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Biomedical subjects

T Haruta

Publications and source records attributed to T Haruta.

At least 127 records · Page 7Linked to original sources

[Penetration of aztreonam and ampicillin to cerebrospinal fluid in the concomitant administration to rabbits with Staphylococcus aureus meningitis].

Aztreonam (AZT) and ampicillin (ABPC) were independently administered to 6 and 7 rabbits respectively, with S. aureus meningitis. Additionally, AZT and ABPC were concomitantly given to 6 rabbits with S. aureus meningitis. Concentrations of AZT and ABPC in cerebrospinal fluid (CSF) and serum were determined by HPLC method, and the results in concomitant treatment were compared with those for single treatment of each agent. Results were as follows: Maximum serum concentrations of AZT in concomitant treatment of AZT and ABPC were higher than those in single treatment of AZT. However, there was no significant difference between the 2 treatment groups with regard to maximum CSF concentration, percentage of AUC of CSF to serum, and T1/2 of the CSF and serum concentrations of AZT. ABPC in the concomitant treatment did not influence the CSF concentration of AZT. There was no significant difference in serum concentration of ABPC between concomitant treatment and the single one. However, the values of maximum CSF concentration, percentage of maximum CSF to serum concentration and percentage of AUC of CSF to serum in the concomitant treatment were lower than those in the single treatment of ABPC. With regard to T1/2 of CSF concentration of ABPC, there was no remarkable difference between the 2 treatment groups. The above results suggest that the distribution of ABPC into CSF is suppressed in the concomitant treatment of AZT and ABPC. AZT has no antimicrobial activity against Gram-positive bacteria. The CSF concentration of ABPC is suppressed in the concomitant treatment. Those facts suggest that AZT should be administered for meningitis cases after the identification of causative pathogens.

Ampicillin↗

Cerebrospinal fluid penetration after combined administration of cefotaxime and ampicillin to rabbits with staphylococcal meningitis.

The pharmacokinetics of cefotaxime and ampicillin in the cerebrospinal fluid (CSF) were studied by a HPLC method after administering each of the antibiotics singly or as a mixture to rabbits with experimental meningitis caused by Staphylococcus aureus. The half-lives of cefotaxime and desacetyl-cefotaxime in the serum and of ampicillin in the CSF were found to be significantly shorter in the mixture group than in the respective single administration groups. No other statistically significant differences were observed between the mixture and single administration groups with respect to the maximum concentrations (Cmax) of the antibiotics in the serum and the CSF, to the relative percentage of the Cmax of each antibiotic in the CSF to the Cmax in the serum, and to the relative percentage of the AUC of each antibiotic in the CSF to that in the serum. These results differ from earlier findings that the concentration of ampicillin in the CSF of rabbits was significantly lower in animals concomitantly dosed with latamoxef (moxalactam) and ampicillin than in a group dosed only with ampicillin.

Ampicillin↗

[Basic and clinical studies of sulbactam/cefoperazone in pediatric field].

We conducted several studies using a combination of sulbactam (SBT) and cefoperazone (CPZ) in a ratio of 1:1 with the following results. Serum and cerebrospinal fluid (CSF) concentrations of the drugs were determined in 2 rabbits with meningitis caused by S. aureus. Following intravenous injection, serum concentrations of CPZ were higher than those of SBT in both rabbits whereas CSF concentrations were much higher with sulbactam than with CPZ indicating good penetrability of SBT into CSF. The serum concentration of SBT at 1/2, 1, 2 and 4 hours after an intravenous administration of 9.8 mg/kg of the combination to a child were 3.5, 1.4, 0.3 and 0.1 microgram/ml and those of CPZ 19.0, 13.0, 6.7 and 2.9 micrograms/ml, respectively. The half-lives were 0.705 hours for SBT and 1.31 hours for CPZ. An intravenous dose of this combination (19.6 mg/kg) was given 3 times a day to 13-year-old girl with decreased neutrophil chemotaxis due to periblepharal abscess caused by S. aureus. The therapeutic effect was excellent. Though very slight transient eosinophilia was noted, no adverse reaction was found. The susceptibility of the isolated organism to this drug was not determined, but it was found to be resistant to the CTX using the disc method.

