Cefamandole sodium (CMD) was intravenously administered and following laboratoric and clinical results were obtained.
(1) The peak blood concentration was 32-44μg/ml when the drip infusion was finished. At lhour after the end of the drip infusion the blood concentration was 7.6-8.1μg/ml.
Half life was approximately 0.64 hours.
(2) Urinary recovery rate was 84.5-95% in active state within 6 hours.
(3) Penetration of cerebrospinal fluid was found in 2 cases.
(4) In most of 170 strains of Streptococcus haemolyticus MICs of cefamandole were 0.05μg/ml. They were less susceptible to cefazoline, cefmetazole and ceftezole.
(5) CMD was administered to 35 pediatric patients (upper or lower RTI, lymphadenitis, enteritis or UTI) at 100mg/kg/day for 3-9 days, the efficacy rate was 97.1%.
(6) Side effect: Rash occurred in one case, and eosinophilia was observed in 4 cases.
No abnormal finding of renal and liver function was observed.

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Laboratory and clinical studies were performed on a new semisynthetic cephalosporin, cefamandole (CMD), and following results were obtained.
(1) Serum concentrations and urinary recovery rates of CMD were determined after an intravenous administration of CMD 30mg/kg in 13 children with normal renalfunction.
In 5 of 13 children, mean serum levels after a one shot intravenous injection were 112.5μg/ml at 15 minutes, 52.2μg/ml at 30 minutes, 23.3μg/ml at 1 hour, 4.9μg/ml at 2 hours and trace at 4 hours.
In other 5 children, mean serum levels after drip infusion for 1 hour were 78μg/mi at 30 minutes, 59μg/ml at 1 hour, 9.8μg/ml at 2 hours and trace at 4 hours, after the onset of drip infusion.
In the remaining 3 children who received CMD by drip infusion for 2 hours, mean serum levels were 24.3μg/ml at 30 minutes, 35.3μg/ml at 1 hour, 30.2μg/ml at 2 hours, 5.3μg/ml at 3 hours and 1.5μg/ml at 4 hours after the onset of drip infusion.
Urinary recovery rates in 5 children were 154.7%, 98.3%, 93.2%, 111.8% and 66.9%, respectively, during 8 hours.
(2) CMD was administered to 40 patients with various infections (acute U.T.I. 8, acute angina lacunaris; 2, acute bronchitis; 5, cervical purulent lymphadenitis; 2, post-measles bronchopneumonia; 3, acute bronchopneumonia; 18, pyothorax; 2, S.S.S. syndrome; 1) by one-shot intravenous injection at a dose of 40-120 mg/kg per day. The clinical efficacy rate was 92.5% and bacteriological efficacy rate was 79.2%.
(3) As the side effect of CMD, eosinophilia was observed in 1 case, rash and elevation of GOT and GPT in 1 case, and proteinuria in 1 case.

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Excretion of a new semisynthetic analogue of cephalosporin, cefotiam (CTM), and cefazolin (CEZ) in bile was investigated in dogs. with experimental obstruction of biliary tract.
In the control group, peak concentrations of antibiotics in bile after 50 mg/kg intravenous administration were as follows: In CTM administrated group, 5,302μg/ml at one hour after administration; and in CEZ administrated group, 1,249μg/ml after one hour. The total biliary excretory rates summed to 6 hours after administration of antibiotics were 7.8% in the CTM group, and 2.1% in the CEZ group.
On the other hand, in the biliary tract obstruction group, the peak concentration in bile in CTM group was 65.7μg/ml after 1 hour, and in CEZ group, 62.4μg/ml after 2 hours. The total biliary excretory rate in the CTM group was 0.202%, while in the CEZ group 0.12%.
The peak concentration and the excretory rate of CTM in bile was four times higher than that of CEZ in the control group. No significant difference was revealed in the peak concentration and the excretory rate in bile between CTM and CEZ in the biliary tract obstruction group.

