Sulbactam (SBT) inactivates penicillinase (PCase)-and lc-type β-lactamases strongly and cephalosporinase (CEPase)-type enzymes moderately.
A combination drug of sulbactam (SBT) and ampicillin (ABPC) in the ratio of 1:2, SBT·ABPC showed MIC_60s of 6.25, 6.25, 1.56, 6.25, 6.25, 6.25, 12.5, 50, 50, 6.25, 0.39, and 1.56ug/ml for S.aureus, coagulase-negative staphylococci (CNS), E. faecalis, E. coli, K. pneumoniae, C. freundii, E. cloacae, E. aerogenes, A. calcoaceticus, H. influenzae and B. fragilis, respectively. SBT-ABPC, however, manifested little bacteriostatic activity against S. marcescens, P. aeruginosa, and P. putida.
ABPC combined with SBT caused stronger morphological changes not only in β-lactamase-producing P. vulgaris but also in β-lactamase-non-producing S. aureus and Itinfluenzae than did ABPC alone, suggesting that the former possesses a stronger bactericidal effect than the latter, since ABPC combined with SBT has a stronger binding affinity to the bacterial PBPs than dose ABPC alone. A synergy of inhibitory effect between SBT and ABPC on the site of action in bacteria, was confirmed.
We expect SST·ABPC to be a highly useful chemotherapeutic for infections due to β-lactamase-producing bacteria, especially staphylococcal infections, despite the large number of third-generation cephems presently available.

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We investigated the in vitro and in vivo antimicrobial effect of a combination of ampicillin (ABPC) and the potent irreversible β-lactamase inhibitor, sulbactam (SBT).
The in vitro antibacterial activity of ABPC combined with SBT at a ratio of 2:1 was enhanced against clinical isolates of various species, especially S. aureus, M. morganii, penicillinase-producing N. gonorrhoeae and B. fragilis, as compared with that of ABPC alone.
SBT combined with ABPC prevented the hydrolysis of ABPC by β-lactamases and potentiated the bactericidal activity of ABPC against β-lactamase-producing bacteria.
In the treatment of experimental infections due to ABPC-resistant bacteria, a single injection of SBT-ABPC demonstrated potent therapeutic activity, while no such activity was observed with ABPC or SBT alone.

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The combination of sulbactam (SBT) and ampicillin (ABPC) in the ratio 1:2 (SBT·ABPC) was found to be widely effective against both Gram-positive and-negative bacteria, showing particularly strong activity against β-lactamase-producing ABPC-resistant strains of Staphylococcus spp., B. catarrhalis, H. influenzae and B. fragilis.
The bactericidal activity of ABPC was also potentiated by the addition of SBT, and the bactericidal action of SBT·ABPC was observed at a concentration of around its MIC value.
The in vitro and in vivo antibacterial activities of various ratios of SBT and ABPC were compared using β-lactamase-producing strains of Staphylococcus spp., B. catarrhalis, E. coli, P. vulgaris, H. influenzae and B. fragilis, the most effective ratio being between 1:2 and 1:1.
In mice, the therapeutic effect of SBT·ABPC was remarkable against not only infections caused by ABPCresistant strains, but mixed infections due to S. pneumoniae and avirulent β-lactamase producers against which ABPC alone proved to be ineffective.

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We evaluated the safety of sulbactam·ampicillin (SBT·ABPC) using rats, mice, dogs and cats.
The acute intravenous LD₅₀. of SBT·ABPC was greater than 6000 mg/kg in rats and mice.
In a subacute intravenous toxicity study, SBT·ABPC at doses of 90, 300, 900 and 1800 mg/kg, or ABPC at a dose of 1200 mg/kg for 28 days was well tolerated by all rats treated, and a non-toxic dose of SBT·ABPC was considered to be 300 mg/kg. SBT did not enhance the toxicity when combined with ABPC. The higher doses of SBT·ABPC produced slight growth inhibition, cecal enlargement, and a deposition of glycogen-like dropletsin the liver cells without any functional or morphological abnormalities. The ABPC group had no deposition of the droplets in the liver cells.
In the chronic toxicity study, the rats treated intraperitoneally with SBT·ABPC at doses of 150, 300 and 750 mg/kg for 6 months tolerated the drug well, and the results obtained were comparable to those in the subacute toxicity study. The non-toxic dose was evaluated as 300 mg/kg/day.
No significant general pharmacological effects were found in rats, mice, dogs or cats at intravenous doses of 375-3000mg/kg of SBT·ABPC.

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We studied the pharmacokinetics of sulbactam (SBT) and ampicillin (ABPC) in combination (1:2) or alone, after intravenous administration to rats and dogs. The following results were obtained.
1) The serum levels of SBT and ABPC achieved after intravenous administration of SBT·EABPC (1:2) were close to and maintained a ratio of 1:2; they were higher in dogs than in rats. The serum half-life of bot h SBT and ABPC was c. 20 min in rats and 30 min in dogs. The dose-related serum level and AUC were observed in rats given 60, 120 and 300mg/kg of SBT and ABPC in combination. The pharmacokinetic parameters in males were almost the same as in females.
2) SBT and ABPC were rapidly and widely distributed in various tissues after dosing. The concentrations of both SBT and ABPC were highest in the kidney and liver followed by serum, skin, lung, salivary gland and heart. In almost all tissues, SBT and ABPC levels declined from a ratio of 1:2 to 1:1. SBT and ABPC penetrated well into exudate in rat pouches.
3) After intravenous administration of SBT and ABPC, both drugs were predominantly recovered in urine at rates of 80% and 58% in rats, and 94% and 70% in dogs, respectively. No other active metabolites were detected in urine by means of TLC-bioautography. Fecal excretion of SBT and ABPC was almost negligible in rats and dogs and biliary excretion of SBT and ABPC in rats was 2 and 23%.
4) When SBT and ABPC were administered intravenously to HgCl₂-induced renal failure rats, urinary excretion of both drugs decreased and the serum elimination half-lives increased in comparison with those of normal rats. In rats with CCl₄-induced chronic hepatic failure, suppressed biliary excretion, increased urinary excretion and decreased serum half-life of ABPC were observed but none of the SBT values was affected. In Masugi-type glomerulonephritis rats and acute hepatic failure rats, no significant changes in serum concentrations and urinary recoveries were seen.
From these studies, We conclude that co-administration of SBT and ABPC (1:2) appears to have little effect on the pharmacokinetics of each drug. SBT and ABPC appear to be pharmacokinetically well mached and the ratio of SBT to ABPC achieved in serum and tissues is in the range of 1:2 to 1:1, which we consider optimal for producing synergistic activity against β-lactamase-resistant organisms.

