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We present a case of a 24-year-old female who presented with a history of fever and back pain. She had no particular medical history and was not taking any medication. Transthoracic echocardiology and computed tomography showed a patent ductus arteriosus with vegetation in the pulmonary artery. She was treated with penicillin G;however, the vegetation embolized into the left pulmonary artery. After the antibiotics was changed to clindamycin and ceftriaxone, the resolution of the lung abscess was shown by computed tomography( CT). Two months later, a surgical repair of the patent ductus arteriosus was successfully performed. Patent ductus arteriosus-associated infectious endocarditis is relatively rare in adulthood.

Twenty-eight pediatric patients were treated with ceftriaxone (Ro 13-9904, CTRX) in the doses ranging from 8.75 to 25 mg/kg every 12 hours for 3.5 to 11.5 days, and the clinical efficacy and side effects were evaluated. Among the 21 children with bacterial infections including pneumonia, acute bronchitis, otitis media, tonsillitis and urinary tract infections, the results were excellent in 9, good in 11, and fair in 1 patient. Out of the 28 patients, 2 patients had diarrhea, 3 patients had slightly elevated serum concentrations of transaminases, and 2 patients showed eosinophilia. The serum concentrations of CTRX in 5 children ranged from 50.0 to 93.8 micrograms/ml (mean 75.0 micrograms/ml) at 15 minutes and from 10.2 to 15.6 micrograms/ml (mean 13.4 micrograms/ml at 6 hours after 10 mg/kg intravenous bolus injection of CTRX. The serum half-lives were from 2.61 to 8.30 hours (mean 6.16 hours), and urinary recovery rates were from 43.3 to 58.0% (mean 48.5%) during 0-6 hours and from 52.0 to 66.1% (mean 59.4%) during 0-12 hours. After 20 mg/kg intravenous bolus injection of CTRX in 4 children, the serum concentrations of CTRX were from 118.8 to 162.5 micrograms/ml (mean 139.1 micrograms/ml) at 15 minutes and from 18.0 to 21.1 micrograms/ml (mean 19.2 micrograms/ml) at 6 hours. The serum half-lives were 4.07 to 6.34 hours (mean 5.13 hours), and urinary recovery rates were 38.6 to 51.1% (mean 45.4%) during 0-6 hours and from 54.8 to 64.0% (mean 59.0%) during 0-12 hours. Patients with impairment of renal function were excluded from this pharmacokinetic study.

The study was done to evaluate the usefulness of ceftriaxone (Ro 13-9904, CTRX) injection for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made and following results were obtained. When 1 g of CTRX is administered by intravenous single shot, the concentrations in various tissues of female genital organs were as follows: 40 micrograms/g in oviduct, 30 micrograms/g in ovary, 23 micrograms/g and 32 micrograms/g in corpus uteri and cervix uteri, respectively, at 2 hours 20 minutes after single shot. As for the transfer to the exudate in the pelvic dead space, the peak concentrations were 66-69 micrograms/ml after 4-5 hours. In the clinical studies, CTRX was given to 20 cases with female genital organ infections and others. As for the clinical effects, responses were excellent in 2 cases, good in 18 cases among 20 cases in total. The efficacy rate was 100%. As for the clinical effects on causative bacteria, the efficacy rates were 100% for single infections due to Gram-positive bacteria (6/6), due to Gram-negative bacteria (1/1), for mixed infection (3/3). Side effect was observed in 1 case with diarrhea. CTRX 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 CTRX will be a useful addition to the antibiotics for the therapy of these infections.

Ceftriaxone (Ro 13-9904, CTRX) was administered to 3 cases with gynecological infections and following results were obtained. CTRX was administered by intravenous drip infusion or intravenous injection with 2 g per day for 4 to 6 days. The clinical efficacy was good in all cases (2 cases with pyometra, 1 case with adnexitis and endometritis). No side effect could be determined in all cases.

Clinical studies were made on ceftriaxone (CTRX, Ro 13-9904), a new long-acting cephalosporin antibiotic, with the following results. Following a single intravenous injection of 1 g, the transfer of CTRX to the internal genital organs was found to be good. The transfer of CTRX to exudate of the dead space of pelvis was also good. Elbow vein and uterine artery blood serum levels revealed marked increase immediately after administration, then followed by gradual reduction at very slow rate. CTRX was given to 3 patients of female genital infections. Efficacy was excellent in 1 case and good in 2 cases. As to side effect, 2 cases of diarrhea and 1 case of leukopenia were observed.

