mild and temporary.

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We performed clinical studies on 7432-S, a new synthetic oral cephem antibiotic, in lower respiratory infections.
Twenty patients with chronic lower respiratory infections (chronic bronchitis 13, chronic pulmonary emphysema 7) were given 7432-S orally at 400 mg per day for 5-7 days. Twenty-one of 22 causative organisms (Streptococcus pneumoniae 1, Haemophilus influenzae 20, Branhamella catarrhalis 1) were eradicated by 7432-S therapy. Nineteen patients were cured. One patient infected with H. influenzae and S. pneumoniae improved only partially, because S. pneumoniae was not eradicated. The clinical efficacy of 7432-S therapy in this study was 95%. No adverse effect was observed. From our results, we concluded the 7432-S is an effective and useful oral antibiotic for the treatment of respiratory infections.

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We clinically evaluated the new oral cephem 7432-S (ceftibuten) with the following results.
1. Absorption and excretion: When a single 200 mg dose of the drug was orally administered to 6 healthy adult volunteers in a fasting state or after breakfast, the average maximum blood concentration was 9.28±3.29μg/ml at 2 h after administration and 5.72±2.02μg/ml at 6 h. The blood concentrations declined to 0.43 and 0.97μg/ml at 12 h with half-lives (β-phase) of 1.74 and 2.15 h. A delay observed in reaching the maximum blood concentrations when taken after breakfast was probably due to the heavy Japanese-style meal. When probenecid 1000 mg was used concomitantly, the blood concentration of ceftibuten after administration of 200 mg reached a peak of 10.44±1.08μg/ml at 3 h, the blood half-life was prolonged (1.74→2.29 h), the area under the blood concentration time curve increased (43.2→56.2μg·h/ml) and urinary recovery within 12 h decreased (64.5→58.4%). There results suggest that not only glomerular filtration but tubular secretion is involved in the drug's mode of renal excretion.
2. Clinical: The drug was administered in a daily dose of 300 mg (100mg×3) to 2 patients with acute cystitis for 5-7 days. The clinical response was excellent in one case and good in the other. Bacteriologically, the causative organism was eliminated in one case of Proteus mirabilis which could be isolated. No side effects or abnormal changes in laboratory values were observed.

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We studied the pharmacokinetics and clinical effect of 7432-S, a new cephem-derivative antibiotic for oral administration.
For the phamacokinetics, 3 male volunteers were given 7432-S three times each at a dose of 100 mg, 200 mg and 200 mg in combination with probenecid. When 100 mg was administered, the mean maximium blood concentration was 6.2μg/ml; for 200 mg the dose response was noted. The β-phase half life was 2.2-2.4 h and there was no difference in dose and no influence on the blood concentration or on the β-phase half life due to the concomitant use of probenecid.
The clinical effect was examined in 14 cases and was more than effective in all 5 patients with acute bronchitis, effective in all 4 patients with chronic bronchitis in exacerbation, fairly effettive in one patient each with chronic phalyngitis and chronic pharyngolaryngitis, markedly effective in one patient with bronchopneumonia, and in one patient each with acute and chronic pyelonephritis. Overall, a marked effect was shown in 5 patients and some effect in another 7 patients, the overall efficacy being 85.7%. Bacteriologically, causative bacteria were found in 7 patients, . in six of whom they disappered, while Staphylococcus aureus remained in one.
A side effect, mild epigastric pain, was noted in one patient, and laboratory investigation showed abnormalities in four patients, all of which were mild and improved when the drug was discontinued.

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We administered 7432-S, a new oral cephelosporin-derived antibiotic, to 9 patients (chronic bronchitis 2, bronchiectasis + infection 1, acute bronchitis 2, bronchopneumonia 4) at a daily dose of 400mg-600mg 2 or 3 times a day with the following results. The clinical effect, was excellent in 1 case of bronchopneumonia, good in 8 cases, and fair in 1 another case of bronchopneumonia, the overall efficacy rate being 88.9%.
In a bacteriological study, there was only one strain of Haemophilus influenzae, which was eradicated after treatment. There were no side effects or abnormal laboratory findings due to treatment. From the above results, we consider 7432-S a useful drug. But more study of its application in general respiratory tract infection is necessary.

