[in Japanese]

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The incidence of preoperative and postoperative infections among 46 patients who underwent transurethral prostatectomy (TUR-P) was studied. Perioperative antibacterial schedule was as follows: one gram of cefotaxime (CTX) was intravenously injected just before the beginning of TUR-P. One gram of the antibiotic was intravenously infused once more on the day after TUR-P, twice on the next day, and once during each of the succeeding 2 days. Thirteen cases out of 46 (28.3%) had significant preoperative bacteriuria (≥1×10⁴/ml), but the postoperative eradication of the bacteria was observed for 10 of the 13 cases (76.9%). Among the 33 cases that did not have significant preoperative bacteriuria, only one case developed significant bacteriuria. In this case, a non-significant bacterial contamination of the urine had been observed before TUR-P.

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Cefminox (CMNX), a new cephamycin, was administered by one shot intravenous injection twice daily with a dose of 1,000 mg each time for 5 days to seven healthy male volunteers whose ages ranged from 21 to 28 years (mean: 25 years) and body weights were from 60 to 92 kg (mean: 72 kg). The effect of the drug on fecal bacterial flora was investigated and the concentrations of the drug in feces were measured on 5th day before the treatment, on 0, 3rd, and 5th day (the final day of the treatment) during the treatment, and on 3rd, 5th, and 10th day after the treatment. Antibiotic susceptibility tests of CMNX, cefmetazole (CMZ) and cefotaxime (CTX) against several strains of organisms isolated from feces of the seven volunteers were performed. Clinical adverse reactions and effect on laboratory examinations were also investigated. The results of the study are described as follows.
1. Among Enterobacteriaceae, populations of E. colt, Klebsiella sp. and Citrobacter sp. temporarily disappeared during the treatment of CMNX. After 5-day-treatment, that of Citrobacter sp. transiently increased and the isolation of Enterobacter sp. increased during treatment and up to 5 days after treatment, while those of Proteus sp., H. alvei, or Serratia sp. did not show a definite change. The mean Enterobacteriaceae population in general was 10⁸ to 10⁹ cells/g feces, showing almost no variation, on all examination days except 5th day during treatment when these organisms were not isolated from only one subject. No remarkable change was not found in populations of other isolated organisms including Gram-negative bacilli; Aeromonas sp., Pseudomonas sp. and Acinetobacter sp., and Gram-positive bacteria; Staphylococcussp., Enterococcus sp., Micrococcus sp. and Candida sp. Among anaerobes, the mean ponulation of Baeteroides sp. was 10¹⁰ to 10¹¹ cells/g feces, showing almost no variation, and C. difficile was not isolated from any subject, however the toxin was detected in samples from 5 of 7 subjects; one subiect showed always positive for toxin on all examination days; 1 on 5th day during treatment to 10th day after treatment; 2 on 5th and 10th day after treatment, and 1 only on 10th day after treatment. Total mean anaerobe population was 10¹¹ cells/g feces on any examination day, showing almost no variation.
2. The fecal concentrations of CMNX were below the detectable limit in all the subjects throughout the study.
3. Antibiotic susceptibilities of CMNX, CMZ, and CTX were tested against several organisms isolated from the feces of the same 7 subjects. The antibacterial activity of CMNX was lower than those of the other two antibiotics with both inoculum sizes against S. aureus, coagulase-negative Staphylococci, E. faecalis, and E. faecium among Gram-positive cocci, but was similar to those of other antibiotics with both inoculum sizes (10⁸ and 10⁶ cells/ml) against Micrococcus sp. The MIC was determined against four Gram-positive cocci excluding Micrococcus sp. isolated from feces before, during, and after the treatment. The MICs of 3 antibiotics against S. aureus stayed constant before the treatment, but varied with a broader range after the treatment than before and during the treatment with both inoculum sizes. Those of CMNX and CMZ against Coagulase-negative Staphylococci appeared to be lower during the treatment than before or after the treatment, but the MIC of CTX did not change with both inoculum sizes. Those of CMNX and CMZ against E. faecalis staved constant but that of CTX appeared to be higher during the treatment than before or after the treatment with both inoculum sizes. As for E. faecium, there were no changes in the MICs of the 3 antibiotics with both inoculum sizes.