The MICs and MBCs of cefotaxime (CTX), desacetylcefotaxime (Des-CTX) and ceftriaxone (CTRX) were determined in relation to 4 of the principal bacterial species which cause meningitis, i.e., S. pneumoniae, S. agalactiae, H. influenzae and E. coli. These tests were performed using final inocula of 10(8) cells/ml and 10(6) cells/ml. Comparison was made with the MIC and MBC values of benzylpenicillin (PCG) and ampicillin (ABPC). 1. Against 25 strains of S. pneumoniae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.024 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml, respectively; and PCG, less than 0.012 micrograms/ml at both size. Similarly, the MBC 90 values were: CTX, 0.01 and 0.05 micrograms/ml; Des-CTX, 0.78 and 0.39 micrograms/ml; CTRX, 0.20 and 0.10 micrograms/ml; and PCG, 0.024 and 0.012 micrograms/ml, respectively. It is thus apparent that PCG showed the lowest values for both the MIC and MBC, followed by CTX, CTRX and then Des-CTX. Against 25 strains of S. agalactiae, the MIC 90 values with inocula of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and PCG, 0.39 and 0.20 micrograms/ml, respectively. Similarly, the MBC 90 values of Des-CTX were 0.78 and 0.39 micrograms/ml, while the other 3 antibiotics showed the same values with both the 10(8) and 10(6) cells/ml inocula: 0.10 micrograms/ml for CTX, 0.20 micrograms/ml for CTRX and 0.39 micrograms/ml for PCG. Accordingly, CTX showed the lowest values, followed by CTRX and then PCG being about the same as Des-CTX. Against 25 strains of H. influenzae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.10 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.39 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and ABPC, 50 and 6.25 micrograms/ml, respectively. Similarly, the MBC 90 values were: CTX, 0.20 and 0.10 micrograms/ml; Des-CTX, 1.56 and 1.56 micrograms/ml; CTRX, 0.39 and 0.20 micrograms/ml; and ABPC, greater than 100 and 50 micrograms/ml, respectively. Accordingly, in terms of the MIC 90, CTX and CTRX showed the same values, but in terms of the MBC 90 CTX was superior. (ABSTRACT TRUNCATED AT 400 WORDS)

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed and the following results were obtained. As to bacteriological efficacy, bacteria were reduced in the case with S. panama bacteremia, while they were eradicated within 2 to 5 days after CTRX administration in 2 cases with acute urinary tract infections and 1 with recurrent urinary tract infection, both caused with E. coli, and in 1 with acute urinary tract infection with P. mirabilis. The clinical efficacy was excellent in 2 cases and good in 3, the efficacy rate being 100%. No side effects were observed to require the withdrawal of CTRX.

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was performed in the field of obstetrics and gynecology and the following results were obtained. The concentration of CTRX after intravenous injection was determined in the arterial and venous blood, and in the internal genital organs and a favorable tissue transfer was observed. The clinical efficacy rate was not very high (40%); good in 2 out of 5 cases with gyneco-obstetric infections, but it is notable that efficacy was recognized in the case which B. fragilis was detected. Neither adverse reaction nor laboratory test abnormality was seen to be attributable to CTRX in any case.

Ceftriaxone (Ro 13-9904, CTRX), a newly developed third-generation cephem antibiotic, reportedly has an antibacterial spectrum of wide-range and shows a much greater activity than cefazolin especially against Gram-negative bacteria and satisfactory effectiveness against anaerobes. In the gyneco-obstetric infections, the relation between the level in the intrapelvic organs and MIC is an important subject in many respects. The levels in the blood and each tissue determined in 54 cases, as presented in Fig. 2, show that a high concentration can be maintained for a long time. In particular the half-life time in the uterine artery and cubital vein was 8.2 hours and 7.8 hours, respectively, which was longer than that of any other existing antibiotics. This fact suggests that CTRX exhibits sufficient efficacy when administered intravenously even in a small dosage of 1 g in the present study. The clinical efficacy was good or above in all the 7 cases treated. There was neither clinical adverse reaction nor laboratory test abnormality found during and after the administration in any of the 54 cases in the fundamental study and 7 cases in the clinical study. It is suggested from the above-mentioned results that CTRX is an unprecedentedly useful antibiotic with an antibacterial spectrum of wide-range.

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.

Ceftriaxone (Ro 13-9904, CTRX) was administered to 13 cases with gyneco-obstetric infections and the following results were obtained. The responses were excellent in 4 cases (30.8%) and good in 7 (53.8%) out of the 13 cases, the efficacy rate (good or above) being 84.6% (11/13). Two cases showing a poor response were considered inappropriate for a study on the efficacy of an antibiotic, as they had received anticancer drugs concomitantly for treatment of their underlying disease of peritonitis carcinomatosa due to ovarian cancer. From a bacteriological viewpoint, CTRX was effective against E. coli, S. aureus, S. faecalis, Pseudomonas, Staphylococcus, K. pneumoniae, S. epidermidis, etc. No specific side effects were observed.

Ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CTRX into intrapelvic genital organs were good. The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively. High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion. Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time. The penetration of CTRX into intrapelvic dead space exudate was good. The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time. CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day. No side effects were observed.

Fundamental and clinical evaluation of ceftriaxone (CTRX) was performed in the pediatric field and the following results were obtained. The MIC of CTRX against E. coli isolated from urinary tract infections in children ranged from less than or equal to 0.024 to 0.39 mcg/ml except for 1 strain. CTRX was superior to other 3rd generation cephalosporins such as CPZ and LMOX, showing effectiveness also against ABPC-resistant bacteria. The clinical efficacy and bacteriological efficacy in 6 children consisting of 5 with respiratory tract infections and 1 with urinary tract infection were 83% and 100%, respectively. As to the adverse reaction, diarrhea was observed in 2 cases. The determination of PIVKA-II performed during the therapy with CTRX, which is observed when vitamin K is deficient, showed positiveness in 2 cases out of 6 cases including 1 which the clinical efficacy could not be evaluated. The test of platelet function in 3 cases found no inhibition of agglutination. Twice-daily administration with 20 mg/kg CTRX was considered to be a useful and safe method for treatment of bacterial infections in children, although attention should be taken not to cause vitamin K deficiency as in other 2nd and 3rd generation cephalosporins.