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We developed the following two procedures after studies on sensitive assay methods for sulbactam (SBT), a β-lactamase inhibitor, in serum in the presence of ampicillin (ABPC).
I) Relatively low concentrations of SBT in serum could be determined with a detection limit of 0.05μg/ml by high-performance liquid chromatographic amperometry following pre-column reaction with hydroxylamine. This method was not affected by the coexistence of ABPC, cefoperazone (CPZ), or their metabolites in assay samples.
2) We developed an SBT bioassay using the synergistic activity of SBT in the presence of ABPC. In the microbiological assay, the combination of the β-lactamase-producing strain, Branhamella catarrhalis No.8, and the ABPC-sensitive strain, Bacillus subtilis ATCC 6633 were used as test organisms. Mueller Hinton agar containing a 20μg/ml concentration of ABPC as assay medium proved most suitable for sensitive determination of SBT serum levels in the presence of ABPC. The detection limit of SBT in serum was 0.05μg/ml.
Serum levels in patients determined by the HPLC and bioassay methods mentioned above showed high correlation.

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Sulbactam-ampicillin (SST·ABPC) is a formulation consisting of one part of SBT, a β-lactamase inhibitor, and two parts of ABPC, an antimicrobial agent. We investigated the antibacterial activity of ABPC and ABPC with SBT (1, 5 and 10μg/ml) against 172 strains of Staphylococcus aureus, Escherichia coli, Kkbsiella pneumoniae, Proteus mirabilis, Morganella morganii, Sermtia marcescens and Pseudomonas aeruginosa using the plate dilution method. The activity of SBT·ABPC was markedly superior to that of ABPC alone against all strains except P. aeruginosa.
Ten patients with bacterial infections were treated with 1.5g twice daily of SBT·ABPC for 7-14 days. All showed good clinical response. No side effect occured, though slightly elevated GPT was observed in one patient.

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We studied the clinical and adverse effects of sulbactam-Eampicillin in 13 patients with respiratory infections who were given 3 g b.i.d. by drip infusion. Among them were 1 case of chronic bronchitis, 8 of pneumonia and 4 of mycoplasma pneumonia.
The clinical effect was good in 9 patients who were excluded to have mycoplasma pneumonia, the efficacy rate being 100%. As to causative organisms, while the fate of K. oxytoca was unknown, K. pneumonide was found to persist.
No side effect was observed. Laboratory findings revealed one case of slight elevation of GOT, GPT and LDH and one case of slight elevation of GOT and GPT.

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To evaluate the clinical utility of sulbactanyampicillin, we carried out a trial with 7 patients, including 4 with bacterial pneumonia and 1 each with bronchiolitis, secondary infection of bronchiectasis and secondary infection of bulla.
Clinical efficacy was excellent in 1 patient, good in 4, fair in 1 and poor in 1.
Bacteriological efficacy against 6 strains of clinical isolates including H.influenzae, A.calcoaceticus, K.pneumoniae, with M.morganii (mixed infection), S. pneumoniae and S. aureus was: 2 strains eradicated (A. calcoaceticus, S. pneumoniae), 2 strains replaced (H. influenzae→E.agglomerans, S. aureus→K. pneumoniae, unknown→K. oxytoca) and 2 strains reduced (K. pneumoniae with M. morganii →K. pneumoniae). There were no side efects.
As laboratory abnomality, eosinophilia in one patient was observed.

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We examined the in vitro antimicrobial activity of sulbactam. ampicillin (SBT·ABPC), a 2:1 composition of ABPC and SBT, a potent inhibitor of β-lactamases, by a microbroth dilution method using the Dynatech MIC-2000 system, and evaluated its therapeutic effect in lower respiratory infections.
The minimum inhibitory concentrations (MICs) of SBT·ABPC, ABPC, piperacillin (PIPC) and cefazolin (CEZ) against the following 155 clinical isolates were determined: 20 strains each of S. aureus, E. coil, K. pneumoniae, E. cloacae, S. marcescens and P. aeruginosa, 25 strains of H. influenzae and 10 strains of B. catarrhalls.
The determination of MICs showed that SBT·ABPC was more active against all the species, especially against β-lactamase-producing strains such as B. catarrhalis, K. pneumoniae and ABPC-resistant S. aureus, H. influenzae, E. coli and E. cloacae, than ABPC.
A daily dose of 3 to 6 g of SBT·ABPC was given by drip infusion to 10 patients: 4 with pneumonia, 2 with chronic respiratory infection and 4 with infection in association with lung cancer. Clinical effect was good in 7 and poor in 2. One patient with diffuse panbronchiolitis was excluded from the clinical evaluation. Five strains that were identified as causative organisms were all eradicated by SBT ABPC. Drug-induced fever and eosinophilia were observed in one patient each. The adverse reactions disappeared after completion of the therapy.
From the above results, we conclude that SBT·ABPC is most useful as a first choice antibiotic for the treatment of lower respiratory infections.

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This study was performed to examine pharmacokinetics of sulbactam and ampicillin in patients with chronic respiratory tract infection. After sulbactam·ampicillin (SST·ABPC) and ampicillin (ABPC) were given intravenously in a cross-over method, levels of SBT and ABPC in serum and sputum were determined.
Following the administration of 3g SBT-ABPC, the maximum serum levels of SBT and ABPC were 33.4μg/ml and 47.2μg/ml, respectively, and the maximum levels in sputum 2.40μg/g and 1.50μg/g. The ratios of sputum vs. serum C_max were 0.07 for SBT and 0.03 for ABPC. The maximum levels in serum and sputum following a dose of 2g ampicillin were 41.6μg/ml and 0.97 the ratio of the maximum level in sputum vs. serum being 0.02.
ABPC penetrated well into sputum in the patients with acute exacerbation of chronic bronchitis accompanying asthma, but did not penetrate sufficiently into the sputum of diffuse pan bronchiolitis patients.
SBT ABPC was clinically evaluated in 4 patients with respiratory tract infection. With one unevaluable case, the efficacy was rated as good in 3 cases. No side effects were observed.