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We evaluated the pharmacokinetics and clinical efficacy of 7432-S (a new oral cephem) in elderly patiens.
The drug was administered at a dose of 200 mg to 5 elderly patients without apparent renal or hepatic injury (mean age 77 years, mean body weight 50.2kg) under fasting condition, and to 4 patients (mean age 75.8 years, mean body weight 51.0kg) after meals. Serum and urinary concentrations of the cis-and trans-body of 7432-S were determined separately by HPLC.
In a fasting state, the maximum concentration of cis-and trans-bodies was 13.9±2.4μg/ml (2h), and 0.92±0.22μg/ml (3h). The serum half-life (T1/2) of cis-body was 2.7h, and the area under the curve (-12h) was 82.0 μg·h/ml. The urinary recovery to 12 h was 60.7%(cisbody 44.7%; trans-body 15.9%). After meals, the maximum concentrations of cis-and transbodies were 9.0±3.2μg/ml (3h) and 0.6±0.02μg/ml (6h). The serum half-life (T1/2) of the cis-body was 2.88 h. The area under the curve was 59.9μg·h/ml. The urinary recovery to 12 h was 51.6%(cis-body 44.1; trans-body 7.5%). When the drug was given to ambulatory elderly patients in a fasting state, higher levels and longer duration were achieved, in comparison with reported data in healthy younger adult volunteers. Impaired renal function and lower body weight in elderly patients doubtless contributed to these results.
We clinically evaluated 7432-S against infections in elderly patients. Satisfactory response was obtained in 9 of 15 (73.3%) episodes of lower respiratory tract infections and, 1 of 4 episodes of urinary tract infections. Most organisms isolated after the therapy were Gram-positive cocci. As adverse effects, nausea and diarrhea were noted in one patient each.

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7432-S, a new oral third-generation cephalosporin antibiotic, was investigated in 12 patients with respiratory tract infections. The subjects were 9 males and 3 females, 33-77 years old (mean age 54.9). Diseases were chronic bronchitis 6, acute bronchitis 3, diffuse panbronchiolitis 1, and bronchiectasis with infection 2.
The dose of 7432-S was 200 mg twice daily for 7-14 days (mean 8.2 days), with a total of 2.8-5.6g (mean total dosage 1.17g).
Clinically, the effect was excellent in 1 case, good in 10 cases and fair in 1 case, with an overall efficacy rate of 91.7%. Categorized by disease, 7432-S was good in all 6 cases of chronic bronchitis, good in all 3 cases of acute bronchitis, excellent and good in each 1 case of bronchiectasis with infection, and fair in 1 case of diffuse panbronchiolitis.
Sputum from 10 patients was cultured for bacteriological examination. Haemophilia influenzae, Klebsiella pneumoniae were isolated from 3 and 2 patients, respectively. After administration, H. influenzae and K. pneumoniae were eradicated in 2 cases each.
No side-effects (such as drug eruption, fever, nausea, vomiting or diarrhea) were observed, and laboratory values were normal before and after administration of 7432-S.

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We studied the clinical and adverse effects of 7432-S, a new cephem antibiotic, in 16 patients with respiratory tract infections who were given orally 100-200 mg b. i. d. or t. i. d.
Of these, 2 cases were pneumonia, and 14 were lower respiratory tract infections (with bronchial asthma 4, bronchiectasis 3, diffuse panbronchiolitis 3 and pulmonary emphysema 1 as underlying diseases).
The clinical effect was good in 10, fair in 1 and poor in 5 cases, with an efficacy rate of 63%.
As for causative organisms, the results were: of 5 strains of Haemophilus influenzae, 4 were eradicated and 1 decreased; of 4 strains of Streptococccus pneumoniae, I decreased and 3 persisted.
As for adverse effects, slight elevation of GPT was observed in one case after treatment.
From these results, we conclude that 7432-S is a useful drug for the treatment of respiratory infections.

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7432-S was administered in capsule form at 300-400 mg two or three time a day (as a rule, 400mg twice daily) for 4-21 days to 10 paitients with respiratory infections: pneumonia (6 cases), chronic bronchitis (2), and bronchiectasis with infection (2). The clinical response was good in 5, fair in 1 and poor in 4 cases (efficacy rate: 50.0%).
Neither clinical side effects nor abnormal laboratory findings were observed during administration of this drug.

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Three patients were treated with 7432-S, a newly developed cephalosporin antibiotic for oral use.
Of these, a 62 year-old male and a 31 year-old female with infected bronchiectasis were successfully treated with 200 mg t. i. d. or b. i. d. of 7432-S. The duration of 7432-S treatment was 10 and 7 days for each patient. A 77 year-old female patient with infected chronie bronchitis was given 200 mg b. i. d. of 7432-S for 13 days, but did not recover completely. No significant side effects or abnormal laboratory data were observed in these patients.

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We clinically assessed 7432-S, a new oral cephem antibiotic, by administering it to 15 patients with respiratory tract infections. The dose was 300 mg in 3 divided portions and 400mg in 2 after meals for 4-17 days.
Clinical efficacy was good in 10 cases, fair 2, poor 2 and unknown 1, the efficacy rate being 71.4%. As causal bacteria, 8 strains were identified in 7 cases, namely, 1 strain each of Staphylococcus aureus and Streptococcus pneumoniae (as cocci) and 3 strains of Haemophilus influenzae, 2 of Klebsiella pneumoniae and 1 of Pseudomonas aeruginosa (as bacilli). The bacteriological effect of the drug was 2 strains of H. influenzae eradicated; 1 each of H. influenzae and K. pneumoniae (cases of multiple bacterial infections) eradicated but changed to S. aureus and S. pneumoniae; 1 strain each of K. pneumoniae and S. aureus, unknown; and 1 strain of P. aeruginosa, unchanged.
As adverse reactions, mild epigastralgia was observed in 2 cases, and as abnormal clinical laboratory values, mild and transient increase in GOT, GPT, LDH and eosinophils in 3 cases. There was, however, no clinically problematic abnormality.

