Aspoxicillin (ASPC), a new injectable semisynthetic penicillin, was administered to healthy volunteers to elucidate its safety and pharmacokinetics.
No abnormalities obviously attributable to ASPC were observed in the examinations covering subjective and objective symptoms, blood pressure, heart rate, respiratory rate, electrocardiogram and body temperature, as well as in hematology, blood chemistry and urinalysis.
There were slight increase in LDH (1 case), Al-P (1 case) and blood-glucose levels (2 cases) at 2 or 4 weeks after the administration with intravenous bolus consecutive injection (1g×1 or 2/day, 8 to 10 times), but these increase were not considered to be attributable to ASPC.
When ASPC was administered by consecutive intravenous bolus injection, there observed no tendency of accumulation of the drug in serum or urine.
When 1g of ASPC was given intramuscular (i. m.), intravenous injection (i. v.) and intravenous drip infusion (d. i.) route, the maximum antibiotic levels in serum reached 25.2μg/ml, 118.2μg/ml and 70.3μg/ml at 0.75 hour, 0.08 hour and 1 hour after the administration, respectively. The biological half-lives of ASPC attained by these 3 different routes were as follows: 1.73 hours (i. m.), 1.65 hours (i. v.) and 1.44 hours (d. i.).
In a cross-over test with piperacillin (PIPC), serum levels of ASPC were higher than those of PIPC and half-lives of ASPC were longer. The 8 hours urinary recovery of ASPC was 75.9% after intravenous injection, 74.6% after intramuscular injection and 88.0% after intravenous drip infusion. Most of urinary recovery was excreted within 4 hours after administration regardless of dose levels, frequency of dosing or administation route.
Thin layer chromatographic bioautography was conducted with the samples of serum and urine collected from subjects received ASPC. No antibacterial metabolite was observed in the serum obtained 2 hours after administration but a metabolite identified as amoxicillin was detected in a part of urine samples collected after 8 to 10 hours after the injection.

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A double-blind comparative study of S6472 and cefaclor (CCL) was conducted to evaluate the therapeutic efficacy, safety and usefulness in the treatment of skin and soft tissue infections. Either 750mg b. i. d. of S6472 or 750mg t. i. d. of CCL was administered orally to patients for a period of 7 consecutive days.
Of the 250 cases (123 cases of S6472 group and 127 cases of CCL group) recruited in this trial, 228 cases (114 cases of S6472 and 114 cases of CCL) were adopted by the committee members for the evaluation of therapeutic efficacy, 238 cases (118 cases of S6472 group and 120 cases of CCL group) for usefulness, and 245 cases (121 cases of S6472 group and 124 cases of CCL group) were adopted for the evaluation of side effects. The backgrounds of both patients group were almost similar.
The results obtained were as follows:
1. Overall clinical effectiveness
Of the 114 patients treated with S6472, excellent clinical responses were obtained in 11 patients, good in 79, fair in 19, poor in 5 (efficacy rate 78.9%), and of the 114 patients treated with CCL, excellent were in 16, good in 78, fair in 13, poor in 7 (efficacy rate 82.5%). There was no statistically significant difference between the 2 groups.
2. Clinical effectiveness classified by initial severity and bacteriological efficacy
There was no significant difference between the 2 groups in the clinical effectiveness classified by initial severity and in the bacteriological efficacy.
3. Side effects were noticed in 5 patients of 121 treated with S6472 (4.1%) and in 2 patients of 124 treated with CCL (1.6%), and other 13 patients developed some abnormal laboratory findings. But these undesirable reactions were mild, and developed no significant difference between the 2 groups in the incidence of side effects.
4. There was no significant difference between the 2 groups in the usefulness of the drugs.
Conclusively, 750mg b. i. d. of S6472 is anticipative of the same clinical efficacy, safety and usefulness as compared with that of 750mg t. i. d. of CCL in the treatment of skin and soft tissue infections.