Abscess↗

[Clinical evaluation on ceftriaxone in the field of pediatrics].

Ceftriaxone (Ro 13-9904, CTRX), a new parenteral cephalosporin, was used for pediatric infections and the following results were obtained. CTRX was administered twice daily by intravenous injection with about 20 mg/kg in 6 cases consisting of 2 cases with purulent lymphadenitis of the neck, 2 with urinary tract infection, 1 with sepsis and pyelonephritis and 1 with sepsis and purulent lymphadenitis of the neck. The result was excellent in 4 and good in 2. One case with H. influenzae meningitis, receiving 50 mg/kg CTRX by intravenous injection twice daily, showed an excellent response without having any sequela. Among those mentioned above, diarrhea in 2 cases and elevated GOT and GPT in 2 were observed, all of which were transitory and not serious. The blood level of CTRX at 1/2, 1, 2, 4, 6 and 8 hours after intravenous injection with 20 mg/kg to a girl of 8 years and 8 months of age with urinary tract infection was 114, 86, 70, 42, 29 and 21.8 micrograms/ml, respectively. The half-life time was 3.5 hours while the urinary recovery rate up to 6 hours was 58.0%. The concentration in the cerebrospinal fluid of 1 case with H. influenzae meningitis ranged from 2.1 to 8.2 micrograms/ml at 3 hours after administration and from 1.15 to 2.65 micrograms/ml after about 12 hours (prior to the next administration). The above-mentioned results suggest that CTRX is a new antibiotic useful for pediatric infections caused with susceptible bacteria and is effective by intravenous injection with 10 mg/kg twice daily for moderate infections and with 20 mg/kg twice daily for severe ones, except for meningitis. As for purulent meningitis, the administration dosage and frequency will have to be further examined based on the intravenous injection with 50 mg/kg twice daily.

Bacterial Infections↗

[Clinical evaluation of ceftazidime in paediatrics].

Ceftazidime ( CAZ ), a new injectable cephem antibiotic, was used for treatment of infections in children, and the following results were obtained. After an intravenous injection of CAZ at a dose of 20 mg/kg, the mean blood levels in 2 patients were 41.5 micrograms/ml at 30 minutes, 18.1 micrograms/ml at 2 hours and 2.55 micrograms/ml at 6 hours, with the half-life (T 1/2) of 1.37 hours. In a 22-day-old baby with meningitis given CAZ intravenously at a dose of 43.5 mg/kg, the blood levels were 100 micrograms/ml at 30 minutes, 68 micrograms/ml at 2 hours and 25 micrograms/ml at 6 hours, with the half-life (T 1/2) of 2.96 hours. After intravenous administration of CAZ in doses ranging from 35.7 to 50 mg/kg, CSF concentrations ranged from N.D. to 6.3 micrograms/ml in 3 patients with purulent meningitis, although 19 micrograms/ml at 1 hour and 13 micrograms/ml at 2 hours in 1 patient after intravenous administration of 46.7 mg/kg. In patient with mumps meningitis, CSF concentrations were undetectable after intravenous administration of 35.7 mg/kg. Seventeen patients (each 1 patient with lymphadenitis, tonsillitis and septicemia, each 2 patients with pneumonia, bronchiectatic bronchitis, pyothorax and purulent meningitis, each 3 patients with pyelonephritis and enteritis) were treated with CAZ intravenously, at the daily doses of 178.2 mg/kg and 200 mg/kg in 4 divided doses in patients with meningitis and 44.1 to 103.4 mg/kg in 3 divided doses in patients with other infections (two of them were given by intravenous drip infusion for 30 minutes). The clinical responses were excellent or good in all the patients except for 1 case of Salmonella enteritis (poor) and 1 case of Campylobacter enteritis (poor). The efficacy rate was 88.2%. It was noteworthy that the clinical response was excellent in 1 case of septicemia with P. aeruginosa with leukemic stage of malignant lymphoma and in 2 cases of purulent meningitis. As side effects, fever, eruption, leukocytopenia, elevation in GOT and positive CRP considered to be allergic, were observed on day 16 of administration in 1 case of pyothorax. These symptoms disappeared by discontinuance of administration. In addition, there were elevation in GOT and GPT in 2 cases and elevation in GOT in 2 cases and elevation in GPT in 1 case; they were all mild or transient, and there was nothing to be worried about.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Clinical evaluation for T-1982 (cefbuperazone) in the field of pediatric infection].