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Sulbactam-Ampicillin was administered intravenously to 3 patients with bacteremia caused by Streptococcus pneumoniae, Klebsiella pneumoniae and α-streptococcus, 5 patients with respiratory tract infection and 2 with soft tissue infection. The patients received the drug for 6 to 20 days in a dose of 1.5-6.0g/day, except 1 patient who was given the drug every other day.
Clinical effect was excellent in 1 case and good in 9. Bacteriological effect was eradication in 6 cases and unknown in 4.
As for abnormal laboratory findings possibly related to this drug, eosinophilia and elevation of GOT, GPT were seen in one case each.
No side effects, however, were found.

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Sulbactam·Ampicillin was given by intravenous injection to 15 patients: 8 with respiratory tract infection, and 7 with intraabdominal infection including 5 with biliary tract infection.
The serum levels of sulbactam and ampicillin were measured in 3 patients with renal failure. The half-lives of both drugs were slightly prolonged in 2 patients with moderately impaired renal function, and serum levels remained high in 1 uremic patient for a long time.
Clinical efficacy was excellent in 2, good in 10, and poor in 3. In 5 of the 10 cases with good efficacy, beta-lactamase-producing bacteria were isolated as causative organisms. No clinical side-effects were observed in general. Specifically, however, an exacerbation of liver dysfunction and a decrease in prothrombin activity appeared in one elderly patient, and liver and renal damage in another. Other serious adverse effects did not occur.

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SBT·ABPC was administered to 14 patients with acute tonsillitis (1), peritonsillar abscess (1), acute bronchi. tis (3), chronic bronchitis (1), bronchopneumonia (1), pneumonia (3), secondary respiratory infection (1), acute pyelonephritis (1), chronic pyelonephritis (1), and septicaemia (1). In all 14 cases, good clinical effect was obtained. Six causative organisms isolated from 6 patients were all eradicated. Drug fever was observed in 1 case. Abnormal laboratory findings were elevation of GOT, GPT and γ-GTP in 2 cases, and eosinophilia in another 2. A leucocyte migration inhibition test done in 3 of these patients was positive in 1 with eosinophilia.

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Sulbactam (SBT) is an inhibitor of several bacterial beta-lactamases and works synergistically against many resistant organisms when co-administered with ampicillin (ABPC). SBT-ABPC is a fixed combination of SBT and ABPC in a 1:2 ratio.
SBT-ABPC was given intravenously to 3 patients with pneumonia, 1 with 2 episodes of acute purulent meningitis, 1 with chronic cystitis and 1 with lung cancer and suspected pneumonia. These patients received the drug for 5 to 21 days in doses of 3g/day. Four (5 episodes) of these patients responded well to the therapy.
Although no adverse reaction was observed, mild leukopenia, an abnormal laboratory finding, was seen in two patients.

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Eight patients with lower respiratory tract infection were treated with sulbactam·ampicillin (combination ratio 1:2) intravenously at a dose of 1.5 g twice a day for 6-16 days. The overall clinical efficacy rate was 75% and the bacteriological efficacy rate was 100%. An adverse reaction was noted in one patient who complained of itching, though without eruption.

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We studied the pharmacokinetics, clinical efficacy and safety of sulbactam, a β-lactamase inhibitor, and ampicillin in combination (hereafter referred to as SBT-ABPC) to obtain the following results.
When a single dose of 750 mg and 1500 mg of SBT-ABPC was given intravenously in a cross-over method to healthy male subjects, the maximum serum levels of ABPC and SBT at 5 min were 39.2±5.73 μg/ml and 18.7±1.97 μg/ml at a dose of 750 mg and 78.8±7.06 μg/ml and 40.0±3.50 μg/ml of a dose of 1500 mg.
Serum half-lives were 0.91±0.02 h for ABPC and 0.96±0.02 h for SBT at 750 mg and 1.06±0.04 h and 1.10±0.08 h at 1500 mg. The urinary recovery rates up to 24 hours after intravenous injection were 82.10±3.36%; 88.40±2.73% and 79.97±2.72%;78.09±1.99%.
SBT-ABPC in a daily dose of 1.5 g to 6g was given by intravenous infusion for 5-19 days to 4 patients with pneumonia, 1 with cholecystitis, 1 with septicemia and 1 with infectious endocarditis. The results of treatment were good in 5 patients, fair in 1 and failed in 1. No side effects or abnormal changes in laboratory tests performed before and after treatment were observed.

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Sulbactam·Ampicillin (SBT·ABPC) is a fixed combination of ampicillin and a beta-lactamase inhibitor, sulbactam, in a 2:1 ratio which has been developed by Pfizer Inc.
The present study was carried out to evaluate the clinical and side effects of SBT·ABPC given to 7 patients with respiratory infection.
The subjects were 4 males and 3 females aged 29-78 years (mean 67.1 years). Diseases were pneumonia in 4 cases, acute bronchitis in 2 and bronchiectasis with infection in 1.
Patients were given 1.5 g SBT·ABPC twice daily by intravenous drip infusion for 8-26 days (mean 13.4 days), a total dose of 24-78g (mean total dose 40.5g).
The clinical efficacy of the drug was excellent in 2 cases, good in 4 and fair. in 1, with an efficacy rate of 85.7%(6/7). Categorized by disease, SBT·ABPC was rated as excellent in 1 case, good in 3 of 4 cases of pneumonia, good in 1, fair in 1 of 2 cases of acute bronchitis, and good in 1 of bronchiectasis. For bacterial examination, sputum from 4 patients was cultured. S. pneumoniae, H. influenzae and B. catarrhalis were isolated from 3 patients. S. pneumoniae and B. catarrhalis were eradicated after administration of SBT·ABPC.
No side effects such as drug eruption, fever, nausea, vomiting or diarrhea were noted, but in one case occult fecal blood was observed. Laboratory test values were normal before and after administration of SBT·ABPC.

