[in Japanese]

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Flomoxef (FMOX) has a broad antibacterial spectrum against Gram-positive and Gramnegative bacteria; especially its potent antibacterial activity against Staphylococcus aureus is a significant advantage that may not be found with other cephem compounds.
In our determination of its antibacterial potency against various clinical isolates obtained from clinical materials (amniotic fluid, intrauterine secretions, exudates of the pelvic dead space) of patients with various infections, we obtained results representing specific features of this drug.From the results, the drug may be expected to produce an excellent effect in the treatment of various infections.
Our study on drug concentrations in body fluids and genital tissues demonstrated a good transfer of this drug into various tissues; in every tissue examined, the drug administered by the usual method in the usual dose yielded a concentration exceeding MIC for principal pathogens, thus promising a good clinical response.
Indeed a high clinical efficacy rate of 90.1% (good to very good responses) was obtained in a clinical trial involving 222 cases. Administration of the drug in 2 g quantity daily produced a high response rate of 92.8%. Its was especially noteworthy that a good response was obtained in 30 of 32 cases (93.8%) in which other cephem compounds had failed.
In evaluation of the bacteriological effect, furthermore, the drug showed an excellent rate of bacterial elimination.
In conclusion, this drug is expected to be greatly useful in the light of its good transfer into genital tissues and its strong antibacterial activities against Gram-positive cocci, Gram-negative bacteria and anaerobes as well as against multiple bacterial infections predominating among women with genital infections.

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Sultamicillin (SBTPC) fine granules were given to 15 patients with respiratory tract infections at a dose of 375 mg 3 times a day. The results were excellent in 4 patients, good in 8, fair in 1 and poor in 2 with an efficacy rate of 80% which is comparable to that of SBTPC tablet (Unasyn® tablet).
One patient complained of difficulty in swallowing the drug probably due to its fine granular nature.
No side effects nor abnormal laboratory test values due to this drug were observed in any of the patients enrolled in this study. From the above results, SBTPC fine granules seem to be useful in the treatment of pediatric and elderly patients who sometimes have difficulties in taking tablets.

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Sultamicillin fine granules (SBTPC), a mutual prodrug of sulbactam (SBT) and ampicillin (ABPC), were administered to 16 pediatric patients with bacterial infections. The efficacy rate was 93.3%.
MICs (10⁶ cells/ml) of SBTPC against β-lactamase non-producing strains were not significantly different from those of ABPC, and ranged from ≤0.05 to 1.56 μg/ml. MICs of SBTPC, however, were 2-4 fold smaller than MICs of ABPC against β-lactamase producing strains. Diarrhea and loose stool as side effects were observed in 4 (25%) of 16 patients, but none of them were severe. After oral administration of SBTPC (10mg/kg), serum levels of ABPC and SBT peaked at 3.41 μg/ml and 2.43 μg/ml after 0.6 hour, and declined with half-lives of 1.79 and 1.00 hours, respectively.

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Sultamicillin (SBTPC) is a mutual prodrug of sulbactam (SBT) and ampicillin (ABPC). A study has been performed to evaluate pharmacokinetic properties and clinical usefulness of SBTPC fine granules in the treatment of pediatric infections.
After an oral dose of 5-15mg/kg of SBTPC fine granules, peak serum concentrations of ABPC and SBT were 1.18-3.26 μg/ml and 0.97-3.05 μg/ml, respectively at 1 hour. Serum half-lives for elimination (T 1/2(β)) of ABPC and SBT were 0.83-4.83 hours and 0.94-4.71 hours, respectively. Serum concentrations of ABPC at 1-6 hours after an oral administration of SBTPC fine granules were similar to those of SBT. Serum concentrations of ABPC and SBT were proportional to dose levels of SBTPC fine granules.
Following oral administrations of 5-15mg/kg, 33.9-64.8% of ABPC and 38.1-76.6% of SBT were recovered in urine in 6 hours.
SBTPC fine granules were administered in a daily dose of approximately 30mg/kg divided into 3 doses to 14 pediatric patients with bacterial infections. All 14 were cured with 11 excellent and 3 good clinical response to this drug.
Microbiological eradication was obtained in 85.7%. β-Lactamase-producing ABPC-resistant strains were eradicated.
Adverse effects including laboratory test values that may be attributed to the administration of SBTPC fine granules were not observed except a treatment episode of diarrhea in 1 patient.