T-1982 (cefbuperazone), a new injectable cephamycin antibiotic, was employed for bacterial infections in children, and the following results were obtained. 1. When administered intravenously at a dose of 20 mg/kg to a 6-year-old female child, serum levels were 62 micrograms/ml at 30 minutes, 39 micrograms/ml at 1 hour, 17.6 micrograms/ml at 2 hours, 6.8 micrograms/ml at 4 hours and 2.9 micrograms/ml at 6 hours with serum half-life (T 1/2) of 76 minutes. Urinary excretion rates were 41.0, 5.3% and 2.4% respectively at 0-2, 2-4 hours and 4-6 hours, and urinary levels were 820 micrograms/ml, 182 micrograms/ml and 310 micrograms/ml, respectively. The total urinary recovery within 6 hours was 48.7%. 2. A total of 11 cases of pediatric infections was treated with T-1982. The clinical efficacy evaluated for 9 cases, excluding 2 cases of non-bacterial infections, was as follows; excellent in 4, good in 1 out of 5 cases of pneumonia, good in 1 case of cervical purulent lymphadenitis, and excellent in 1, good in 1, poor in 1 out of 3 cases of urinary tract infection. 3. As side effect, mild diarrhea in 1 case and slight elevation of GOT, GPT in 2 cases were observed. 4. These results suggest that T-1982 is of good use for bacterial infections in children and the expected efficacy is obtained at a dose of 20 mg/kg 3 times a day.

Anti-Bacterial Agents↗

[Clinical application of cefotetan in pediatrics].

Clinical evaluation was made on cefotetan (CTT), a new cephamycin antibiotic, and the following results were obtained. Following 6 patients were treated with a daily dose of 31.0-47.5 mg/kg of CTT, which was given in 3 divided doses by an intravenous injection or a 1 hour drip infusion; 2 patients with cystitis (causative organism: E. coli and P. mirabilis, respectively), 3 with pyelonephritis (E. coli in 3) and 1 patient with Salmonella enteritis (S. typhimurium). CTT showed a remarkable therapeutic effect on cystitis and pyelonephritis but was ineffective against Salmonella enteritis. Neither adverse clinical reactions nor abnormal laboratory findings were noted. Based on the above results, CTT is considered to be an appropriate and useful new antibiotic in the treatment of bacterial infections, particularly urinary tract infections in children. The fact that longer duration of blood concentrations has made is possible to give this antibiotic in 2 divided doses will be of great practical benefit.

Age Factors↗

[Fundamental and clinical studies of T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

Human pharmacokinetics and clinical studies of T-1982 (cefbuperazone) were carried out and the following results were obtained. Transference into pelvic cavity fluid T-1982 level in pelvic cavity fluid showed the peak level of 48.0 micrograms/ml at 30 minutes after 2 hours drip infusion of 1 g in 1 case. The concentration tended to be more sustained than that of venous blood. Clinical study T-1982 was administered to 2 cases with pelveoperitonitis, 2 cases with puerperal fever and 1 case with adnexitis at a dose of 1 g twice a day for a period of 4 or 5 days. The clinical effect was excellent in 3 and good in 2 cases. Neither side effects nor abnormalities of laboratory findings were observed.