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To objectively evaluated the usefulness of the standard formulation of cefaclor (CCL) and the long-acting formulation of cefaclor (S6472) in noncatheterized complicated urinary tract infection (UTI), a double-blind comparison study was carried out using cephalexin (CEX) as a control.
Patients were orally treated with either 500mg of CCL 3times/day, 750mg of S6472 2times/day, or 500mg of CEX 4times/day for 14 days. Overall clinical effect was evaluated on days 5 and 14 in accordance with the UTI therapeutic evaluation standard, with check for recurrence on day 21.
1. There was no demographic difference between the groups.
2. There was no difference in the effective rate on day 5 among the 3 treatment groups: 58.1% in S6472 group, 66.0% in CCL group and 61.9% in CEX group. Nor on day 14, was there any significant difference in the effective rate among the 3 groups: 70.8% in S6472 group, 63.4% in CCL group and 61.8% in CEX group.
3. Stratification analyses (by UTI group, infection site, in-or out-patient, time of starting treatment, pretreatment severity of pyuria, total number of bacteria before treatment) revealed no significant difference among the 3 groups.
4. Therapeutic effect evaluated by physicians in charge was not significantly different among the 3 groups on day 5 or day 14.
5. In terms of overall therapeutic effect, all 3 products were very effective in patients infected with sensitive bacteria: On day 5, 85.4% in S6472 group, 84.4% in CCL group, and 83.7% in CEX group. There was no significant difference among the 3 groups on either day.
6. The incidence of side effects was not significantly different among the 3 groups: 4 out of 129 patients treated with S6472 (3.1%), 2 of 131 treated with CCL (1.5%) and 2 of 128 with CEX (1.6%). Clinical laboratory tests revealed 4 abnormal findings in 4 patients treated with S6472, 6 findings in 4 treated with CCL, and 4 findings in 2 treated with CEX, showing no significant difference in incidence among the 3 groups. Both side effects and abnormal clinical laboratory findings were mild and reversible.
7. Physicians in charge judged the usefulness of the 3 drugs on days 5 and 14, taking efficacy and safety into consideration. Significant difference was not observed.
8. The presence of recurrence was examined 7 days after drug withdrawal in patients regarded as remarkable responders to 14-day treatment by overall therapeutic effect evaluation. Recurrence rate was 24% in S6472 group, 23% in CCL group, and 23% in CEX group, not significantly differing from one another.
In conclusion, the standard formulation of CCL and S6472 can be equally effective, safe, and useful to CEX in patients with noncatheterized complicated urinary tract infection.

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Ceftriaxone (CTRX), a newly developed antibiotic agent, was administered at 1,000mg intravenously twice a day for 5 days to 7 healthy volunteers aged 21 to 26, weighing 61 to 79kg (mean: 67.7kg). The fecal bacterial flora was examined and the fecal level of CTRX was determined before, on 3 and 5 days after starting the administration, and on 3, 5 and 10 days after terminating the administration. At the same time, various bacteria isolated from the collected fecal specimens were studied for the sensitivity to CTRX, CEZ, CMZ and CTX. Adverse reactions and influence on various clinical laboratory parameters of CTRX were also examined. The results were as follows.
1. Fecal bacterial flora:
Enterobacteriaceae was at the level of 10⁵ to 10⁸ cells/g (mean: 10⁷ cells/g) before starting the administration. The bacteria were detected from none of the 7 subjects on 5 days after starting the administration and on 3 days after terminating the administration. On 10 days after terminating the administration, the bacteria were detected in 6 out of the 7 subjects at the level of 10³ to 10⁷ cells/g (mean: 10⁷ cells/g). The level was the same as before starting the administration as a whole, but it had not been recovered to the initial level in any individual subject. With regard to other Gram-negative bacilli, P. aeruginosa which was isolated from none of the 7 subjects before starting the administration was detected at the level of 102 to 106 cells/g in 1 or 2 subjects on 3 days after starting, and on 3, 5 and 10 days after terminating the administration.
Concerning Gram-positive bacteria, Staphylococcus sp. was isolated at the level of 10³ to 10⁴ cells/g in 3 subjects before starting the administration. The detection rate was decreased after starting the administration; it was detected in 2 and 1 subjects on 3 and 5 days after starting the administration, respectively, and in 1 subject on 3 days after terminating the administration. Then the detection rate was gradually increased; i. e., in 3 and 5 subjects on 5 and 10 days after terminating the administration, respectively. The level became gradually higher from on 5 days after terminating the administration than before starting the administration. Enterococcus sp. was isolated at the level of 10⁵ to 10⁸ cells/g (mean: 10⁷ cells, g) in all of the 7 subjects before starting the administration. It was not detected in 1 and 4 subjects on 3 and 5 days, respectively, after starting the administration. On 3, 5 and 10 days after terminating the administration, the bacteria were isolated at the level of 10⁶ to 10⁹ cells/g (mean: 10⁸ cells/g) in all of the 7 subjects. The level was higher in 5, 5 and 4 subjects, respectively, than before starting the administration and there was no marked difference in 2 subjects.
There was no tendency observed in changes in the level of Micrococcus sp. Candida sp. was isolated at the level of 10² to 10⁴ cells/g (mean: 10⁴ cells/g) in 5 subjects before starting the administration. The bacteria were isolated in 6 cases on 3 days after starting the administration. The level was over 100-times as high as the level before starting the administration in 3 cases and there was no remarkable difference on 1 case. The similar tendency was observed also on 5 days after starting the administration and on 3 days after terminating the administration. On 5 days after terminating the administration, the bacteria were detected at the level of 10² to 10⁶ cells/g (mean: 10⁵ cells/g) in all of the 4 subjects; the level of bacteria was 10,000-times as high in 1 case, and 100-times as low in 1 case, as the level before starting the administration. There was no remarkable difference in 3 cases.