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Sulbactam·ampicillin (SBT·ABPC), a combination of sulbactam (SBT) and ampicillin (ABPC) in a ratio of 1:2, was intravenously administered to 14 patients with respiratory tract infection.
Clinical efficacy in the 14 cases was excellent in 4, good in 7, poor in 2, and unevaluable in 1. The efficacy rate was 84.6%.
Thirteen strains of organisms were isolated from 9 cases. All isolated organisms were eradicated except 3 strains in 2 cases, for which no bacteriological tests were conducted after treatment. As side effects, rash/redness and drug eruption were observed, also slight eosinophilia and leukopenia in 1 case each. Sulbactam.ampicillin showed good clinical and bacteriological efficacy.

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We evaluated the clinical efficacy of sulbactam·ampicillin, which has been developed by Pfizer, in 16 patients with various infections, namely acute pneumonia 4, acute bronchitis 2, chronic bronchitis 1, lung abscess 1, acute cholecystitis 3, acute pyelonephritis 4, and meningitis 1.
The clinical efficacy was excellent in 2 patients, good in 10, fair in 2 and poor in 2, with an efficacy rate of 75%.
Bacteriologically, pathogenic organisms were unidentifiable in the majority of patients. Pathogenic organisms were eradicated in 3 cases, remained unchanged in 1 and were not identified in 12.
No side effects of clinical significance were observed. But decrease in platelets was found in 1 case in laboratory tests.
From the results obtained, this drug appears to be useful for the treatment of moderate or severe infections.

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Sulbactam·Ampicillin (SBT·ABPC), β-lactamase inhibitor plus ampicillin, was evaluated in an open trial comprising 21 patients with respiratory infections, who were given 1.5g b. i. d. by drip infusion.
Of these, 7 had lower airway infections, and 14 had pneumonia.
Clinical effect was excellent in 3 cases, good in 13, fair in 4 and poor in 1. The efficacy rate was 76.2%.
As for bacteriological effect, all 3 strains of Haemophilus influenzae, 1 of Klebsiella ozaenae and 1 of Staphylococcus sp. were eradicated.
Slight fever was noted as an adverse reaction in one case. Laboratory findings revealed leukopenia in 1 case, transient rise in total bilirubin in 2, slight elevation of hepatic enzymes in 5, and eosinophilia in 1.
Based on our results, we conclude that SBT·ABPC is effective in the treatment of respiratory infections and without serious toxicity.

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Three patients admitted to Kawasaki Municipal Hospital with one case each of pulmonary abscess, pneumonia and chronic bronchitis, were successfully treated with sulbactam·ampicillin, 1.5g b. i. d.
No causative organisms were detected in 2 patients, 1 with pulmonary abscess, and 1 pneumonia. Haemophilus influenzae was isolated from the patient with chronic bronchitis and determined to be a causative organism.
Serum GOT and GPT levels were slightly and transiently elevated in the patient with pneumonia. No significant side effects, however, were detected.

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Sulbactam·ampicillin was administered intravenously to 21 patients with respiratory tract infections. The daily dose ranged from 3-6g given in two divided doses, and the treatment period, from 3.5-22 days.
The subjects enrolled were: 17 with acute pulmonary parenchymatous infection (pneumonia 12, pulmonary suppuration 5) and 4 with chronic airway infection (chronic bronchitis 2, bronchiectasia 1, chronic pulmonary emphysema with infection 1).
Clinical efficacy was rated as excellent in 1 patient, good in 15, fair in 1, failed in 2 and unknown in 2, with an efficacy rate of 84.2%.
Of the 6 strains from 5 patients judged to be the pathogens, 2 were Staphylococcus aureus, 1 klebsiella pneumoniae, 1 Pseudomonas aeruginosa, 1 Peptostreptococcus sp.and 1 Peptococcus sp. Bacteriological efficacy was evaluated in these 6 strains and the results were: the bacterial counts were reduced in one of 2 strains of S. aureus, the other being superceded by K. pneumoniae; K. pneumoniae persisted; P. aeruginosa, unknown; Peptostreptococcus and Petococcus eliminated.
Rash as a side effect was observed in one patient and subsided soon after the drug was withdrawn. No significant abnormal parameters in laboratory tests were observed throughout the study.
The results obtained suggest sulbactam. ampicillin to be useful in the treatment of respiratory tract infection, especially as the first choice for pulmonary parenchymatous infection.

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In this paper, the author reports the results of a clinical investigation on SBT·ABPC, a combination of ABPC and the β-lactamase inhibitor sulbactam. We evaluated the clinical efficacy and safety of the drug in 5 patients with respiratory tract infections, namely, 2 with acute exacerbation of chronic bronchitis and 3 with bronchiectasis.
The clinical response was excellent in 1 case and good in 4, the clinical efficacy rate being 100.0%.
No adverse event was noted.

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We evaluated clinical isolates (Gram-positive cocci group, 320 strains; Enterobacteriaceae, 160 strains; non-Enterobacteriaceae GNR, 122 strains; Haemophilus sp. and Neisseria sp., 67 strains) in the Central Clinical Laboratory of Kanazawa Medical University Hospital for β-lactarnase production and drug susceptibility. The penicillinase production ratio of Staphylococcus aureus was 58.1% and all these strains were resistant to ABPC. However, the ABPC-resistance rate of penicillinase non-producers was 18.4%. The penicillinase production rates of Branharnella sp. and Moraxella sp. were 45.5% and 16.7%, respectively.
We therefore consider SBT·ABPC a useful drug for the microbiolggical eradication of S.aureus, Branhamella sp. and Moraxella sp.
To evaluate the clinical efficacy of SBT·ABPC, this drug was administered to 19 patients with 20 episodes of respiratory tract infection. The clinical efficacy of SBT·ABPC, except in mycoplasmal pneumonia, was excellent in 2 episodes, good in 11, fair in 5 and poor in 1, the overall efficacy rate being 68.4%. In 6 episodes (fair 5, poor 1) the patients were over 70 years old except for 1 patient, who had severe underlying diseases and complications.
The causative organisms were isolated in 16 episodes. The bacterial eradication rate was 87.5%.
No severe side effects or abnormalities in clinical laboratory values were found.
We consider SBT·ABPC to be a useful antimicrobial agent for the treatment of respiratory tract infections.