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I. Pharmacokinetics
(1) CXM 24. 4 and 31.9mg/kg were administered by intravenous drip infusion for 4 hours. The plateau levels were obtained at 1-2 hours, the blood levels at which time were 25.6 and 33.8μg/ml respectively with dose response observed.
(2) The respective half-lives were as short as 49.4 and 36.2 minutes.
(3) The total clearances were 74.6 and 127.2 ml/min respectively; when calculated on plateau level and infusion rate, these were 81.6 and 111.0 ml/min. These differently determined values were near each other.
(4) The respective renal clearances were 157.8 and 101.9ml/min.
II. Clinical results
CXM for intravenous use was administered to 21 pediatric patients, and the clinical results were good and excellent in 19 (90.5%). Excluding 2 cases with elevation of cold hemagglutination values, the efficacy rate of 94.7% (18/19 cases) was achieved.
The doses administered ranged 44-100 mg/kg body weight, and this dosage level was considered enough to achieve clinical effect. With the current clinical trial we considered that although the effectiveness of this drug was proved in 3-7 day intravenous drip infusion and intravenous injection, the continued treatment with other oral antibiotic following CXM treatment would be necessary from the patients' general conditions and laboratory examination findin.
No noteworthy side effects were observed in any of the patients. No abnormality was seen in biochemistry and electrolyte findings, either.

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Cefuroxime, a new synthetic cephalosporin, was administered to 10 pediatric patients (6 with respiratory tract infection, 2 with urinary tract infection, 1 with sepsis of E. coli and 1 with enterocolitis). The clinical result was good and excellent in all the 10 cases. No side effect was observed in any of them.

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Cefuroxime (CXM) was administered to 11 patients with pediatric bacterial infections, and clinical effective results were obtained in all these cases.
Causative organisms detected in 5 cases with respiratory tract infection, and with urinary tract infections were all eliminated, and the bacterial count decreased in patients with colitis.
As for side. effect, 1 case developed eosinophilia, and another case with impaired liver function as underlying disease showed transitory exacerbated examination values.
Time-course determinations of blood levels and urinary excretions were performed in 1 case. Fecal levels were determined in 2 cases but could not be detected; inactivation action of CXM was observed from the same fecal filtrate.

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Cefuroxime (CXM), a new cephalosporin antibiotic, was used in pediatric field, and the following results were obtained.
1. Absorption and excretion
CXM was administered by intravenous drip infusion to 3 patients aged 14 years, 1 year and 1 month, and 5 years and 3 months, respectively, at doses of 15.4 mg/kg, 14.1 mg/kg, and 13.2 mg/kg. The following blood levels were obtained; 71pg/ml at the completion of infusion, 26.8μg/ml at 30 minutes, 13.2μg/ml at 1 hour, 5.05μg/ml at 2 hours, 2.07μg/ml at 4 hours, and <0.45μg/ml at 6 hours after the infusion. Urinary excretion of the drug administered was measured in one of these cases. The urinary excretion rate at 1-6 hours after intravenous drip infusion was 50.4%.
2. Clinical result
CXM 17-55mg/kg were administered for 2-4 days to 6 patients with acute respiratory tract infection, 1 with acute cervical lymphadenitis, and 1 with acute enteritis. The clinical result was poor in the case with acute enteritis and good in the other 7 cases. No side effect was observed in 9 cases (the above 8 cases plus 1 unassessable case), and the laboratory examination results showed no abnormality, either.

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Cefuroxime, a new cephalosporin C antibiotic, was administered to 15 children with respiratory tract infection, urinary tract infection, or subcutaneous tumour. The following results were obtained.
1) CXM 30-100mg/kg/day were used in treatment of respiratory tract infection. Eight of the eleven patients treated responded to the therapy.
2) CXM 45-75mg/kg/day were given to 3 patients with urinary tract infection. Excellent results were obtained in all these cases.
3) One patient with subcutaneous tumour responded to CXM therapy.
4) Clinical isolates from the foci involved, i. e., Staphylococcus aureus(4 strains), Group A Streptococcus hemolyticus(1 strain), Streptococcus pneumoniae(1 strain), Haemophilus influenzae(1 strain), and Escherichia cola(3 strains) were all eliminated by CXM therapy except 2 unassessable strains.
5) No noteworthy side effect was noted.