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We evaluated efficacy and safety of 7432-S, a new oral cephem antibiotic, by administering it to patients with respiratory tract infections, and the following resuits were obtained.
The study involved a total of 6 Patients 1 with acute bronchitis, 3 with an acute exacerbation of chronic bronchitis, 1 with infected bronchial asthma and 1 with pneumonia, wbo orally receivewd 7432-S at 200 mg 3 times a day (2 times a day for 1 patient) for 10 to 14 days.
The clinical response was evaluated as good for the patient with acute bronchitis, good for 1, fair for 1 and poor for 1 of the 3 patients in an acute exacerbatiom of chronic bronchitis, fair for the patient with in fected bronchial asthma and good for the patient with pneumonia. The causative organisms could be identified in 4 patients; 7432-S was capable of eliminating the organisms in only one patient with H.influenzae, while the organisms persisted in 2 others with H.influenzae and one patient with P.aeruginosa even after the treatment with 7432-S.
Eosinophilia occurred in 1 patient and increases of GOT and GPT with eosinopbilia occurred in another patient, but they were all minor changes. In addition, none of the pdients presented any adverse reaction subjectively or objectvely.

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We performed bacteriogical and clinical studies on 7432-S, a new oral cephem antibiotic, in respiratory tract infections and obtained the following results.
1) The peak MIC of 7432-S against Staphylococcus aureus was 100-200μg/ml, which was inferior to those of cephalexin, CS-807 (R-3746) and ampicillin. 7432-S showed excellent antibacterial activity against Escherichia coli, Klebsiella sp., Serratia marcescens and Proteus spp., the peak MICs of these strains being 0.25-0.18μg/ml MICs of 7432-S for Pseudomonas aeruginosa, Pseudomonas cepacia and Acinetobacter calcoaceticus were high, the peak values being more than 200μg/ml.
2) 7432-S was administered to 10 patients with respiratory tract infection at daily doses of 300mg t. i. d. or 400 mg b. i. d. The clinical effect was “good” in 8, “fair” in 1, and unevaluable in 1, the efficacy rate being 88.9%.
As a side effect, diarrhea with abdominal pain was observed in one case and slight elevation of LDH in another.

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We performed laboratory and clinical studies on 7432-S, a new oral cephalosporin antibiotic, with the following results.
1. Antimicrobial activity
MICs of 7432-S against various clinical isolates were determined with an inoculum size of 10⁶ cells/ml. The MIC₈₀ was > 100μg/ml for Staphylococcus aureus and Enterococcus faecalis, 0.39 for Escherichia coli, 6.25 for Klebsiella spp., 100 for Enterobacter spp., 3.13 for Serratia marcescens, 0.05 for Proteus mirabilis, 0.10 for Proteus vulgaris, 100 for Pseudomonas aeruginosa and Citrobacter spp., and 50 for Acinetobacter spp. and Flavobacterium spp. 7432-S was less active against Gram-positive cocci than cefaclor or cephalexin, but it was much more active against Gram-negative bacilli except P. aeruginosa than CCL and CEX.
2. Clinical efficacy
Two patients with acute exacerbation of chronic bronchitis, 7 with chronic bronchitis, 1 with acute pharyngolaryngitis and 1 with cystitis and common cold were treated with 7432-S at a daily dose of 0.3-0.4 g for 4-42 days. Clinical response was excellent in 2, good in 4, fair in 3, and poor in 2 patients. The clinical efficacy rate was 54.6%. The antimicrobial effect on patients with normal flora was low. Epigastralgia and nausea were observed in 1 patient. No abnormal laboratory finding was seen.

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We carried out laboratory and clinical studies on 7432-S, a newly developed oral cephem antibiotic.
The following results were obtained.
1) Antibacterial activity
The antibacterial activity of 7432-S was examined by the serial microbroth dilution method using the MIC-2000 system (Dynateck Co.). The minimum inhibitory concentration (MICs) of 7432-S against 29 standard strains and 473 clinical isolates of 14 different species were compared with those of cefixime (CFIX), cephalexin (CEX), cefaclor (CCL), amoxicillin (AMPC) and ofloxacin (OFLX). The antimicrobial activity of 7432-S against Gram-negative bacilli was excellent, particularly against enterobacteriaceae, but it was weak against Gram-positive cocci.
2) Clinical efficacy and adverse reactions.
Twenty-three patients with respiratory infection (chronic bronchitis 16, pneumonia 2, bronchiectasis 1, diffuse panbronchiolitis 1, pulmonary fibrosis with infection 1, acute bronchitis 1, pneumoconiosis with infection 1) were treated with 7432-S. The overall efficacy rate was 61.9%(excellent 2, good 11, fair 4, poor 4, unevaluable 2). No significant side effect was observed. One patient, however, showed epigastralgia. A transient increase in eosinophils, and elevation of GOT, GPT and ALP was noted in 3 patients.