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A new oral cephem antibiotic, T-2588, the pivaloyloxymethyl ester of (+)-(6R, 7R)-7-[(Z)-2-(2-amino4-thiazolyl)-2-methoxyiminoacetamido]-3-[(5-methyl-2H-tetrazol-2-yl) methyl]-8-oxo-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid (T-2525), is mainly absorbed from the intestinal tract and biotransformed to T-2525 thereafter. General pharmacological activities of T-2588 were studied and following results were obtained.
On the central nervous system, T-2588 did not show any effects at oral doses of 500-2,000 mg/kg and T-2525 produced only a slight elevation of body temperature in rabbits without any other effects at an intravenous dose of 500 mg/kg.
On the respiratory and cardiovascular systems, T-2525 caused a slight hypotension and increased both respiratory rate and femoral blood flow, but no changes were observed in heart rate and electrocardiogram in dogs at an intravenous dose of 500 mg/kg. The T-2525 exerted no significant influence on blood pressure response to isoproterenol, acetylcholine or histamine, but showed a slight tendency to decrease pressor response to adrenaline in dogs at intravenous doses of 100-500 mg/kg.
For the renal function in rats, T-2588 had no effects on urine volume, electrolytes and PSP excretion at oral doses of 500-2,000 mg/kg. Intravenous administration of T-2525 caused an increase of sodium excretion at 500 mg/kg and dose-dependent increases of PSP excretion at 20-500 mg/kg.
Hematological studies revealed that both T-2588 at oral doses of 500-2,000 mg/kg and T-2525 at intravenous doses of 100-500 mg/kg had no effects on bleeding time in mice, blood coagulation and platelet aggregation in rats.
The T-2588 exerted no effect on the gastrointestinal system in rats or mice and had no antiinflammatory activity in rats at oral doses of 500-2,000 mg/kg. The T-2525 scarcely affected the motilities of isolated smooth muscle preparations in experimental animals including stomach, ileum, colon, uterus, was deferens and trachea at a concentration as high as 10^-3 g/ml. The T-2525 increased bile secretion in rats at intravenous doses of 100-500 mg/kg.
The T-2525 slightly decreased the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at an intravenous dose of 500 mg/kg.
These results indicate that T-2588 is a pharmacologically inactive antibiotic.

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Absorption, distribution and excretion of T-2588 were studied in rats and mice using (aminothiazole-2-¹⁴C) T-2588 and (pivaloyloxymethyl-¹⁴C) T-2588. Results are summarized below.
1. The binding rate of ¹⁴C-T-2525, an activated form of ¹⁴C-T-2588 in vivo, to serum protein was 90-100% in rats and mice after an oral administration of (aminothiazole-2-¹⁴C) T-2588.
2. Blood levels of radioactivity reached to the highest concentration at 1 hour after an oral administration of (aminothiazole-2-¹⁴C) T-2588 to rats, and then gradually diminished.
3. After an oral administration of (aminothiazole-2-¹⁴C) T-2588 to rats and mice, the highest radioactivity distribution was found in kidney among all the organs except stomach, intestine and bladder. Radioactivity was widely distributed into other organs such as adrenal, lung, liver, heart and pancreas. But little radioactivity was found in the brain. In new born rats, tissue levels of radioactivity were lower and diminished slower than those of adult rats.
4. After an oral administration of (aminothiazole-2-¹⁴C) T-2588 to rats and mice, urinary excretion of radioactivity was about 26% and 35% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 76% and 63% of the dosed radioactivity in rats and mice, respectively.
5. Urinary and fecal excretion patterns of radioactivity after multiple oral administration of (aminothiazole-2-₁₄C) T-2588 for 7 days to mice were similar to those after a single administration. This result suggests that T-2588 did not accumulate in the body.
6. After an oral administration of (pivaloyloxymethyl-¹⁴C) T-2588 to rats and mice, urinary excretion was both about 8% of the dosed radioactivity, and fecal excretion was both about 6%. Then excretion of ¹⁴CO₂ into respiratory air was about 55% and 66% of the dosed radioactivity in rats and mice, respectively.
7. Biliary excretion was about 6.5% of the dosed radioactivity after an oral administration of (aminothiazole-2-¹⁴C) T-2588 to rats.
8. Small amount of radioactivity was secreted to the milk after intravenous administration of (aminothiazole-2-¹⁴C) T-2525 to nursing rats.
9. After an administration of (aminothiazole-2-¹⁴C) T-2588 to pregnant mice, radioactivity hardly transfered into the fetus.