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[in Japanese]

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A series of studies on cefuroxime (CXM) were carried out and the following results were obtained.
1) Most of MICs to recent clinical isolates of Group A hemolytic Streptococcus were less than 0.0125μg/ml.
2) A single intravenous bolus dose of 36.5mg/kg of CXM was given to two children, and the peak blood levels of 30 and 40μg/ml were obtained at 30 minutes after injection; mean half-life in blood was 1.02 hours. The doses of 25-50mg/kg were given over 1 hour by intravenous instillation to six children. The peak blood level appeared at the end of instillation, and half-life in blood was distributed between 0.56 and 0.81 hour. With both of these administrations, measurable blood levels were maintained up to 6 hours, and urinary excretion rate in active form up to 6 hours was distributed between 40.5 and 96%.
3) Serious upper respiratory tract inflammations, low respiratory tract inflammations (acute bronchitis and bronchopneumonia), staphylococcal e, anthema and acute urinary tract infections mostly responded well to CXM intravenous administration (one shot injection, or instillation at dose of 50-104mg/kg/day in 2-3 daily divided doses.
4) Staphylococcal pyothorax was completely cured by 17 day-long CXM intravenous instillation at dose of about 150mg/kg/day.
5) No difference in CXM therapy result was seen between the two administration forms used, i.e., one shot. injection and instillation.
6) Clinical efficacy rate in 48 patients was 100% (excluding 1 unassessable case). As for side effect, transitory elevations of GPT and Al-P were seen in only 1 case each.
The summary of this paper was reported on June 9, 1979 at 27th General Meeting of Japan Society of Chemotherapy (Fukuoka).

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Having resistance to β-lactamase-producing strains and showing resistance to not only cephalosporin resistant strains of E. coin and Kiebsiella but also to Citrobacter, Proteus and Enterobacter, Cefuroxime (CXM) was used in pediatric field for both fundamental and clinical studies. CXM was found to be a useful antibiotic in views of high, clinical efficacy rate obtained and no side effect noted.
As for the dose, the single dose of 25mg/kg achieved sufficient blood levels. Also in view of good clinical effect, the dose of 25mg/kg three or four times daily seems appropriate for treatment of children.

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1.Cefuroxime (CXM) was studied for absorption and excretion in 4 pediatric patients given one shot intravenous injection of 20-25mg/kg.The following serum levels weredetermined: 24.5-38.0μg/ml at 30 minutes (mean 33.3±6.1μg/ml), 10.0-17.0μg/ml at 1 hour (mean13.9±3.3μg/ml), 3.4-7.6μg/ml at 2 hours (mean5.2±1.9μg/ml), 0.7-2.1μg/ml at 4 hours (mean, 1.3±0.6μg/ml), 0.1-0.3μg/ml at 6 hours (mean O.2±0.1μg/ml). Half-lifb (T1/2) was 0.65-0.88 hour (mean0.75±0.10 hour).Urinary levels were 1,280-7,100μg/ml at 0-2 hours, 96-3,400μg/ml at 2-4 hours, 68-250μg/ml at 4-6 hours. Urinary recovery rate at 0-6 hours was 54.1-74.4% (mean61.8±9.4%).
2. From the study on spinal fluid concentration in pediatric patients with Haemophilus influenzae-induced meningitis, the dose of CXM 52.2 mg/kg was given to 1 pediatric case with this disease by one shot intravenous injection. Spinal fluid levels were presumed as 9.0μg/ml at 30 minutes, 6.8μg/ml at 1 hour, 3.8μg/ml at 2 hours and 1.2μg/ml at 4 hours.
3. CXM was studied in 19 pediatric patients with bacterial infection for clinical efficacy, bacteriological effect and side effect. Clinical result was found good in 1 with purulent meningitis; excellent in 9 out of 15 with acute lobar pneumonia or acute bronchopneumonia, and good in remaining 6 cases; good in 2 with acute bronchitis; excellent in 1 with acute pyelonephritis. This represents efficacy (“excellent” plus “good”) rate of 100%.
Of 5 strains of H.influenzae presumed as causative organisms, 4 were disappeared and 1 was reduced. Two strains of Streptococcus pneumoniae and 1 strain of Escherichia coil were disappeared.
No side effect was noted in terms of clinical symptom. Laboratory examination showed elevation of GOT and GPT in 1 case, but these elevated values returned to normal after the end of CXM treatment.