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Clinical studies were carried out on sultamicillin (SBTPC) fine granule in the field of pediatrics. The results obtained are summarized below.
1. Thirty children with bacterial infections were treated with SBTPC fine granule. The clinical results were excellent in 24 and good in 5, with an efficacy rate of 96.7%.
2. Bacteriological screening identified 26 pathogenic organisms of which 14 were Grampositive cocci and 12 Gram-negative rods. Eradication rates were 91.7% in Gram-positive cocci and 66.7% in Gram-negative rods.
3. As side effects, diarrhea was observed in 12.9%, loose stool in 16.1% and eosinophilia in 3.2% of the patients. From the above results, it appeared that SBTPC fine granule was a useful drug for treating bacterial infections in the field of pediatrics.

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Pharmacokinetic and clinical studies on sultamicillin (SBTPC) were carried out in the field of pediatrics.
1. Absorption and excretion
A crossover study with a single oral administration of 10mg/kg of SBTPC in fasting and after meal, and that with 10mg/kg and 20mg/kg of SBTPC after meal were carried out in 11 children (5-15 years) and in 6 children (8-15 years), respectively.
Serum levels and urinary excretion of sulbactam (SBT) and ampicillin (ABPC) were determined.
Mean serum concentrations of ABPC after oral administration of 10mg/kg of SBTPC with in fasting or after meal, in the former study, peaked at 4.75±1.97μg/ml in 1 hour and declined with a mean half-life of 0.81±0.18 hour and the mean serum concentration of ABPC at 6 hours after administration was 0.06±0.07μg/ml. Mean serum concentration of ABPC study in the latter peaked at 2.95±0.79μg/ml in 1 hour, and declined with a mean half-life of 1.35±0.43 hours, and the mean serum concentration of ABPC at 6 hours was 0.22±0.13μg/ml. Mean urinary recovery rates of ABPC in 6 hours after administration were 54.5±17.6% in the former study, and 63.2±14.3% in the latter.
These results suggested a delay of absorption with meal.
Mean serum concentrations of ABPC after oral administration of 10mg/kg or 20mg/kg of SBTPC after meal, in the former study, were 3.10±0.72μg/ml at 1 hour and declined with a half-life of 1.22±0.32 hours, and those of ABPC were 0.22±0.12μg/ml at 6 hours, and they were 6.46±1.57μg/ml, 1.48±0.51 hours and 0.55±0.40μg/ml, respectively in the latter study. Mean urinary recovery rates of ABPC in 6 hours, were 50.4±10.2% in the former study and 57.7±11.4%, in the latter.
A dose response was observed with time course of mean serum concentrations. Mean serum concentrations of SBT were lower than those of ABPC, and they declined in a similar manner. The mean urinary recovery rate of SBT was similar or lower than that of ABPC.
2. Clinical study
SBTPC was used for the treatment of a total of 38 pediatric patients with ages 6 months to 11 years and it's clinical effectiveness, bacteriological efficacy and adverse effects were evaluated.
Clinical efficacies in 8 patients with acute purulent tonsillitis, 22 with acute pneumonia, 1 each with acute pharyngitis, acute purulent otitis media, acute purulent parotitis and impetigo were judged to be excellent in 28 cases and good in 6 cases with an efficacy ratio of 100.0%. Clinical efficacies in 5 patients with infections caused by β-lactamase producing strains were judged to be excellent or good in all cases.
Bacterioiogical efficacies of SBTPC were assessed on 2 strains of Staphylococcus aureus (β-lactamase producing strains), 3 strains of Streptococcus pyogenes, 2 strains of Streptococcus pneumoniae and β-Streptococcus, 9 strains of Haemophilus influenzae (2β-lactamase producing strains, 7 β-lactamase non-producing strains) and 1 strain of Haemophilus parainfluenzae (β-lactamase producing strain). All strains except 1 strain of S. aureus (β-lactamase producing strain) which decreased in number, 1 strain of β-Streptococcus which persisted and 1 strain of H. influenzae (β-lactamase non-producing strain) which decreased in number, were eradicated with a bacteriological eradication rate of 84.2%.
Only 1 patient complained of diarrhea which was suspected to be related to the drug.
No other side effect was reported. Abnormalities in laboratory test values included 3 casesof eosinophilia, 1 case of elevated platelet number and 1 case of GOT elevation. The above results suggested that SBTPC was a useful drug with a preferable safety profile in the treatment of pediatric patients with infectious diseases caused by β-lactamase producing strains as well as non-β-lactamase producing strains.

