[in Japanese]

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Amounts of particulate matter present in 17 small volume antibiotic injections marketed in Japan were determined using light obscuration particle analyzer (HIAC). The vial volume range of each batch of product was 7-20ml, and each vial contained 1g as antibiotic potency.
In 4 products, contents of particles between 2.5 and 10μm in diameter were counted 2, 000-7, 000 per vial, and particles in other products were counted less than 2, 000 per vial.
Numbers of particles ≥10μm in diameter were much less than the USP XXI criteria for particulate matter in small volume injections.
The product of the highest counts for particles between 10 and 25μm in diameter showed counts amounted to 0.13% of the USP XXI criteria. In the 25-50μm particulate diameter range, particulate matters were detected only in 2 products, and they were less than 0.2% of the USP XXI criteria.
Particles over 50μm in diameter were not detected in any products.
These results showed that 17 small volume antibiotic injections marketed in Japan had good qualities regarding contents of particulate matter.

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We made an attempt to treat with cefmetazole (CMZ) 25 patients who developed severe infectious diseases while suffering with granulocytopenia associated with the treatment of malignant hematological disorders.
1. Determination of bacteriological efficacy
While 20 strains were isolated and identified from 15 patients, no significant bacteria were detected in 9 patients. Isolates obtained were: 5 strains of Enterococcus faecalis, 3 strains of Haemophilus influenzae, 2 strains of Staphylococcus epidermidis, 2 strains of Klebsiella oxytoca, 2 strains of Staphylococcus aureus, and 1 strain each of Neisseria sp., Pseudomonas maltophilia, Enterobactor sp., α-Streptococcus, β-Streptococcus and Gram-positive cocci. Causative organisms were eradicated or markedly in 7 of the 15 patients from whom bacteria were isolated. Clinical findings, including fever, revealed that none of the patients, in whom bacteriological efficacy was determined to be poor, exhibited sufficient clinical response. E. faecalis was isolated from 4 of 6 patients bacteriologically determined to have no response.
2. As for 23 patients, who were found to be evaluable among the 25 patients, 8 (34.8%), 4 (17.4%), 4 (17.4%), and 7 (30.4%) demonstrated excellent, good, fair and poor responses, respectively, showing a 69.6% efficacy rate which indicates a sum of percentages of patients with excellent, good and fair responses.
3. While an efficacy rate of 100% was obtained for 3 patients with number of peripheral neutrophils less than 500/mm³ before the beginning of CMZ administration, only an efficacy rate of 66.7% was obtained for 15 patients with neutrophils more than 500/mm³.
4. Among 13 evaluable patients treated with CMZ alone, 6, 3, 1, and 3 showed excellent, good, fair and poor responses, respectively, indicating a 76.9% efficacy rate. As for 10 patients receiving CMZ in combination with aminoglycoside, penicillin or fosfomycin, an efficacy rate was calculated to be 60%.
5. No side effects were observed in 25 patients who recieved chemotherapy with CMZ.
These results indicated that chemotherapy with CMZ is effective in the treatment of severe infectious diseases accompanied by hematological disorders except in some cases caused by some particular bacteria.

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Pharmacokinetic and bacteriological studies were carried out on sulbactam/ampicillin (SBT/ABPC) in the field of pediatrics. The results obtained are summarized as follows:
1. A total of 248 clinical isolates were employed to determine minimum inhibitory concentrations (MIC) of SBT/ABPC against various bacterial species. SBT/ABPC showed stronger antibacterial activity against Gram-positive organisms than against Gram-negative rods.
2. The peak serum level of ABPC was about twice as high as that of SBT, and serum levels of ABPC and SBT declined with time. Both drugs showed almost the same trend of changes in concentrations. The half-lives of both drugs were about 1 hour.
3. The urinary recovery rates over 6 hours after administration were 52-80% for ABPC and 70-73% for SBT.
4. The effect of SBT/ABPC on coagulation system was examined. No case showed changes in PT, APTT, TT and HPT before and after administration of SBT/ABPC. Platelet aggregation during administration of SBT/ABPC was slightly faster than that before administration, suggesting that SBT/ABPC had no effect on platelet aggregation. Generally speaking, it seemed that SBT/ABPC was a safe antibiotic for bleeding.
5. The effect of SBT/ABPC on the intestinal bacterial flora in experimental animals was examined. Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve were reduced after administration of SBT/ABPC, suggesting that the intestinal bacterial flora was affected by the administration of SBT/ABPC more greatly than by the administration of ABPC alone. In a similar investigation being made with clinical cases, both aerobes and anaerobes showed great changes. Concentrations of the drugs in feces increased with increasing dosage, resulting in greater changes of the intestinal bacterial flora. Thus, the total number of aerobes and anaerobes was reduced. No diarrhea was observed in any subjects examined.
From the above results, it appeared that SBT/ABPC was a safe and useful antibiotic for various bacterial infections in the field of pediatrics.