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We performed basic and clinical studies on 7432-S, a new oral cephem, in most cases, chronic respiratory tract infection.
The minimal inhibitory concentrations (MICs) of 7432-S at 10⁶ CFU/ml were all≤ 0.01μg/ml against 43 strains of Haemophilus influenzae, ≤1.56μg/ml against 8 strains of Klebsiella pneumoniae, 0.1-1.56μg/ml against 5 of 6 strains of Escherichia coli, 0.05-100 <μg/ml against 48 strains of Branhamella catarrhalis, with a peak of MIC was 3.13μg/ml, 0.78-100 <μg/ml against 42 strains of Streptococcus pneumoniae with a peak of MIC of 3.13μg/ml, and 100≤μg/ml against 42 strains of Staphylococcus aureus.
The serum concentrations of 7432-S were measured in 4 patients after a single dose of 200 mg, and all the peak concentrations were obtained 2 hours after administrations and ranged from 8-12μg/ml. In 2 of 4 cases, the sputum concentrations were measured and the peak levels were 0.26 and 0.73μg/ml. The ratios of peak sputum to peak serum level ranged from 3.3-6.0%.
Twentyeight patients with respiratory tract infection were treated with 7432-S in daily doses of 400 mg in most cases. Of these, 22 were effective or excellent and the clinical efficacy was 78.6 %.
Sixteen of 22 causative organisms (12/13 H. influenzae, 1/3 S. pneumoniae, 1/2 B. catarrhalis, 1/1 K.pneumoniae, 0/1 S.aureus) were eradicated.
No adverse effect was observed.
From these results, we conclude that 7432-S is an effective and useful antibiotic, particularly for infections due to H.influenzae.

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We studied 7432-S, a newly developed cephem antibiotic, for its antibacterial activity, serum and sputum concentrations, and clinical efficacy in respiratory infections.
The results obtained were as follows.
1. Antibacterial activity
The minimum inhibitory concentrations (MICs) of 7432-S against
40 strains of Haemophilus irlfluenzae, 52 strains of Escherichia coli,
53 strains of Klebsiella pneumoniae, 53 strains of Proteus mirabilis,
54 strains of Morganella morganii, 53 strains of Enterobacter cloacae and 54 strains of Serratia marcescens, (in total 359 strains)
were measured and compared with the MICs of cefteram, cefixime and cefaclor measured at the same time.
The MICs of 7432-S were generally similar or slightly superior to those of cefteram and cefixime, and several times higher than those of cefaclor.
2. Serum and sputum levels
When 7432-S 200mg was administered orally, the blood level showed a peak of 11.0-12.2μg/ml after 3-4 h and the concentration was 2.7-3.8μg/ml after 8 h.
When 100mg was administered, a peak level of 4.4μg/ml was obtained after 3 h and the concentration was 0.82μg/ml after 8 h.
When 200mg was administered, a sputum level of 0.02μg/ml was obtained, but after 100mg the level was below the detection limit.
3. Clinical effect
We administered 300mg/day t. i. d.(6 patients) and 400mg/day b. i. d. (3 patients) for 7-14 days to 9 patients (bacterial pneumonia 2, acute bronchitis 2, chronic bronchitis 2 and broncchiectasis 4). The results were excellent in 1 patient, good in 4, fair in 3 and poor in 1.
Subjective or objective side effects attributable to this drug were not observed. Although a slight elevation in the LDH was seen in 1 patient, this returned rapidly to the pretreatment value after discontinuation of administration.

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7432-S, a new cephem antibiotic, was basically and clinically evaluated with the following results:
1) Antimicrobial activity: The minimum inhibiratory concentration (MICs) of 7432-S against 134 strains consisting of 12 standard strains and 122 clinical isolates (6 species) were compared with those of cefaclor (CCL) and cefotiam (CTM). Against Staphylococcus aureus, Streptococcus pneumoniae 7432-S was five tubes less potent in antibacterial activity than CCL and CTM, but equal against Branhamella catarrhalis.
On the other hand, 7432-S was four to eight tubes more potent than either antibiotic against Haemophilus influenzae and the same or one tube more potent against Klebsiella pneumoniae. None of the three antibiotics showed antibacterial activity against Pseudomonas aeruginosa.
2) Clinical efficacy: 7432-S was administered at a daily dose of 300 or 400 mg for 3-14 days to 11 patients with various respiratory infections. Clinical response was good in 7, fair in 3, and poor in 1.
The overall efficacy rate was 63.696 (7/11 cases).
Subjective and objective symptoms, hematological and biochemical data and renal functions were checked before and after administration of 7432-S, and one patient showed minim elevation of S-GPT. We therefore conclude that 7432-S is a useful antibiotic in treating respiratory infections.