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The distribution of T-2588 was studied with whole body autoradiography in normal male mice and pregnant mice using two radioactive T-2588 labeled at the aminothiazole or pivaloyloxymethyl moieties.
1. When (aminothiazole-2-¹⁴C) T-2588 was orally administered, the radioactivity was distributed widely to whole tissues except central nervous systems such as brain and spinal cord. In pregnant mice, no detectable radioactivity was present in the fetus. These results suggested that T-2588 was well absorbed and hardly crossed the blood-brain barrier and placenta. At 4 hours after administration, radioactivity was only observed in gastrointestinal tract implying rapid excretion of T-2588.
2. When (pivaloyloxymethyl-¹⁴C) T-2588 was orally administered, radioactivity was accumulated to all tissues and fetus. From these results we speculated that formaldehyde formed by hydrolysis at the pivaloyloxymethyl ester and entered the C₁-metabolic pathway.

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Antibacterial activities of imipenem (MK-0787), cefazolin (CEZ), cefmenoxime (CMX) and cefoperazone (CPZ) were measured by using an agar dilution method against 243 strains of bacteria isolated from the patients with urinary tract infections. The MIC₈₀ of MK-0787 against S. epidermidis, E. faecalis, E. coli, K. pneumoniae, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris and P. aeruginosa was ≤ 0.10, 3.13, ≤ 0.10, 0.20, 0.78, 1.56, 3.13, 3.13 and 6.25μg/ml, respectively. MK-0787 was more active than CEZ, CMX and CPZ against all bacterial species except Proteus spp.
Imipenem/cilastatin sodium (MK-0787/MK-0791) 500mg/500mg two times a day for 5 days was given to 31 cases of chronic complicated urinary tract infections and a case of acute prostatitis. Overall clinical effectiveness rate judged by the criteria proposed by the Japanese UTI committee in 22 cases of chronic complicated urinary tract infection treated with MK-0787/MK-0791 was evaluated to be 86% including excellent in 6 cases, moderate in 13 cases and poor in 3 cases.
As side effects, 2 cases encountered eruption or anorexia. Abnormal laboratory findings were observed in 6 cases.

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A new β-lactamase-stable oral cephem antibiotic, cefixime (CFIX), was evaluated for safety, efficacy and pharmacokinetics in children. CFIX was effective in 19 of 20 cases (95%) with bacterial infections. The drug was especially effective against the cases of pneumonia due to β-lactamase-producing H. influenzae or B. catarrhalis.
Pharmacokinetic parameters of CFIX (3mg/kg) with premeal administration were as follows: Kel 0.328±0.066 hr^-1, T 1/2 2.14±0.36 hrs, AUC 10.9±8.7μg.hr/ml, and Vd/F 1.64±1.42L/kg. In most of the cases tested, the urinary excretion rate in 12 hours was 5 to 17%. A dose of 3mg/kg twice daily seems to be adequate for a regular treatment.

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A newly developed cephalosporin, cefixime (CFIX), was evaluated clinically in 35 pediatric patients. A pharmacokinetic study was also performed with 11 patients.
CFIX was administered as granules.
The pharmacokinetic study was conducted in 11 patients, each of 6 patients was given CFIX at a dose of 3mg/kg and each of the remaining patients was given CFIX at 6mg/kg. Serum concentrations of CFIX were measured at 2, 4, 6, 8 and 12 hours after dosing. Urinary concentrations of CFIX were measured for periods of 0-6 and 6-12 hours after dosing. CFIX was assayed by the disk method using E. coli ATCC 39188 as the test organism.
The clinical evaluation was conducted in 35 children including 5 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 1 of purulent lymphadenitis, 1 of scarlet fever, 8 of acute bronchitis, 5 of pneumonia, 3 of urinary tract infections and 1 of paratyphoid B. One additional patient was included only in the evaluation of safety since he was suffering from Mycoplasma pneumonia. The patients were from 4 months to 8 years 2 months old and 11 of them were inpatients. Daily doses were from 6.0 to 13.5mg/kg.
After CFIX administration in doses of 3mg/kg and 6mg/kg, peak serum concentrations were 1.75 and 3.36μg/ml, half-lives were 2.65 and 2.86 hours and urinary excretion rates up to 12 hours after dosing were 16.1 and 12.4%, respectively. Serum concentrations were dose dependent and the half-life was fairly long compared with other known oral cephalosporins.
Clinical efficacies of CFIX in 34 patients were “excellent” in 25 children, “good” in 8 and “poor” in 1 with effectiveness rate of 97.1%.
Twenty-two strains of causative organisms, including 6 strains of S. aureus, 3 of S. pyogenes, 2 of S. pneumoniae, 3 of E. coli, 5 of H. influenzae, 2 of H. parainfluenzae and 1 of S. paratyphi B, were isolated. After treatment all strains except 2 strains of S. aureus (one was unknown and the other was decreased), 1 strain of S. pneumoniae (unknown) and 1 strain of H. influenzae (unknown) were successfully eradicated but S. paratyphi B was proved again in feces 9 days after treatment.
No adverse reaction was observed. Among 18 children who went through laboratory test, however, an elevation of eosinophile and elevations of GOT and GPT were observed in 2 children and 1 child, respectively.