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Concentrations of sulbactam (SBT) and ampicillin (ABPC) in the blood and cerebrospinal fluid (CSF) following an intravenous administration of SBT/ABPC at a dose of 150mg/kg (SBT/ABPC=1: 2) were determined in 12 rabbits with staphylococcal meningitis. Drug concentrations were measured 9 times, 6 times each with intervals of 15 minutes and thereafter with intervals of 30 minutes. The results were compared with those of a group of 9 rabbits given 100mg/kg of ABPC alone.
1. The maximum concentration of SBT in the CSF and the percentages of both the maximum concentration and the area under the concentration-time curve (AUC) of SBT in CSF vs. those in serum of the SBT/ABPC group were higher than those of ABPC and the half-life of SBT in the CSF was also longer than that of ABPC, all with significant difference. When these parameters for SBT of SBT/ABPC groups were compared with those of ABPC of the ABPC group, not much differences existed between the 2 groups except that the CSF half-life of SBT was much longer than that of ABPC.
2. The percentages of both the maximum concentration and AUC of ABPC in CSF vs. those in serum of the SBT/ABPC group were significantly lower than those of ABPC of the ABPC group. The CSF half-life of ABPC of the former group was longer than that of the latter.
3. The above results suggest that when SBT and ABPC are administered simultaneously, the penetration of ABPC into the CSF is inhibited.

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During 8 months from October 1986 to May 1987, the clinical efficacy of sulbactam/ampicillin (SBT/ABPC) was evaluated in 63 pediatric inpatients with various infections. Clinical efficacies were evaluable in 58 patients among them (consisting of 2 patients with sepsis, 3 with tonsillitis, 12 with bronchitis, 6 with bronchopneumonia, 24 with pneumonia, 1 with phlegmon, 2 with lymphadenitis, 1 with impetigo and 7 with urinary tract infection) and were excellent in 40 patients and good in 17 with an overall efficacy rate of 98.3%.
Bacteriological efficacies were assessed in 25 patients and 27 strains of organisms (consisting of 3 strains of Staphylococcus aureus, 2 Streptococcus pneumoniae, 1 Streptococcus pyogenes, 2 β-Streptococcus, 1 Gram-positive cocci, 5 Escherichia coli, 1 Enterobacter aerogenes, 7 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 1 Branhamella catarrhalis, 1 Proteus mirabilis and 1 Salmonella subgenus I). Bacteriological eradication rates were 88.9% for Gram-positive organisms, 66.7% for Gram-negative organisms and 74.1% overall. No superinfection was observed in any of patients treated.
Side effects and clinical laboratory parameter abnormalities observed consisted of diarrhea in 7 (11.1%) of the 63 patients, eosinophilia in 2 (3.3%) of 61 tested, thrombocytosis in 3 (5.5%) of 55, elevation of direct bilirubin in 1 (3.3%) of 30, elevation of total bilirubin in 1 (3.1%) of 32, elevation of GOT in 4 (6.8%) of 59 and elevation of GPT in 1 (1.7%) of 59 patients tested. As an effect on the hemostatic mechanism of this drug, PIVKA II was detected in 1 patient (4.2%) of 24 tested, but findings of other coagulation tests were normal and none of patients showed bleeding tendency or inhibition of platelet aggregation.
From the above results, it appears that SBT/ABPC is an efficacious and safe drug in the treatment of bacterial infections of pediatric patients.

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Sulbactam/ampicillin (SBT/ABPC) was administered to 33 pediatric inpatients with 34 bacterial infections. Clinical efficacies were judged to be good in 33 cases (97.1%) out of 34 which included 13 cases of 14 with infections caused by β-lactamase-producing strains of organisms, and successfully cured by this drug.
There were no particular side effects to comment except some cases of diarrhea and loose stool.
These results indicated that SBT/ABPC would be useful in the treatment of pediatric infections as a first choice of drug. Serum half-lives of ABPC and SBT were 0.79 hour and 1.02 hours, respectively, hence, q. i. d. dosage regimen would be appropriate.

