Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of2.5, 5.0, 10.0or25.0mg/kg/day for13weeks.Physiological saline was given as a control.Some dogs given5.0or10.0mg/kg/day were retained undosed for a further5weeks in order to assess recovery.Premature deaths from acute renal tubular nephrosis occurred in dogs given25.0and10.0mg/kg/day.Dogs which survived treatment at10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after4weeks'treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after13weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined5weeks after the last dose of DKB at5.0mg/kg/day.All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.

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[in Japanese]

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A microbiological method for quantitative determination of cefadroxil in biological specimens isdescribed. This method is essentially a cylinder-plate or a paper-disc method using Micrococcus luteus ATCC 9341 as the test organism grown in the tryptosoya broth added with 1.5% agar. Cefadroxil standard calibration curves are prepared in pooled human serum, mord-trol I or consera for the determination of serum level of human, and 0.1 M phosphate buffer (pH 6.0) to determine urine level. Cefadroxil in human serum and urine specimens can be measured by cylinder-plate method as low as 0.16-0.31μg/ml and 0.08-0.16μg/ml, respectively. Further, any active metabolites of cefadroxil were not detected on human and rat urine specimens by bioautography.

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1. Human serum protein binding of cefadroxil and some other cephalosporins were determined by centrifugal ultrafiltration (U.F.) method and equilibrium dialysis (E.D.) method. The binding rates of cefadroxil were 28.1% by U.F. method and 3.8% (β₁*), 11.6% (β₂*) by E.D. method.
2. Protein binding of cefadroxil with sera of various animal species were also determined by E.D. method. The binding rates were low as well as that with human serum.
3. With two popular calculation formula for E.D. method, binding rate was considered on the alteration of the ratio of V₂/V₁.

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A single dose 50 mg/kg of cefadroxil was administered orally to rats in fasting and non-fasting.
In both fasting and non-fasting, the serum levels of cefadroxil were higher than those of cephalexin.
In fasting, the biological half-life (T 1/2) of cefadroxil was longer than that of cephalexin. This indicates its prolonged durable action.
Ingestion of cefadroxil with food affected the serum level less than that of cephalexin with food, and the serum levels of cefadroxil in non-fasting were same as those of cephalexin in fasting.

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[in Japanese]

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Cefoperazone (CPZ) at dose levels of 80-100 mg/kg/day, divided 3-4 times, was drip-infused or intravenously injected for a period of 2-6 days to 10 patients.
All 10 cases, 4 cases of bronchopneumonia from which H.influenzae was detected (Group A S. pyogenes and S.pneumoniae were also detected in each 1 case), 2 cases of coli urinary tract infection, 1 case of acute colitis from which pathogenic E.coli war detected, 1 case of E. coli carrier, 1 case of acute bronchitis (bacteria were not detected), and 1 case of urinary tract infection (bacteria were not detected) showed rapid improvement of clinical symptoms with rapid eradication of the pathogenic bacteria.
In one case of urinary tract infection where S.epidermidis and S. faecalis were simultaneously detected, S.epidermidis was removed but S.faecalis was merely decreased.
The effective antibacterial concentration after intravenous injection of CPZ in the feces was determined and found to be present in sufficient concentrations to prevent colon infection.
No particular side effects were observed during CPZ therapy.

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Clinical studies of cefoperazone (CPZ) were performed and the following results were obtained.
1) CPZ was intravenously administered at the daily dose of 35-107 mg/kg to 10 children with infection: urinary tract infection (6 cases), respiratory infection (3 cases), and acute enterocolitis (1 case).The overall efficacy rate was 80%, and in urinary tract infection including one case caused by Pseudomonas aeruginosa, efficacy rate was 100%.
2) The bloody stools were noted in one case, 2 days after the administration of CPZ, but improved gradually. No abnormal laboratory data were found.

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Studies in the pediatric field on cefoperazone (CPZ), a newly synthesized broad spectrum cephalosporin, were carried out, and the following results were obtained.
1) In 3 infants, the concentration of CPZ was measured after intravenous instillation.The blood concentrations were maintained at the high level for a long time and the measurable amount of blood levels were detected for 8 hours after the end of injection.The excretion rates in urine for 12 hours after the end of drip infusion were distributed between 34.2-56.1%.
2) Twenty-three patients with respiratory tract infections, 8 patients with enteritis, 4 patients with urinary tract infections, 3 patients with meningitis, 1 patient with sepsis and 4 patients with other infections were administered CPZ mainly by intravenous instillation.
3) Any effect on hepatic or renal function was not observed.
4) Clinical response obtained in these cases was excellent in 33 cases (82.5%), good in 7 cases (17.5%), and none of poor case.