In vitro activity of ceftriaxone (CTRX) was examined by agar plates dilution method against 398 strains isolated from the infections in the field of obstetrics and gynecology. MIC90 of CTRX against Staphylococcus (107 strains), E. coli (54 strains), K. pneumoniae (27 strains), Peptococcus and Peptostreptococcus (106 strains) and Bacteroides (104 strains) was more than 100 micrograms/ml, less than 0.20 micrograms/ml, less than 0.20 micrograms/ml, 6.25 micrograms/ml and 50 micrograms/ml, respectively. The concentrations of CTRX 16.9 hours after 1 hour intravenous drip infusion with 1 g were 46.2 micrograms/ml in the uterine artery, 48.0 micrograms/ml in the cubital vein, 11.0 micrograms/g in the endometrium, myometrium and cervix uteri, and 14.0 micrograms/g in the portio vaginalis. These concentrations of CTRX in the serum and uterine tissues were higher than the level required to inhibit 90% of the strains of E. coli, K. pneumoniae, and Peptococcus and Peptostreptococcus, isolated from the infections in the field of obstetrics and gynecology. Clinical efficacy of CTRX was evaluated in 7 cases consisting of 2 with puerperal fever and one each with puerperal intrauterine infection, intrauterine infection, pyometra, adnexitis and Bartholin's abscess. Clinical and bacteriological efficacies were seen in 6 and 4 cases, respectively. Neither noteworthy adverse reactions nor laboratory abnormalities were observed throughout this study.

It is reported that ceftriaxone (Ro 13-9904, CTRX) has a half-life time of 7 to 8 hours. In the present study, the serum level 18 hours after intravenous injection with 1 g CTRX was as high as 9.3 micrograms/ml while obviously a higher tissue concentration was maintained compared with other drugs. These facts suggest that CTRX is effective against infections and that the dosage and frequency of administration could be reduced. The global evaluation revealed that CTRX was clinically effective in all the 4 cases with infections. As the adverse reaction, light leukopenia was observed only in 1 case out of the present 4 cases and 20 others administered with CTRX.

One gram of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was given intravenously to a total of 25 patients prior to abdominal total hysterectomy for uterine myoma with or without small benign ovarian tumor. Bilateral uterine arteries were clamped at 0.5, 1, 2, 6, 12 and 24 hours after administration, and serum samples and uterine tissues were taken for the measurement of CTRX concentration by bioassay method. A little difference was found in the serum concentration between cubital venous and uterine arterial serum, the half-lives being 8.0 and 7.9 hours, respectively. The initial concentrations were estimated to be 153 micrograms/ml and 160 micrograms/ml, respectively. The tissue peak concentrations were obtained at 30 minutes in the myometrium, portio vaginalis, oviduct and ovary, and at 1 hour in the endometrium and cervix uteri. These were 41, 51, 51, 39, 42 and 47 micrograms/g, respectively. The tissue concentrations after peak decreased in the same manner as the serum concentrations. Judging from its favorable transfer into the uterine tissues, CTRX was evaluated to be clinically useful in the treatment of obstetrical and gynecological infections.

Fundamental and clinical evaluation on ceftriaxone (CTRX, Ro 13-9904) was performed in the pediatric field and the following results were obtained. The MIC of CTRX against the recently isolated 10 strains of B. pertussis was less than or equal to 0.05 microgram/ml at inoculum size of 10(6) CFU/ml. The blood level of CTRX after intravenous drip infusion with 10 to 20 mg/kg for 30 minutes to 1 hour reached a peak ranging from 45.3 to 137 micrograms/ml at the end of infusion. The effective blood level was maintained up to 12 hours to be 3.52 to 26.7 micrograms/ml at that time. The half-life time was over 6 hours in most cases, but the multiple intravenous dosage did not cause any elevation of the blood level. The urine excretion rate till 12 to 24 hours after intravenous drip infusion ranged from 58.2 to 84.2%. The excretion of CTRX into the cerebrospinal fluid was favorable in the acute period when administered by intravenous drip infusion in the child with S. pneumoniae purulent meningitis, which was considered to be satisfactory for treatment against the bacteria susceptible to CTRX. The active CTRX was transferred into the feces by the multiple dosage. CTRX was administered by intravenous drip infusion in 26 cases with acute pediatric infections. The clinical efficacy was observed in all the cases with upper/lower respiratory tract infections including bronchopneumonia and pertussis, and the cases with acute urinary tract infections caused by ABPC-resistant E. coli, administered by intravenous drip infusion twice daily with about 40-50 mg/kg/day. The bactericidal efficacy was seen against all bacteria except Salmonella. CTRX by intravenous drip infusion was effective against S. pneumoniae purulent meningitis; the clinical symptom was rapidly improved while the culture of causative strains from the cerebrospinal fluid turned negative. Although CTRX was clinically effective against Salmonella enteritis and typhoid, bacteriological and symptomatological relapses were observed in some cases. An increase in dose of CTRX is considered to be needed for these diseases. No adverse reaction was found clinically but soft stool in 1 case while eosinophilia and thrombocytosis were observed each in 1 out of 30 cases in laboratory test. The efficacy was good or higher in all the 26 cases (100%) administered by intravenous drip infusion. The above-mentioned results indicate that CTRX is useful in the pediatric field.

