Fundamental and clinical studies on cefoperazone (CPZ, T-1551), a new semisynthetic cephalosporin, were investigated and the results obtained were summarized as follows.
1) Antimicrobial spectrum
CPZ showed a broad antimicrobial spectrum against both gram-positive and gramnegative bacteria.
2) Antimicrobial activities against clinical isolates
CPZ was less active than other cephalosporins against Staphylococcus aureus, but it was more active than most of the other cephalosporins against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens and Pseudornonas aeruginosa.
3) Serum and urinary concentrations
CPZ was intraveneously injected at the dose of 1, 000mg in three healthy human volunteers. For the results, blood levels of CPZ were reached the maximal levels of 280μg/ml at 1/12h and 6.9μg/ml at 6h after administration.
The urinary concentrations showed the peak levels of 2, 600μg/ml at 30 min. after administration and the mean recovery rate was 26.0% within six hour's urine sample.
4) Pharmacokinetics
From the above data, the pharmacokinetic parameters were analysed to computer from the two compartment open model method, and the parameter of Kel, K₁₂, K₂₁, T_1/2 (α), T_1/2 (β) and Vd (I) was 1.17, 2.37, 2.20, 0.26, 1.40 and 2.71, respectively.
5) In vivo metabolism
The metabolites of CPZ were studied on human urine after administration. With bioautogram drawn up by TLC, it was revealed that CPZ was not metabolized in living body.
6) Tissue concentration of rats
According to results obtained with intramuscular injection of CPZ 20mg/kg to SD strain rats, the highest concentration was observed in the kidney and then liver, serum, in order.
7) Result of clinical application
CPZ was used for the treatment of 20 cases of surgical field infections and the results showed that 5 cases were excellent, 13 cases good and 2 cases poor.
The efficacy rate was 90%.
8) Side effects No severe side effects were observed clinically and in laboratory findings.

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Fundamental and clinical studies with cefoperazone (CPZ, T-1551) were performed in the surgical field, and following results were obtained.
1) Antibacterial activity
To E. coil and Klebsiella, the antibacterial activity of CPZ was more excellent than cefazolin by two or three tubes. Similarly, to Pseudomonas aeruginosa, CPZ was more excellent than carbenicillin by two or three tubes.
2) Biliary excretion
The biliary excretion of CPZ in human and rabbits was very excellent and it came under high level group.
3) Clinical effectiveness
CPZ was administered to 17 patients with surgical infection and the results were excellent in 3 cases, good in 12 and unknown in 2. And no side effects were found.

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Cefoperazone (CPZ, T-1551), a new derivative from cephalosporin C, was investigated on its serum level, the bile concentration, urinary excretion, clinical effectiveness and side effects.
1) Following a one hour intravenous drip infusion of 1g CPZ with a 200ml 5% glucose solution in 3 healthy volunteers, the mean serum level showed a peak of 101.3μg/ml at one hour and continued detectable level as high as more than 3.8μg/ml for 8 hours.
The average excretion in urine within 2 hours after drip infusion was 174.5mg and within 8 hours following the drip infusion 349.7mg (35% of the dose) was excreted in urine.
2) The biliary distribution was also studied on the bile collected through a PTCD catheter indwelt in 2 patients.
Following a one hour intravenous drip infusion of 2 g CPZ, the average bile concentration reach its peak of 1000-2400μg/ml in 2 to 4 hours and maintained a high level thereafter up to 6 hours after the drip infusion.
3) CPZ was given to 29 patients with various infections in the field of surgery. The results obtained were “excellent” in 14, “good” in 9, “fair” in 2, “poor” in 3 and “unknown” in one patient (efficacy rate: 82.1%).
Particularly satisfactory results obtained were as follow: Excellent and good in 5 cases out of 6 patients with biliary tract infection, excellent and good in 7 cases out of 8 patients with peritonitis, excellent and good in 5 cases of appendicitis and postoperative wound infection, excellent and good in 4 cases out of 6 patients with abscess and excellent in 2 cases out of 3 cases of other infections.
4) Side effects noted were eruption in one case and eruption and GOT elevation in one case.

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Cefoperazone (CPZ, T-1551), a new cephalosporin antibiotic was investigated on the clinical effectiveness and the toxic effects.
CPZ was given to 9 patients with the various infections (abdominal abscess 2, pancreatitis with cystitis, acute appendicitis, pneumonia, infectious atheroma, cystitis, cholecystitis and abdominal wall abscess).
The clinical evaluation of effectiveness was as follows: excellent in one patient with cholecystitis, good in 5 patients (abdominal abscess, pancreatitis with cystitis, acute appendicitis, infectious atheroma and abdominal wall abscess), poor in 2 patients (pneumonia and cystitis) and unknown in 1 patient (abdominal abscess of Candida and Yeast infection).
No toxic effect was noted in every case.