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We assessed the clinical efficacy of sulbactam·ampicillin (SBT·ABPC) in a study of 19 patients with respiratory tract infections. The drug was administered by intravenous infusion in a dose of 1.5g twice a day.
Those detected included H. influenzae in 10 patients, S. pneumoniae in 8, B. catarrhalis in 2, H. parahaemolyticus in 2, K. pneumoniae in 1 and Peptostreptococcus in 1. In 5 patients the organisms detected by transtracheal aspiration together with other organisms.
1) Efficacy was judged to be excellent in 2 patients, good in 16 and poor in 1, the efficacy rate being 94.7%.
2) The organisms were all eradicated except H. influenzae (1 strain) and K. pneumoniae (1 strain).
3) Nausea as a side effect was observed in 1 patient, but no abnormal laboratory findings were observed. From these findings, we believe this drug to be useful in the treatment of respiratory tract infections.

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We evaluated the clinical efficacy and safety of sulbactam·ampicillin (SBT·ABPC), a fixed combination in the ratio of 2:1 of ampicillin and sulbactam, a β-lactamase inhibitor, in patients with a variety of infections. The results are summarized as follows.
A total of 17 patients were given 1.5-3.0g of SBT·ABPC twice daily for 1.5-19.5 days by intravenous drip infusion. The patients enrolled in the study consisted of 1 with septicemia, 1 with septicemia and pneumonia, 8 pneumonia, 1 pneumonia and cholecystitis, 2 pulmonary congestion with infection, 1 pulmonary emphysema with infection, 1 old pulmonary tuberculosis with infection, and 2 pyelonephritis. The clinical efficacy in 15 evaluable patients was exellent in 1, good in 8, fair in 4 and poor in 2. In 11 patients, in whom bacteriological efficacy was evaluable, organisms were eradicated in 4, partially eradicated in 1, replaced in 1 and persisting in 5. Other than diarrhea, reported by 1 patient, there were no subjective or objective adverse reactions. As abnormal laboratory test parameters suggesting a possible relation with SBT·ABPC, hepatic function disorder was observed in 3 patients, renal function disorder in 1 and eosinophilia in 1.

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We carried out clinical studies on sulbactam·ampicillin (SBT·ABPC), a new injectable antibiotic composed of a 2:1 mixture of ABPC and SBT, a β-lactamase inhibitor. The following results were obtained.
A total of 12 patients (3 with pneumonia, 2 with pyothorax, 5 with bronchiectasis, 1 with phlegmon and 1 with pyelonephritis) were treated with 1.5-3.0 g of SBT·ABPC twice a day for 3-16 days.
Clinical efficacy was evaluated as good in 10 and poor in 2. The overall efficacy rate was therefore 83.3%.
All 4 cases whose causative bacteria were β-lactamase producers (S. aureus 2, H. influenzae 2) were evaluated as good, but the eradication rate of these bacteria was only 33.3%.
No subjective side effect was noted, but slight and transient eosinophilia was observed in one patient and elevation of GOT, GPT in another during therapy.

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We performed bacteriological and clinical studies on sulbactam·ampicillin consisting of a β-lactamase inhibitor, sulbactam (SBT) and ampicillin (ABPC).
1) MICs of SBT·ABPC against β-lactamase-producing Haemophilus influenzae (24 strains) and Branhamella catarrhalis (61 strains) were determined using a plate dilution method with an inoculum size of 10⁶ cells/ml.
The antimicrobial activity of SBT·ABPC against these strains was 2-to 4-fold higher than that of ABPC alone.
2) SBT·ABPC was given to a total of 13 patients with pneumonia by intravenous drip infusion.
In 11 patients judged evaluable for efficacy, clinical response to the treatment with SBT·ABPC was excellent in 1 case, good in 7, fair in 1 and poor in 2.
One strain of S. pneumoniae, 2 of H. influenzae and 1 of B. catarrhalis, recovered from the sputum of these patients at the start of treatment with SBT·ABPC, were eradicated. One strain each of S.aureus and K. pneumoniae persisted and clinical efficacy in these 2 patients was poor.
As to side effects, nausea and vomiting were observed in 1 case.
These symptoms disappeared, however, soon after cessation of the therapy.
In the laboratory test, transient slight eosinophilia and thrombocytopenia were observed in 1 case each

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Sulbactam·ampicillin (SBT·ABPC) is a combination drug containing sulbactam and ampicillin in a ratio of 1:2. The clinical efficacy and safety of SBT·ABPC were evaluated in 29 patients with moderate or severe respiratory tract infections (pneumonia 13, bronchitis 9, emphysema 3, lung abscess 3, bronchiectasis 1). The drug was administered by intravenous drip infusion twice or three times a day at a dose of 1.5 g of SBT·ABPC (one vial containing 0.5 g of SBT and 1.0 g of ABPC). The following results were obtained.
1) Clinical effect was excellent in 17, good in 8, fair in 1 and poor in 3 patients, and the overall efficacy rate was 86.2%.
2) As adverse effects, urticaria was observed in one case and drug eruption with itching in another. Abnormal changes in laboratory tests, though not serious, were also observed during treatment: basophilia in 1 case, elevation of S-GOT and S-GPT in 1, of S-GOT and LDH in 1, and eosinophilia in 2.

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We performed clinical studies on Sulbactam·Ampicillin (SBT·ABPC), a new injectable antimicrobial agent, combining Ampicillin (ABPC) and Sulbactam (SBT), a new β-lactamase inhibitor, in respiratory tract infections.
In all 22 patients with bronchiectasis (3), panbronchiolitis (2), acute excerbation of chronic bronchitis (6), pneumonia (8), obstractive pneumonia (1), old pulmonary tuberculosis+infection (1), and suspected mycoplasma pneumonia (1), were treated with 1.5-3.0g of SBT·ABPC daily by intravenous drip infusion.
Clinical response was excellent in 5, good in 8, and fair in 4 patients; 5 patients were not evaluable. The overallefficacy rate was 76.5%.
Of 17 strains isolated from 14 patients in whom assessment of bacteriological efficacy was possible, 14 were finally eradicated (82.3%).
As a side effect, skin eruption was observed in 1 patient. As abnormal change in the clinical laboratory test, eosinophilia was noted in 2 patients, and mild elevation of S-GOT and/or S-GPT in 3. We therefore conclude that SBT·ABPC is a useful antibiotic in treating patients with respiratory tract infections.