The pharmacokinetics of ceftriaxone (Ro 13-9904, CTRX) was studied in 14 children receiving a dose of 10, 20 mg/kg or 1 g as a intravenous bolus. The mean half-lives of CTRX were 4.5, 6.3 +/- 0.5 and 5.2 +/- 0.7 hours, respectively, while the urinary recovery rates up to 12 hours were 51.7, 48.6 and 48.9%. Forty-one patients, aged 2 months to 10 years, were treated with an intravenous dosage of 10 to 58 mg/kg CTRX every 12 hours for 2 to 29 days. The diseases consisted of upper respiratory tract infections (4), bronchitis (7), pneumonia (18), pyothorax (2), urinary tract infections (4), pertussis (4), meningitis (1) and endocarditis (1). Clinical cures were achieved in 38 cases, overall clinical response rate being 92.7%. No serious side effects were observed, although mild diarrhea was seen in 2 cases.

Fundamental and clinical evaluation of ceftriaxone (Ro 13-9904, CTRX) was performed in the pediatric field. Antibacterial activity The MIC80 of CTRX against clinical isolates such as S. aureus (23 strains), S. pyogenes (23 strains), E. coli (20 strains), K. pneumoniae (23 strains), H. influenzae (15 strains) and P. aeruginosa (23 strains) were 6.25 micrograms/ml, 0.024 microgram/ml, 0.20 microgram/ml, 0.05 microgram/ml, less than or equal to 0.006 microgram/ml and 12.5 micrograms/ml, respectively. The antibacterial activity of CTRX was therefore poor against S. aureus and P. aeruginosa, but quite excellent against S. pyogenes, E. coli, K. pneumoniae and H. influenzae. Compared with cefotaxime (CTX), cefoperazone (CPZ), cefmetazole (CMZ), cefazolin (CEZ) and ceftazidime (CAZ), CTRX was the highest in the antibacterial activity against H. influenzae, next to CTX against S. pyogenes, E. coli and K. pneumoniae, similar to CTX, CPZ and CAZ against S. aureus and similar to CTX against P. aeruginosa. Absorption, Excretion The mean serum levels of CTRX after an intravenous one shot injection with about 20 mg/kg in 3 children aged 10 to 14 years were 160.0 +/- 23.3 micrograms/ml after 1/4 hour, 134.3 +/- 27.5 micrograms/ml after 1/2 hour, 115.0 +/- 33.2 micrograms/ml after 1 hour, 95.3 +/- 28.4 micrograms/ml after 2 hours, 75.3 +/- 14.5 micrograms/ml after 4 hours, 30.3 +/- 13.5 micrograms/ml after 12 hours and 8.2 +/- 3.1 micrograms/ml after 24 hours, while the half-life time was 5.92 +/- 0.43 hours on the average. The mean urinary levels were 1,060 +/- 461 micrograms/ml from 0 to 2 hours, 309 +/- 122 micrograms/ml from 2 to 4 hours, 375 +/- 83 micrograms/ml from 4 to 6 hours, 237 +/- 77 micrograms/ml from 6 to 12 hours and 122 +/- 23 micrograms/ml from 12 to 24 hours, the mean urinary recovery rate up to 24 hours being 38.9 +/- 13.6%. The concentration in the cerebrospinal fluid The mean levels of CTRX in the cerebrospinal fluid of the patients with purulent meningitis were 4.30 +/- 4.22 micrograms/ml 1 hour after an intravenous one shot injection with 42 to 51 mg/kg, 4.64 +/- 3.53 micrograms/ml after 3 1/2 hours to 6 hours, 3.79 +/- 2.15 micrograms/ml after 7 1/2 hours to 12 hours and 1.79 +/- 0.23 microgram/ml after 19 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904) were performed in the field of obstetrics and gynecology and the following results were obtained. The serum concentration was maintained at a high level to remain 22 micrograms/ml about 24 hours after intravenous injection with 1 g CTRX. The level in each tissue except myometrium reached a peak of 50 micrograms/g or higher at 54 minutes after intravenous injection with 1 g CTRX. The peak level in the dead space exudate, obtained 4 to 6 hours after intravenous injection was 77 micrograms/ml with 1 g, and 125 micrograms/ml and 115 micrograms/ml with 2 g. The clinical efficacy was observed in all the cases (excellent in 1 and good in 3) consisting of 1 with Bartholin's abscess, 2 with adnexitis and 1 with pelvioperitonitis. Neither adverse reaction nor posttreatment laboratory test abnormality was observed in any case.