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Pharmacokinetic, bacteriological and clinical studies on sultamicillin (SBTPC) fine granule were carried out in the field of pediatrics. The results obtained are summarized as follows.
1. Antibacterial activities of SBTPC against clinically isolated strains of Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Branhamella catarrhalis, and Escherichia coli were compared with those of ampicillin (ABPC). SBTPC was superior to ABPC especially against β-lactamase producing H. influenzae, E. coli, S. aureus, and B. catarrhalis.
2. Serum concentrations and urinary excretion rates of sulbactam (SBT) and ABPC after administration of SBTPC fine granule at a dose level of 10mg/kg in 2 cases were determined. Mean half-lives of SBT and ABPC in the serum following oral administration were about 1.33 and 1.61 hours respectively. Mean urinary recovery rates of SBT and ABPC in 6 hours after oral administration at a dose of 10mg/kg were 58.7% and 49.6% respectively.
3. SBTPC fine granule was administered to 20 pediatric patients with various bacterial infections (pneumonia 8 cases, bronchitis 2, pharyngitis 2, tonsillitis 4, subcutaneous abscess 1 and urinary tract infection 3). The overall clinical efficacy rate was 100% and the overall bacteriological eradication rate was 75%.
4. No adverse reactions were observed except 1 case of loose stool. No abnormal laboratory test values were observed. These results indicate the usefulness of SBTPC fine granule in the treatment of bacterial infections in children.

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Sultamicillin (SBTPC) is a combination drug of sulbactam (SBT) and ampicillin (ABPC) in an ester bonding at 1:1 ratio.
SBT, a new semisynthetic β-lactamase inhibitor restores and extends the spectrum of ABPC against resistant strains of bacteria.
SBTPC granules were administrated to 26 pediatric patients with infections, and clinical efficacies were studied in 23 patients.
The clinical efficacy rate was 95.7% and the drug was evaluated to be highly effective for the treatment of infectious diseases in the pediatric field. SBTPC was safe and well tolerated.

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The clinical efficacy and the safety of sultamicillin (SBTPC) fine granules, which is a semisyntheticβ-lactam antibiotic for oral use with ester linked ampicillin (ABPC) and sulbactam (SBT), a β-lactamase inhibitor, in a ratio of 1:1, were evaluated in 31 patients with ages from 6 months old to 10 years and 4 months old with various bacterial infections. The results obtained are summarized as follows.
1. In a pharmacokinetic study with a dose level of 10mg/kg SBTPC, serum levels reached a peak in 1 hour after oral administration, with peak levels of 3.94μg/ml for ABPC and 4.08μg/ml for SBT. Half-lives of ABPC and SBT were 64.8 minutes and 63.6 minutes, respectively. The urinary excretion of ABPC over 6 hours was 66.2% and that of SBT was 60.4%.
2. SBTPC fine granules were administered orally to 1 patient with bronchitis, 9 patients with bronchopneumonia, 7 patients with tonsillitis, 4 patients with scarlet fever, 1 patient each with pharyngitis, otitis media, purulent parotitis, and urinary tract infection and 6 patients with skin and soft tissue infections at daily dosage levels of 26.1-31.6mg/kg divided into 3 or 4. Clinical evaluations of these 31 patients were as follows, excellent: 20 patients, good: 10 patients, poor: 1 patient. The efficacy rate was 96.8%.
3. Diarrhea was observed in a patient with otitis media on the fifth day of SBTPC administration. No other clinical adverse reaction was observed in any of the remaining 30 patients. No abnormal laboratory data was found in any of 23 patients who were subjected to laboratory examinations for safety.
4. The MICs of SBTPC against strains with strong β-lactamase activities were as follows. MICs against 2 out of 4 strains of Staphylococcus aureus were 1.56μg/ml and those of remaining 2 strains were 3.13μg/ml, and 12.5μg/ml. MICs against 1 strain of Escherichia coli was 0.78 g/ml and Klebsiella pneumoniae was 3.13μg/ml. All of these bacteria were eradicated after treatment with SBTPC fine granules and good clinical responses were obtained.
5. SBTPC fine granules appeared to be a new useful and safe antibiotic in pediatrics with an excellent bactericidal activity.

