The effect of S-1108, a new oral cephem antibiotic, on intestinal bacterial flora was studied in tetra-contaminated mice and pediatric patients.
S-1108 in a fine granular form was administred at a dose of 15mg/kg once a day for 5 consecutive days to mice infected with Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. The viable fecal bacterial cell count of each of these 4 species of bacteria was slightly reduced in 5 days after the start of the drug administration.
Five boys (weighing 12.0 to 42.0kg) with bacterial infections were entered into this pediatric study. Their ages ranged from 2 years 4 months to 9 years 3 months. S-1108 (fine granules) was administered at a dose of 2.3 to 6.0mg/kg, 3 times a day for 5 to 11 days.
Cell counts of primary aerobes, anaerobes and total anaerobic cells decreased markedly in three patients, but in the remaining two patients the total number of aerobic and anaerobic cells did not change appreciably. Glucose-nonfermentating Gram-negative rods did not become predominant during the period of S-1108 administration. Candida became predominant in the three patients in whom the other bacteria had markedly decreased. Counts of predominant aerobic and anaerobic bacteria decreased markedly during the regimen in 3 out of 5 cases. S-1006 was detected in stools of the 3 cases at concentrations ranging from 235 to 516μg/g during the administration of S-1108.
Intestial bacteria that produce β-lactamase were not present in the feces of any of the patients.
Based on these results, S-1108 (fine granules) appears to have relatively little effect on intestinal bacterial flora similarly to other new oral cephems. Because of individual differences, however, the drug may be excreted in the feces at high concentrations, and this would result in changes in intestinal bacterial flora.
Therefore, attention must be given to fecal drug concentrations.

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We studied the pharmacokinetics of a new cephem antibiotic, S-1108, in patients with impaired kidney functions. Serum and urinary levels of S-1006 were determined after oral administration of S-1108 at 150mg to 9 patients with renal dysfunction. In patients with severe renal impairment, high serum levels were maintained over long periods of time. Urinary excretion rates of S-1006 were lower as degrees of kidney failure were severer.
S-1108 was administered to treat 27 patients with respiratory tract infections, and its clinical efficacy and safety were evaluated. The clinical efficacies were good in 26 patients, but poor in 1, yielding an efficacy rate of 96.3%. As to adverse reactions, diarrhea was observed in one case. Laboratory tests revealed elevated GOT and GPT in 1, and elevated γ-GTP in another. These abnormalitis, however, were slight and no severe side effects were caused by the drug.

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A clinical study in children has been performed on S-1108, a newly developed cephem antibiotic. S-1108 was given orally to 30 patients, at doses between 8 and 12mg/kg/day in 3 divided doses for 2 to 10 days. Clinical evaluations were made on 26 patients consisting of 12 patients of pharyngitis, 5 of tonsillitis and of impetigo, one each of bronchitis, cystitis, lymphadenitis and cellulitis. Overall clinical effects were excellent in 10, good in 15, fair in 1 with an efficacy rate of 96%. As to adverse reactions, mild diarrhea (2 patients) and transients elevation of transaminases (one patient) were observed.
These data suggest that S-1108 is a useful oral antibiotic for the treatment of bacterial infections in children.

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We studied the clinical use of S-1108 granules in the pediatric field. The results are summarized as follows.
1. S-1108 was administered orally at doses ranging 6.85 and 17.6mg/kg/day t. i. d. to 9 patients, including 5 cases of pharyngitis and 1 case each of lacunar tonsillitis, bronchitis, pneumonia and urinary tract infection. Clinical efficacies were excellent in 4 cases and good in 5 cases, hence an efficacy rate of 100% was obtained.
2. Haemophilus influenzae, Haemophilus parainfluenzae (2 strains each) and Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli and Enterococcus faecalis (1 strain each) were indentified in these cases. Seven of the 8 strains were eliminated upon treatment and the other strain was decreased, hence an eradication rate of 87.5% was obtained.
3. Side effects observed were 1 case each of soft stools and diarrhea. As an abnormal laboratory test result, an increase in GPT level was observed.
4. No refusal of the drug occurred.
5. From the above results, we consider that this drug would be a useful new oral antibiotic for the pediatric field.

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1. S-1108 granules were administered to 22 children with bacterial infections (8 cases of bronchitis, 1 case of pneumonia, 3 cases of scarlet fever, 2 cases each of tonsillitis, pharyngitis, pertussis, purulent lymphadenitis and impetigo).
2. Clinical efficacies were excellent in 12 patients and good in 7, fair in 1, poor in 1 and unevaluable in 1 with an efficacy rate of 90.5%.
3. Neither side effects nor abnormal laboratory test values were observed.
4. There was no rejection of the drug during the therapy.
From the above results, we consider S-1108 in granular form to be a useful and safe drug in the treatment of various bacterial infection in pediatric patients.