Ceftriaxone (Ro 13-9904, CTRX) was evaluated for its safety and efficacy in 33 children with various bacterial infections including 10 cases of bacterial meningitis. CTRX was effective in all but 1 case who had acute mucositis due to a resistant strain of Enterobacter cloacae. The serum half-life (T1/2 beta) was 4.5 +/- 1.6 hours after an intravenous bolus injection in children. Cerebrospinal fluid levels of CTRX in the acute phase of bacterial meningitis were 7.69 +/- 4.75 mcg/ml. The only side effect was mild to moderate diarrhea observed in 10 of the 33 cases, but in no case was it necessary to discontinue the drug.

Ceftriaxone (Ro 13-9904, CTRX) was studied about the tissue transfer in the gyneco-obstetric field and the following results were obtained. The transfer of CTRX into the uterine tissues and adnexa was favorable following an intravenous injection with 1 g. The mean serum level 1 hour after administration was 123.3 micrograms/ml while the tissue level ranged from 26 to 48 micrograms/g. The level in the pelvic dead space exudate reached a peak 3 to 6 hours after administration and got higher than the serum level at 5 to 6 hours.

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX), a newly-developed injectable cephem antibiotic was performed as follows. The serum and urine concentrations of CTRX as well as the urinary recovery rate were determined in 7 children at 3 different dose levels; 3 cases administered with 10 mg/kg, 3 with 20 mg/kg and 1 with 48 mg/kg by one shot intravenous injection. The concentration in the cerebrospinal fluid was determined in 1 case of purulent meningitis associated with bacteremia, administered by one shot intravenous injection with 47.6 mg/kg. CTRX was also examined in its clinical and bacteriological efficacies by one shot intravenous injection for 8 days on average in a mean daily dose of 46.5 mg/kg, divided into twice a day in 31 cases, 3 times in 1 case, and 4 times changed from twice in 1 case; in a total of 33 children consisting of 3 with tonsillitis, 1 with chronic bronchitis, 20 with pneumonia, 2 with purulent meningitis associated with bacteremia, 3 with urinary tract infections, 1 with osteomyelitis associated with phlegmon, 3 with purulent lymphadenitis. The adverse reactions and laboratory test values were examined in a total of 40 cases, i.e., the above-mentioned 33 cases plus the 7 drop-out cases in which the clinical efficacy could not be evaluated. The results were as follows. The serum levels of CTRX in 7 cases consisting of 3 administered with 10 mg/kg, 3 with 20 mg/kg and 1 with 48 mg/kg reached their peaks 5 minutes after one shot intravenous injection and the mean values of them were 93.6 mcg/ml, 143.0 mcg/ml and 558.0 mcg/ml, respectively, indicating the existence of a dose-response among these groups, while the half-life times were 4.41, 5.86 and 4.09 hours. Among the 7 cases examined in the urinary levels as well as the serum levels, the 3 cases administered with 10 mg/kg reached the mean peak of 334.0 mcg/ml 2 to 4 hours after administration, while another 3 cases administered with 20 mg/kg showed peaks of 793.0, 522.0 and 536.0 mcg/ml, respectively, 2 to 4 hours, 4 to 6 hours and 6 to 12 hours after injection; this dispersion being partly because of that the urine specimen was unable to be collected regularly every hour in this dose group. In the case administered with 48 mg/kg, urinary level reached the highest value of 6,100.0 mcg/ml from 0 to 2 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceftriaxone (Ro13-9904, CTRX), a newly developed cephalosporin antibiotic, was fundamentally evaluated through determination of the levels in the female genital organ tissues and in the pelvic dead space exudate. CTRX was also studied on its clinical efficacy in 13 cases with gyneco-obstetric infections. The transmission of CTRX into the female genital organ tissues was favorable: the peak level in each tissue was as high as 38 to 63 micrograms/g 18 to 37 minutes after administration. The level in each tissue even after about 18 hours remained around 10 micrograms/g, suggesting its better transmission into the tissues than other drugs. The transmission into the pelvic dead space exudate was also good: the level reached a peak of 100 to 120 micrograms/ml 1 to 3 hours after administration and still ranged from 74 to 76 micrograms/ml even after about 12 hours. The clinical efficacy was excellent in 5, good in 5 and poor in 3 out of 13 cases with gyneco-obstetric infections and the efficacy rate was 76.9%. Neither adverse reaction nor laboratory test abnormality was observed in any case. The above-mentioned results suggest that CTRX is a useful antibiotic for gyneco-obstetric infections.

Ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was basically and clinically studied in the field of obstetrics and gynecology. The following results were obtained. The pelvic dead space exudate and serum levels of CTRX were measured in patients with radical hysterectomy with pelvic lymphadenectomy for uterine cervical cancer after the intravenous injection of 1 g. Immediately after the injection, the serum level increased to 146 micrograms/ml on average and thereafter declined rapidly. The pelvic dead space exudate level attained the peak of 88 micrograms/ml after 4 hours and thereafter declined gradually but was 74 micrograms/ml even at 8 hours after the injection. A total of 13 cases comprising 2 with intrauterine infection, 5 with pelveoperitonitis, 4 with adnexitis and 2 with external genital organ infection were intravenously treated with CTRX at a dose of 1 g twice daily for 3-7 days. The clinical results were good in 12 cases and unknown in 1 case. Eruption was noted in 1 case.