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The in vitro susceptibilities of various causative organisms racently isolated from patients with primary respiratory tract infections to BRL 25000 (a formulation of amoxicillin, 2 parts, and potassium clavulanate, 1 part), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined. β-Lactamase producing strains were detected by nitrocefin chromogenic method and PCG acidometric method.
1. The frequency of isolation of p-lactamase production in strains of S. aureus, H. influenzae, B. catarrhalis and K. pneumoniae was 92%, 18%, 36% and 98%, respectively.
2. Against S. aureus strains with MIC values to AMPC of ≤100μg/ml and CEX of ≤25μg/ml BRL 25000 showed MIC values in the range 0.39-6.25μg/ml with inocula of 10⁶ CFU/ml, while BRL 25000 required 12.5-100μg/ml of concentrations for inhibition of the strains with MIC values to AMPC of 100μg/ml and CEX of 25μg/ml.
3. Against S. pyogenes and S. pneumoniae BRL 25000 showed MIC values in the range < 0.024-0.10μg/ml with inocula of 10⁶ CFU/ml, which is much more active than CCL, CEX, CDX and CXD and slight less active than AMPC.
4. Against H. influenzae and B. catarrhalis BRL 25000 showed MIC values in the range 0.20-6.25μg/ml with inocula of 10⁶ CFU/ml, which showed most potent activity among the agents tested.
5. The activity of BRL 25000 against K. pneumoniae was approximately equal to that of CCL and superior to that of AMPC, CEX, CDX and CXD.

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Cefmenoxime (CMX) was administered to protect against postoperative infections in 52 cases of cesarean section and 50 cases of total abdominal hysterectomy. These two represent common operations in the gynecological field. Group I was given the agent at a total dose of 14g (postoperatively 4, 4, 2, 2 and 2g), group II at a total dose of 10g (postoperatively 2, 2, 2, 2 and 2g) and group III at a total dose of 10g (2g during operation and postoperatively 2, 2, 2 and 2g).
1. When comparing the fever index between the groups, group III showed the lowest level regardless of the type of operation.
2. When comparing clinical test values between the groups, low values of white blood cell count (P< 0.05, P< 0.01) and erythrocyte sedimentation rate (P < 0.05) were observed in group III with cesarean section, and significant decreases in white blood cell count (P < 0.05) and CRP (P< 0.01, P< 0.001) were observed in group III with total abdominal hysterectomy.
The above results indicate that the administration of CMX during operation was the most effective method of administration for protection against postoperative infections in terms of changes in fever index and clinical test values.

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Variations in the actual doses with vials and ampules due to causes of dosage forms and human operations have been discussed. The differences between the labeled doses and actually administered doses with ampules and vials have been studied. The comparison of resulting blood levels revealed peaks of 4.88±1.08 μg/ml and 3.85±0.71 μg/ml actually determined with ampule preparations and vial preparations, respectively, showing some appreciable differences. These values were analyzed with compartment models. C_max values were 5.13 μg/ml and 3.94 μg/ml, respectively, showing significant differences (P<0.05) between the ampule and vial preparations. However, AUC and Tmax values were equal to each other, so that it was assumed that there would be no problem about the similarity of the 2 types of dosage forms.
As to the differences due to human operations, the nurse A did normally collect only 83.0% (75.2 mg) volume of the labeled doses of vials, and, even when she did it with greater care, she collected still 90.0% (81.5 mg) of the labeled doses. On the other hand, the nurse B normally collected 89.8% (81.4 mg) of the labeled dose of vials, and when she used greater care, she collected 92.4% (83.7 mg) of the labeled doses. In the group of ampule preparations, the nurses A and B collected 93.1% (94.8 mg) and 98.1% (99.9 mg), respectively. It was beyond the amount expected in advance for the actually collected dose from ampules. The differences in the collected doses between ampules and vials were within the expected range because ampule preparations usually contain approximate 10% overage, but as to the differences added to this difference due to the human operations, the nearly twice as much speed for collecting the filled preparation by the nurse A would not have been denied for the smaller doses collected on the basis of the abovementioned results. It was noted therefore that care should be taken in collecting the filled doses from containers into injection syringes.