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The effects of S-1108, an orally active cephem antibiotic newly synthesized by Shionogi Res. Lab., on pediatric bacterial infections was studied. S-1108 was administered orally at a daily dose between 9.3 and 12.4mg/kg in three divided doses (after each meal) for 5 to 11 days to patients with pharyngitis (2), tonsillitis (1), bronchitis (3), pneumonia (1), lymphadenitis (1), enteritis (1) and cystitis (1).
The clinical efficacy rate was 100% with excellent responses in 3, good in 6 and undetermined in 1. Bacteriological effects observed indicated that one strain each of Streptococcus pneumoniae, Streptococcus pyogenes, Klebsiella pneumoniae and two strains of Haemophilus influenzae were eradicated by the treatment. No clinical side effects and laboratory test abnormalities were observed at all in this study.
These results suggested that S-1108 would be a useful antibiotic for the treatment of bacterial infections in the pediatric field.

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S-1108 in a fine granular form was administered to 14 children and its safety and efficacy in bacterial infections were evaluated. Among them, 2 cases of cystitis and 1 case of pneumonia were considered unevaluable for the efficacy. The results obtained are summarized as follows.
1. The overall clinical efficacy rate was 81.8% in the eleven evaluable cases treated with S-1108 fine granules including 5 cases of pharyngitis, 2 cases each of tonsillitis, pertussis and cystitis.
2. Bacteriological efficacy of 100% was achieved against pathogens identified in 5 children including 1 case each of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae and 2 cases of Escherichia coli.
3. The only abnormal laboratory test results observed were eosinophilia and leukocytopenia in one case each. Diarrhea was recorded in 1 case.
Judging from the above results, it appears that S-1108 in the fine granular form is an effective, useful and safe antibiotic of first choice for the treatment of infections in the pediatric field.

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We have evaluated S-1108 fine granules for therapeutic effectiveness in children. The results are summarized as follows.
1. A clinical study was performed with 16 children with infections, including 8 with acute tonsillitis, 3 with acute pharyngitis, 2 with scarlet fever, 1 each with acute bronchitis, pertussis and urinary tract infection.
Doses ranging from 8.8 to 10.6mg/kg body weights were given in 3 divided portions. Durations of treatment ranged from 2 to 15 days.
The therapeutic responses were considered “excellent” in 1 and “good” in 13, with an efficacy rate of 87.5%, and the bacteriological eradication rate was 91%.
2. No adverse reactions were observed. In laboratory tests, eosinophilia was observed in one patient.
It was concluded the S-1108 was promising drug for the treatment of bacterial infections in children.

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Clinical studies of S-1108, a new oral cephem, in pediatric patients were conducted and results are summarized below.
1) Clinical effects of S-1108 against 18 cases of bacterial infections were excellent in 5 cases, good in 10 cases, fair in 1 case and poor in 2 cases, thus the clinical efficacy rates was 83.3%.
2) Bacteriological effects were evaluated in 16 strains. The elimination rate was 100%.
3) No adverse effects nor abnormal laboratory test results were observed in any of the cases.

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S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against β-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows.
1. A drug sensitivity test revealed that MIC₈₀, of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25μg/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56μg/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was≤0.025μg/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were≤0.025μg/ml, 0.10μg/ml or 0.39μg/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10μg/ml which are similar to those of CFTM.
2. When S-1108 granule preparation was administered to 1 patient at 4.0mg/kg, the peak plasma concentration of S-1006 was 1.25μg/ml. S-1108 granule preparation was also administered to 2 patients at 6.0mg/kg, and the peak plasma concentrations were 2.43μg/ml and 2.23μg/ml. Plasma half-lives were 1.11 hours after 4.0mg/kg and 1.28 hours in both patients given 6.0μg/ml. AUCs were 4.06, 8.37 and 7.73 μg·hr/ml, respectively. A dose-response relationship was observed between the two doses.
3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0mg/kg. The peak concentrations were 25 8.0, 602.0 and 500.0μg/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively.
4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%.
5. As to the bacteriological effects 43 of 48 strains were eliminated, with an elimination rate of 89.6%.
6. Adverse reactions observed included dizziness in a patients and diarrhea in 2 patients (2.1%).
7. Laboratory tests revealed eosinophilia in 1 of 47 patients (2.1%) examined.

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