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Cefoperazone (CPZ, T-1551), a new cephalosporin for injection, has been evaluated fundamentally and clinically in the infectious diseases of surgical field.
1) Results of studies on the susceptibility distribution of clinical isolates to CPZ were as follows:
E. coil In the 12 strains investigated, a peak of distribution was observed at 0.78μg/ml, and all strains showed MICs of 12.5μg/ml or less, indicating good susceptibility.
Klebsiella In the 10 strains investigated, peaks were observed at 1.56 and 3.13μg/ml which were distributed each 3 strains. CPZ was effective against these strains.
P. aeruginosa In the 25 strains investigated, 60% of the strains distributed at 50μg/ml or less, indicating relatively good susceptibility.
2) One gram of CPZ was administered intravenously to two cases in which drainage from the bile duct was being conducted. The highest concentrations of CPZ in bile were 571μg/ml in No.1 case during the 1st to 2nd hour, and 1, 920μg/ml in No.2 case during the 2nd to 3rd hour after administration. Even at 5 to 6 hours, the concentration was maintained a level of 300μg/ml. From these points of view it was able to expect that CPZ was effective against infectious diseases in bile duct.
3) CPZ was administered to 10 patients, and the results obtained were excellent in 4, good in 3, fair in 2 and poor in 1 case. CPZ was recognized as being highly effective clinically with a rate of effectiveness of 70%.
No side effects were observed.

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Biliary excretion of cefoperazonc (CPZ, T-1551) and its clinical evaluation in the hepato-biliary infections were investigated. The results are summarized as follows.
1) Biliary excretion
CPZ was intravenously administered to five cases in a dose of 2 g for 2 hours. In four cases with cholelithiasis biliary levels attained to the peak at 2-4 hours after drip infusion and average concentration was 2, 967 μg/ml (963-5, 046 μg/ml). In the case of cholangiocarcinoma with a prolonged jaundice, maximum level was 351.8μg/ml.
2) Clinical result
CPZ was administered to ten patients with hepato-biliary tract infections. The results showed that remarkably effective cases were 3, effective cases 4 and poor cases 2. The overall effective rate was 77.8%(remarkably effective and effective cases). As side effect eruption was observed in one case and any other abnormality was not detected in hematological and biochemical examination.
From these results it is considered that CPZ is a useful antibiotic for hepato-biliary infections.

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The concentration of cefoperazone (CPZ, T-1551) in serum, urine and bile was estimated after single intravenous injection or drip infusion of 2 grams of the drug into 6 patients received choledochotomy and T-tube drainage for gallstone diseases and biliary excretion of CPZ was extremely higher than that of ampicillin or cefazolin.
Bacterial investigation in bile following administration of CPZ in 3 subjects demonstrated no bacterial flora grown in culture bottles in 2 cases 3 hours after injection of the drug.
Variable dose of CPZ administered to 12 subjects received biliary tract surgery for gallstone diseases and the efficacy of this substance were excellent or good in 83.8 percent, out of 12 subjects. There is no side effects except a case of exanthem in spite of long-term or great amount of CPZ administration.
Newly developed cephalosporin, CPZ, can therefore be a suitable and favourable chemotherapeutics for biliary tract infection.

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The new antibacterial agent, cefoperazone (CPZ, T-1551), was studied fundamentally and clinically. The results were as follows.
1) Antibacterial activities
The antibacterial activity of CPZ was superior to that of CEZ or CEX against the clinically isolated E. coli, S. marcescens, P.aeruginosa, Enterobacter sp. and Proteus sp. On the other hand, CPZ showed the same antibacterial activity as CEZ. against K. pneumoniae.
2) Clinical studies
Fifteen cases with complicated urinary tract infection were treated with CPZ, ranging from 2.0 g to 4.0 g in daily dose. We had the overall effectiveness rate of 62.5% in 1 st group, 83.3% in 3 rd group, 100% in 4 th group. In the whole, the overall effectiveness rate of CPZ was 73.3%. As for the side effects, nothing was noticed after the administration of CPZ.

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Clinical effect of cefoperazone (CPZ, T-1551), a newly developed synthetic cephalosporin, was studied in 20 patients with complicated urinary tract infections. CPZ was administered at a dose of 0.5-2.0 g by one shot iv injection or drip infusion 1-2 times day for a period of 5 days to 19 patients and 6 days to I patient, respectively.
CPZ was found excellent in 1 case, good in 9 cases and poor in 6 cases in chronic complicated cystitis group, and good in 2 cases and poor in 2 cases in complicated pyelonephritis group. Thus, the overall efficacy rate in chronic complicated urinary tract infections was 60%.
Bacteriological effects were as follows. Five out of 7 strains of Serratia, 3 out of strains of Klebsiella and 4 out of 5 strains of Pseudomonas were effective. Thus, the bacteriological efficacy was 66.7%.
During the treatment with CPZ, S-GOT increased in 1 case and Al-P also increased aridther case, but they returned to normal range after cessation of therapy. No other side effect was observed subjectively or objectively.

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The following conclusions were drawn from results of fundamental and clinical evaluations on cefoperazone (CPZ, T-1551), a new semi-synthetic cephalosporin:
1) MICs of CPZ were determined against clinically isolated gram-negative, rods. In 10⁶ cells/ml of E. coli, Klebsiella and indole-positive Proteus, MICs for nearly all of the strains were 6.25 μg/ml or less. In 10⁸ cells/ml, MICs were 12.5 μg/ml or less. In 10⁸ cells/ml of Proteus mirabilis, the number of resistant and sensitive strains were nearly the same: in 10⁶ cells/ml of Serratia and P.aeruginosa, the distribution of resistant strains was nearly the same as that of sensitive strains.
2) The effect of CPZ in 19 cases of complicated urinary tract infection (10 cases of cystitis and 9 cases of pyelonephritis) was excellent in 4 cases, good in 11 cases, and not effective in 4 cases. The effective rate was 78.9%.
There were no subjective side effects, however as abnormal clinical laboratory values, a slight increase of S-GOT was observed in 2 cases.