The concentrations of ceftriaxone (Ro 13-9904, CTRX) in peripheral venous serum, uterine arterial serum and intrapelvic genital organs were determined by bioassay, using the cylinder-plate diffusion method, in 26 women with simple total hysterectomy. With an intravenous injection of CTRX 1 g, the maximum levels of peripheral venous serum and uterine arterial serum were 116.23 micrograms/ml and 112.76 micrograms/ml, respectively. Also, the biological half-life (T 1/2) was 6.85 hours in peripheral venous serum and 7.31 hours in uterine arterial serum. The concentrations of CTRX in peripheral venous and uterine arterial serum were more than 7.8 micrograms/ml at 24 hours after injection and maintained at a higher level than the minimal inhibitory concentration necessary for most E. coli strains for at least 24 hours. The concentrations of CTRX in intrapelvic genital organs were kept higher than the minimal inhibitory concentration against E. coli at 24 hours after injection, and the ratios of the concentrations in uterine tube and endometrium to that of in peripheral venous serum were 0.474 +/- 0.080 and 0.272 +/- 0.087, respectively. Since CTRX is characterized by more potent antibacterial activity than some other antibiotics and the long-acting efficacy, intravenous administration of CTRX at 1 g or 2 g per day may be an adequate dose for infections of the female urogenital tract.

Fundamental and clinical studies on ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, were carried out with the following results. Following each 1.0 g of drip infusion, transfer of CTRX to female genital organs was found to be excellent. Transfer of CTRX to exudate of the pelvic dead space was also excellent. And high concentration of CTRX was kept for long time after administration. CTRX was given to 7 cases. It was effective for 5 cases and ineffective for 2 cases. The above results demonstrated that CTRX is a safe and effective drug.

Clinical studies on ceftriaxone (Ro 13-9904, CTRX) were carried out and the results were as follows: Twelve patients (acute purulent tonsillitis 1, pneumonia 6, urinary tract infection 5) were treated with CTRX, in doses of 21-48 mg/kg divided 2 times per day for 3.5-8 days intravenously. The overall efficacy rate was 100%. No adverse reactions were observed. No abnormal laboratory data were noted.

Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904), a new cephalosporin antibiotic, were carried out with the following results. Concentration of CTRX was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 1.0 g dose. The venous serum level of CTRX was 156 micrograms/ml at 5 minutes after the administration. The favorable transfer of CTRX to internal genital organs and retroperitoneal fluid was demonstrated. In clinical trial, CTRX was given to 10 cases with obstetrical and gynecological infections such as endometritis, adnexitis, pelvic peritonitis and parametritis. The efficacy was evaluated as excellent in 1 case, good in 8 cases and poor in 1 case. No side effects were observed in any of the cases treated with CTRX.

The efficacy and safety of ceftriaxone (Ro 13-9904, CTRX) a new broad-spectrum semisynthetic cephalosporin with an outstanding long serum half-life, was evaluated in 22 patients with chronic complicated urinary tract infections. Although the overall clinical efficacy evaluated on day 5 and 10 were similar, the rate of excellent effectiveness was higher on day 10 than on day 5. Eighteen bacterial strains were cultured from freshly voided urine. Eighty percent of the bacteria were eradicated on day 5 and 86.2% were eradicated on day 10. Bacterial replacement had occurred in 3 cases on day 5 and in 6 cases on day 10.

Ceftriaxone (Ro 13-9904, CTRX), a newly developed parenteral cephalosporin antibiotic was clinically evaluated in gynecoobstetric infections and the following results were obtained. CTRX was administered by intravenous drip infusion twice a day in a daily dose of 2 to 4 g to 10 cases with gynecoobstetric infections, consisting of 8 with intrauterine infections, 1 with adnexitis and 1 with infection of external genitalia. The global clinical efficacy was excellent in 2 and good in 6 out of 8 cases with intrauterine infections, and in 2 others, the efficacy rate being 100%. Bacteriologically, the eradication of bacteria was observed in 5, unchange in 2 and alternation of bacteria in 2 among 9 cases where the causative strains were detected. Neither adverse reaction nor laboratory test abnormality was observed. The above-mentioned results suggest that CTRX is a highly safe antibiotic expected to be excellent in the clinical efficacy and bacteriological effects.

Ceftriaxone (CTRX), a new cephalosporin antibiotic, was evaluated in the field of obstetrics and gynecology and the following results were obtained. The concentration of CTRX after an intravenous injection with 1 g was determined in the uterine artery, cubital vein and in the intrapelvic genital tissues such as the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis. The peak level was 160 micrograms/ml at 26 minutes after injection both in the uterine arterial serum and cubital venous serum, 48 and 38 micrograms/g at 1 hour and 18 minutes in the tissues of oviduct and ovary, respectively, 54 and 50 micrograms/g at 48 minutes in the myometrium and cervix uteri, respectively, while 46 micrograms/g at 39 minutes in the portio vaginalis. The mean level 18 to 24 hours after administration was 19 micrograms/ml in the uterine arterial serum and cubital venous serum and 6.3 micrograms/g in the intrapelvic genital tissues. A case of intrapelvic infection clinically showed an excellent response without any side effects by intravenous drip infusion with 2 g divided as twice a day for 7 days. The above results show that CTRX is useful in the field of obstetrics. and gynecology.