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Intravenous administration of sulbactam/ampicillin (SBT/ABPC) was evaluated in pediatric patients.
The serum half-lives of both ABPC and SBT were approximately 1 hour following the intravenous injection or intravenous drip infusion of 20-35mg/kg, and 30-50% of ABPC and 30-70% of SBT were recovered in the urine 6 hours.
Cerebrospinal fluid concentrations of ABPC and SBT were 0.76 and 0.68μg/ml, respectively, at 1 hour after intravenous drip infusion of the58 mg/kg, and concentration ratios of the drugs in cerebrospinal fluid/serum were 6.39 and 5.71%, respectively.
Thirty-four pediatric patients were treated with intravenous drip infusion of SBT/ABPC in doses ranging from 54 to 150mg/kg divided into 3 times a day. The rate of clinical efficacy was 93.5% and the bacterial elimination rate was 92.3%. The synergistic activity of sulbactam with ampicillin was demonstrated against β-lactamase-producing Staphylococcus aureus and Haemophilus influenzae isolated from patients in the present study. The side effects of SBT/ABPC were observed in 6 patients (5 diarrheas; 1 diarrhea with vomiting) out of 34 patients administered. Eosinophilia (2 patients) and a slight elevation of GOT (1 patient), GPT and LDH (1 patient) were observed. The tolerance to the therapy, however, was good.

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Clinical trials were carried out on the use of sulbactam/ampicillin (SBT/ABPC)(combination rate of 1:2) in pediatric infections. Results were as follows:
1. The mean half-lives of SBT and ABPC in the serum following intravenous injection of SBT/ABPC were about 1.05 and 0.90 hours, respectively.
2. The mean urinary excretions of SBT and ABPC in 6 hours after intravenous injection of SBT/ABPC were 71.2% and 62.2%, respectively.
3. SBT/ABPC was administered to 23 pediatric patients with various infections: 17 patients with pneumonia, 3 with tonsillitis, 2 with urinary tract infection and 1 with cervical lymphadenitis. The overall efficacy rate was 95.7%. In particular, 2 urinary tract infections caused by highly β-lactamase producing Escherichia coli were improved by the treatment with SBT/ABPC.
4. No adverse reactions were observed except 2 cases of mild diarrhea. Abnormal laboratory test values included thrombocytosis in 4 and slight elevation of GOT and GPT in 1, but they were transient.

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The new antibiotic, sulbactam/ampicillin (SBT/ABPC) was administered to 25 children. The results obtained are summarized as follows.
1. In 5 cases of children administered with SBT/ABPC (30mg/kg) by intravenous drip infusion for 30 minutes, the mean values of T 1/2(β) were 0.94 hour (SBT) and 0.86 hour (ABPC) and the mean 6.5 hour urinary excretion rates were 64.2% and 42.9%, respectively.
2. The antibiotic was administered to a total of 25 patients with bronchopneumonia, pneumonia, bronchitis, cervical lymphadenitis, tonsillitis, streptococcal infection, urinary tract infection, felon, periappendicular abscess, sepsis or purulent meningitis. Responses to the treatment were excellent in 17 cases, good in 7, fair in 1, and poor in none. The efficacy rate was 96%. From our results, this drug appears to be particularly effective against bronchopneumonia, bronchitis and urinary tract infection.
3. Eruption occurred in 1 of 25 patients and elevation of eosinophil, GOT/GPT, platelet in 3 and descent of WBC in 1 were observed, but these were transient. These results showed that SBT/ABPC is a drug which can be safely used in the pediatric field as well as for adults.