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Cefoperazone (CPZ, T-1551), a new cephalosporin derivative, was studied experimentally and clinically.
Minimum inhibitory concentrations of CPZ, CEZ, CER, CBPC and GM against Pseudoinonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Serratia marcescens isolated clinical specimens were measured. CPZ was found to be more active than CEZ, CER and CBPC.
In pharmacokinetical studies of CPZ in young four adult volunteers, absorption and excretion were observed, and it showed a relatively short half life in blood and rapid excretion to urine following intravenous injection of 1 or 2g.
In a clinical field, CPZ was administered intravenously or intramuscularly to 12 cases of chronic complicated urinary tract infections at the dosage of 1 to 2g twice per day. Clinical responses of this drug to 10 cases were as follows; excellent in 2 cases, good in 6 cases and poor in 2 cases, and the total clinical effective rate was 80%.
Bacteriological responses of this drug 19 strains isolated from 10 clinical cases were studied. Seventeen strains out of 19 were eradicated after the 5 days administration of this drug.
Apparent abnormal manifestation was not observed in those clinical cases.

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Cefoperazone (CPZ, T-1551), a new injectable cephalosporin antibiotic, was evaluated experimentally and clinically. The results obtained were as follows:
1) CPZ was administered in a single dose of 1.0 g intravenously to 4 male healthy adult volunteers. The mean peak concentration in serum was 168.6μg/ml at 15 minutes following administration, and the half-life of CPZ was calculated for 97 minutes. Twentytwo per cent of administered dose was excreted in the urine during the first 6 hours of administration.
2) The clinical results of 23 patients with complicated urinary tract infections were excellent in 3 cases, moderate in 13 cases and poor in 7 cases.
3) The clinical results of 9 patients with infections of the male genital organ were excellent in 6 cases and moderate in 3 cases.
4) No marked side effects were observed, except slight elevations of serum transaminase and alkaline phosphatase in one patient.

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1) Cefoperazone (CPZ, T-1551) was administrated to 62 cases of complicated urinary tract infection, resulting 15 excellent cases, 28 good cases and 19 poor cases. The effective rate was 69.4%.
2) CPZ was administrated to 5 cases of acute prostatitis, resulting 1 excellent case and 4 good cases. The effective rate was 100%.
3) Total Bacteriological eradication rate after CPZ administration was 71.6% and in clinical isolated Serratia which had almost resistance to CPZ (MIC≥100μg/ml), the eradication rate was 53.3%.
4) Serum levels of CPZ following intravenous drip infusion were slowly eliminated untill six hours.
5) Side effect was observed diarrhea in 1 case.

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We investigated the serum concentration, the urinary concentration and the urinary antibacterial activity after intravenous administration of cefoperazone (CPZ, T-1551) 1 g or CBPC 2 g in 4 healthy volunteers, by a cross over method. The average serum concentration of CPZ was higher than that of CBPC after one hour. But, the average urinary concentration of CPZ was quite lower than that of CBPC. Nevertheless, the urinary antibacterial activity of CPZ against E. coli was 2³-2⁴ times as strong as that of CBPC. When Pseudomonas was used as the test organism, the urinary antibacterial activity of CPZ was nearly equal to that of CBPC. It is suggested that, the better bacteriological response will be obtained against E. coli by means of administration of CPZ 1. g twice a day.
Fourteen patients with complicated urinary tract infections were treated with CPZ at a daily dose of 4 g for 5 days, and 57% of overall effectiveness rate was obtained. The effectiveness rate was thought to be very high. Four strains of E. coli were all eradicated.
No side effect was observed in all cases.

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Cefoperazone (CPZ, T-1551), a new cephalosporin antibiotic, was investigated on the antibacterial activity, clinical evaluation and side effect.
The following results were obtained.
1) Antibacterial activity
The antibacterial activity of CPZ against Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa and Enterobacter cloacae, was superior to those of CEZ and ABPC.
2) Clinical evaluation
Clinical results of CPZ for the complicated urinary tract infections were excellent in 6, good in 13 and poor in 11. The effective rate was 63%.
3) Side effect
No side effect was observed at all cases.

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Twenty-one patients with complicated urinary tract infection were treated with cefoperazone (CPZ, T-1551) by intravenous injection for 5 days. The patients were classified into 2 groups by the daily dose. To Group 1 patients, 1 gram of CPZ was administered twice a day. Two grams of CPZ was administered to Group 2 twice a day. In accordance with “UTI criteria for clinical evaluation of antimicrobial agents”, the following results were obtained:
1) Clinical result in Group 1 was good in 6, poor in 4 cases. The effective rate was 60%. The result in Group 2 was excellent in 1, good in 4, poor in 6 cases. The effective rate was 45.5%. Overall clinical efficacy of CPZ classified by type of infection was more than 50%, except for the cases of single infection with indwelling catheter.
2) On bacteriological evaluation, all strains of Proteus were eradicated with CPZ. Against Serratia and Pseudomonas, CPZ was effective more than 50%.
3) Minimal inhibitory concentrations of CPZ against 26 strains of causative organisms were more than 200μg/ml except for 4 strains of Proteus.
4) No side effects were observed in these cases.