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Latamoxef (LMOX)(50 mg/kg) was administrated intravenously to burned patients over 1 hour period. Burn blister fluid and serum were taken during 8 hours after injection, and concentrations of LMOX in burn blister fluid and serum were determined by bioassay using E. coli as a test organism.
The serum concentrations of LMOX were 170.8 ±30.6 μg/ml at 30 minutes, 227.0 ±19.8 μg/ml at 1 hour, 90.3±21.4 μg/ml at 2 hours, 52.9±14.6 μg/ml at 3 hours, 38.7±13.3 μg/ml at 4 hours, 25.1 ± 8.1 μg/ml at 5 hours, 20.5±8.1 μg/ml at 6 hours, 13.0±5.5 μg/ml (mean±S.D., n=5) at 8 hours after the injection. The LMOX concentrations in burn blister fluid were 36.9±32.8 μg/ml at 30 minutes, 77.5 ±42.2 μg/ml at 1 hour, 85.4±19.6 μg/ml at 2 hours, 76.4±18.5 μg/ml at 3 hours, 63.5±17.8 μg/ml at 4 hours, 54.9±17.1 μg/ml at 5 hours, 34.8 ±10.3 μg/ml at 6 hours, 25.2±4.8 μg/ml (mean±S.D., n=7) at 8 hours after the injection.
The data obtained were analysed pharmacokinetically. The serum levels were analysed by two-compartment model, and the LMOX levels in burn blister fluid were analysed by the model, in which blister was considered as a small part of the peripheral compartment. In results, T_max and C_max of LMOX levels in burn blister fluid were calculated as 1.81 hours and 90.6 μg/ml, respectively. The transfer rate constant of LMOX from serum to burn blister fluid shown as a hyblid parameter-Kis₁₈ (transfer rate constant from serum to burn blister fluid) divided with V₃ (volume of burn blister fluid)-was 12.25 hr^-1·kg/L. The transfer rate constant of LMOX from burn blister fluid to serum K₃₁ was 0.61 hr^-1.

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Aztreonam (AZT), a new synthetic monocyclic β-lactam antibiotic, which is resistant to β-lactamase and has a strong and specific activity against aerobic Gram-negative bacteria including Pseudomonas aeruginosa.
The patients of 13 cases with localized peritonitis due to acute appendicitis, 3 cases with panperitonitis (1 case with perforative appendicitis, 1 with acute cholecystitis and 1 with pancreatic necrosis) and 4 cases with skin and soft tissue infection (anal fistula and abdominal abscess etc.) were treated by AZT. AZT was administered in a dose of 1 g twice a day by intravenous drip infusion using 100 ml-volume bottle preparation with saline for 4 to 10 days.
Clinical efficacy was rated excellent in 2 cases, good in 16 cases, fair in 1 case and poor in 1 case (efficacy rate 90.0%). Adverse effects were small skin rash in 1 case, and increased GOT and GPT in 1 case. No adverse effect was recognized in other cases.
Therefore, AZT appears to be very useful drug when used for chemotherapy of infectious diseases in surgery.

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Ceftizoxime suppository (CZX-S) was evaluated for its safety, clinical efficacy and pharmacokinetics in pediatric patients. The C_max, 4.8 to 9.5 μg/ml, was obtained 15 to 30 minutes after administration of CZX-S, and the serum half-life was 0.93 hour. Cross-over comparison with intramuscular CZX in a child showed approximately one-third bioavailability of the suppository against intramuscular injection.
CZX-S was effective in all the 26 bacterial infections including acute pharyngitis, pneumonia, soft tissue infection, and urinary tract infections. The causative organisms were eradicated in 95%. Mild diarrhea (17%) was the only side effect observed in the study. The data suggest that CZX-S is an excellent alternative to oral and injectable antibiotics for the treatment of mild to moderate bacterial infections due to the susceptible organisms.

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Fundamental and clinical studies were carried out on ceftizoxime suppository (CZX-S), and the following results were obtained in pediatrics.
In 4 patients of the CZX-S 125 mg-administered group (9.4-9.9 mg/kg), the serum concentration of CZX reached a peak of 5.55 μg/ml on the average, 30 minutes after dosing, i.e. at the time of initial blood collection, and decreased gradually to 0.20 μg/ml 6 hours after dosing. The half-life was 1.09 hours. In 5 patients of the CZX-S 250 mg-administered group (8.4-18.1 mg/kg), the serum concentration of CZX peaked at 7.07 μg/ml on the average and then gradually declined to 0.16 μg/ml 6 hours after dosing. The half-life was 1.00 hour. The urinary recovery rate varied as widely as 6.5-38.0% in all the patients of both groups.
CZX-S was given to total 19 patients; 8 patients with urinary tract infection (UTI), 3 with pharyngitis or tonsillitis, 4 with bronchitis, 2 with pneumonia, 1 with otitis media and 1 with staphylococcal scalding skin syndrome. The overall effect of CZX-S in 15 patients was “effective” or better response, with an effectiveness rate of 83.3%, except one who discontinued the drug because of side effects.
CZX-S was given to most of the patients weighing 15 kg or higher in a dose of 250 mg 3-4 times a day and frequently to patients weighing less than 15 kg in a dose of 125 mg 3-4 times a day.
As to side effects, slight diarrhea was encountered in 1 patient. Laboratory examinations disclosed an increase in GOT in 1 patient, which returned to normal after continual insertion of the suppository.