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The antibacterial activity of the oral cephem antibiotic 7432-S was In%, basically and clinically.
In the basic study, minimal inhibitory concentrations (MICs) of 7432-S, cefpodoxime proxetil (CS-807), cefixime (CFIX) and cefaclor (CCL) against clinical isolat, of Esherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positive Proteus spp., Enterobacter spp. Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis Enterococcus faecalis and Enterococcus faecium were determined at an inoculum size of 10⁵ CFU/ml by Dynatec MIC-2000 System.
The MIC₈₀s of 7432-S against clinical isolates were 0.20μg/ml for E.coli 0.025μg/ml for Proteus mirabilis, 0.39μg/ml for indole-positive Proteus spp. and 25μg/ml for S. marcescens. The MIC₈₀s of 7432-S against Gram-negative bacilli were superior to those of the other three antibiotics. Against K. pneumoniae, the MIC₈₀ of 7432-S was 0.20μg/ml, which was next ti, that of CFIX. The MIC₈₀ of 7432-S against Enterobacter spp. was 100μ/ml and those against P. aeruginosa and four Gram-positive cocci were more than 100μg/ml. These organisms were not responsive to this antibiotic.
In the clinical study, 25 patients with complicated urinary tract infection (UTI) were trotted with 7432-S orally at a dose of 300 mg t. i. d. for 14 days as a rule.
Clinical efficacy and side effects were evaluated on 5th day of trertment according to the criteria proposed by the Japanese UTI Committee (3 rd ed.). A similar evaluation was also made on the 10th day or 14 th days.
Twenty of the 25 patients were evaluable for drug efficacy on the 5th day, The overall clinical results after 5-day treatment were excellent in 9 cases, good in 4 and poor in 7, the overall efficacy rate being 65%.
In 13 patients, after completion of 10-day or longer treatment, the overall efficay rate increased by 7% to 69% as compared with the results on the 5th day.
Bacteriologically, 25 of 27 (93%) strains of causative organisms were eradicated and 12 new strains appeared in 10 patients after 5-dsay treatment. Thirteen of 20 (85%), strains of causative organisms were eradicated and 5 new strains appeared in 4 patients after a 10-day or longer treatment.
No subjective side effects or remarkable abnormal laboratory findigs were observed in any of the patients after treatment.
We believe that 7432-S is a highly useful oral antibiotic in treating complicated UTI.

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We conducted a controlled study to evaluate the efficacy of 7432-S in female patients with urethritis or cystitis.
Patients were given orally 50 mg or 100 mg of 7432-S once or twice a day for seven days. Clinical efficacy was evaluated on the third and seventh day of treatment. A test for recurrence was done on the seventh day after the end of treatment.
Overall clinical efficacy by our criteria on the third day of treatment was 98.296 in group 1 (55 patients) who received 25 mg of the drug twice a day, 100% in group 2 (62 patients), 50 mg once a day, 100% in group 3 (61 patients), 50 mg twice a day and 95.3% in group 4 (64 patients), 100 mg once a day. Likewise, it was 100% for all groups at the seventh day of treatment.
Recurrence after treatment was observed in one patient each in groups 2 and 4, the overall recurrence rate being only 3.4%(2/59 patients).
Considering only patients evaluable by the criteria of the Japanese UTI committee, the overall clinical efficacy on the third day of treatment was 96.6% in group 1 (29 patients), 100% in group 2 (31 patients), 97.1% in group 3 (34 patients) and 88.2% in group 4 (34 patients). Recurrence was observed in one patient in group 4.
The overall recurrence rate was 2%(1/51 patients).
No significant difference among the groups was observed in the evaluation of overall clinical efficacy, effects on symptoms, pyuria, bacteriuria, and recurrence rate.
From the present study, we conclude that 50 mg/day (in one or two divided doses) of 7432-S is effective in the treatment of female urethritis or cystitis.

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7432-S, a new oral cephem antibiotic, was administered at a daily dose of 300 600 mg to patients with urological infections.
A total of 48 patients was treated: 1 with acute uncomplicated cystitis, 1 with gonococcal urethritis, 4 with chronic prostatitis and 42 with complicated urinary tract infection.
The overall clinical efficacy assessed by the doctors in charge was as follows;1 case of acute uncomplicated cystitis was excellent, 1 of gonococcal urethritis was good and 4 of chronic prostatitis were good in 1, fair in 2 and poor in 1.
Thirty-seven patients with complicated urinary tract infections were evaluated according to the criteria of the Japanese UTI commitee, and the clinical response to 7432-S was excellent in 11, moderate in 10 and poor in 16, the efficacy rate being 56.8%.
As for side effects, 1 case of diarrhea was observed, slight elevation of GOT, of T. bilirubin, and of GPT, ALP and T.bilirubin in 1 case each were found.