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Twenty-eight patients with complicated urinary tract infection were given cefoperazone (CPZ, T-1551) at a daily dose of 2g or 4g by intravenous drip infusion for 5 days, and following results were obtained.
Clinical results were excellent in 6 (21.4%), good in 13 (46.4%) and poor in 9 (32.1%). The effective rate was 67.9%.
In bacteriological results, there were eradication of organisms in 15 (45.5%), decrease in 7 (21.2%), unchange in 8 (24.2%) and colonization in 3 (9.1%) out of 33 strains.
As the side-effect, serum GOT and GPT were slightly elevated in 2 cases, though these were soon reverted to the normal level after the administration of CPZ was finished.

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1) Cefoperazone (CPZ, T-1551) was administered to 8 cases in department of Urology, Kyushu University hospital, diagnosed as chronic complicated urinary tract infection.
2) CPZ was injected intravenously with 2 or 3 gr per day for 5 days.
3) The clinical results were excellent in 3 cases, good in 1 and poor in 3, with effective rate of 57%.
4) No subjective side effects and abnormal laboratory findings were observed in this investigation.

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Cefoperazone (CPZ, T-1551) was administered to 30 cases of urinary tract infections. The results were as follows:
1) Of the 30 cases, CPZ was excellent in 15 cases, good in 8 cases and poor in 7 cases. Thus, the rate of effectiveness was 76.7%.
Of the 26 cases of the complicated urinary tract infections. CPZ was excellent in 13 cases, good in 8 cases and poor in 5 cases, showing a very high effectiveness rate of 80.8%.
2) In bacteriological study, of the 32 strains, 24 strains eradicated. The rate of eradication was as high as 75%. It must be noted that all the E. coli, Enterobacter, Proteus and P. cepacia were eradicated.
3) No side effect was found in any of the cases.

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MICs of cefoperazone (CPZ, T-1551) and CBPC against 154 strains of GNB, each 27 strains of E. coli, Klebsiella, Serratia, Proteus mirabilis and Pseudomonas and 19 strains of Proteus vulgaris were measured by agar dilution method. The MICs of CPZ against E. coli, Klebsiella, Proteus mirabilis and Pseudomonas aeruginosa was three to four fold stronger than that of CBPC. Antibacterial activity of CPZ against Proteus vulgaris and Serratia seemed to be as same as that of CBPC.
Serum levels and urinary excretion of CPZ and CBPC after intravenous injection of each two grams were measured by thin layer cup method by cross over study. Peak serum levels of both drugs obtained were almost equal, but decrease of the drug looked slow. Urinary recovery rate of CPZ up to 12 hours reached 21.4%, which seemed to be relatively low as cephalosporin antibiotic.
Clinical result by this drug administered to 21 cases of chronic complicated UTI was recorded 57.1% of effectiveness rate including 7 cases of excellent and 5 cases of moderate. Nausea and headache was seen in only one case following the administration but no abnormality in blood chemistry was marked.

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Fundamental and clinical studies in the field of obstetrics and gynecology on cefoperazone (CPZ, T-1551), a new parenteral cephalosporin derivative having broad spectrum, was carried out. The result was summarized as follows.
1) Antibacterial activity of CPZ against gram-negative bacilli especially Pseudomonas, E. coli and Klebsiella was superior to that of CET and CEZ.
2) As for materno-fetal transfer of CPZ, the transfer to umbilical cord blood was 34.4% of the mother's serum level at an intravenous dose of 1 g. By continuous administration of CPZ every 12 hour, umbilical cord blood transfer rate and amniotic fluid concentration showed significant increasing tendency.
3) CPZ was administered in principle daily 2g to total 20 cases consisting of intrapelvic infection (puerperal fever, endometritis, adnexitis, septicemia and pelveoperitonitis) and urinary tract infection. The effective rate was 75%, that is to say, excellent in 4 cases, good in 11 and poor in 5 cases.
4) Clinical effect classified by isolated organism was 72.7% in single infections and 80.0% in mixed infections.
5) As the side effect, any noteworthy effect was not observed.

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Fundamental and clinical investigation on cefoperazone (CPZ, T-1551), a new semisynthetic cephalosporin, in the field of obstetrics and gynecology were carried out, The results are summarized as follows.
1) The antibacterial activity of CPZ against clinical isolated strains was cornparatively investigated, employing cefazolin, ampicillin, carbenicillin, piperacillin, gentamicin as the control drug. The antibacterial activity of CPZ against gram-negative microorganisms such as E. coli, Klebsiella, Proteus morganii, Citrobacter was superior to those of other drugs. The antibacterial activity of this drug against Pseudomonas was same level as piperacillin.
2) The clinical results; The rate of effectiveness with intrapelvic infection was 80%, with postoperative infection was 100%, with urinary tract infection was 66.7%. And the bacteriological response was also good.
3) No serious side effects were observed.
In the light of these clinical findings, CPZ appears to be a potent antibiotic agent with an effective clinical application.

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Cefoperazone (CPZ, T-1551), a new cephalosporin derivative synthesized in Japan, was evaluated experimentally and clinically on gynecology infection. The result was summarized as follows.
1) Transference into the uterus
CPZ concentration ratio of uterus to maternal blood was 25% in endometrium, 28% in myometerium and 35% in perimetrium. In the case of CEZ those were 41, 35 and 45% respectively. Concentration of CPZ and CEZ in, each tissue ranged almost from 10 to 20μg/g.
2) Clinical effect
CPZ was administered to 8 patients (2 cases with genital organ infections and 6 cases with the secondary infection of uterine cancer or carcinomatous peritonitis). The result was effectiveness in 4 cases, fair in 1 case and poor in 1 case. Any side effect was not observed except one case of diarrhoea.