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This paper deals with fundamental and clinical results, in the field of pediatrics, of the newly developed rectal suppository (CZX-S) of a cephem antibiotic ceftizoxime (CZX).
1. CZX-S was well absorbed in children. The mean peak serum concentrations of CZX in the 125 mg-administered group (average: 9.9 mg/kg) and the 250 mg-administered group (average: 13.4 mg/kg) were 5.10-7.71 μg/ml at 15-30 minutes after dosing. Serum concentrations of CZX were measurable level in almost all the children at 6 hours after administration with the half-lives were 1.34-1.55 hours. The 6-hour urinary excretion rate accounted for 16.5-22.0%.
2. CZX-S was administered to 30 children with acute upper or lower respiratory tract infections about 20-60 mg/kg/day in 3-4 divided portions.
CZX-S provided favorable therapeutic-effect in most of the children 3-5 days after administration.The effectiveness rate was 93%.
3. The causative organisms of H. influenzae (3 cases) and S. aureus (4 cases) isolated clinically from pharyngeal mucous and sputum were eradicated after administration of CZX-S.
4. Anal pain and diarrhea experienced in 5 of the 30 children and CZX-S was withdrawn in 4 (of the 5) children, but exhibited satisfactory therapeutic-effect in 2 of the 4 cases up to withdrawal of the drug.
5. An increase in GOT and GPT was observed in 3 cases. The values returned to the normal range in 1 case after the treatment with CZX-S. The test was not reexamined in the other 2 cases.
6. The present clinical result suggests the usefulness of CZX-S substituted for oral and injectable forms in the treatment of various pediatric infections caused by organisms sensitive to CZX.

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The fundamental and clinical studies of ceftizoxime suppository (CZX-S) in the field of pediatrics were made, with the following results.
1. The serum concentration of CZX in the CZX-S 250 mg-administered group peaked 6.00-22.5 μg/ml during the period of 15 minutes to 1-hour after dosing, and gradually declined thereafter.
The half-life was 1.37-3.81 hours. In the CZX-S 125 mg-administered group, the serum concentration peaked 2.25-21.0 μg/ml at 15-30 minutes after dosing and decreased with time. The half-life was 0.95-1.84 hours.
2. The 6-hour urinary recovery rate of CZX in the CZX-S 250 mg group was 22.0-47.5%. The 6-hour urinary recovery rate in the CZX-S 125 mg group was 17.2-25.3%.
3. CZX-S was given 12-73 mg/kg/day (devided into 1-3 times) to 7 children with respiratory tract infection etc. who were considered to respond well to the drug.
The clinical effectiveness rate was 100% inclusive of “excellent” and “good”.
4. The side effect of pain on insertion was encountered in 1 child.

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Ceftizoxime suppository (CZX-S) was given to 19 children with infections, including upper and lower respiratory tract infections, urinary tract infections and otitis media at dose level of 18-83 mg/kg/day divided into 2-3 times.
Clinical response was excellent in 12 patients, good in 6 patients and poor in 1 patient.
Bacteriological response was eradicated in 11 strains, decreased in 3 strains and unchanged in 4 strains.
No severe side effects were observed with this drug.
These results obtained suggest that CZX-S should be a useful antibiotic in treatment of infections in pediatric field.

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Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained;
1. Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3mg/kg in 5 cases were 3.26-23.3μg/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively.
2. Clinical effects were excellent in 3 and good in 2 cases.
3. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed.
4. The patients' tolerability against rectal suppository was good.
From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.