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Sulbactam, a derivative of the penam nucleus, is an effective irreversible inhibitor of bacterial β-lactamase and displays synergistic effects against β-lactamase-producing organisms when combined with ampicillin in vitro.
We conducted a clinical study to evaluate the efficacy and safety of intravenous drip infusion of sulbactam. ampicillin in the treatment of hospitalized patients with respiratory tract infections. Sulbactam·ampicillin, a fixed combination of sulbactam and ampicillin in a 1:2 ratio, was used to treat twenty-four episodes of respiratory tract infections, including pneumonia (8), chronic bronchitis (14), and bronchiectasis (2). The overall bacteriologic elimination rate for all causative organisms was 91.3%(21/23). Eight strains, including 1 Haemophilus influenzae, 6 Staphylococcus aureus and 1 Branhamella catarrhalis were determined as β-lactamase producers.
The elimination rate for these, β-lactamase-producing strains was 100%(8/8). The bacteriologic eradication rate was 100% for all of the H. influenzae (6), Streptococcus pneumoniae (2), S. aureus (7), B. catarrhalis (1), Klebsiella pneumoniae (1), Acinetobacter calcoaceticus (1), and Corynebacterium (2) isolates, including, β-lactamase-producing strains. Two of three strains of Pseudomonas aeruginosa isolated before treatment persisted. One P. aeruginosa and one Serratia marcescens were isolated at more-than 10⁷ cfu/ml in the sputum during and/or after treatment.
Clinically significant superinfections with these organisms did not occur. The only side effect was a cutaneous rash, which resolved when treatment was stopped. No adverse laboratory test results were noted in any of the twenty-four cases.
Sulbactam·ampicillin is a safe, effective initial therapy for respiratory tract infections, even those due to β-lactamase-producing strains of H. influenzae, S. aureus, and B. catarrhalis.

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A multi-center double-blind three-group comparison study of sulbactam·ampicillin (SBT·ABPC) vs. ampicillin (ABPC) was performed to evaluate their efficacy, safety and usefulness in the treament of patients with respiratory tract infections.
The clinical efficacy rated by Investigators' Judgment Committee was compared among three dosage groups of 3 g SBT·ABPC, 6g SBT·ABPC and 4g ABPC. In the patients with pulmonary parenchymal infections, the efficacy rate was 82.5%, 92.1% and 94.6%, respectively. In chronic respiratory tract infections, that rate was 86.7%, 81.6% and 82.1%, respectively. All of these three groups showed excellent efficacy rates, and there were no significant differences among them.
The bacterial eradication rate was 93.2%, 83.7%and85.4%, respectively, suggesting that there were no significant differences in the bacteriological efficacy among the three dosage groups. The MICs, determined at a central laboratory, indicated that almost all the strains were sensitive to SBT·ABPC and many to ABPC alone. The MICs of ABPC were 25 μg/ml and above against 13 strains, whereas those of SBT·ABPC were 2-to 5-fold lower.
All dosagegroups exhibitedhigh usefulness rates with a low incidence of side effects and parameter abnormalities in laboratory tests, suggesting no significant differences in safety and usefulness.
The results obtained in this study indicate that SBT· ABPC is useful in the treatment of patients with respiratory tract infections.

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We performed a clinical study of a new injectable combination drug, sulbactam·ampcillin, in 51 patients with surgical, mainly intra-abdominal infections.
These comprised diffuse peritonitis, localized peritonitis, pelvic peritonitis, cholecystitis, cholangitis, phlegmon, subcutaneous abdominal abscess, periproctal abscess, osteomyelitis, Pneumonia, pleurisy, erysipelas, wound infection, lymphadenitis, decubitus infections and epididymitis.
Clinical efficacy was excellent in 7 patients out of 51, good in 34, fair in 5 and poor in 5, with an efficacy rate of 80.4%. The severity grade of infection was rated as being serious in 8 patients (15.7%), moderate in 37 (72.5%) and mild in 6 (11.8%). The severity of underlying diseases was rated as serious in 8 patients (15.7%), moderate in 17 (33.3%) and mild in 2 (3.9%), while 24 (47.1%) had no underlying disease.
Bacteriological efficacy was excellent in 1 of 21 Gram-positive strains, good in 18 and fair in 2, with an efficacy rate of 90.5%. In Gram-negative organisms, it was excellent in 4 strains, good in 33, fair in 8 and poor in 7, with an efficacy rate of 71.2%. Against 31 strains of anaerobes, the efficacy was excellent in 1 strain, good in 23, fair in 2 and poor in 5, with an efficacy rate of 77.4%. Bacteriological efficacy by isolated organism was rated as eradicated in 66 strains out of 105, persisted in 15 and replaced in 24, with an eradication rate of 85.7%. Sulbactam·ampicillin showed excellent or good clinical efficacy in 14 of 20 patients who did not respond to previous therapy with other antibiotics, with an efficacy rate of 70% in this group of patients.
No subjective or objective side effects were observed in any of the patients enrolled in the study. Abnormal values in clinical laboratory tests were observed in 6 of 51 patients (11.8%), eosinophilia in 1 and abnormal liver function in 5.
The MIC of the drug was determined for 83 strains of 33 different organisms isolated from clinical specimens 69 strains (81.1%) were found to be susceptible to the drug at 12.5 μg/ml or lower concentrations.

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We evaluated the clinical effect of SBT·ABPC in 5 patients with surgical infections. The concentration of SBT·ABPC in postoperative intraperitoneal exudate was also determined. SBT·ABPC was administered by intravenous drip in a dose of 1.5g b. i. d. dissolved in 100ml of 0.9% NaCl.
The clinical effect of SBT·ABPC was good in 1 case of infected burn injury, fair in 2 cases of wound infection and left subphrenic abscess, and poor in 2 cases of left subphrenic abscess and intrapelvic abscess. No postoperative infections were observed in three patients covered with SBT·ABPC after gastrectomy. Adverse effects directly attributable to SBT·ABPC were not detected.
The mean concentrations of SBT·ABPC in postoperative intraperitoneal exudate were 1.82/2.71μg/ml, 1.61/2.51μg/ml and 1.12/1.76μg/ml for days 1-3 after gastrectomy.