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Pharmacokinetic and clinical studies on sulbactam/ampicillin (SBT/ABPC) were carried out in the field of pediatrics.
1. Absorption and excretion
Serum levels and urinary excretion of SBT/ABPC were studied in 4 children with ages 6 to 8 years.
The mean serum concentration of SBT at 15 minutes following a single intravenous injection of 30 mg/kg of SBT/ABPC was 27.4±2.2 μg/ml and that of ABPC was 42.8±3.9 μg/ml, and their concentrations declined with mean half-lives of 1.06±0.15 hours and 0.84±0.05 hour, respectively, and at 6 hours were 0.3±0.2 μg/ml and 0.2±0.1 μg/ml on the average, respectively.
The urinary recovery rates of SBT and ABPC at 6 hours after the injection were 59.0±22.4% and 58.4±25.3% on the average, respectively.
2. Clinical study
SBT/ABPC was used for the treatment of a total of 36 pediatric patients with ages ranging 2 months to 11 years and it's clinical effectiveness, bacteriological efficacy and adverse effects were evaluated.
Clinical efficacies in 5 patients with acute purulent tonsillitis, 26 with acute pneumonia and 1 with acute pyelonephritis were judged to be excellent in 27 cases and good in 5 cases with an overall efficacy ratio of 100.0%.
Clinical efficacies in 6 patients whose infections were caused by β-lactamase producing strains were judged to be excellent in all cases.
Bacteriological efficacies of SBT/ABPC were assessed on 1 strain of Staphylococcus aureus (β-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 16 strains of Haemophilus influenzae (5 β-lactamase producing strains and 11 non-β-lactamase producing strains), 1 non-β-lactamase strain of Haemophilus parainfluenzae and 2 strains of Escherichia coli (non-β-lactamase producing strains). All strains except 1 strain of H. influenzae (β-lactamase producing strain) which decreased in number were eradicated with a bacteriological eradication rate of 95.5%.
Only 1 patient complained of diarrhea which was suspected to be related to the drug.
No other side effect was reported. Elevations of GOT and GPT were observed in only 1 patient.
The above results suggested that SBT/ABPC was a useful drug with preferable safety profile in the treatment for pediatric patients with infectious desease caused by β-lactamase producing strains as well as those by non-β-lactamase producing strains.

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Sulbactam/Ampicillin (SBT/ABPC), a combination at a fixed ratio of ABPC and SBT which is an irreversible inhibitor of β-lactamase in a 2:1 ratio, was clinically evaluated for its efficacy and safety in 24 patients with ages from 5 month-old to 12 years old with bacterial infection. The results obtained are summarized as follows.
1. A pharmacokinetic study following 30mg/kg SBT/ABPC administration by 30 minutes drip infusion or intravenous bolus injection showed that mean half-lives of SBT and ABPC were 48.9 minutes and 40.2 minutes, respectively, and mean urinary excretion rates of SBT and ABPC in the first 6 hours were 67.1% and 48.3%, respectively.
2. SBT/ABPC was administered to 14 patients with bronchopneumonia, 4 patients with tonsillitis, a patient each with acute upper respiratory infection, with submandibular lymphadenitis, with phlegmon, with enterocolitis, with pyelonephritis and with crystitis at a daily dosage of 88.2-133.3 mg/kg, divided into 3 or 4, by intravenous bolus injection or by 30 minutes drip infusion. Clinical responses of the 24 patients were as follows: excellent: 17 patients, good: 7 patients. The efficacy rate was 100%.
3. Neither clinical adverse reactions nor abnormal laboratory test values, except slight eosinophilia in a patient and an elevation of GOT, GPT in another were observed.
4. MICs of SBT/ABPC against 7 strong β-lactamase producing strains isolated from some of the patients were as follows.
MIC against a strain of Staphylococcus aureus was 3.13 μg/ml, MICs against 2 out of 5 strains of Branhamella catarrhalis were 0.10μg/ml and those of the remaining 3 strains were 0.20 μg/ml. MIC against a strain of Haemophilus parainfluenzae was 3.13 μg/ml.
5. These data described above show that SBT/ABPC has excellent bactericidal capacity against β-lactamase producing bacteria as well as β-lactamase non-producing Gram-positive and negative bacteria and suggest that SBT/ABPC is a very useful antibiotic for pediatric patients.