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A fundamental and clinical study of ceftizoxime (CZX) suppositories was performed in pre-school and school-age children.
1. The average time courses of CZX serum and urinary concentrations after administration of CZX suppository 250mg (i.e. per kg body weight doses of 8.3-10.9 mg) to 4 school-age children were as follows.
Serum concentrations: 6.1μg/ml at 15 minutes, 6.3μg/ml at 30 minutes, 3.8μg/ml at 1 hour, 1.7μg/ml at 2 hours, 0.5μg/ml at 4 hours and 0.2μg/ml at 6 hours with a biological half-life of 1.43 hours.
Urinary concentrations: 885μg/ml for 0-2 hours, 209μg/ml for 2-4 hours and 112μg/ml for 4-6 hours with an average 6-hour urinary recovery rate of 25.6%.
2. The clinical and biological effectiveness and adverse reactions were studied in 11 infants and school-age children afflicted with various infections (acute purulent tonsillitis, 1; acute bronchitis, 3; acute pneumonia, 4; and UTI, 3). The clinical responsiveness was “excellent” in 8, “good” in 2, and “failure” was recorded in 1, with an overall efficacy of 90.9% inclusive of “excellent” and “good”.
The microbiological effectiveness of CZX suppositories on presumed pathogenic organisms comprising 4 strains of H. influenzae, 1 strain of H. parainfluenzae, and 3 strains of E. coli was satisfactory, as evidenced by the substantially high eradication rate of 87.5%. The only organism that survived CZX suppository treatment was 1 strain of H. influenzae which however was greatly decreased.
The only side effect was diarrhea in 1 patient, which however did not necessitate withdrawal of the drug. The only laboratory test abnormality was GOT and GPT elevation in 1 patient which was normalized within 8 days.
In conclusion, CZX suppositories were found to be efficacious and safe for treatment of bacterial infections in children.

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Pharmacokinetic and clinical studies of ceftizoxime suppository (CZX-S) were performed in 10 children with the following results.
1. CZX-S attained a peak serum concentration of 6.85μg/ml 30 minutes after dosing with the drug 5.6mg/kg (one suppository of CZX-S contains 250mg of CZX in potency). The mean 6-hour urinary excretion rate in 4 children was 18.9%.
2. The subjects consisted of 8 patients comprising 1 with pharyngitis, 3 with tonsillitis, 1 with gingivitis and 3 with urinary tract infection. The overall effect of CZX-S was “excellent” in 5 patients and “good” in 3, with an effectiveness rate of 100%.
3. No side effects ascribable to CZX-S were encountered in any of the patients.
4. A few patients complained of discomfort after the first or second insertion of the drug. However, the discharge of the suppository was as infrequent as 1.5% of the total 133 insertions. CZX-S is therefore well tolerated for clinical use in children.
5. It is concluded that the unique suppository formulation of CZX-S is useful in the treatment of infections in children with heavy psychophysiologic disorders and in children who cannot take oral drugs because of severe vomiting.

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A bacteriological and clinical study of ceftizoxime suppositories (CZX-S) let to the following results.
1. The CZX serum concentration 10 minutes after insertion of one 250mg suppository (i.e. 5.7-15.2mg CZX per kg body weight) ranged from 1.64 to 6.53μg/ml (average: 4.41μg/ml). In one child the concentration 7 minutes after insertion was 4.13μg/ml.
2. Therapeutic responsiveness was recorded as “effective” in 8 (88.9%) of the 9 children who were broken down into 6 with tonsillitis, 1 with pharyngitis, and 2 with UTI. Bacteriological studies conducted in 5 children have confirmed eradication in 4 children, one of whom showing appearance of another strain.
3. The rate of discharge of the suppository within 10 minutes after insertion was 20.4%.
Reddening and erosion of the anus were observed in 1 child.

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Ceftizoxime suppositories (CZX-S), containing 250mg or 125mg of CZX, were given to 6 children, 4 with acute bronchopneumonia and 2 with acute pharyngobronchitis, who were not suited to treatment with injectable or oral form of the drug.
The clinical response was “good” in all the children and the causative organisms were eradicated in 2 children (H. influenzae or S. aureus).
Adverse reactions consisted of 1 case each of diarrhea and transiently increased GPT.
In conclusion, CZX-S proved to be highly effective in the treatment of bacterial infections in children.

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A clinical trial of ceftizoxime suppositories (CZX-S) was conducted in children whose chemotherapy was considered to be best performed in this dosage form at the physician's discretion.
The subjects were 5 children with infection, consisting of 2 with pneumonia, 1 with tonsillitis, and 2 with UTI. The results were as follows.
1. The clinical response to CZX-S was “markedly effective” in 3 and “effective” in 2, with the 100% effectiveness rate.
2. Neither adverse drug reactions nor abnormal laboratory tests were detected. No unwanted expulsion of the suppository occurred.
3. The serum concentration of CZX 30 minutes after the first insertion ranged from 8.38 to 11.4μg/ml, and the urinary concentration of CZX in the 6-hour urine collections, from 23.6 to 290μg/ml.

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A clinical trial of ceftizoxime suppositories (CZX-S) was performed to evaluate the therapeutic effectiveness in children with bacterial infection. The subjects were 10 children comprising 4 with pneumonia, 3 with lacunar tonsillitis, 2 with pharyngitis, and 1 with UTI. They were given 1 suppository containing either 125mg or 250mg of CZX 2 to 4 times a day. The daily per kg body weight dose ranged from 17.1 to 60.0mg.
The result was “markedly effective” in 3, “effective” in 6, and “failure” was recorded in 1. Bacteriologically, successful eradication of causative organisms was confirmed in all the 4 children who underwent the test.
No clinical side effects were observed. The only laboratory test abnormality recorded in a single patient was eosinophilia, which was not definitely ascribable to CZX-S.
In conclusion, CZX-S have proved to be a clinically safe and effective antibiotic preparation in infantile infection, even in children whose treatment with conventional antibiotics is associated with difficulties.