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We have carried out laboratory and clinical studies on sultamicillin (SBTPC). The results are summarized as follows.
SBTPC was given by oral administration to 2 children in a single dose at 5mg/kg and to 3 children in a single dose at 10mg/kg. After the oral administration, mean peak serum levels of ampicillin (ABPC) and sulbactam (SBT) obtained for the 2 dose levels were 1.91±1.34 and 2.06±1.06μ and 2.43±0.68 and 2.96±0.77μg/ml at 1 hour, respectively, and mean half-lives were 0.80±0.10 and 0.98±0.46 hour and 1.57±0.57 and 2.01±0.70 hours, respectively. SBTPC was given to 2 children in a single dose at 15mg/kg. After oral administration, the mean serum levels of ABPC and SBT at 30 minutes were 6.55±1.63 and 6.00±1.00μg/ml, and the mean half-lives were 0.90±0.13 and 0.82±0.16 hour. SBTPC was given to 1 child at a single dose of 20mg/kg. The peak serum levels of ABPC and SBT were 11.3 and 8.64μg/ml, and the half-lives were 0.87 and 0.92 hour.
Mean urinary excretion rates of ABPC and SBT were 38.4±2.7 and 34.6±4.7%, 43.0±3.6 and 41.6±5.8%, 47.7±5.2 and 51.6±3.5% in 6 hours and 66.1 and 59.2% in 8 hours after oral administration of 5mg/kg, 10mg/kg, 15mg/kg and 20mg/kg, respectively.
Treatment with SBTPC was made in 34 cases of pediatric bacterial infections; 2 cases of pharyngitis, 19 cases of tonsillitis, 2 cases of bronchitis, 3 cases of impetigo, 2 cases of staphylococcal skalded skin syndrome, 4 cases of urinary tract infection and 1 case each of pneumonia and scarlet fever. Results obtained were excellent in 20 cases, good in 13 cases and poor in 1 case.
No significant side effect due to the drug was observed in any cases.

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Sultamicillin (SBTPC), a mutual prodrug for ampicillin (ABPC) and β-lactamase inhibitor sulbactam (SBT), was evaluated for its antibacterial activity, pharmacokinetics and clinical efficacy.
Pharmacokinetic studies were done in 2 subjects (a male and a female) following single oral administrations of 5mg/kg and 10mg/kg SBTPC fine granules after meal.
Peak serum concentrations of ABPC and SBT in the 2 cases were 0.85 and 0.38μg/ml and 3.74 and 3.79μg/ml, respectively.
Urinary excretion rates in 6 hours were 43.5-58.1% for ABPC and 33.6-53.6% for SBT.
A total of 20 patients including 14 with respiratory infections, 1 with urinary tract infection and 5 with skin and soft tissue infections were treated with daily oral dose of 15.4-39.3mg/kg SBTPC fine granules t. i. d. for 4 to 13 days.
Responses were excellent in 5, good in 13 and fair in 2, hence the overall efficacy rate was 90.0%.
Bacteriological responses were confirmed on 5 (62.5%) out of 8 strains which were eradicated by the treatment.
SBTPC showed strong antibacterial activities against an ABPC-resistant strain of Escherichia coli.
Side effects of the drug were observed in 3 patients: diarrhea in 2 and loose stool in 1.
An abnormal laboratory test value, eosinophilia, was observed in only one patient