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We have carried out laboratory and clinical studies on sulbactam/ampicillin (SBT/ABPC).
The results are summarized as follows.
SBT/ABPC was given by 30-minute drip infusion to 1 child at a single dose of 15mg/kg and to 2 children at a single dose of 30 mg/kg. After the 30-minute drip infusion, peak serum levels of ABPC (SBT) obtained for the 2 dose levels were 18.0μg/ml (12.4μg/ml) for the former dose level and 81.0μg/ml (53.7μg/ml) and 300μg/ml (200μg/ml) for the latter at the end of injection, and half-lives were 0.84 hour (0.82 hour) for the former and 0.96 hour (1.44 hours) and 0.93 hour (1.19 hours) for the latter. In another trial, SBT/ABPC was given to 1 child at a single do,se of 60 mg/kg. After the 30-minute drip infusion, peak serum level of ABPC (SBT) was 82.3,ug/ml (45.9μg/ml), and half-life was 1.20 hours (1.36 hours).
The urinary excretion rates of ABPC (SBT) were 51.3% (49.5%), 55.8±10.4% (65.3±9.1%), 74.0% (76.1%) up to 6 hours after the 30-minute drip infusion of 15 mg/kg, 30 mg/kg and 60mg/kg, respectively.
Treatment with SBT/ABPC was made in 21 cases of pediatric bacterial infections: 8 cases of tonsillitis, 4 cases of bronchitis, 3 cases of pneumonia and 1 case each of pharyngitis, peritonsillar abscess, lymphadenitis, impetigo, abscess and urinary tract infection. Results obtained were excellent in 14 cases, good in 7 cases.
No significant side effect due to the drug was observed in any cases except 1 case of fever and rash.

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Laboratory and clinical studies of sulbactam/ampicillin (SBT/ABPC) in children have been carried out, and the following results were obtained.
1. Antibacterial effect MICs of SBT/ABPC were only one-tube less than or similar to those of ABPC against susceptible organisms. Against ABPC-resistant organisms at the inoculum size of 10⁸ cells/ml however, SBT/ABPC was superior to ABPC when evaluated in terms of their MIC values.
When MICs of SBT/ABPC were compared to those of ABPC against organisms with high β-lactamaso producing activitios, it was found that many of ABPC-rosistant organisms were much susceptible to SBT/ABPC.
2. Absorption and urinary excretion In 2 cases to which 50mg/kg and 20mg/kg SBT/ABPC were respectively given over 30 minutes by drip infusion, peak serum levels were obtained at the end of the drip infusion with peak levels of SBT of 45.5μg/ml, 12.5μg/ml, respectively and those of ABPC of 83.0μg/ml, 22.9μg/ml, respectively.
The half-lives of SBT and ABPC were 0.94 hour and 0.98 hour, respectively.
The mean urinary excretion rates in the first 6 hours after the end of administration were 84.4% for SBT and 63.1% for ABPC.
3. Clinical results Clinical efficacies were evaluated in 24 cases including 9 cases of pneumonia, 2 cases of upper respiratory infection, 7 cases of urinary tract infection and 1 case each of bronchopneumonia, pyothorax, tonsillitis, streptococcal infection, phlegmone and staphylococcal scalded skin syndrome.
Clinical efficacies were excellent or good in 19 cases with an overall efficacy rate of 86.4%.
Adverse effect was found in 1 case with nausea and vomiting, and abnormal laboratory test values observed were 2 cases each of eosinophilia, slight elevation of GOT and GPT and elevation of LDH, but they were not serious.

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The usefulness of sulbactam/ampicillin (SBT/ABPC) in the treatment of pediatric infections was evaluated.
1. Twenty pediatric patients with infection were treated with SBT/ABPC and an intravenous dosage of 27.8-47.4mg/kg, 3 to 4 times a day. Clinical efficacies in 18 patients excluding 2 patients ofMycoplasma pneumonia (9 cases of pneumonia, 6 urinary tract infection, 1 tonsillitis, 1 maxillary sinusitis and 1 osteomyelitis) were judged to be excellent in 13 patients and good in 5. There was no case of failure.
2. Bacteriological efficacies against 16 strains (1 Staphylococcus aureus, 3 Enterococcus faecalis, 4 Haemophilus influenzae, 2 Haemophilus parainfluenzae, 5 Escherichia coil and 1 Serratia sp.) isolated from 13 of the 18 patients were rated as “eradicated” for 13 strains,“decreased” for 1 and “unchanged” for 2 with an eradication rate of 81.3%. Of 13 strains eradicated, 3 were those with high β-lactamase productivity.
3. Rash as a side effect developed in 1 patient and eosinophilia and elevated GOT and GPT were observed in 7 patients but none of them were serious.
4. Blood levels of the drug following an intravenous dose of 30mg/kg were determined in 2 pediatric patients. Blood levels of SBT and ABPC at 30 minutes after intravenous administration were 19.0 and 29.2μg/ml in one patient and 21.0 and 31.6μg/ml in another, respectively, and those at 4 hours were 0.48 and 0.62μg/ml in one patient and 0.59 and 0.89μg/ml in another, respectively. The half-lives of SBT were 0.67 and 0.70 hour and those of ABPC were 0.64 and 0.69 hour in the 2 patients, respectively.
5. The above results suggest that SBT/ABPC is a useful medication in the treatment of pediatric bacterial infections and is effective at an intravenous dose of 30 mg/kg t. i. d. or q. i. d.