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The therapeutic effect of ceftizoxime suppositories (CZX-S) was studied in 8 physically handicapped patients, comprising 6 with pharyngitis, 1 with pneumonia, and 1 with urinary tract infection. The clinical effect was “excellent” in 7 and “good” in 1.
Neither adverse reactions nor abnormal laboratory test findings attributable to CZX-S were detected.
CZX-S proved to be useful in physically handicapped children, especially in those not suited to treatment with oral or intravenous preparations.

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Ceftizoxime suppositories (CZX-S) were given to 5 children comprising 3 with acute bronchitis, 1 with acute bronchitis complicated by enteritis, and 1 with acute urinary tract infection, in doses of 12.5-17.4mg/kg with 1 suppository containing 125mg or 250mg (potency) given 3 times a day.
The clinical response was “markedly effective” in 2 and “effective” in 3. Microbiologically CZX-S caused a eradication of 1 strain each of S. aureus and E. coli and caused a decrease of organisms in 1 strain of S. aureus.
There were no adverse reactions or abnormal laboratory test findings attributable to CZX-S.
In conclusion, CZX-S proved to be a clinically useful antibiotic preparation for the treatment of infection in children not suited to treatment with oral or intravenous preparations.

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1. The peak levels of serum ceftizoxime (CZX) after a single rectal administration of CZX-S at doses of 125 and 250mg in 157 pediatric patients were occurred at 21-25 minutes in pediatric patients aged less than 1 year and over than 7 years, at 16-20 minutes in 1-3 years patients, at more than 26 minutes in 4-6 years patients. They were 9.45, 9.58, 11.71, 12.43mcg/ml, respectively.
2. The mean highest levels of serum CZX were 8.56, 10.66, 12.50mcg/ml after the administration of CZX-S as less than 10.0, 10.1-15.0, 15.1-20.0mg/kg dose respectively, all of which were occured at 21-25 minutes. A close dose response was observed.
3. The pain of insertion was not observed in any cases. The discharge of melted suppository or defecation after administration was observed in 15.2% of total 184 cases, which was noticed more frequently in the lower aged children. There was no influence by dose.
4. Clinical effects of CZX-S were studied in 72 pediatric patients with various infections. CZX-S was administered rectally at the mean daily dose of 41.0mg/kg devided into 3 or 4 times for 6 days. Clinical responses were excellent in 46 cases, good in 24 cases, fair in 2 cases. The efficacy rate was 97.2%.
Regarding side effects, the pain of insertion was noted in 2 cases (2.8%), diarrhea in 6 cases (8.3%), the elevation of eosinophil in 1 case (1.7%).
5. Bacteriologically, 23 strains (92.0%) out of 25 strains isolated from the patients were eradicated.