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceftriaxone was used in single intravenously dose of 1 g to treat 20 men with gonorrhoea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG) and non-PPNG. Of 14 patients followed up, 13 (92.9%) were cured. Cure rates for PPNG infections and non-PPNG infections were 100% and 90.9% respectively. No side effect was observed except 1 case of vomiting out of 20 cases. It is concluded that this drug is safe and effective in treating both PPNG and non-PPNG infections.

Excretion of ceftriaxone (Ro 13-9904, CTRX) into female genital organs was studied by determining its concentration in the dead space exudate of the patients who received radical hysterectomy due to uterocervical cancer. Data analysis was performed by the three-compartment model. The serum peak level of CTRX in the cubital vein was 177.74 micrograms/ml 1 hour after the initiation of intravenous drip infusion for 1 hour with 1 g. The concentration of CTRX in the exudate of pelvic dead space reached a peak of 62.75 micrograms/ml 4.61 hours after the start of administration and still showed a very high level of 25 micrograms/ml at 24 hours. The AUC of the excretion into the exudate of pelvic dead space was 1,432.43 micrograms X hr/ml. These results indicate that CTRX is a clinically useful drug, being excreted into the exudate of pelvic dead space favorably.

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed in the field of pediatrics and the following results were obtained. The antibacterial activity of CTRX was determined against clinically isolated strains at our department. CTRX was definitely superior to CEZ and CMZ and almost equal or slightly superior to CTX in activity against Gram-negative bacteria, while the MIC of CTRX against Gram-positive bacteria was higher than that of CEZ and CMZ and about equal to that of CTX. The blood concentration of CTRX after one shot intravenous injection with 10 mg/kg was 67.98 micrograms/ml at 15 minutes, 51.96 micrograms/ml at 30 minutes, 37.51 micrograms/ml at 1 hour, 28.91 micrograms/ml at 2 hours, 20.71 micrograms/ml at 4 hours, 13.97 micrograms/ml at 6 hours and 6.45 micrograms/ml at 12 hours, while the half-life time was 3.74 hours. The blood concentration of CTRX after one shot intravenous injection with 20 mg/kg was 179.55 micrograms/ml at 15 minutes, 120.01 micrograms/ml at 30 minutes, 100.01 micrograms/ml at 1 hour, 53.75 micrograms/ml at 2 hours, 33.13 micrograms/ml at 4 hours, 26.41 micrograms/ml at 6 hours and 21.49 micrograms/ml at 12 hours, while the half-life time was 4.15 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 10 mg/kg was 19.54 micrograms/ml at 15 minutes, 27.19 micrograms/ml at 30 minutes, 36.57 micrograms/ml at 1 hour, 23.83 micrograms/ml at 2 hours, 19.69 micrograms/ml at 3 hours, 14.46 micrograms/ml at 5 hours, 11.02 micrograms/ml at 7 hours and 7.27 micrograms/ml at 13 hours, while the half-life time was 6.59 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 20 mg/kg was 61.72 micrograms/ml at 30 minutes, 108.1 micrograms/ml at 1 hour, 54.95 micrograms/ml at 2 hours, 35.68 micrograms/ml at 3 hours, 28.13 micrograms/ml at 5 hours, 20.51 micrograms/ml at 7 hours and 11.43 micrograms/ml at 13 hours, while the half-life time was 4.23 hours. There was noticed a tendency of the blood level being elevated by consecutive administration. The urinary recovery rate of CTRX ranged from 36.5 to 71.6%. The excretion rate of CTRX into the cerebrospinal fluid ranged from 5.2 to 11.6%. The excretion rate of CTRX into the pleural fluid was 31.0%. The clinical efficacy rate was 87.5% (excellent or good) in 8 children with infections treated with CTRX. The eradication of bacteria was observed in all of 5 cases bacteriologically evaluation.(ABSTRACT TRUNCATED AT 400 WORDS)

The authors have carried out the laboratory and clinical studies of ceftriaxone (Ro 13-9904, CTRX) and obtained the following results. The antibacterial activities of CTRX against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, Citrobacter sp. and P. aeruginosa were measured by the agar dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to CTRX ranged from 0.2 to 12.5 micrograms/ml, and the peak of distribution was 3.13 micrograms/ml. The peak of susceptibility distribution of E. coli and K. pneumoniae were 0.1 microgram/ml or lower, and the distribution of E. aerogenes and E. cloacae ranged from 0.1 to 100 micrograms/ml, Citrobacter sp. and S. marcescens, from 0.1 to 12.5 micrograms/ml and that of P. aeruginosa, from 0.39 to 100 micrograms/ml or more. For pharmacokinetic study, CTRX was given in a single dose of 10 mg/kg in 1 child and 20 mg/kg in 2 children by drip infusion for 1 hour. After drip infusion of CTRX in a single dose of 10 mg/kg, the peak serum level was 61.4 micrograms/ml on completion of the infusion, and 8.43 micrograms/ml at 12 hours. Half-life time was 4.6 hours. With drip infusion of CTRX in a single dose of 20 mg/kg, the peak serum level was 105.5 micrograms/ml on completion of the infusion, and 19.1 micrograms/ml at 12 hours. Half-life time was 8.7 hours. CTRX was effective all cases out of 8 cases with bacterial infection. No side effect was observed except for elevation of serum GOT in 2 cases and eosinophilia in 1 case.