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A combination drug of sulbactam/ampicillin (SBT/ABPC) was intravenously administrated to 18 patients with ages 3 months to 10 years 10 months with various acute infections including 14 cases of pneumonia, 1 case each of tonsillitis, subacute bacterial endocarditis, empyema and suspected sepsis.
Clinical responses were excellent in 14 cases and good in 4 cases.
Bacteriological responses of 8 isolated strains were: 7 strains were eradicated and 1 strain was decreased. No side effect was observed in any case.
Eosinophilia was observed in 2 cases, thrombocytosis in 2 cases, elevation of GOT in 1 case and elevations of GOT and GPT in 1 case.
From the above results, it seemed that SBT/ABPC was a useful drug for the treatment of bacterial infections in the pediatric field.

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Sulbactam/ampicillin (SBT/ABPC) was given intravenously to 20 children with the following acute bacterial infections; 14 cases of pneumonia, 2 cases of purulent cervical lymphadenitis and 1 case each of bronchitis, pyothorax, cellulitis and purulent meningitis. Good clinical responses were obtained in 18 out of 20 patients, and bacteriologically, all of the 14 isolated strains were eradicated. No side effect was observed except 2 cases of eosinophilia, and 1 case each of loose stool and elevated thrombocyte.
From the above clinical results, it is apparent that SBT/ABPC is a useful antibiotic for the treatment of pediatric patients with various kinds of bacterial infections.

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The pharmacokinetics, efficacy and safety of sulbactam/ampicillin (SBT/ABPC) were evaluated in 21 children with a variety of infections. The results obtained are summarized as follows.
1. Pharmacokinetics in 4 children, each receiving a single dose of 60 mg/kg, were evaluated. The average half-life of SBT was 1.03 hours and that of ABPC was 0.83 hour.
2. In vitro antimicobial activity (MIC) of SBT/ABPC in which SBT and ABPC are combined at a ratio of 1: 2 was stronger than ABPC alone and was quite effective against Staphylococcus aureus and Haemophilus influenzae, but activity against Escherichia coli was relatively low.
Antimicrobial activity of SBT/ABPC against S. aureus was almost equal to those of piperacillin (PIPC), cefazolin (CEZ) and cefmetazole (CMZ), but against H. influenzae was stronger than those of CEZ and CMZ. Activity against E. coli was lower than those of PIPC, CEZ and CMZ.
3. A total of 21 patients including 3 with pharyngitis, 10 with bronchitis, 5 with pneumonia, 1 each with acute enteritis, pyelonephritis and suspected sepsis were treated with SBT/ABPC.
The clinical efficacy rate for these patients was 95.2% (20/21). The bacteriological eradication rate was 80% (8/10).
4. There were 4 instances of side effects, 1 case each of eruption, diarrhea, thrombocytosis and eosinophilia, but all symptoms were transient.

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Pharmacokinetic and clinical studies of sulbactam/ampicillin (SBT/ABPC) were conducted and the obtained results are summarized as follows.
For pharmacokinetic investigation, SBT/ABPC at 30 or 60 mg/kg was administered by intravenous drip infusion over 30 minutes. The maximum blood concentration was reached just after the completion of the drip infusion in both groups.
The mean peak serum concentrations of SBT and ABPC were 22.4±0.8μg/ml and 32.8±1.0μg/ml, respectively, in the 30 mg/kg group, and they were 54.2μg/ml and 93.8μg/ml, respectively, in the 60 mg/kg group.
The concentrations were dose-related.
The mean half-lives of SBT and ABPC following 30 mg/kg SBT/ABPC administration were 0.91±0.04 hour and 0.90±0.05 hour, respectively, and those following 60 mg/kg SBT/ABPC were 1.08 hours and 0.84 hour, respectively.
The highest urinary concentration occurred 0-2 hours after the 30 minutes drip infusion. Mean urinary excretion rate of SBT and ABPC over 6 hours were 71.4±2.5% and 54.6±3.3%, respectively, in the 30 mg/kg group, and they were 80.0% and 63.7%, respectively, in the 60mg/kg group.
In the clinical investigation conducted with a total of 24 patients (15 with respiratory tract infections, 3 with urinary tract infections, 2 with lymphadenitis, and others), SBT/ABPC was found to be excellent in 14 cases, good in 9, fair in 1. The efficacy rate was, therefore, 95.8%.
In the bacteriological evaluation, 9 out of 11 clinically isolated strains were eradicated, 1 unchanged and 1 unknown. The elimination rate was 90.0%.
Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, a slight elevation of GOT was observed.