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Sultamicillin fine granules were used orally in 18 pediatric patients with infections in doses ranging 7.3-10.0mg/kg t. i. d. or q. i. d. The following is a summary of the results:
1. Clinical efficacies in 16 cases with tonsillitis were excellent in 13 cases, good in 2 cases and fair in 1 case. Efficacy in 1 case of bronchitis and 1 case of pneumonia were good. The overall efficacy rate in the 18 cases was 94.4%.
2. Four out of 5 strains of Staphylococcus aureus were eradicated but 1 strain persisted. Three out of 7 strains of Haemophilus influenzae were rated as eradicated, 1 strain as decreased and 3 strains as persisted. Two strains of Streptococcus pyogenes and 3 strains of Haemophilus parainfluenzae were eradicated. The bacteriological efficacy rate for the 17 strains was 70.6%. Four strains out of the 17 were found to produce beta-lactamase and 3 strains were suspected, to produce the enzyme, but of these 7 strains, 5 strains were eradicated.
3. Diarrhea and loose stool were observed as side effects in each of 2 cases. It appeared that diarrhea was related to this drug. A slight elevation of GOT was observed in 1 case in laboratory tests.
4. This drug appears to be easy for children to take in terms of taste and smell.

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Sultamicillin, a mutual prodrug of a β-lactam antibiotic and β-lactamase inhibitor, was administered to 19 child patients with infectious diseases. The patients included 9 boys and 10 girls from 11 months to 13 years old and they were given orally a dosage of 15.4-40.8mg/kg/day for 3 to 12 days.
Clinical efficacies were excellent in 2 cases, good in 13 cases, fair in 3 cases, unknown in 1 case, and the total efficacy rate was 83.3%.
Loose stool in 1 case and mild diarrhea in another occurred as side effects of the drug, but no abnormal laboratory test values were found upon the treatment.

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Sultamicillin (SBTPC) fine granule was given orally to 15 children with acute bacterial infections including 4 with acute pharyngitis, 5 with acute tonsillitis, 2 each with acute bronchitis and urinary tract infections, and 1 each with acute pneumonia and cervical purulent lymphadenitis.
Good to excellent clinical responses were obtaind in all of the 15 patients and bacterial eradication of all 4 strains found in these cases. Loose stool was observed in 1 case. From the above clinical results, it appears that SBTPC is a useful antibiotics for the treatment of pediatric patients with various bacterial infections.

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Pharmacokinetics, safety and effects on bacterial infection of sultamicillin (SBTPC) fine granule were evaluated in 17 children. The results obtained are summarized as follows.
1. Pharmacokinetics in 3 children receiving a single dose of 10mg per kg body weight were evaluated. The half-life of ampicillin (ABPC) was 1.38±0.14 hours and that of sulbactam was 0.93±0.26 hour.
2. Fourteen cases, including 7 tonsillitis, 2 pharyngitis, 2 bronchitis, and 1 each of cystitis, scarlet fever and cellulitis were treated with SBTPC fine granule.
The clinical efficacy rate was 100%.
3. Bacteriological efficacies classified by causative organisms were evaluated in 5 children. Staphylococcus aureus was responsible in 3 cases, Streptococcus pyogenes in 1 case, Escherichia coli and Proteus mirabilis in 1 case. Eradication rate was 100%. SBTPC was more active than ABPC against ABPC-resistant strains and almost equal to or more active than cephalexin or cefaclor.
4. The only abnormal laboratory test value observed was eosinophilia in 2 children.
No side effects were recorded.
From the above results it is concluded that SBTPC fine granule is one of first choices of effective, useful and safe antibiotics for the treatment of infections in pediatric field.