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Fundamental and clinical studies of cefixime (CFIX) granules, a new oral cephalosporin, were carried out with the following results:
1. The MICs of CFIX against 234 clinical isolates were determined. Antibacterial activities of the drug against S. aureus, S. epidermidis and E. faecalis were weaker than those of conventional oral cephalosporins but antibacterial activities against Gram-negative bacteria were almost the same as those of cephem antibiotics of the Fumes group 5.
2. Peak serum concentrations of CFIX after oral doses of 3 and 6mg/kg were, respectively, 1.51-4.89μg/ml at 2-6 hours and 3.22-7.76μg/ml at 4-8 hours. Serum concentrations of CFIX were dosedependent in a patient given 3 and 6mg/kg in a cross-over study.
3. CFIX granules were administered mainly to children suffering from respiratory tract infection, otitis media and urinary tract infection at a dose of 3mg/kg b. i. d. or t. i. d. for 3-27 days. The clinical responses to CFIX were excellent to good in 44 of the 50 children with infections, with an effectiveness rate of 88%.
4. Thirty-five strains of the 40 clinical isolates were eradicated by the treatment with CFIX. The bacteriological eradication rate was 87.5%.
5. Side effects observed were diarrhea and soft stool in 2 patients each, and elevated GOT·GPT and eosinophilia in 1 patient each. These symptoms and laboratory abnormalities disappeared on the day after the completion of therapy with CFIX.
From the above results it has been concluded that CFIX is a useful and safe antibiotic for treating various bacterial infections in children.

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Fundamental and clinical studies were carried out on cefixime (CFIX) 5% granules, and the results are summarized below.
1. Antimicrobial activity Antimicrobial activities of CFIX, cefaclor, cefroxadine, cephalexin and amoxicillin (AMPC) were studied against clinical isolates.
CFIX showed greater activities than all the other antibiotics against E. coli, K. pneumoniae, H. influenzae, P. mirabilis, E. cloacae and S. marcescens, but it was slightly less active than AMPC against S. pyogenes.
2. Absorption and excretion Serum concentrations and urinary excretions of CFIX were determined following single or repeated oral administration. In 8 patients given single dose of CFIX 1.5 or 3.0mg/kg, mean serum concentrations were 1.27 and 1.09μg/ml at 2 hours, 1.27 and 1.35μg/ml at 4 hours, 0.85 and 1.10μg/ml at 6 hours, 0.17 and 0.24μg/ml 12 hours after administration, respectively. Mean serum half-lives were 2.54 hours for the dose of 1.5mg/kg and 2.60 hours for 3.0mg/kg.
Urinary recovery rates in the 12-hours urine varied 6.7 to 33.6%, with an average of 13.5%.
In 3 patients given a repeated dose of CFIX 3.0 or 5.6mg/kg b. i. d., the serum concentrations were 0.23-1.01μg/ml at 0 hour, 1.91-2.80μg/ml at 2-4 hours and 1.13-2.07μg/ml at 6-8 hours after administration.
3. Clinical study The CFIX was given orally by mainly b.i.d. at a daily dose of 4.4-11.6 mg/kg for 4-15 days to a total of 33 patients consisting of 3 patients with pneumonia, 3 with bronchitis, 9 with tonsillitis, 15 with UTI, one each with scarlet fever, lymphadenitis and colitis. Clinical responses were excellent in 24 patients, good in 8 and fair in 1, with an effectiveness rate of 97.0%. All of the 21 bacterial isolates examined were eradicated after CFIX treatments including 3β-lactamase producing strains. No side effects or abnormal laboratory findings were observed in these patients.