Fundamental study on tissue distribution of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin parenteral antibiotic, was studied and the following results were obtained. CTRX had been administered by intravenous drip infusion with 1 g to 9 cases who received simple total hysterectomy. The level of CTRX in the cubital venous serum and uterine arterial serum was determined as well as the tissue concentration in the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis. The level in the oviduct and portio vaginalis was generally high, although it was observed only in a few cases. The variation of the level in the myometrium was large. CTRX is expected to be clinically useful considering the fact that its half-life time is 8.5 hours, which is longer than that of existing cephalosporin antibiotics.

Ceftriaxone CTRX was evaluated about its antibacterial activity against clinical isolates at our department and tried clinically in 10 children of 6 months to 10 years and 6 months of age. The antibacterial activity was equal to cefotaxime or higher while the clinical results were almost satisfactory. Three out of 4 strains were eradicated (75%). As to the adverse reaction, eosinophilia was observed only in 1 case.

Ceftriaxone (CTRX) was examined in the blood level and urinary excretion between a healthy group of 2 persons receiving 1 g CTRX for 1 day and the other of 3 patients with renal failure receiving 1 g for 3 days, both by intravenous injection or intravenous drip infusion. In the healthy group, the blood half-life time of CTRX was 6.0 hours in 1 person and 8.2 hours in the other, being 7.1 hours on average. The mean blood level in the healthy group was 199 micrograms/ml at peak and was 13 micrograms/ml at 24 hours after administration. In patients with renal failure, the peak blood level ranged from 136.8 to 161.1 micrograms/ml on the 1st day, from 163.1 to 217.0 micrograms/ml on the 2nd day and from 156.4 to 189.7 micrograms/ml on the 3rd day, showing no tendency of getting higher, while the bottom level did from 15.2 to 47.4 micrograms/ml on the 1st day, from 23.3 to 67.9 micrograms/ml on the 2nd day and from 10.9 to 72.6 micrograms/ml on the 3rd day. The urinary excretion rate was 54.6 +/- 3.7% on average in the healthy group while it ranged from 13.7 +/- 1.8 to 27.9 +/- 7.9% in the patient group. CTRX was effective especially against E. coli among the strains clinically isolated from the patients with renal failure. No side effects were observed in any case.

Ceftriaxone (Ro 13-9904, CTRX) was evaluated in 20 children with a suspicion of bacterial infections, 18 were shown to be effective (efficacy rate, 90%). The diagnosis included upper respiratory tract infection (3), bronchitis (3), pneumonia (8) and urinary tract infection (6). The etiologic pathogens isolated were S. pneumoniae (1), and enteropathogenic E. coli (6). These strains were eradicated after treatment. No severe adverse reaction was encountered with the CTRX therapy. The data suggest that CTRX is an effective and safe parenteral antibiotic in the treatment of susceptible pediatric bacterial infections.

Ceftriaxone (Ro 13-9904, CTRX), developed by F. Hoffmann-La Roche Ltd. in Switzerland, was used for the pediatric infections and the following results were obtained. The mean blood level of CTRX in 2 children after a 60-minute intravenous drip infusion with 20 mg/kg was 58.6 micrograms/ml at 30 minutes, 75.0 micrograms/ml at 1 hour, 39.85 micrograms/ml at 2 hours, 27.74 micrograms/ml at 4 hours, 20.71 micrograms/ml at 6 hours, 11.72 micrograms/ml at 12 hours and 3.91 micrograms/ml at 24 hours while the half-life time was 5.9 hours in one child and 7.6 hours in the other. CTRX was used in 22 children with acute infections consisting of 3 with acute pharyngeal tonsillitis, 4 with acute bronchitis, 8 with bronchopneumonia, 6 with infections of skin soft tissue and 1 with salmonellosis. The results were excellent in 5 cases and good in 17, indicating an efficacy rate of 100%. Out of 10 cases where the causative strains were detected, 4 cases were followed about the activities of the respective bacteria, i.e., H. influenzae, Streptococcus group A, S. aureus and Salmonella group B, all of which were eradicated after the end of administration. The daily dose of CTRX ranged from 30 to 50 mg/kg and generally a larger dose was used for serious infections. CTRX was administered twice daily in 20 out of 22 cases, by an intravenous injection in 4 and an intravenous drip infusion in 18, for 2 to 4 days in 16 and 5 to 8 1/2 days in 6. No clinical adverse reactions were observed while the laboratory test found a slight elevation of GOT in one and that of GOT and GPT in another. From the above results, CTRX was judged to be a highly useful drug for treatment of pediatric infections.