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Recently, it has been known that the aminosidine has marked anthelmintic efficacy against tapeworm. In this investigation, aminosidine was used for treating 14 cases with Diphyllobothrium latum infection and 5 cases with Taenia saginata infection.
Aminosidine was administered orally in a single dose of 50mg/kg, followed by a purge after the treatment. Fourteen patients with D. latum infection and 5 patients with T. saginata infection expelled long strobila in all cases. Although only 7 scolices of 18 worms of D. latum were found in the stool and no scolex of T. saginata was found, follow-up examination for a long period showed no evidence of remaining infection with one exception of D. latum.
Mild nausea, vomiting and abdominal pain were observed in only one of 19 cases given aminosidine. But in the other 18 cases, no side effects were encountered.
It was concluded that aminosidine is safe, effective therapeutic agent for the treatment of cestodiasis in man.

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In the course of treating twenty patients with acute urinary tract infections, the toxicity and efficacy of a small dosage regimen (50mg p.o., t. i. d.) of minocycline were evaluated. No vestibular symptoms attributable to minocycline treatment were observed in any of the cases entered in this study. Adverse reactions included mild nausea in 1 case and urticaria in another case. Minocycline with this dosage regimen sterilized the urine of 90% of patients with acute urinary tract infections.

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Effect of tobramycin on bacteriostatic and bactericidal activities of β-lactam antibiotics was studied by agar plate method. Two sets of agar plate series containing graded concentrations of tobramycin and a β-lactam antibiotic, in combination and separately, were prepared. Plates were inoculated with 10³-10⁴ (order of magnitude) CFUs/inoculum of Escherichia coli, Klebsiella sp. and Pseudomonas aeruginosa. One set of the plates was incubated at 35°C for 20 hours, and the minimal concentrations A and B of either tobramycin and the β-lactam drug yielding no bacterial growth on the plates were designated as minimal inhibitory concentrations (MICs).
The concentrations A' and B' of the two drugs in combination producing the most effective inhibition were determined. The sum of A'/A and B'/B (fractional inhibitory concentrations (FICs)) was defined as FIC index. After reading these bacteriostatic data, the surface of the plates was treated with β-lactamase spray to inactivate the β-lactam antibiotic, and the plates were further incubated at 35°C overnight. The minimal concentration C of the β-lactam drug which produced a 99.9% kill, designated as minimal lethal concentration (MLC), was determined. The concentrations C' and D' of either the β-lactam drug and tobramycin used in combination which produced the best result in terms of a 99.9% kill activity were also determined. The sum of D'/MIC of tobramycin (designated as “fractional lethal concentration” (“FLC”)) and C'/C of the β-lactam drug (FLC) was defined as FLC index.
Another set of the plates was incubated at 35°C for 3 hours. The surface was then treated with β-lactamase spray, and these plates were further incubated at 35°C overnight. The minimal concentration E of the β-lactam drug which produced a 99.9% kill (designated as 3h-MLC) and the concentrations E' and F' of either the β-lactam drug and tobramycin producing the best result in terms of a 99.9% kill activity were determined. The sum of F'/MIC of tobramycin (designated as “3h-FLC”) and E'/E of the β-lactam drug (3h-FLC) was defined as 3h-FLC index.
If the FIC index, FLC index and/or 3h-FLC index was <0.8, ≥0.8-<1.2 or ≥1.2, the combined effect was interpreted as synergistic, additive or antagonistic, respectively. When the combined effect of tobramycin and cephalothin was assessed at bacteriostatic (MIC) level, synergy was detected for 20 of 26 strains of ^{E. coli}, 15 of 27 strains of Kiebsiella sp. If assessed at bactericidal (MLC) level, much more strains showed synergistic effect. Most of the remainder of these strains yielded additive effect. Almost all these strains showed synergy if assessed at bactericidal level with 3 hours exposure to the β-lactam antibiotic (3h-MLC level). The combined effect of tobramycin and carbenicillin on 36 strains of P. aeruginosa showed synergism for most of these strains, both at bacteriostatic and bactericidal levels. Antagonism also occurred among some of these test strains.

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[in Japanese]

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[in Japanese]

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