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7432-S, a newly developed cephem, was orally administered at 100 mg twice a day for 3-5 days to 11 patients with urinary tract infection (acute uncomplicated cystitis 5 cases, acute uncomplicated pyelonephritis 1, chronic complicated cystitis 4, chronic complicated pyelonephritis 1).
The clinical efficacy of uncomplicated UTI was excellent in 5 cases and poor in 1 by the physicians evaluation and excellent in 4 by the Japanese UTI Drug Evaluation Criteria.(Two of 6 cases were not suitable for evaluation by the UTI-Criteria). The efficacy rate was 83.3% by the physician's and 100% by the UTI evaluation.
The clinical efficacy in uncomplicated UTI was evaluated in 4 cases, the rate being 75% by either, criteria (excellent 1, good 2, poor 1).
No subjective or objective side effects were not found.

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7432-S, a new synthetic oral cephem, was used in the treatment of urological infections, and its therapeutic efficacy and safety were evaluated.
Twenty-six patients with acute uncomplicated cystitis, 1 with acute uncomplicated pyelonephritis, 21 with complicated urinary tract infection (UTI) and 4 with genital infections were treated with 7432-S at the Department of Urology, Faculty of Medicine, Tokyo University and affiliated hospitals.
The clinical effects in 9 patients with acute uncomplicated cytitis, 1 with acute uncomplicated pyelonephritis and 13 with complicated UTI were assesed according to the Japanese Criteria Clinical Evaluation of Antimicrobial Agents in Urinary Tract Infections (3 rd ed.).
Overall clinical efficacy in the 9 patients with acute uncomplicated cystitis was excellent in 7 and moderate in 2, the efficacy rate being 100%.
Clinical efficacy in, one patient with acute uncomplicated pyelonephritis was excellent.
Clinical, efficacy in the 13 patients with complicated UTI was excellent in 6 and moderate in 3, the overall efficacy rate being 69.2%.
According to doctor's evalution, 7432-S was effective in 23 of 26 cases of acute uncomplicated cystitis, 15 of 21 with complicated UTI and 2 of 3 with urethritis.
Adverse effect during treatment were transient diarrhoea in one patient and a heavy sensation on head in another. No abnormal change in laboratory values was observed.
We consider 7432-S to be a safe and effective drug for the treatment of urinary tract infection.

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We carriel out basic and clinical studies on 7432-S, a new oral cephem antibiotic in urinary tract infection (UTI)., The results were as follows.
1) Antibacterial activity (MIC): The MICs of 7432-5, T-2525, cefaclor (CCL) and cephalexin (CEX) were determined for six species of bacteria (Staphylococcus epidermidis, Enterococcus. faecalis, Escherichia coli, Serratia marcescens, Citrobacter freundii and Pseudomonas aeruginosa, isolated in our department. Against E. coli, the MIC distributions of 7432-S were less than 0.39μg/ml for all strains and its activity was the highest of these 4 antibiotics. Against C. freundii, the MIC₈₀ of 7432-S was 6.25μg/ml, and against of S. marcescens, it was 12.5μg/ml, namely the biological effect of 7432-S was the same as T-2525, and stronger than those CCL and CEX. Against S. epidermidis, E. faecalis and P. aeruginosa, the activity of 7432-5 was weak or there was resistance.
2) Clinical results: Four patients diagnosed as having acute uncomplicated cystitis, were given 7432-S or 3 days at a daily dose of 300 mg, and the efficacy rate was 75%. Nine patients diagnosed as having complicated urinary tract infection, were given the drug for 5 days at a daily dose of 300 mg, and the efficacy rate was 44.4%.
No side effects were found in any of the 20 patients.

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The antimicrobial activity of benzyl penicillin (PCG) and 7432-S was measured against a total 48 strains of Neisseria gonorrhoeae (4 strains of PPNG, 44 strains of non-PPNG) isolated from male patients with gonorrhoea who had been seen at the Department of Urology, Tokyo Metropolitan Taito Hospital between August 1986 and January 1987.
Against four strains of PPNG, the MICs of PCG ranged from 3.13-100μg/ml, and against 44 strains of non-PPNG from 0.0125-3.13μg/ml. In contrast, the MICs of 7432-S against PPNG and non-PPNG were distributed from 0.006-0.0125.μg/ml, and ≥ 0.003-0.1μg/ml. Thus the antimicrobial activity of 7432-S was far more potent than that of PCG both against PPNG and non-PPNG.
A total of 24 male patients with gonococcal urethritis who had been seen at the Department of Urology, Metropolitan Taito Hospital and the Department of Urology, The Jikei University School of Medicine from November 1986 to January 1987, were given 7432-S.
In 24 cases of gonococcal urethritis, a group of 14 patients were given 7432-S at 300 mg/day and another group of 10 patients were given the drug at 400 mg/day. In each group, one case of PPNG was included, but there were no case in which no medicinal effect noted, hence the efficacy rate was 100% for either dosage.
No side effects were observed in any of the cases.