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We have evaluated sultamicillin (SBTPC) fine granules for pharmacokinetics and therapeutic effectiveness in children. The results are summarized as follows.
1. Pharmacokinetic parameters after the oral administration of single dose of 5.0mg per kg body weight in 1 child were as follows: The peak serum concentrations of ampicillin (ABPC) and sulbactam (SBT) were 1.92 μg/ml at 1 hour and 1.85 μg/ml at 1 hour, respectively.
The half-lives in serum and urinary excretion rate for ABPC and SBT were similar.
2. A clinical study was performed on 15 children with infections, including 4 with tonsillitis, 5 with pharyngitis, 2 each with bronchitis, cystitis, and urinary tract infections.
Doses ranging from 6.7 to 18.2mg/kg body weight were given tid. or qid. Lengths of treatment ranged from 5 to 10 days.
The therapeutic responses were considered “excellent” in 6 and “good” in 9, with an effectiveness rate of 100%.
3. As to side effects of the drug, diarrhea was observed in 1 patient.
It was concluded that SBTPC was a promising drug for the treatment of bacterial infections in children.

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Sultamicillin (SBTPC) is a combined drug of ampicillin (ABPC) and sulbactam (SBT) which is an inhibitor of β-lactamase, in a clinical form of tosylate with equivalent molecules in ester linkages. A tablet form of this combined drug has been released since July, 1987 in Japan and now a granular form for pediatric patients has been developed.
Hence, the granular form of SBTPC was administered to 6 boys (age: 8 years 5 months-11 years 5 months) to determine plasma and urinary concentrations of the drug and its urinary recovery-rates. The dose of 10mg/kg or 15mg/kg was given orally just after meal to 3 boys.
To study clinical and bacteriological effects of this drug, a mean daily dose of 27.1mg/kg divided 2-4 times a day was administered for 9 days on the average to a total of 57 cases with pharyngitis (5), tonsillitis (5), laryngitis (1), bronchitis (1), pneumonia (8), scarlet fever (1), typhoid fever (1), impetigo (16), furuncle (2), abscess (6), lymphadenitis (1) and urinary tract infection (10) except 2 cases which were unevaluable for clinical effects.
MICs of 7 drugs (SBTPC, ABPC, SBT, methicillin (DMPPC), cloxacillin (MCIPC), cephalexin and cefaclor) against 12 of 22 strains isolated from patients with infections of skin and soft tissue were determined with inoculum-sizes of 10⁸ and 10⁶ CFU/ml to study β-lactamase producing activities.
Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients including dropped-out cases.
The results obtained are summarized as follows.
1. Mean plasma peak levels of ABPC and SBT were observed at 1 hour after administration in both of the 10mg/kg and the 15mg/kg groups with values of 2.34 and 5.57 μg/ml for ABPC and 1.87 and 4.66 μg/ml for SBT, respectively. Mean concentrations of SBT were lower than those of ABPC in both groups and individuals. Dose-responses in plasma levels and AUCs were observed in both groups. Mean half-life values of ABPC and SBT in the 2 groups were 1.93 and 1.12 hours for ABPC and 1.97 and 1.22 for SBT, respectively. Mean half-life values for ABPC and SBT were similar in each group and this tendency was also seen among individuals. Mean half-lives in the 10mg/kg group were longer than those in the 15mg/kg group for both ABPC and SBT.
2. Most of urinary peak concentrations of ABPC and SBT were observed during 2-4 hours after administration in cases for which plasma concentrations of the drug were determined. Mean values of urinary recovery-rates during the 6 hours after administration in the 10mg/kg and the 15mg/kg groups were 62.4 and 72.0% for ABPC and 57.8 and 65.4% for SBT, respectively. Those values for ABPC were slightly higher than those for SBT in both groups.
3. Clinical effects were “excellent” or “good” in 50 of 57 cases and the efficacy rate was 87.7%.
4. In the evaluation of bacteriological effects, 30 out of 35 strains of organisms were eradicated with an eradication rate of 85.7%, thus the bacteriological effect was similar to the clinical effect.
5. β-Lactamase activities were observed in all 12 strains of Staphylococcus aureus. Five strains (41.7%) were low producers and 7 strains (58.3%) were high producers. In susceptibility test for drugs against the same 12 strains with inoculum sizes of 10⁸ and 10⁶ CFU/ml, MICs of SBTPC tended to be similar to or smaller than those of ABPC and slightly larger than those of MCIPC and DMPPC, and similar values to those of DMPPC.
6. Adverse reactions due to this drug were observed in 3 cases with diarrhea, one of which was with diarrhea and rash. No complaint against the medication of this drug was recorded.
7. As abnormal laboratory test values, eosinophilia was noted in 2 out of 23 patients.