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Fundamental and clinical studies on cefixime (CFIX), a new oral cephem antibiotic, were carried out in the pediatric field.
The results were as follows:
1. Serum concentrations and urinary recovery rates were determined after oral administration of CFIX at doses of 3 mg/kg and 6mg/kg in 2 cases each (4 cases in total). The mean serum concentrations of CFIX were 0.52 and 0.58μg/ml at 2 hours, 0.80 and 1.42μg/ml at 4 hours, 0.73 and 1.36μg/ml at 6 hours, 0.54 and 1.12μg/ml at 8 hours, respectively. The mean peak serum concentration of CFIX was obtained at 4 hours after administration, with serum half-lives (T1/2) of 3.77 and 5.30 hours, respectively. The mean cumulative urinary recovery rates within 12 hours after administration of CFIX at doses of 3mg/kg and 6 mg/kg were 8.4% and 6.8%, respectively.
2. Antibacterial activities of CFIX against clinically isolated strains of S. pyogenes, S. pneumoniae, E. faecalis, S. aureus, E. coli, H. influenzae, H. parainfluenzae were compared with those of amoxicillin (AMPC), cefaclor (CCL), and cephalexin (CEX). It was observed that CFIX was a little less active than AMPC against S. pyogenes and S. pneumoniae, but CFIX was more active than CCL and CEX. CFIX was the most active against E. coli, H. influenzae and H. parainfluenzae.
3. Twenty-one pediatric patients with bacterial infections (10, tonsillitis; 4, pharyngitis; and 7, urinary tract infections) were treated with CFIX at doses of 1.5-6.0mg/kg in 2 or 3 times daily for 4-10 days. The efficacy rate was 95.2% clinically and 91.3% bacteriologically.
4. No adverse reactions were observed. An abnormal laboratory finding (slight elevation of S-GOT and S-GPT) was observed in 1 case.

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Bacteriological, pharmacokinetic, and clinical studies of cefixime (CFIX), a newly developed oral cephalosporin, was conducted in our pediatric department as outlined below.
1. Bacteriology The prevalent MICs of CFIX by microbiological species, compared with those of the reference drugs, were detailed below. Against 16 strains of S. aureus, the MICs averaged 6.25μg/ml, and were found to be nearly the same as the MICs of amoxicillin (AMPC) but higher than those of cephalexin (CEX) and cefaclor (CCL). For 4 strains of S. pyogenes, the MICs averaged 0.05μg/ml, and were higher than the MICs of AMPC but lower than those of CEX and CCL. Mean MICs of CFIX against other clinical isolates were lower than those of CEX, CCL, or AMPC; E. coli (20 strains), 3.13μg/ml; K. pneumoniae (9), 0.10μg/ml; P. mirabilis (16), 0.025μg/ml; P. vulgaris (5), 0.10μg/ml; H. influenzae (11), 0.05μg/ml; and S. typhimurium (4), 0.10μg/ml. The MICs of CFIX against 10 strains of P. aeruginosa were distributed at and above 25μg/ml, a range much lower than≥100μg/ml for CEX, CCL, or AMPC.
2. Pharmacokinetics The serum concentrations and urinary recovery were studied in 3 children ranging from age 7 to 13. They were given CFIX on empty stomach in 2 different single doses of 3 and 6 mg/kg in a cross-over design. Average serum CFIX concentrations were dose-dependent, as evidenced by the respective peak concentrations of 1.70μg/ml for a 3mg/kg dosage and 2.72μg/ml for 6mg/kg, which were attained 4 hours after the administration of the drug. The average half-lives of CFIX in the serum were 3.09 hours and 3.11 hours, respectively, and the 12-hour serum concentrations were 0.32μg/ml and 0.77μg/ml, respectively, for the 2 different dose levels. The average 12-hour urinary recovery was 25.2% and 22.3%, respectively.
3. Clinical study Clinical effectiveness, bacteriological effectiveness, and side effects were studied in 27 children with infection including 4 patients with acute pharyngitis, 13 with acute purulent tonsillitis, 5 with acute pneumonia, 3 with urinary tract infection, and 1 each with acute rhinitis and acute bronchitis. One child with acute pneumonia (Mycoplasma pneumonia) was excluded from the study. The therapeutic effectiveness was “excellent” in 21, “good” in 3, “fair” in 1, and “poor” in 1, with an effectiveness rate of 92.3%. Suspected causative organisms, including 9 strains of S. pyogenes, 4 strains of H. influenzae, 2 strains of H. parainfluenzae, and 3 strains of E. coli, were eradicated except 3 strains of S. pyogenes and 1 strain of H. influenzae, which were reduced in counts. No side effect, refusal of ingestion, or abnormal laboratory test findings were observed.
In conclusion, CFIX was considered to be a safe and highly effective antibiotic in pediatric infections.