Adolescent↗

[Clinical evaluation of an ampicillin suppository (KS-R1)].

Clinical evaluations of ampicillin (ABPC) suppository (KS-R1) were performed in 9 cases with infectious diseases in the pediatric field and the following results were obtained; When 2.7 mg/kg of KS-R1 was rectally administered to 1 case, the plasma levels of ABPC were 3.9 micrograms/ml at 15 minutes, 2.2 micrograms/ml at 30 minutes and 1.2 micrograms/ml at 60 minutes after administration. The urinary excretion rate within 6 hours was 5.0%. Clinical effects of KS-R1 were examined in 6 cases (4 cases of tonsillitis and 2 cases of urinary tract infection) at the dose of 20 approximately 50 mg/kg/day for 3 approximately 7 days. Clinical responses were excellent in 4 cases, good in 1 case and poor in 1 case (tonsillitis). As to the side effects, slight increase of eosinophil was observed in 1 case, but no diarrhea, perianal redness and eruption were observed. Since discharge ratio of KS-R1 within 5 minutes was 11.0%, the tolerance of KS-R1 was considered to be good. From the above results, KS-R1 is useful for treating the pediatric patients with various infections, who refuse to oral administration or are impossible to give oral administration because of vomiting and are multiple handicapped ones.

Age Factors↗

[Clinical evaluation of cefpiramide in pediatrics].

A clinical study was made of cefpiramide (CPM) a new cephem-type antibiotic for injection and the following results were obtained. Blood level of CPM, after 20 mg/kg administration by drip infusion over a period of 1 hour, reached its peak of 86 micrograms/ml at the end of the infusion and declined to 19.8 micrograms/ml at 4th hour after infusion with the half-life value of 3.02 hours. Its urinary recovery rate up to 9 hours was 29.2% and the urine concentration from 0 to the 3rd hour was 820 micrograms/ml and from the 3rd to the 5th hour 650 micrograms/ml. In another case of the same dose with intravenous administration, the blood level at the end of the first 1 hour reached 56 micrograms/ml and by the 4th hour it had fallen to 20.6 micrograms/ml and by the 6th hour to 13.6 micrograms/ml. The half-life value was estimated as 2.44 hours. CPM was administered in 2 or 3 divided doses at a daily dosage ranging from 41.7 to 62.5 mg/kg by intravenous injection or by 1-hour drip infusion to 6 patients (3 cases of pneumonia, 2 cases of urinary tract infections, 1 case of purulent cervical lymphadenitis) and the following clinical results were obtained; "markedly effective" 3 cases, "effective" 2 cases, and "ineffective" 1 case. The overall efficacy rate was 83.3%. No side-effects or abnormal laboratory findings were found in any of the 7 patients including 1 patient who was excluded from the efficacy evaluation because of Kawasaki's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Evaluation of latamoxef in the treatment of infections of newborn infants].

The usefulness of latamoxef (LMOX) in the treatment of newborn infants was investigated. The results that were obtained are summarized below. LMOX was injected intravenously in a dose of about 20 mg/kg, and 30 minutes later the concentration of the drug in the serum was determined. In a very low-birth-weight infant, weighing only 978 g at the time of birth, the serum concentration on the 3rd day after birth was 94 micrograms/ml, while it was found to be 100 micrograms/ml when the dosing and determination were performed on the 37th day after birth. Another premature infant weighed 1,980 g at birth, and on the 8th day of life the serum concentration was 73 micrograms/ml. The half-lives of LMOX in these 3 administrations were 4.74, 3.95 and 3.20 hours, respectively. LMOX was administered by intravenous injection to 4 patients diagnosed as having 6 diseases (2 patients each had both septicemia and a urinary tract infection; 1 patient had pneumonia; 1 patient had septicemia). Each dose ranged from about 15 to 25 mg/kg, and 3 doses were administered daily (in 1 patient, 4 doses were given over a 2-day period). The evaluation of the clinical results for each disease case showed 4 excellent cases and 2 poor cases. The 2 poor cases consisted of 1 case of pneumonia caused by S. aureus, and 1 case of a mixed urinary tract infection caused by E. coli and S. faecalis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

[Fundamental and clinical studies of piperacillin in the field of obstetrics and gynecology].