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Experimental and clinical studies were conducted on a new synthetic cephalosporin antibiotic cefoperazone (CPZ). Antibacterial activity of CPZ against S. aureus, E. coli, Klebsiella sp., Proteus sp. and P. aeruginosa was compared with that of cefazolin (CEZ), cephalothin (CET), gentamicin (GM) and cefotaxime (CTX).
Ordinary cephalosporin C antibiotics, CEZ and CET showed an excellent antibacterial activity against S. aureus, while CPZ showed a low MIC of 3.13 mcg/ml even 108/ml inoculation.
CPZ showed an antibacterial activity against Gram-negative bacteria such as E. coli, Klebsiella sp. and Proteus sp. Its activity was very similar to CTX and superior to CET and CEZ.
CPZ showed the greatest activity against P. aeruginosa, i.e., 2tubes greater than CTX.
By intravenous injection, the peak of blood concentration of CPZ treated with25mg/kg was 42mcg/ml (4cases);in the case of 1 hr. drip infusion, the peak of blood concentration with same dose was 41.25 mcg/ml at the end of drip infusion.
By both routes of administration, the half lives were noted to be as long as 101.4 and 84.8 minutes, respectively.
The recovery rates (3cases) in the urine were quite different: 60.8%, 22.6%and76.8% at 6 hours after administration.
The spinal fluid concentration of CPZ was about 5 mcg/ml in the acute stage during the first 5 days and the CSF/serurn ratio was above 10%.
Clinical evaluation of CPZ was performed in a total of 31 cases; 13 cases of respiratory tract infection, 8 cases of urinary tract infection, 2 cases of staphylococcal scalded skin syndrome, 2 cases of enterocolitis, 2 cases of septicemia and 4 cases of purulent meningitis.
Of 31 cases, CPZ proved to be markedly effective or effective in 28 cases, an efficacy rate of 90.3%.
CPZ was found to be ineffective in 1 case of pyothorax and 2cases of septicemia. Of the two cases of septicemia, one who had been also suffering from ecthyma gangrenosum suspected to be caused by P. aeruginosa and died within 10 hours of admission. Therefore, it may be better to consider this case an unknown case.
Side effects observed during the therapy were 1 case of rash and 1 case of a rise of BUN.

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As a result of conducting experimental and clinical tests with the newly developed cephalosporin, cefoperazone (CPZ), the following conclusions were obtained:
(1) When tested against 10 strains of Staphylococcus aureus and 16 strains of Staphylococcus epidermidis, the antibacterial activity of CPZ was found to be weaker than that of CEZ.Against 5 strains of A-β-Streptococcus and 4 strains of Streptococcus pneumoniae, both CPZ and CEZ exhibited similar excellent antibacterial activity.CPZ was effective against 18 strains of Escherichia coli though its activity was influenced by the amount of inoculated bacteria present. Against 15 strains of Haemophilus influenzae and10strains of Haemophilus parahaemolyticus, CPZ was found to be more effective than CEZ though several high-resistant strains were noted.CPZ also showed more excellent antibacterial activity than CEZ against 4 strains of Haemophilus parainfluenzae, 5strains of Klebsiella pneumoniae, 8strains of Salmonella sp., 4 strains of Pseudomonas aeruginosa and 4 strains of Proteus sp.
(2) The mean half-life in the blood following intravenous injections of25mg/kg and 10 mg/kg of CPZ to three children was 70 minutes.
(3) One hour after intravenous injection of 25mg/kg of CPZ to3cases of aseptic meningitis, drug concentration in the cerebrospinal fluid (CSF) was1.20 mcg/ml, less than 0.39mcg/ml and1.55 mcg/ml.In one case, the CSF/serum ratio was 2.7%.
(4) The average recovery rate in the urine of children who had received intravenous administrations of 25mg/kg (3 children) and10mg/kg (1child) was 17.8% between 0 and 6 hours.
(5) Eighteen pediatric patients received CPZ in doses ranging from 48 to 170 mg/kg divided three-four times a day. They were RTI in 7, URI in 5, UTI in 5, SSSS in1and enteritis in 1 children.The clinical effectiveness of CPZ was judged to be remarkably effective in 11 children, effective in 5 children and ineffective in 3 children, with an overall effective rate of 84.2%.One patient of tonsillitis combined sinusitis was considered 2 cases. The three cases in which the drug was found to be ineffective were 2 cases of pyothorax and 1 case of sinusitis.
(6) Side effects were 1 case of eosinophilia, 2 cases of elevation of GOT and GPT, and 1 case of mild elevation of GOT.All were considered to be minor.

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