Twenty-two newborn and young infants, including 13 premature infants, were treated with ceftriaxone (CTRX) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 106 days, and their body weights from 1.19 to 3.92kg. Dose levels were 15 to 23mg/kg every 12 to 24 hours for 2 to 13.5 days. Eighteen infants with sepsis and 1 infant with purulent coxitis were considered to have responded to the CTRX treatment. The results were excellent in 13 and good in 6 patients. The drug was well tolerated, although diarrhea occurred in 2 patients, eosinophilia in 6 patients, slightly elevated serum concentrations of transaminases in 2 patients and thrombocytosis in 1 among the 22 patients.
The pharmacokinetic studies on CTRX were done in 8 patients including 3 premature infants. The ages ranged from 3 to 50 days, and body weight from 2.20 to 3.94kg. Plasma concentrations 30 minutes after single 10mg/kg intravenous bolus injection in two 4-to 5-day-old premature neonates were 48.4 and 50.0μg/ml and those at 6 hours were 22.7 and 23.4μg/ml, respectively. In 2 mature neonates, plasma levels were 42.2 and 39.1μg/ml at 30 minutes and 23.4 and 26.6μg/ml at 6 hours after single 20mg/kg doses. In four 12-to 50-day-old patients, plasma concentrations ranged from 35.9 to 175.0μg/ml at 30 minutes and from 21.9 to 32.8μg/ml at 6 hours after multiple doses of 20mg/kg intravenous bolus injection. The plasma half-lives of the drug ranged from 6.6 to 16.8 hours in these 8 patients. Excretion rates of this drug into urine within 12 hours were 21.4 to 63.4% in 7 patients. Urine concentrations of the drug in 34 samples collected at various times from the 7 patients ranged from 28.3 to 469.0μg/ml.
The cerebrospinal fluid level at 2 hours after a dose was 3.33μg/ml on the 5th day of treatment in 1 patient with sepsis receiving 18mg/kg of the drug every 12 hours. Its level at 3 hours after a dose was 6.07μg/ml on the 6th day of treatment in another patient with aseptic meningitis receiving 20mg/kg every 12 hours.
The influence of CTRX on the fecal flora was studied in 3 patients receiving 20mg/kg×2/day.The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium and Enterobacteriaceae, the preservation of Streptococcus and Staphylococcus, and the increase in Candida. The antibiotic concentrations were from 12 to 210μg per g of wet feces. On the 5th day after cessation of the drug administration, considerable numbers of Bifidobacterium and Enterobacteriaceae appeared, but recovery of Bifidobacterium-predominant flora required about 2 weeks.

View full abstract

A pharmacokinetic study on ceftriaxone (CTRX) was conducted and the results obtained are summarized as follows.
1. CTRX was given in a dose of 20mg/kg by intravenous bolus injection to 13 neonates, and statisfactory blood concentrations of the drug were achieved. However, since even a once daily administration revealed trough values of 10-20μg/ml, CTRX may accumulate if administered to neonates of low weight.
2. The rate of CTRX transfer to cerebrospinal fluid was 5.7% in a neonate given a dose of 20mg/kg by intravenous bolus injection.
3. The urinary recovery rate was 8.4% up to 12 hours in a neonate given a dose of 20mg/kg by intravenous bolus injection.

View full abstract

The antibacterial efficacy of ceftriaxone (CTRX) against group B Streptococcus and its clinical efficacy in newborns were examined, and the results obtained are summarized as follows.
1. MIC's of CTRX against 55 strains of B group Streptococcus from the pregnant vagina were 0.10μg/ml or lower.
2. Efficacies of CTRX were good to excellent in 8 cases administered for treatment, 3 cases for prophylaxis and 1 for observation of adverse reactions. Observed adverse reactions included diarrhea in 4 cases and vomiting in 2 cases. As abnormal laboratory parameters, eosinophillia and thrombocytosis were observed in 1 case each.
3. An examination of intestinal bacteria in 9 cases revealed that CTRX gave as much influence to the flora as other third-generation cephems.
4. An examination for the vitamin K deficiency in 11 cases found a prolongation of prothrombin time (PT) in 3 cases and protein induced by vitamin K absence (PIVKA) II positive in 2 cases.
5. Testing of platelet aggregation with adenosine diphosphate (ADP) in 7 cases showed little influence of CTRX.