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Sultamicillin (SBTPC) is a semi-synthesized β-lactam antibiotic consisted of ampicillin (ABPC) and a β-lactamase inhibitor, sulbactam (SBT), linked with an ester linkage. Pharmacokinetic and clinical studies using SBTPC 10% fine granules were performed in pediatric patients with a variety of infections.
1. Pharmacokinetic investigation:
SBTPC was given at 30 minutes after meal at a dose of 10mg/kg. Peak serum levels were attained at 1 hour after dosing with average levels of 3.83±0.27 μg/ml for ABPC and 2.73±0.30 μg/ml for SBT. The average half-life of ABPC was 1.52±0.25 hours and that of SBT was 1.13±0.09 hours. The urinary recovery rate of ABPC during 6 hours after dosing was 58.2±4.9% and that of SBT was 59.7±6.4%.
2. Clinical investigation:
Enrolled in the study were a total of 26 patients including 12 with tonsillitis, 6 with pharyngitis, 5 with urinary tract infections, and 1 each with bronchitis, with Salmonella enteritis and a case with fever of unknown case. Responses were excellent in 15 patients, good in 8, fair in 2 and poor in 1 with an efficacy rate of 88.5%. In the assessment of the bacteriological efficacy, 11 out of 14 strains of organisms isolated previous to the treatment were eradicated, 1 strain was found reduced in number and 2 strains remained unchanged with an eradication rate of 78.6%. One patient (3.8%) out of the 26 had diarrhea as side effects and 3 patients (16.7%) of 18 showed eosinophilia in laboratory examinations.

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Effects of sultamicillin (SBTPC) fine granules, a new oral β-lactam antibiotic, on the intestinal bacterial flora were studied in tetra-contaminated mice and in pediatric patients.
SBTPC was administered at a dose of 100mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. In all of the 4 species, bacterial populations in feces were markedly reduced on days 4 to 5 after the start of the treatment.
Subjects in the pediatric study were 5 children with bacterial infections (4 boys and 1 girl) at ages from 1 year 3 months to 10 years 8 months and with their body weight ranging from 11.8kg to 35.0kg. SBTPC fine granule was administered at a dose of 10mg/kg 3 to 4 times a day for 4 to 7 days. Although there were some variations in the fecal bacterial flora noticed among these subjects during the treatment, populations of main aerobes and anaerobes such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium decreased markedly in all cases. These decreases were more pronounced for anaerobes and total numbers of anaerobes were markedly reduced in all cases. Glucose non-fermenting Gram-negative rods and fungi tended to increase with administration of SBTPC fine granule. Although these changes tended to return to pre-dosing state after the cessation of the treatment with SBTPC fine granule, attention must be paid to possible occurrences of diarrhea, superinfection or bleeding tendency when treatment with the drug is continued for a long period of time.
Fecal concentrations of both ampicillin and sulbactam during SBTPC fine granule treatment showed relatively high values except 1 sample with a high β-lactamase activity in feces. These high concentrations suggest the possibility of biliary excretion of absorbed drugs and the possibility of hydrolysis of SBTPC in the intestine due to high pH. Fecal concentrations of the drug also appeared to be closely related to β-lactamase activity in feces.