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Studies on the antibacterial activity, absorption, excretion and clinical evaluation of cefoperazone (CPZ, T-1551), a new semisynthetic cephalosporin, were carried out and the following results were obtained.
1) Approximately 90% of the minimal inhibitory concentrations (MIC) of CPZ against the recently clinically isolated strains of S. aureus were distributed in the range of 0.78 to 6.25μg/ml and the median MIC of CPZ was located at the concentration of 1.56μg/ml.
Most of MICs against gram-negative bacteria were distributed very widely but against the strains of E. coli, Enterobacter and P. morganii showed two peaks.
Compared with the common used cephalosporins, CPZ was more sensitive against gram-negative bacteria than gram-positive bacteria, especially CPZ showed very unique susceptibility to the strains of E. coli, Klebsiella, Serratia, Enterobacter, Pseudomonas and Proteus.
2) In a pregnant woman, the blood level of CPZ was very high and urinary recovery rate within 24 hrs was about 30%.
As to the transfer to a fetus and ascites, CPZ showed similar to common cephalosporins.
3) CPZ was given at a daily dose of 2 to 8 g during 3-15 days to 29 patients with various infections in the field of the obstetrics and gynecology and the effective rate was 79.3%.
No side effect was observed except a vascular pain and slight elevation of serum transaminase (S-GOT, S-GPT).
These results suggest that CPZ might be a very safe and effective drug against infectious diseases.

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Fundamental and clinical investigations on cefoperazone (CPZ, T-1551), a new semisynthetic cephalosporin, in the field of obstetrics and gynecology were carried out. The results were summarized as follows.
1) The antibacterial activity of CPZ against clinically isolates was investigated, compared with CET, CEZ, GM and AMK. The minimum inhibitory concentrations (MICs) of CPZ against gram-negative microorganisms such as E. coli, Klebsiella, Proteus mirabilis, P. vulgaris and Pseudomonas aeruginosa were superior to those of CET and CEZ, but were almost similar to those of GM and AMK. To the contrary, the MICs of CPZ against Staphylococcus aureus were rather inferior to those of CET, CEZ and GM.
2) The peak concentrations of CPZ in maternal and umbilical cord blood at 13 minutes after intravenous injection of 1g were 88μg/ml and 12.5μg/ml, . respectively. In amniotic fluid it was 7.55μg/ml at 270 minutes after administration, and decreased slowly until 650 minutes (5.9μg/ml). In neonate CPZ showed low blood level. Transfer of CPZ into mother's milk was rather moderate, compared with the conventional antibiotics.
3) As the clinical studies CPZ was administered to 19 cases including 12 cases of UTI, 3 cases of post-operative infection and 4 cases of puerperal uterine infection. The results were effective to all cases. As side effect, any abnormality was not observed.

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The results of laboratory and clinical studies of cefoperazone (CPZ, T-1551), a new broad spectrum cephalosporin, were as follows;
1) Nineteen cases, aged from 2 weeks after birth to 59 years, with various cutaneous bacterial infections were treated with this antibiotic.
The daily dose was mainly 0.5 g per day in children and 2 g per day in adults, and was chiefly given by intramuscular injection in 2 divided doses for 3 to 17 days. The total dose of this antibiotic given in this study was 1.5-34g.
2) In several clinical isolates, namely 17 strains of Staphylococcus aureus, MIC of this antibiotic was determined with the dilute plate method. Its peak was shown at 3.13μg/ml in inoculum sized 10⁶/ml and 6.25μg/ml in 10⁸/ml, respectively.
3) Most of all cases caused by not only Staphylococcus aureus, but also gram-negative rods revealed excellent results in the administration of this drug.
The overall efficacy rate was 94.7%, i. e., excellent in 14 cases, good in 4 cases and fair in only one case.
4) No adverse reactions were noted.

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Cefoperazone (CPZ, T-1551), a new semisynthetic cephalosporin derivative, was used in the treatment of pyoderma. The results were shown as follows.
CPZ was given to 15 patients with pyoderma. In 14 patients, marked improvement was seen in 6, good effectiveness seen in 5 and slight improvement seen in 3.
Total clinical effectiveness was 78.6%.
As side effects, urticaria was observed in only one case, but no dysfunction was shown in liver and renal function.

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1) MICs of cefoperazone (CPZ, T-1551), cefazolin, cephalothin and cephaloridine against 32 strains of Staphylococcus aureus isolated from the lesions of skin infection were studied. MIC of CPZ was inferior to cefazolin, cephalothin and cephaloridine.
2) Serum and skin levels of CPZ (20mg/kg im) were determined in rats at 1/4, 1/2, 1, 2 and 4 hours. Serum levels were 9.8±3.02, 6.2±2.30, 0.66±0.19μg/ml at 1/4, 1/2 and 1 hour, respectively. The corresponding skin levels were 4.6±1.35, 3.9±1.39, 1.08±0.37μg/g. At 2 and 4 hours those levels were trace (wet skin)(n=4).
3) CPZ was used clinically in 5 cases of skin infection with the following result: excellent in 3 cases, poor in 1 case. In 1 case evaluation was not possible. Any side effects were not observed.