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We determined the susceptibility of Neisseria gonorrhoeae to 7432-S, a new oral cephem antibiotic, and evaluated the therapeutic effect of the drug in male gonococcal urethritis.
The MICs of 7432-S against 48 isolated strains of N. gonorrhoeae were ≤ 0.003-0.78μg/ml, and the MIC₉₀ was 0.05μg/ml.β-lactamase-producing strains also proved sensitive to the drug.
7432-S was administered to 14 patients with N. gonorrhoeae at a dose of 100 mg or 200 mg b. i. d. orally for 3 days. The overall clinical efficacy was good or excellent in all cases at 3 and 7 days after the treatment.
No post-gonococcal-urethritis (PGU) was found during a 7 day follow up.
No side-effects were noted in any of the 14 patients observed.

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Clinical studies were carried out on 7432-S, a new cephem antibiotic, and the following results were obtained.
7432-S was administered orally to a total 16 patients (acute uncomplicated cystitis 11 cases, chronic complicated urinary tract infection 4, and non-gonococcal urethritis 1) for 3-6 days at a dose of 100 mg.
The clinical efficacy of 7432-S was assessed according to the Japanese UTI Committee Criteria, and by the attendant physician in the cases unevaluable by the criteria.
Clinical effect according to the UTI criteria was excellent in 2 and good in 6 of 8 cases of acute uncomplicated cystitis, with an efficacy rate of 100 %, and good in 2 of 3 cases of chronic complicated UTI, with an efficacy rate of 66.7%.
No side effects or abnormal laboratory findings were observed.

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We carried out laboratory and clinical studies on a new oral cephem antibiotic, 7432-S, and obtained the following results.
1) Diffusion into human prostatic fluid (PF): the mean drug concentration in PF was 0.06 μg/ml at 1 h after administration of 200 mg in 3 specimens, but in 3 other specimens no drug concentrations was detected.
2) Clinical results: 33 patients with urological infection were treated with 200-600 mg of 7432-S per day for 3-20 days.
Acute simple UTI: Of all 7 cases evaluable by the Japanese UTI Comittee's criteria, results were judged as excellent in 6 and moderate in 1 after 200 mg/day admininstration of the drug for 3 days.
Chronic complicated UTI Of 15 cases evaluable by the criteria, results were judged as excellent or moderate in 9 cases after 200-600 mg daily administration.
The overall efficacy rate was 60%. The drug was poor against infections with catheter indwelt.
Genital infection: Of 10 cases of bacterial prostatitis, results were good in 3, fair in 2 and poor in 5 after 600 mg/day administration for 7-20 days.
The, bacteriological eradication rate was 40% and the clinical efficacy rate 30%.
3) Safety: As to side-effects, stomatitis occured transiently after 400 mg/day administration in 1 case.
In laboratory tests, slight elevation of GOT, GPT was observed in 1 case.
No side-effects were encountered in the other cases.
All side-effect and abnormal values were slight and transient, and returned to normal after discontinuance of the drug.
4) Ponclusions: 7432-S was more potent in acute simple cystitis and chronic complicated UTI no-catheter, indwelt), except in cases infected by Pseudomonas aeruginosa or GPC. The drug was effective against bacterial prostatitis caused by Escherichia coli but poor in cases infected by GPC.
We therefore conclude that 7432-S is a useful and safe antibiotic against urological infections caused by GNR at a daily dose of 400-600 mg/day.

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We performed experimental and clinical studies on 7432-S, a new cephem antibiotic for oral use.
1) 7432-S had potent antibacterial activity compared with cephalexin (CEX) and cefaclor (CCL) against Escherichia coli, Klebsiella pneurnoniae, Proteu mirabilis and other Gram-negative bacilli.
7432-S was less active, however, than CEX and CCL against Gram-positive cocci.
2) 7432-S was administered orally to healthy volunteers. The drug was given in a single dose of 100 mg with food.
A maximal mean blood level of 4.20 μg/ml was achieved 2 h after administration and a maximal urine level was detected 2-4 h after administration.
The recovery rate in urine after 10 h was 48.3%.
3) Sixteen patients with complicated urinary tract infection were evaluated by the criteria of the Japanese UTI Committee.
The results were excellent in 6 cases and moderate in 2, and the overall clinical efficacy rate was 50%.