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Sultamicillin fine glanules were administered orally to 21 patients with impetigo contagiosa and 1 patient with erysipelas, and its clinical efficacy and safety were assessed. The dosage was 10-30mg/kg daily.
Clinical efficacies of impetigo contagiosa were “excellent” in 20 cases and “fair” in 1 case, with an overall efficacy rate of 95%. The result of treatment in erysipelas was “good”.
Out of 19 strains of Staphylococcus aureus isolated from foci, 17 strains had high β-lactamase activities. In these 17 strains, sensitivity to the drug was 2-32-fold higher than to ampicillin, and in 14 out of these 17 strains 4-8-fold higher sensitivity was noted.
As side effects, mild diarrhea was seen in 2 patients, but those recovered spontaneously in 3-4 days without particular treatment.

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Clinical studies of sultamicillin (SBTPC) fine granules, an oral antibiotic with ester linked ampicillin and β-lactamase inhibitor, sulbactam, were performed in acute uncomplicated cystitis and complicated urinary tract infections.
1. SBTPC fine granules were administrated at a dose of 187.5mg 2-3 times daily for 5-7days to 6 patients with acute uncomplicated cystitis. Clinical emcacies as judged according to the criteria of the UTI Committee were excellent in 5 cases and moderate in 1 case with an effectiveness rate of 100%. All of 7 identified bacteria were eradicated by the treatment.
2. SBTPC fine granules were administrated at a dose of 187.5mg or 375mg 3 times daily for 5-7 days to 17 patients with complicated urinary tract infections. Clinical efficacies as judged according to the criteria of the UTI Committee were excellent in 8 cases, moderate in 4 cases and poor in 5 cases with an effectiveness rate of 70.6%. Out of 17 identified bacteria, 14 (82.4%) were eradicated by the treatment.
3. As adverse reactions, glossitis, diarrhea and pharyngeal redness were observed in 1 case out of 31 cases treated with the drug. These symptoms, however, were mild and transient. No abnormal laboratory test values were observed. From the above results, it appears that SBTPC fine granules are useful in the treatment of urinary tract infections.

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This study was performed to evaluate the clinical efficacy and the safety of sultamicillin (SBTPC) fine granules in the treatment of patients with meibomianitis.
A dose of 375mg SBTPC granules was orally given to 10 patients with meibomianitis after each meal, three times a day.
The results obtained are summarized as follows.
Efficacies were rated as good in 7 cases, fair in 2 and poor in 1 with an efficacy ratio of 70.0%. No side effects were observed throughout the study. The organisms isolated were Gram-positive bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, coagulase negative Staphylococcus and Streptococcus sanguis, and Gram-negative bacteria such as Alcaligenes denitrificans subsp. denitrificans, Alcaligenes denitrificans subsp. xylosoxidans, Xanthomonas maltophilia and Acinetobacter lwoffii. A bacteriological study showed lower MICs of SBTPC than those of ampicillin (ABPC), suggesting that SBTPC has more potent antibacterial activity than ABPC. Such bacteriological activity of SBTPC was well reflected in its clinical efficacy; the drug was effective in patients with infections caused by organisms moderately or highly resistant to ABPC or cefaclor.

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In an attempt to examine the effect of sulbactam (SBT) on βA-lactamase activity, three hundred clinical isolates from the infected upper respiratory tract were tested for MICs and disk sensitivities of ampicillin (ABPC) and sultamicillin (SBTPC).β-Lactamase production was tested using the acidometry disk method(βA-Check, Taito Pfizer Co.).
For strains such as Klebsiella spp. which form mucoid type colonies, we used the SS culture medium which, by reducing the influence of huge amounts of capsular material, allows a better reaction to the acidometry disk.
Penicillinase, produced by Branhamella catarrhalis, Haemophilus influenzae, Neisseria spp., etc. was detected clearly by direct application of portions of colonies onto acidometry disks. For cephalosporinase, however, a direct application of such fractions resulted in weak reactions. We, therefore, used fractions which had undergone the enzyme induction, and obtained better reactions.
Sensitivities of tested bacteria to ABPC and SBTPC were inversely related to MIC values.
β-Lactamase-producing strains showed weaker sensitivity to ABPC than non-producing strains. To SBTPC, however, β-lactamase-producing strains and non-producing strains showed very similar sensitivity. We thus confirmed that the inhibitory action of SBT to β-lactamase can well be demonstrated using the disk sensitivity method.

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