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Cefoperazone (CPZ, T-1551) was tested clinically in 15 cases (7 with sinal, tonsillar or laryngeal acute infections, 6 with Pseudomonas aeruginosa infections following total resection of sinal, laryngeal or glossal cancers, one with reticulosarcoma of nose infected by Staphylococcus aureus and one with rhinitis gangrenosa infected by Klebsiella) by the intravenous injection or intravenous drip infusion of 0.5-4 g of CPZ daily for a short or long duration.
As a result, the responses were “excellent” in 4 cases, “good” in 9 and “poor” in 2. It was concluded that the effective results (good to excellent) was obtained in a large number as 13 out of 15 (86%) by the intravenous administration of CPZ. No side effect was found in all 15 cases.

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Fundamental and clinical investigations with cefoperazone (CPZ, T-1551), a new cephalosporin derivative, were performed with the results which might lead to the following conclusions:
1) In vitro antibacterial activity: The minimum inhibitory concentration of CPZ was tested by an agar plate dilution method. CPZ resulted an excellent, broad spectrum antibacterial activity against standard strains of various bacteria. CPZ had same antibacterial spectrum like those of other cephalosporin antibiotics. The MIC of S. aureus isolated from otorrhoea was distributed at a range from ≤0.2 to 50μg/ml of CPZ, showing its peak at 1.56μg/ml. Other strains of E. coli, P. mirabilis, K. pneumoniae were inhibited by ≤0.2 to 12.5μg/ml of CPZ. CPZ showed the MICs of 0.78 to ≥100μg/ml, its peak at 6.25μg/ml against 60 strains of pathogenic P.aeruginosa.
2) Concentration in serum: The serum level of CPZ in healthy adults given 500 mg reached a maximum of 71.5μg/ml at 15 minutes after intravenous injection. Even 6 hours after intravenous injection, clinically effective serum CPZ concentration 2.3μg/ml was still demonstrable.
3) Concentration in tissues: Activity of CPZ was demonstrable at the concentration of 5.1μg/g in human palatine tonsilla and 4.9μg/g in mucous membrane of maxillary sinus one hour after intravenous injection, when the serum concentration of CPZ was 31.3 and 31.7μg/ml, respectively.
4) Results of clinical treatment: When CPZ was intravenously injected to 32 cases of representative infection in the otorhinolaryngologic field, clinical results were excellent in 17 cases, good in 10 cases and fair in 5 cases. When the excellent and good cases were considered together, clinical response were obtained in 27 cases, 84.4 Per cent.
Side effect: No side effect was shown with intravenous injection of CPZ.

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Fundamental and clinical studies of cefoperazone (CPZ, T-1551) in otorhinolaryngological field were carried out.
The peak of MIC against 60 strains of S. aureus and 45 strains of P. aeruginosa were both 1.56μg/ml.
Observing by biophotometer, the growth of S. aureus 209 P was not inhibited but that of E. coli NIHJ was completely inhibited by the serum (diluted 10 fold) of 6 hours after intramuscular injection of 500 mg.
The peak of serum levels were obtained at one hour after intramuscular injection of 500 mg and 1000 mg of CPZ, and they were 32.2 and 61.7μg/ml, respectively.
The concentration in palatin tonsilla, mucous membrane of maxillar sinus and mucous membrane of concha inferior at one hour after intramuscular injection of 500 mg was 6.0, 4.9 and 6.0μg/g, respectively.
The clinical results in 32 cases of otorhinolaryngological infections were excellent in 21 cases, effective in 8 cases and ineffective in 2 cases; the effectiveness were 6 out of 6 in acute suppurative otitis media, 6 out of 8 in chronic suppurative otitis media, 3 out of 3 in paranasal sinusitis, 7 out of 7 in tonsillitis, 2 out of 3 in peritonsillitis, 3 out of 3 in peritonsillar abscess and 2 out of 2 in phlegmon.
The dosage was 1-6 g per day for 2-13 days, intravenous drip infusion.
As side effect, unpleasant feeling was observed in one case.

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Cefoperazone (CPZ, T-1551) was administered to 13 patients of various infections in otorhinolaryngological field. These 13 cases included acute suppurative otitis media, acute exacerbation of chronic suppurative otitis media and perichondritis of the auricle. Clinical response obtained in these cases was excellent in 6 cases (46.2%), good in 4 cases (30.8%), fair in 3 cases (23%) and none of poor case.
No side effect was observed in these 13 cases.

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From the laboratory and clinical studies on cefoperazone (CPZ, T-1551), the following results were obtained.
1) Activity of CPZ was measured by the plate dilution method on 58 strains isolated from pathological materials in our clinic.
The peak of MIC was 1.56μg/ml with 20 strains of Staphylococcus aureus. Growth of 9 strains of Staphylococcus epidermidis was suppressed up to 1.56μg/ml.
MICs against 12 strains of Pseudomonas aeruginosa were 6.25-50μg/ml and the titers were not different from those of PIPC. MICs against 14 strains of Proteus species were 0.78-25μg/ml and they were superior to those of GM and CEZ. Growth of 3 strains of E. coli was suppressed up to 0.787mu;g/ml
2) Tissues concentrations of CPZ were determined 30 minutes after intramuscular injection of 1-18 mg/kg in humans to compare with those of PIPC, CTM and CEZ. The concentrations in serum and palatine tonsilla were 13.3μg/ml and 8.3μg/g respectively.
3) CPZ was used clinically in 8 cases with various infections in oto-rhino-laryngological field, and its effective rate was 88%.
4) As for side effect, slight elevation of GOT was noted in one case.