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The in vitro antibacterial activity of 7432-S, a new oral cephalosporin, against Gram-negative bacteria isolated from urinary tract infections was compared with those of the control drugs, cefaclor, cephalexin and ampicillin.
The antibacterial activity of 7432-S were 2³ to 2⁴ times higher against Escherichia coli, Citrobacter freundii, Kiebsiella pneurnoniae and Serratia liquefaciens and definitely higher against Serraria marcescens, Providencia rettgeri and Morganella morganii than the control drugs.
Four patients with acute uncomplicated cystitis and 19 patients with complicated urinary tract infection were treated with 7432-S at 200-300 mg/day for 3 days and 300 mg/day for 5 days. According to the criteria proposed by the Japanese UTI Committee, the overall efficacy rate of 7432-S in acute uncomplicated cystitis and complicated urinary tract infection was 100% and 50%. Three male patients with gonococcal urethritis were treated with 300 mg/day for 5 days, resulting in an excellent response.
Associated with 7432-S treatment, soft stool and nausea were observed in one case but no abnormal laboratory findings were noted.
We conclude that 7432-S is a useful and safe antibiotic for urinary tract infection caused by Gram-negative rods and for male zonococcal urethritis.

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We studied the, clinical efficacy and safety of a new orally administered cephem antibiotic, 7432-S, on 67 patients with urinary tract infections (UTI). The results were as follows:
(1) Acute uncomplicated cystitis (20 patients)
Twenty patients with acute uncomplicated cystitis were given 200 mg of 7432-S divided into two equal oral doses daily for 3 days. The drug was judged to be effective by the physicians in 90% of the cases. In 18 patients complying with the Japanese UTI Drug Effect Evaluation Standards, 13 showed “excellent”, and “moderate” in 5. There was no case where the drug had no effect, showing 100, % of overall effectiveness rate. The eradication rate was 100%(21/21) and 12 bacterial strains were observed after the treatment.
(2) Complicated urinary tract infections (47 patients)
Fourty-seven patients with complicated UTI were given 200-600 mg of 7432-S divided into two or three equal oral doses daily for five days. The physicians evaluated the response in 45 patients with an efficiency rate of 53%. Of 38 patients complying with the Japanese UTI criteria, 14 showed “excellent”, “moderate” in 1, 2 and “poor” in 12, an overall efficiency rate of 68%. The eradication rate was 82%(42/45) and 13 bacterial strains were observed after the treatment.
(3) Safety (67 patients)
No patients had subjective or objective adverse reactions. Abnormal laboratory findings (neutropenia, increased levels of GOT, GPT, ALP and ALP, BUN) were found in three patients, but these were mild and transient.

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We evaluated 7432-S, a new oral cephem, basically and clinically.
1) The antibacterial activity of 7432-S against 180 strains isolated from urinary tract infections were compared with those of cefaclor, cefadroxil, cephalexin and ampicillin. Its activity against Staphylococcus epidermidis and Enterococcus faecalis was weak, and inferior or equal to the reference drugs; but its activity against Escherichia coli, Klebsielkt pneumoniae, Proteus mirabilis, Proteus vulgaris and Morganella morganii was far superior. Although approximately half the strains of Citrobacter sp., Enterobacter cloacae, Enterobacter aerogenes proved resistant, 7432-S nevertheless showed stronger activity than the reference drugs. The MICs of 7432-S against 15 of 19 strains of Serratia marcescens were less than 12.5μg/ml. Its activity against Pseudomonas aeruginosa was weak, but superior to the other drugs.
2) Twenty-five patients with complicated urinary tract infections were treated with daily doses of 200 mg or 300 mg of 7432-S. The overall clinical efficacy rate was 68%. A side-effect, mild diarrhea, was noted in only one case, and no abnormal laboratory findings were observed.

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We performed clinical studies on 7432-S, a new oral antibiotic agent, with the following results.
7432-S was administered orally in daily doses of 200-300 mg for 5 days to one patient with acute umcomplicated cystitis and 24 patients with chronic complicated urinary tract infections.
1) The clinical result in the case of acute umcomplicated cystitis was excellent, an overall efficacy rate of 100%.
2) Clinical results in chronic complicated urinary tract infections were excellent in 2 cases, moderate in 7, and poor in 7, an overall efficacy rate of 56%.
3) As to bacteriological response, organisms were eradicated in 16 (76%) and persisted in 5 (24%) of 21 strains.
4) No side effects were observed.
Laboratory abnormalities, however, were observed in 2 cases of slightly elevated GOT, GPT and decreased serum kalium.

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We used 7432-S in the treatment of urinary tract infections (UTI) to investigate its clinical efficacy and safety. The subjects were: 5 patients with acute uncomplicated cystitis, 47 with chronic complicated UTI, and one with urethritis.
The following results were obtained.
1) Clinical efficacy was evaluated according to the criteria of the Japanese UTI Committee.
The overall efficacy was 100% in 4 patients with acute uncomplicated cystitis. In 46 patients with chronic complicated UTI, it was excellent in 30, moderate in 6 and poor in 10, the overall efficacy rate being 78%.
2) Bacteriologically, 3 of 4 strains (75%) were eradicated in acute uncomplicated cystitis and 49 of 57 strains (86%) in chronic complicated UTI.
3) Clinical response was fair in one patient with urethritis.
4) As to side-effects, rash of the extremities was observed in one patient, but no abnormal laboratory findings.

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