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The absorption and excretion and clinical effectiveness of cefixime (CFIX) granules, a new oral cephalosporin, were studied with pediatric patients with tonsillitis and urinary tract infection (UTI).
1. Peak serum concentrations in 3 children given orally a single dose of 3mg/kg on fasting were 0.545μg/ml at 2 hours in 1 patient, and 1.56 and 1.26μg/ml at 4 hours in the other 2. The half-lives in the 3 patients were 3.21-3.42 hours, with an average of 3.29 hours. The urinary concentration during the first 6 hours was 36.5μg/ml in 1 patient showing the low serum level, and the first 6-hour urinary recovery rate was 7.3%. In the other 2 patients, urinary concentrations and recovery rates up to 6 hours were 87 and 62μg/ml, and 17.0 and 15.1%, respectively. The second 6-hour urinary concentrations and recovery rates were 35.5 and 20.8μg/ml, and 12.7 and 8.8%, respectively. The urinary recovery rates up to 12 hours were 29.7 and 23.9%, respectively.
2. CFIX was given orally to 19 children with 20 diseases in daily doses of 6.4-12.9 mg/kg in 2 or 3 divided portions for 3 to 12 days. Clinical evaluations were made on 18 diseases.
Clinical effects of CFIX were excellent in 4, good in 7 and poor in 1 of the 12 patients with tonsillitis, and excellent in 5 and good in 1 of the 6 patients with UTI. The overall clinical effectiveness rate was 94.4%.
3. No side effects were observed in any of the 19 patients. Hematological tests, showed slight elevation of blood platelet counts in 2 patients.
4. The taste and odor of CFIX were well accepted by the children.
5. CFIX is a useful oral antibiotic for the treatment of bacterial infection in pediatrics. Especially, children with UTI are satisfactorily treated with CFIX at the outpatient department.

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Pharmacokinetic and clinical studies of cefixime (CFIX) in children were done and the following results were obtained.
1. Serum and urinary concentrations of CFIX were determined in 6 children aged 5 to 14 years given single doses of 1.5 or 6.0mg/kg. Mean serum concentrations peaked at 4 hours after the administration of either 1.5 or 6.0 mg/kg, and respective peak values were 0.71 and 4.46μg/ml. Biological half-lives for the low and the high doses were 5.28 and 4.45 hours, respectively. The 12-hours urinary recovery ranged from 7.0 to 13.8% after administration of 1.5 mg/kg, and the 8-hours urinary recovery was 18.1% after administration of 6.0mg/kg.
2. Therapeutic responses were recorded as excellent or good in 43 (97.7%) of the children, comprising 13 with tonsillitis and 31 with scarlet fever.
The microbiological effectiveness of CFIX on identified pathogens comprising 29 strains of S. pyogenes and 2 strains of S. aureus was satisfactory as evidenced by a high eradication rate of 93.5%.
No clinical side effects were observed. Abnormal laboratory findings were elevation of GOT and/or GPT in 4 patients and eosinophilia in 1 patient.
In conclusion, CFIX was found to be efficacious and safe for the treatment of bacterial infections in children.

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We used cefixime (CFIX), a newly developed oral cephalosporin antibiotic, to treat 21 children with various infections. The results are summarized as follows.
1. The serum half-lives of CFIX after an administration of 6mg/kg to each of 2 children were 2.56 and 2.79 hours. The serum concentrations were high enough to ensure the therapeutic response.
2. The clinical response was “excellent” in 16 children and “good” in 5, with a 100% efficacy rate.
3. No side effects were recorded. The only abnormal finding was slight eosinophilia in 1 child.