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To 30 cases of otorhinolaryngological infectious diseases (otofuruncles, acute or chronic otitis media and sinuitis, acute tonsillitis, acute parotitis), the drug was administered intravenously at a daily dose of 1-4 g for 3-8 days. The results showed that theremarkably effective cases were 37%, effective cases 43%, slightly effective cases 17% and ineffective case 3%. As side effect exanthema was observed in only one case. It was demonstrated that cefoperazone (CPZ, T-1551) was effective against gram positive and negative microorganisms, having excellent effectiveness.

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Bacteriological and clinical studies of cefoperazone (CPZ, T-1551) in the field of ophthalmology were performed and the results obtained were as follows.
1) Minimum growth inhibitory concentration of CPZ was 0.39-0.78 μg/ml for Koch-Weeks bacillus, 0.78 μg/ml for Morax-Axenfeld diplobacillus, 1.56-25 μg/ml for S. pneumoniae, 1.56 μg/ml for C. diphtheriae, <0.1 μg/ml for N. gonorrhoeae, 0.19 μg/ ml for S. hemolyticus, 25-50 μg/ml for S. viridans, 0.39-1.56 μg/ml for S. aureus and 6.25-25 μg/ml for P. aeruginosa.
2) The distribution of sensitivity for 20 strains of S. aureus was in the range of 0.39-3.13 μg/ml and the peak of them was at 0.78 p, g/ml in 12 strains (60.0%). Twenty strains of P. aeruginosa were sensitive at 3.13-100 μg/ml, and the peak at 12.5 μg/ml in 9 strains (45.0%).
3) The serum level after intramuscular injection of 1.0 g in a single dose reached the peak level (84.7, μg/ml) after one hour, and decreased gradually until 6 hours (18.1 μg/ml).
4) Ocular penetration was examined in the rabbit eye.
(1) Intramuscular injection of 50 mg/kg ; The aqueous level reached the highest after one hour, 2.8 μg/ml. The ratio of aqueous level to blood level in one hour was 7.0%.
(2) Intravenous injection of 50 mg/kg ; The peak of aqueous level revealed after 1/2 hour, 3.2 μg/ml, and the ratio of aqueous level to blood level was 6.57%.
3) The ocular tissue concentrations at one hour after intramuscular injection and 1/2 hour after intravenous injection showed high levels in both outer and inner parts of the eye.
5) Clinical results ; The combined therapy with drip infusion of 2.0 g and intramuscular injection of 1.0 g twice a day was performed against several kind of ocular infections.
Good or excellent effects were obtained in Pseudomonas corneal ulcer, iridocyclitis purulenta, postoperative infection, and fair in Pseudomonas panophthalmitis.
6) Side effect ; Rash was encountered in 3 cases, and no other severe side effect and no abnormal findings in hepatic and renal tests were observed.

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Fundamental and clinical studies on cefoperazone (CPZ, T-1551) in the field of ophthalmology were performed, and the results obtained were summarized as follows.
1) The minimum inhibitory concentrations of CPZ and the other cephalosporins against Staphylococcus aureus and S. epidermidis isolated from ophthalmological infectious patients in 1978 were measured. The sensitivity distributions of CPZ against S. aureus and S. epidermidis were 0.39-3.13 μg/ml and≤0.1-1.56μg/ml, respectively.
2) The serum and aqueous humor levels of CPZ in rabbits at a dose of 50 mg/kg were measured. The serum levels of CPZ in the group of intramuscular administration were higher than those of the intravenously injected group, but the aqueous humor levels in the group of im administration were lower than those of iv group.
Therefore, the results suggest the desirability of the route of iv against intra-ocular infections, and the im route against outer-ocular and orbital infections.
3) The aqueous humor levels of CPZ following instillation performed 5 times every one minute and 5 times every 5 minutes in rabbits were less than 1.56μg/ml at a dose of 1 g of CPZ per 20 ml physiological saline solution. But the tear levels were 430-450 μg/mi. at 5 minutes and 40-78μg/ml at 30 minutes after instillation.
4) The clinical effects of CPZ were good on all cases. CPZ proved to be effective at a daily dose of 2-3g for 3-4 days against keratitis, 1-5g for 3-15 days against acute dacryocystitis and 0.5-3g for 6-10 days against the early stage of orbital phlegmone. No severe side effects were observed.

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Clinical investigations were performed on cefoperazone (CPZ, T-1551) in the field of oral surgery, and the following results were obtained.
1) CPZ was intravenously administrated to 18 cases with infection and 2 cases with prophylaxis of postoperative infection at daily dose of 1.0 g to 4.0g.
2) The clinical results of 18 cases with infection were classified as excellent in 8 cases, good in 8 cases and fair in 2 cases. The prophylactic effects of 2 cases were satisfactory.
3) As to the side effects, eruption was observed in 3 cases, elevation of GPT in 2 cases, elevation of ALP in 1 case and unusual value of ALP in 1 case.