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Ceftriaxone (CTRX), a newly developed antibiotic agent, was administered at 1,000mg intravenously twice a day for 5 days to 7 healthy volunteers aged 21 to 26, weighing 61 to 79kg (mean: 67.7kg). The fecal bacterial flora was examined and the fecal level of CTRX was determined before, on 3 and 5 days after starting the administration, and on 3, 5 and 10 days after terminating the administration. At the same time, various bacteria isolated from the collected fecal specimens were studied for the sensitivity to CTRX, CEZ, CMZ and CTX. Adverse reactions and influence on various clinical laboratory parameters of CTRX were also examined. The results were as follows.
1. Fecal bacterial flora:
Enterobacteriaceae was at the level of 10⁵ to 10⁸ cells/g (mean: 10⁷ cells/g) before starting the administration. The bacteria were detected from none of the 7 subjects on 5 days after starting the administration and on 3 days after terminating the administration. On 10 days after terminating the administration, the bacteria were detected in 6 out of the 7 subjects at the level of 10³ to 10⁷ cells/g (mean: 10⁷ cells/g). The level was the same as before starting the administration as a whole, but it had not been recovered to the initial level in any individual subject. With regard to other Gram-negative bacilli, P. aeruginosa which was isolated from none of the 7 subjects before starting the administration was detected at the level of 102 to 106 cells/g in 1 or 2 subjects on 3 days after starting, and on 3, 5 and 10 days after terminating the administration.
Concerning Gram-positive bacteria, Staphylococcus sp. was isolated at the level of 10³ to 10⁴ cells/g in 3 subjects before starting the administration. The detection rate was decreased after starting the administration; it was detected in 2 and 1 subjects on 3 and 5 days after starting the administration, respectively, and in 1 subject on 3 days after terminating the administration. Then the detection rate was gradually increased; i. e., in 3 and 5 subjects on 5 and 10 days after terminating the administration, respectively. The level became gradually higher from on 5 days after terminating the administration than before starting the administration. Enterococcus sp. was isolated at the level of 10⁵ to 10⁸ cells/g (mean: 10⁷ cells, g) in all of the 7 subjects before starting the administration. It was not detected in 1 and 4 subjects on 3 and 5 days, respectively, after starting the administration. On 3, 5 and 10 days after terminating the administration, the bacteria were isolated at the level of 10⁶ to 10⁹ cells/g (mean: 10⁸ cells/g) in all of the 7 subjects. The level was higher in 5, 5 and 4 subjects, respectively, than before starting the administration and there was no marked difference in 2 subjects.
There was no tendency observed in changes in the level of Micrococcus sp. Candida sp. was isolated at the level of 10² to 10⁴ cells/g (mean: 10⁴ cells/g) in 5 subjects before starting the administration. The bacteria were isolated in 6 cases on 3 days after starting the administration. The level was over 100-times as high as the level before starting the administration in 3 cases and there was no remarkable difference on 1 case. The similar tendency was observed also on 5 days after starting the administration and on 3 days after terminating the administration. On 5 days after terminating the administration, the bacteria were detected at the level of 10² to 10⁶ cells/g (mean: 10⁵ cells/g) in all of the 4 subjects; the level of bacteria was 10,000-times as high in 1 case, and 100-times as low in 1 case, as the level before starting the administration. There was no remarkable difference in 3 cases.

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The clinical study of CZX-S in the field of pediatrics was performed and the following results were obtained.
1. The overall effect of CZX-S was “markedly improved” in 2 and “moderately improved” in 4 of the 6 patients with bacterial infection.
2. Bacteriological findings show that causative organisms were eradicated in all the 5 patients observed. The breakdown of the organisms was S. aureus, S. pyogenes, S. pneumoniae, H. influenzae and E. coli.
3. The serum concentration of CZX was 3.3-15.4μg/ml (mean±S. E. 8.9±2.0μg/ml) at 15-37 minutes after initial rectal administration with CZX-S 125 (dose: 7.7-11.9mg/kg). While, in the CZX-S 250 administered group, the serum concentration was 3.1μg/ml and 10.5μg/ml at 20 minutes after initial rectal administration (dose: 5.6mg/kg and 14.7mg/kg).
4. The urinary recovery rate up to 6 hours after initial rectal administration was 68.6% in 1 patient given CZX-S 125 and 28.3-52.5% (mean±S. E. 38.7±7.2%) in 3 patients given CZX-S 250.
5. Side effects and abnormalities in laboratory test values were not observed in any cases

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Ceftizoxime suppository (CZX-S) was given to 6 patients, with the following results.
1. The peak serum concentration of CZX was 1.8-7.5μg/ml at 30 minutes after dosing of CZX-S with 9.6-16.7mg/kg. The antibacterial activity of CZX revealed that the drug can be expected to be effective sufficiently.
2. The overall effect of CZX-S was “markedly improved” in 1 and “moderately improved” in 3 of the 4 patients with pneumonia and “markedly improved” in 1 and “slightly improved” in 1 of the 2 with UTI.
3. CZX-S caused a slight increase in frequency of defecation in 2 of the 6 patients. There were no abnormal findings of symptoms or laboratory test values which were ascribable to side effects.

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The newly developed ceftizoxime rectal suppository (CZX-S) contains 125mg or 250mg ceftizoxime (CZX) in potency. From the laboratory and clinical studies on CZX-S, the following results were obtained.
1. Concentration of CZX in serum and palatine tonsil when 250mg of CZX-S was rectally administered reached the peak level rapidly. The serum levels were 9.39μg/ml in 30 minutes, 6.00μg/ml in 45 minutes, 4.55μg/ml in 60 minutes, 3.87μg/ml in 90 minutes and 2.65μg/ml in 120 minutes. The palatine tonsil levels were 2.73μg/g in 30 minutes, 1.83μg/g in 45 minutes, 1.54μg/g in 60 minutes, 0.99μg/g in 90 minutes and 0.74μg/g in 120 minutes. About 30% of serum concentrations were distributed into palatine tonsil.
2. CZX-S was administered at a daily dose of 375mg or 750mg divided 3 times for 4-9 days in 19 cases of acute suppurative otitis media of children. The overall clinical effect was excellent in 7 cases, good in 7 cases, fair in 2 cases and poor in 3 cases. The effectiveness rate was 73.7%.
3. No side effects were observed in any cases.

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