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Cefixime (CFIX) was given orally to 25 children with acute bacterial infections including 13 with acute tonsillitis, 1 with acute tonsillitis and cervical lymphadenitis, 1 with acute bronchitis, 5 with bronchopneumonia and 5 with urinary tract infection.
Good to excellent clinical response was obtained in 23, and bacteriological response was obtained in 14 of the 16 children who underwent bacteriological tests.
Side effects with soft stool or eosinophilia were observed in 1 child each. The flavor and odor of CFIX appeared to be well accepted by children.
Our clinical experience has suggested the usefulness of this antibiotic for the treatment of various bacterial pediatric infections.

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A clinical study of cefixime (CFIX), a new oral cephalosporin, was carried out to evaluate its therapeutic effectiveness on bacterial infections in children.
CFIX was orally administered to 13 patients including 6 with upper respiratoly tract infection (RTI), 3 with pneumonia, and 1 each with bronchitis, otitis media, skin abscess, and urinary tract infection (UTI). The daily dosage per kg bodyweight ranged from 5.1 to 17.4mg (average: 8.7mg), and was given in 2 or 3 divided doses per day for 3 to 10 days (average: 5.8 days).
The clinical response was excellent in 4 (30.8%), good in 7 (53.8%) and poor in 2 (15.4%), with an overall efficacy rate of 84.6%. Bacteriological efficacy was good, and 6 of the 8 identified causative organisms were eradicated.
Side effects were observed in 3 children, i. e., loose stool in 1 and transient elevations of GOT and GPT in 2.
The above results suggest that CFIX is a useful new oral cephalosporin for the treatment of bacterial infections in children.

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We have evaluated cefixime (CFIX) fine granules for pharmacokinetics and therapeutic effectiveness in children with infections. The results were summarized as follows.
1. Pharmacokinetic parameters after the oral administration of single doses of 1.5mg and 6.0mg per kg body weight in a cross-over design in 1 child were as follows:
The peak serum CFIX concentrations were 0.65μg/ml at 2 to 3 hours and 3.33μg/ml at 4 hours for the low and the high doses, respectively; the respective biological half-lives were 2.4 hours and 2.5 hours, and urinary recovery was 10.3% at 8 hours and 5.2% at 12 hours, respectively.
2. A clinical study was performed on 19 children with infections, including 7 with bronchitis; 3 each with tonsillitis, UTI, and cervical lymphadenitis; and 1 each with pharyngitis, retroauricular lymphadenitis, and enteritis. Doses ranging from 1.8 to 7.8mg/kg body weight were given b. i. d. or t. i. d. The period of treatment ranged from 3 to 13 days. The therapeutic response was considered “excellent” in 15 and “good” in 4, with an effectiveness rate of 100%.
3. No side effects were observed. The only abnormal laboratory findings was a slight elevation of GOT and GTP recorded in 1 child.
It was concluded that CFIX was a promising drug for the treatment of bacterial infections in children.

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Cefixime (CFIX) was evaluated for pharmacokinetics, therapeutic effectiveness on infection, safety, and bacteriological effectiveness in pediatrics. The following is a summary of the results.
1. Pharmacokinetics in 4 children, 2 each receiving a single dose of 1.5mg or 6.0mg per kg body weight, were examined.
Peak serum CFIX concentrations after the dose of 1.5mg/kg were 1.12 and 1.34μg/ml, and the serum half-lives were 1.83 and 3.53 hours. For the children administered with 6.0mg/kg of CFIX, the respective figures were 2.50 and 7.46μg/ml, and 6.77 and 6.64 hours. The 12-hour urinary recoveries were 4.9 and 34.1% and 9.4 and 25.4% for the small and the large doses, respectively.
2. Therapeutic effectiveness in 19 children with infections was “excellent” in 14 and “good” in 5, with an effectiveness rate of 100%.
3. Bacteriological effectiveness was evaluated in 10 children. Classified by causative organisms, 5 cases had H. influenzae, 2 each H. parainfluenzae and S. pyogenes, and 1 mixed infection by H. influenzae and S. pneumoniae. Only the H. influenzae in the child with mixed infection resisted the therapy, and all the other pathogens were successfully eradicated.
4. No side effects were recorded. The only abnormal laboratory test finding attributed to CFIX was eosinophilia in 2 children.