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In order to study oral surgical application of cefoperazone (CPZ, T-1551), fundamental and clinical investigations were carried out and the following results were obtained.
1) Rabbits were intravenously injected CPZ in a dose of 33 mg/kg for 2 hours. CPZ was rapidly absorbed after div. The concentrations in kidney and liver were higher than the tongue, submaxillary glands and submaxillary lymphonodi. Excretion rates of CPZ in urine were 15.6%(0-1 hr), 21.6%(0-2 hr), 40.9%(0-3 hr) and 55.4%(0-4 hr), respectively.
2) When CPZ was intravenously administrated to 5 healthy volunteers at dose of 2 g for 2 or 1 hour, serum concentrations attained to maximum at 2 or 1 hour at the termination of div. The half lives of CPZ in serum in groups of 2 or 1 hour div were 1.67 hr and 1.37 hr, respectively. Excretion rates of CPZ in urine from the initiation to 6 hour after div in groups of 2 and 1 hour div were 21.3%, 22.2% respectively.
3) CPZ was intravenously administrated to 25 cases with infection in oral region at daily dose of 1 g to 4 g. The durations of CPZ were ranged from 4 to 23 days. The clinical results obtained were classified as excellent in 4 cases, good in 21 cases. And the percentage efficacy obtained was 100%.
4) Side effects were observed in 2 cases of 25 cases, but severe side effects were not observed. Side effects were drug eruption, and slight elevation of GPT.
CPZ is the useful antibiotics in the treatment of acute infection in oral regions.

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Fundamental and clinical studies on cefoperazone (CPZ, T-155l) in oral surgical field have been investigated, and the following results were obtained.
CPZ was effective against 108 isolated anaerobic organisms except gram-negative bacteria Bacteroides sp.
The drug was given by intramuscular injection at a dose of 100 mg/kg to rats, to investigate its concentration in serum and in organs. Peak serum and oral organ levels were attained in 30 minutes after administration, most of the drug having been excreted until 3 hours.
The drug was injected intravenously by drip infusion to 7 cases of oral inflammation and 18 cases of post operation, and the results obtained were useful as first choice.
Transient diarrhea was observed in 2 cases after one shot intravenous injection, but no side effects and no abnormalities of laboratory findings were shown at treatment by drip infusion.

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Cefoperazone (CPZ, T-1551), a new cephalosporin derivative synthesized in Japan, has been evaluated experimentally and clinically in the oral surgical field. Results are summarized as follows.
1) The minimal inhibitory concentrations (MICs) of CPZ against gram-positive cocci (20 strains) isolated from the patients with oral infections showed similar to those of cefazolin, while MICs against gram-negative rods (54 strains) were distributed in the range of 25 jig/ml or less.
2) The concentrations of serum and oral tissues were investigated with 10 rabbits and the following results were obtained. The mean serum concentration of CPZ at 60 min. after intravenous injection of 40 mg/kg showed 107.7±38.8 jig/ml, and 27.5±7.7μg/ml at 120 min. after the injection. The level of mandibular bone marrow showed 10.6±5.7 μg/g at 60 min. after and 6.3±2.5 jig/ml at 120 min. after intravenous injection.
According to these experimental results, CPZ was applied clinically to 26 cases in order to determine the concentrations of CPZ in the serum and oral tissues. The concentration of CPZ in mandibular bone marrow reached 25% of serum level. The mean serum level was 115.35 ±50.02 jig/ml at the final point of the drip infusion for 1 hr.(20 mg/kg) and 6.5 ±4.06 μg/ml at 7 hr. after the injection.
3) CPZ was administered by the drip infusion into 23 patients with the various infections in the oral surgical field. The therapeutic effects were excellent in 13 cases (56.5%), effective in 4 cases (17.4%), ineffective in 6 cases (26.1%) and the efficacy rate was 73.9%.
4) No serious side effect was observed except one case of slight diarrhoea.

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In order to evaluate objectively the clinical efficacy and side effects of a new cephalosporin, cefoperazone (CPZ, T-1551), a double-blind controlled study was carried out using carbenicillin (CBPC) as a control drug in patients with complicated urinary tract infection. 1.0 g of CPZ or 2.0 g of CBPC was injected intravenously twice a day (2.0 g of CPZ or 4.0 g of CBPC per day) for 5 consecutive days. The doses were determined according to the results of studies on blood levels, antimicrobial activities, urinary bactericidal activities and open trials of both drugs. To 283 patients the drugs were administered, and the clinical efficacy in 116 patients who were injected CPZ and in 116 patients who were injected CBPC were able to be evaluated completely according to “UTI Criteria for Clinical Evaluation of Antimicrobial Agents.” The two groups were confirmed to have the same characteristics because of no significant difference between their background factors by statistical analysis. The overall clinical effectiveness rate of each group was 59.5% in CPZ group and 30.2% in CBPC group with statistically significant difference between them. The efficacy on both pyuria and bacteriuria of CPZ group were also significantly higher than that of CBPC group. Especially, the superiority of the CPZ group was remarkable in the 2nd group (post prostatectomy single infection without indwelling catheter) and the 4th group (lower urinary tract single infection without indwelling catheter) of UTI criteria. Bacteiologically, eradication rate of CPZ group was higher than CBPC group in almost all species of isolates, especially, in E. coli and Serratia, it was significantly higher than that of CBPC group. The eradication rate of Pseudomonas of CPZ group was 54.2%, which was the equivalent eradication rate of CBPC group (55.0%). The subjective side effects were observed in 2.8%(4/144 cases) of CPZ group and in 2.2%(3/139 cases) of CBPC group, and deteriorations in laboratory hematological test values were observed in 3.7%(5/136 cases) of CPZ group and in 3.8%(5/132 cases) of CBPC group. There was no significant difference between the side effects of both groups. All side effects were transient and not serious. Physicians in change assesed the CPZ to be significantly more useful than CBPC.
Based on above results, CPZ considered to be a less toxic, safe and clinically very useful drug for the treatment of complicated urinary tract infections.

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