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We performed basic and clinical studies on ampicillin in combination with a β-lactamase inhibitor, sulbactam (SBT·ABPC), in the surgical field, and obtained the following results.
1) Clinical results
SBT·ABPC was administered to 14 cases with surgical infection and clinical results were goodin 8 cases, fair in 4 and poor in 2. The clinical efficacy rate was 57.1%. The bacteriological results were: eradicated in 2 cases, decreased in 2, unchanged in 3, replaced in 1 and unknown in 6.
The bacteriological efficacy rate was 37.5%.
No side effect was observed.There was 1 case of elevated GOT, GPT, Al-P, γ-GTP and LDH.
2) Biliary excretion
The mean biliary concentrations o ampicillinisulbactam were 19.8μg/ml and 3.61μg/ml after 1 hour, and 3.04μg/ml and 0.39μg/ml after 8 hours, respectively.

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We studied the efficacy and safety of sulbactam·ampicillin (SST·ABPC) in the treatment of surgical infections.
Clinical efficacy was excellent in 4 and good in 1 of 5 cases with perforation peritonitis; excellent in 3 and fair in 1 of 4 cases with cholangitis; excellent in 1 case of liver abscess; excellent in 1 case of perineum wound infection following surgical procedure for rectal carcinoma, but poor in 1 case of surgical wound infection after removal of breast cancer. Overall efficacy was excellent in 9 cases out of 12, good in 1, fair in 1 and failed in 1 case, with an efficacy rate of 83.3%.
No subjective or objective adverse reactions or changes in clinical test values related to dosing of this agent were observed.

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A combination of sulbactam (SBT), a new β-lactamase inhibitor and ampicillin (ABPC), one of the broadspectrum penicillins, was administered to patients with surgical infections, and its bacteriological effect and clinical efficacy were evaluated.
1. Bacteriological activity:
SBT·ABPC was more potent than ABPC against MRSA as well as coagulase-negative Staphylococcus spp. It was also active against MSSA and Enterococcus spp though a little less potent than ABPC. While SBT·ABPC exhibited superior potency against E.coli, K.pneumoniae, Enterobacter spp and Citrobacter spp in comparison with ABPC, the MICs for Enterobacter spp and Citrobacter spp were so high that no favorable efficacy is expected for infections caused by these organisms. SBT·ABPC showed potent activity against Acinetobacter spp.
2. Clinical results:
SBT·ABPC was used in the treatment of 4 patients with intraperitoneal infection, 8 with biliary tract infection and 4 with soft tissue infection. Its efficacy was good in 14 patients and poor in 2, with an efficacy rate of 87.5%.
No adverse reactions or abnormal laboratory parameters regarded as related to dosing of this combination drug were reported in any patient.

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We performed clinical studies on Sulbactam·Ampicillin (SBT·ABPC), a new combination antibiotic, and obtained the following results.
Twenty-one patients with complicated urinary tract infection were given SBT·ABPC at a daily dose of 3g by intravenous injection or intravenous drip infusion for 5 to 7 days.
Clinical results were excellent in 5 cases, good in 11 and poor in 4; the overall effectiveness rate being 80%. Measured by group, the rate was 100% for group 1, 100% for group 2, 100% for group 3, 100% for group 4, 50% for group 5 and 75% for group 6. By type of infection, the efficacy rate was 100%(10 cases out of 10) formonomicrobial and 60%(6 cases out of 10) for polymicrobial infections.
Bacteriologically, 34 (92%) of 37 organisms isolated from patients with complicated urinary tract infection were eradicated.
No side effect was observed. As laboratory findings, low grade leucocytosis and slight increase of GOT and GPT were observed in cases 1 and 2, respectively. But they were not severe and recovered without treatment.

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Sulbactam·Ampicillin (SBT·ABPC) was administered intravenously at a dose of 1.5g twice a day to 34 patients with complicated urinary tract infection and the therapeutic efficacy of the drug and safety were evaluated. The results were summarized as follows.
1) Clinical effect: in 30 Of 34 patients with complicated urinary tract infection, clinical efficacy was evaluated by the criteria proposed by the Japanese UTI Committee. Excellent and moderate responses were obtained in 66.7% of 30 patients.
2) Bacteriological effect: 51 strains were isolated before SBT·ABPC treatment, and 33 of these were eradicated after treatment. Seven new strains appeared after treatment.
3) Adverse effects: flushing, pyrexia and itching were observed in 1 case. Noted as clinical laboratory test abnormalities were increase of GOT, GPT and Al-P in 1 case.
From the results obtained in this study, we consider SBT.ABPC to be effective in the treatment of urinary tract infections, especially those due to β-lactamase-producing organisms.

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Sulbactam·ampicillin is a fixed combination of sulbactam and ampicillin in a 1:2 ratio. We used the drug to treat 17 patients with complicated urinary tract infections and 2 with prostatitis, and evaluated its therapeutic efficacy and safety.
Eleven cases of complicated UTI were assessed according to the 3rd edition of the Criteria for Clinical Evaluation of Antimicrobial Agents in Urinary Tract Infection (Japanese UTI Committee).
Overall clinical efficacy in the 11 patients with complicated UTI was excellent in 6 and moderate in 3, an efficacy rate of 82%.
According to the doctor's evaluation, SBT·ABPC was effective in 2 cases of prostatitis and in 13 of 17 cases of complicated UTI.
The overall bacteriological response rate for all organisms was 81.2%. No adverse effect during therapy was observed.
An abnormal laboratory finding after treatment was slight elevation of GPT in 1 case.
Thus, SBT·ABPC appears to be a safe and effective drug for the treatment of UTI.

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Sulbactam·ampicillin (SBT·ABPC) was given intravenously to 8 patients with complicated urinary tract infection for 5 days at a daily dose of 3g.
The overall clinical efficacy was rated as moderate in 4, poor in 2 and unjudgeable in 2, with an efficacy rate of 66.7%.
Bacteriologically, 7 (77.8%) of 9 strains were eradicated.
No subjective side effect was observed in any of the treated cases. An abnormal laboratory finding was seen in one patient with slight elevation of S-GPT and Al-P.

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We studied the pharmacokinetics of sulbactam, a β-lactamase inhibitor, and ampicillin combined in a ratio of 1:2 in an injectable form in patients with hydronephrosis. We also assessed its clinical efficacy in chronic complicated urinary tract infection.
1) In the patients with hydronephrosis, the decrease in the recovery rate of sulbactam·ampicillin in urine corresponded to the increase in creatinine clearance and serum half-life, and showed the same values for the two drugs.
2) The therapeutic effect and safety of sulbactam·ampicillin given at a dose of 1.5g twice a day were studied in 31 patients with chronic complicated urinary tract infection, of these, 22 were evaluated according to the criteria of the Japanese UTI Committee, and the overall efficacy rate was 90.9%. No side effects were seen in any of the patients, though eosinophilia was observed in one.