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Pharmacokinetics and clinical effects of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows.
1. CFIX (5% granules) was given to each of 5 children twice in a single dose of 1.5 or 3.0 mg/ kg in a cross-over trial. The mean peak serum concentration of CFIX was 0.64 μg/ml at 4 hours after given the dose of 1.5 mg/kg and 1.15 μg/ml at 4 hours after the dose of 3.0 mg/kg. The mean half-life and the mean AUC values were 2.72 hours and 4.10 μg·hr/ml, respectively after the dose of 1.5 mg/kg, and 2.77 hours and 8.26 μg·hr/ml after the dose of 3.0 mg/kg. The urinary recovery was investigated in 5 children after the dose of CFIX of 1.5 mg/kg and in 4 children after the dose of 3.0 mg/kg. The mean peak urinary concentrations of CFIX and the mean 12-hour urinary recovery rates were 10.6-67.9 μg/ml at 2-10 hours and 15.7% after the dose of 1.5 mg/kg, and were 6.16-230 μg/ml at 2-8 hours and 18.9% after the dose of 3.0 mg/kg, respectively.
2. CFIX was given to 6 children twice in a single dose of 50 mg either in the form of 5% granules or in capsules in a cross-over trial. The mean peak serum concentrations, half-life and AUC values were 1.26 μg/ml at 4 hours, 3.09 hours and 9.63 μg·hr/ml, respectively after the dose of 50 mg CFIX in 5% granules, and were 1.16 μg/ml at 4 hours, 2.87 hours, and 7.82 μg·hr/ml, respectively after the dose of 50 mg in capsules. The urinary recovery was investigated in 5 children. The mean peak urinary concentrations and the mean 12-hour urinary recovery rates were 19.1-114 μg/ml at 4-10 hours and 15.7%, respectively after the dose of 50 mg in 5% granules, and were 8.16-89.0 μ/ml at 4-10 hours and 11.3%, respectively after the dose of 50 mg in capsules.
3. Clinical efficacy of CFIX was investigated in a total of 26 children including 2 with tonsillitis, 2 with acute bronchitis, 2 with scarlet fever and 20 with urinary tract infection. Each of children were given orally a dose of 2.6 mg/kg CFIX 2-3 times a day for 11 days in average. The clinical effective rate was 92.3%. The bacteriological effect was investigated in 16 children and it was found that all the causative organisms were eradicated. However, microbial replacement was observed in 2 children.
4. The minimum inhibitory concentrations (MICs) of CFIX against clinical isolates were compared with those of amoxicillin (AMPC), cephalexin (CEX) and cefaclor (CCL). CFIX was less active than AMPC, CEX and CCL against 1 strain of S. aureus with inoculum size of 10⁶ cells/ml, and was equal to AMPC and inferior to CEX and CCL in antimicrobial activity with inoculum size of 10⁸ cells/ml. CFIX was more active than AMPC, CEX and CCL against 7 strains of E. coli and 1 strain each of K. pneumoniae subsp. pneumoniae, P. mirabilis and M. morganii with inoculum size of 10⁸ and 108 cells/ml.
5. As for clinical adverse reaction, diarrhea appeared in 1 (3.8%) of 26 children. This side effect was considered to be ascribable to the drug. Two patients had abnormal laboratory findings of liver function. One showed elevation of GOT that was thought to be caused by this drug, and the another had elevation of both GOT and GPT that was due to side effect of this antibiotic.

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Cefixime (CFIX), a new oral cephalosporin, was administered clinically at a daily dose of 3.4 mg/kg to 10.4 mg/kg to each of 12 children, aged from 2 months to 14 years old.
An additional separate study was done to compare the serum and urinary levels of CFIX in 3 children when each was administered with 100 mg of the drug in capsule with the serum and urinary levels of the drug in the same children when each was given the same amount of drug in the form of 5% granules.
The results of these trials are summarized below.
1. Peak serum levels of CFIX administered in capsules and 5% granules averaged 1.4 μg/ml and 1.9 μg/ml, respectively. The half-life of the former was 5.13 hours, while that of the latter was 4.17 hours. The difference in the peak levels was statistically insignificant.
2. The urinary excretion of CFIX in either form of the drug (capsules and granules) was about 14-18% in 12 hours.
3. In 9 cases of respiratory infections, therapeutic results were excellent in 3 cases, good in 6 cases, and the effective rate was 100%. In 2 cases of urinary tract infection, results were excellent in 1 case and good in 1 case. The drug efficacy was poor in 1 case of purulent cervical lymphadenitis, probably caused by Staphylococcus aureus.
4. No adverse reactions attributable to the drug were observed.
CFIX may be expected to be a highly effective and safe agent in moderate respiratory and urinary tract infections of childen.

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