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Sulbactam (SBT) is a new derivative of the basic penicillin nucleus. It effectively and irreversibly inhibits several important bacterial β-lactamases and displays synergistic effects against the resistant organisms when co-administered with ampicillin (ABPC). SBT/ABPC, which is a fixed combination of SBT and ABPC in a 1: 2 ratio, was studied for clinical efficacy in the field of pediatrics.
Patients treated were infants and children ranging from 12 days to 13 years and 2 months old suffering from acute tonsillitis in 2 cases, acute bronchitis in 2 cases, septicemia in 2 cases, acute enteritis, acute pyelonephritis and osteomyelitis in 1 case each, a total of 9 cases. SBT/ABPC was administered 100-300mg/kg in daily doses and durations of treatment ranged from 4 to 17 days.
Clinical results were “excellent” in 6 and “good” in 2: the efficacy rate was 88.9% or 8 cases out of 9.
Neither clinical side effects nor abnormal laboratory findings obviously attributable to SBT/ABPC were observed in any cases.

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Plasma and urine concentrations of sulbactam (SBT) and ampicillin (ABPC) were determined following bolus administration of injectable SBT/ABPC combined in a fixed ratio of 1: 2 to 6 pediatric patients, 3 at a dose of 30mg/kg and the other 3 at 60mg/kg. Clinical and bacteriological efficacies of SBT/ABPC were evaluated in a total of 65 patients composed of 45 cases with pneumonia, 3 cases each with bronchitis, urinary tract infections, staphylococcal scalded skin syndrome, purulent lymphadenitis, 2 cases each with tonsillitis, pleuropneumonia, phlegmon and 1 case each with pyothorax, submaxillaritis. The dosage used was 101.2mg/kg daily given in 3 or 4 divided doses (t. i. d. in 24 patients and q. i. d. in 41 patients) by bolus intravenous injection for 7 days on an average. Side effects and effects on clinical laboratory parameters were monitored in the 65 patients. The results of these evaluations are summarized as follows.
1. Mean serum concentrations of SBT and ABPC in 3 children each given an intravenous bolus injection of 30mg/kg and other 3 each given 60mg/kg reached peak levels at 5 minutes after administration with values of 49.8 and 90.3μg/ml, respectively, for SBT and 99.8 and 189.7μg/ml, respectively, for ABPC. The latter values were about twice as high as SBT, and both were dose-related. Mean half-lives were 0.889 hour for SBT and 0.857 hour for ABPC in the 30mg/kg group and 0.882 hour for SBT and 0.834 hour of ABPC in the 60mg/kg group, showing similarities between the 2 dosage groups as well as between SBT and ABPC.
2. Mean urine concentrations in the 2 groups mentioned above were the highest for both SBT and ABPC during the first 2 hours after administration, with values of 1,677μg/ml for SBT and 2,730μg/ml for ABPC in the 30mg/kg group and 2,693μg/ml and 3,623μg/ml, respectively, in the 60mg/kg group. Mean recovery rates in urine in the first 6 hours were 72.4% for SBT and 56.8% for ABPC in the low dosage group and 72.7% and 52.0%, respectively, in the high dosage group. In the 2 groups, the amounts of ABPC recovered were less than those of SBT.
3. Clinical efficacies of SBT/ABPC in 65 patients with various bacterial infections were excellent or good in 62 (95.4%) patients.
4. The bacteriological efficacy was evaluable with 10 patients. The pathogenic bacteria were eradicated in 9 patients and the efficacy rate was 90%.
5. In a total of 65 patients administered with SBT/ABPC, eruption as side effect of the drug occurred in 1 patient (1.5%), laboratory parameter abnormalities found were granulocytopenia in 1 patient (1.7%), eosinophilia in 4 (6.9%), thrombocytosis in 2 (4.3%), thrombocytopenia in 1 (2.1%), elevation of GOT in 2 (3.7%), elevation of GOT and GPT in 2 (3.7%) and elevation of LDH in 1 (2.4%). There was no case with abnormal values of Al-P, BUN or creatinine.

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