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We studied the antimicrobial activity against urinary bacteria and clinical efficacy in urinary tract infections of sulbactam·ampicillin (SBT·ABPC), a new combination drug. This drug consists of sulbactam (SBT), a β-lactamase inhibitor, and ampicillin (ABPC) in a 1:2 ratio.
The in vitro activity of SBT·ABPC against Gram-positive bacteria was nearly the same as that of ABPC. SBT·ABPC, however, was more active against Gram-negative bacteria than was ABPC.
One patient with acute uncomplicated pyelonephritis and 22 with complicated urinary tract infection were given 1.5g of SBT·ABPC twice a day for 5 days by intravenous route. Clinical efficacy in the patient with acute pyelonephritis was evaluated as excellent. In 17 of the 22 patients with complicated urinary tract infection, it was evaluated by the criteria of the Japanese UTI Committee; excellent and moderate responses were obtained in 82%.
Of 21 strains isolated from patients with complicated urinary tract infections, 19 (90%), including 6 high β-lactamase producers, were eradicated after treatment.
Clinical adverese reactions were evaluated in 23 patients. Skin rash was observed in 2, but spontaneously resolved after treatment.
From the results obtained in this study, SBT·ABPC was considered to be effective in the treatment of urinary tract infections, especially those due to β-lactamase-producing organisms.

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We performed clinical studies using sulbactam·ampicillin (SBT·ABPC), an injectable formulation comprising sulbactam (1 part) and ampicillin (2 parts), to evaluated its clinical effect in the treatment of 30 patients with complicated urinary tract infections.
1) The results from 27 cases were evaluated according to the criteria of the Japanese UTI Committee. Seven cases were classified as excellent, 11 as good and 9 as poor. Overall efficacy was 66.7%.
2) Bacteriologically, 24 of 32 isolated strains were eradicated, the overall eradication rate being 75%.
3) As for side effects, 1 of 30 cases showed urticaria. Laboratory data revealed abnormalities in 2 cases: anemia in one and elevated alkaline phosphatase activity in another.

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We clinically investigated a new combination drug, sulbactam·ampicillin (SBT·ABPC) at the ratio 1:2, in the urological field.
SBT·ABPC was administered to 24 patients with complicated urinary tract infections at a dose of 1.5 g twice daily for 5 days.
The clinical efficacy rate was 75% according to the criteria of the Japanese UTI committee. Bacteriologically, 23 of 29 organisms (79%) were eradicated.
There were no subjective side effects, but slight elevation of transaminase was noted in three cases.

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SBT·ABPC, a combination of Sulbactam and Ampicillin, was evaluated for its clinical efficacy and safety in the treatment of chronic complicated urinary tract infection (UTI).
The drug was administered to 18 patients by single i.v. injection or i.v. drip infusion in a daily dose of 3g in two divided doses for 5 days, and the following results were obtained.
1) Thirteen cases were evaluated according to the Japanese UTI Committee's Criteria. Excellent results were observed in 7 cases, moderate in 3 and poor in 3. The overall efficacy rate was 76.9%.
2) Bacteriologically, all of 22 isolates were eradicated, and the eradication rate for β-lactamase-producing strains was as good as for non-producing strains.
3) No side effects were observed. Abnormal changes in laboratory findings were found in 2 patients (eosinophilia 1, elevation of GOT and GPT 1) but none was serious.
The above results suggest that SBT·ABPC is a useful drug for chronic complicated UTI.

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A controlled comparison of sulbactam·Eampicillin and piperacillin was carried out in the treatment of complicated urinary tract infections. Patients were randomly assigned to receive either 1.5g of sulbactam ampicillin (0.5g of sulbactam and lg of ampicillin) or 2g of piperacillin twice a day for 5 days by intravenous injection.
All patients had pyuria of at least 5 WBCs per high power field, bacteriuria of at least 10⁴ bacteria per ml of urine and identifiable underlying urinary tract disease. The overall clinical efficacy of the treatment was evaluated by the criteria proposed by the Japanese UTI Committee as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria. Because significant deviation was observed in the MIC distribution of PIPC between the two treatment groups, statistical analysis of the clinical efficacy was performed using the Mantel-Haenszel method.
Excellent and moderate responses were obtained in 65.3% of 101 patients receiving sulbactam-ampicillin and in 60.2% of 98 patients receiving piperacillin. This difference was not statistically significant. The overall bacteriological eradication rates obtained were 80.7% of 171 strains in the sulbactam · ampicillin group and 78.2% of 170 strains in the piperacillin group. This difference also was not significant.
Clinical adverse reactions were observed in 2 patients (1.4%) in the sulbactam·ampicillin group and in 1 patient (0.7%) in the piperacillin group. There were no significant differences between the two treatment groups regarding the incidence of both clinical and laboratory adverse reactions, and sulbactam-ampicillin appeared to be as well tolerated as piperacillin.
From the results obtained in this study, we concluded that sulbactam-ampicillin was as useful as piperacillin in the treatment of complicated urinary tract infections.

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Intravenous administration of sulbactam·ampicillin (SBT·ABPC) was clinically evaluated for its efficacy and safety in obstetrics and gynecological infections.
Six patients (3 with pelvic peritonitis, 1 with adnexitis, and 2 with puerperal intrauterine infection) were treated with intravenous drip infusion of SBT·ABPC.
Overall clinical efficacy was 100% and the bacterial elimination rate was 100%, although a superinfection occurred in 1 patient.
No side effect was observed. An abnormal laboratory finding was observed in 1 case (increase in eosinophils).
From the above results, we concluded that intravenous administration of SBT·ABPC is useful obstetric and gynecological infections.1

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In a clinical study, sulbactam.ampicillin was administered to 9 patients, including 7 with pelvic peritonitis and 1 each with intrauterine infection and adnexitis.
The results were excellent in 3 cases and good in 6, with an efficacy rate of 100%.
There were no side effects, except eruption in 1 case, and no abnormal laboratory findings were observed.

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