Human pharmacokinetics and clinical studies of piperacillin (PIPC) were carried out and the following results were obtained. 1. Transference into various uterine tissues PIPC transference into various uterine tissues was 27.3 approximately 67.9% (the ratio with respect to uterine artery blood level) at 1 hour after the completion of PIPC 1 or 2g dripping infusion for 1 hour in 5 cases. 2. Transference into retroperitoneal space exudate PIPC level in retroperitoneal space exudate showed the peak level 38.0 micrograms/ml at 30 minutes after the completion of PIPC 2g dripping infusion for 1 hour in 1 case. The pattern of the concentration trends was more continuous than that of venous blood level. 3. Clinical study We administered PIPC to 5 patients with pelveoperitonitis in 3 cases, puerperal fever in 1 case and wound infection in 1 case at a dose of 4 g per day (twice a day) for a period of 5 approximately 9 days. The clinical effect was excellent in 1, good in 3 and poor in 1 case. Neither side effects nor abnormality of laboratory findings were observed.

Adolescent↗

[Experimental and clinical studies of cefmenoxime in the field of obstetrics and gynecology].

The study group was organized to evaluate the usefulness of cefmenoxime (CMX) injection, a new synthetic cephalosporin, for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made by the society and the following results were obtained. 1. The peak distribution of CMX's MIC for E. coli, Klebsiella sp., Enterobacter sp., Bacteroides sp. and Peptococcus sp. isolated from obstetrical and gynecological infections with relatively high frequencies area 0.1, less than or equal to 0.05, 0.2, 3.13, 1.56 micrograms/ml, respectively, with an inoculation of 10(6) cells/ml. 2. When 1 g of CMX is administered by intravenous drip infusion for 1 hour, the maximum concentrations in various tissues of female genital organs were as follows: 14.2 and 13.2 micrograms/g in ovary and oviduct, respectively, at 1.20 hours after the start of administration, and 16.9 and 26.3 micrograms/g in corpus uteri and cervix uteri, respectively, after 1 hour. As for the transfer to the exudate in the pelvic dead cavity, the peak concentration was 15.6 micrograms/ml after 2.13 hours. 3. In the clinical studies, CMX was given to 258 cases with female genital organ infections and others. As for the clinical effects, with exclusion of 3 cases in which other antibiotics are concomitantly used, responses were excellent in 76 cases, good in 162 cases and poor in 17 cases, among 255 cases in total. The efficacy rate was 93.3%. The efficacy rates by diseases were 97.1% (68/70) for intrauterine infections, 88.8% (79/89) for intrapelvic infections, 98.4% (62/63) for adnexitis, and 100% (23/23) for infections of external genital organs. As for the clinical effects on causative bacteria, the efficacy rates were 100% (19/19) for single infections due to Gram-positive bacteria, 94.8% (55/58) for single infections due to Gram-negative bacteria, and 88.2% (15/17) for single infections due to anaerobic bacteria. And its efficacy rates were 89.6% (69/77) for mixed infection cases. Side effects were observed in 2 cases (0.8%); 1 case with eruption, and 1 case with diarrhea and vomiting. As for abnormal laboratory findings, lower white blood cell count was observed in 2 cases and elevation of the values regarding hepatic functions in 9 cases. All cases were returned to the normal after the completion of the administration. Cefmenoxime showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infections in the field of obstetrics and gynecology, and it has been concluded that cefmenoxime will be useful addition to the antibiotics for the therapy of these infections.

Adolescent↗