View full abstract

Pharmacokinetic and clinical studies on ceftriaxone (CTRX) in mature and premature neonates were carried out.
The results are summarized as follows.
The mean serum peak level of CTRX after intravenous administration at a single dose of 10mg/kg in 4 to 13 day-old-neonates was 34.1±11.4μg/ml at 30 minutes. The mean serum level at 12 hours after dosage was 11.1±2.1μg/ml. The mean half-life time was 11.6±1.4 hours. Mean serum peak levels of CTRX after intravenous administration at a single dose of 20mg/kg were 64.6±15.4μg/ml in 1 to 3 day-old-neonates, 44.6±1.1μg/ml in 5 day-old-neonates at 30 minutes. Mean serum levels at 12 hours after dosage in these two groups of neonates were 16.4±4.8μg/ml and 12.4±2.5μg/ml, respectively. Mean half-life times were 13.7±3.7 hours in 1 to 3 day-old-neonates and 10.2±1.3 hours in 5 day-old-neonates.
CTRX was clinically effective in a case of urinary tract infection. No side effect was observed except an elevation of GOT.

View full abstract

Ceftriaxone (CTRX) was administered to the newborn and its clinical effectiveness as well as its blood and cerebrospinal fluid levels were studied.
1. Average blood levels of CTRX 1 hour after single intravenous administration were 39μg/ml in 2 cases receiving about 10mg/kg, 70μg/ml in 2 other cases receiving 20mg/kg and 208μg/ml in one receiving 52.6mg/kg. As is apparent from these cases data, blood levels of CTRX were dose dependent. Blood levels of the drug were between 3.7 to 12.4μg/ml 24 hours later. Half-lives of the drug in blood in the 5 newborns ranged from 7.13 to 10.6 hours. In a 53-day-old patient receiving 43.4mg/kg of CTRX via intravenous injection, the one-hour blood level of the drug was 140μg/ml and the half-life was 3.68 hours. The blood level of the drug 36 hours after single intravenous administration with 17.3 to 20.0μg/ml to 5 other cases 0 to 5 days of age ranged from 4.6 to 13.7μg/ml.
2. The cerebrospinal fluid level of CTRX 4 hours after intravenous administration with 49.6mg/kg to cases of Escherichia coli meningitis was 9.7μg/ml on the first day following the start of the treatment. It increased to 23.6, 25.2 and 31.0μg/ml on the third, fourth and fifth days, respectively, and then gradually decreased. Cerebrospinal level was still 5.8μg/ml on the 22nd day during the recovery period. These levels were far more than 1,000 times as much as the MIC for the pathogen at the highest level, and more than 100 times even at the lowest level.
3. CTRX was administered via intravenous injection once or twice a day (11.0-39.5mg/kg in total) to 13 newborns and 3 infants.
The efficacy of CTRX was good to excellent in 10 cases for treatment of 11 diseases (sepsis 1, pneumonia 4, urinary tract infection 4 and fetal infection 2) and all the pathogens (Streptococcus agalactiae 1, E. coli 3, Klebsiella pneumoniae 2, Citrobacter diversus 1) disappeared. In 6 cases where CTRX was used prophylactically, infection did not occur at all. The efficacy was excellent in another newborn with E. coli meningitis intravenously receiving 49.6mg/kg of CTRX twice daily for 25 days.
4. No adverse reactions were observed. Mild eosinophilia was observed in 4 cases. Follow-up examinations of 3 of the 4 cases showed that these abnormal levels were returned to normal.
5. It is judged from the above results that CTRX is suitable for the treatment of neonatal infections, considering its antibacterial spectrum and activity, especially as an initial-choice drug to be used before pathogens are detected.

View full abstract

Pharmacokinetics and clinical studies on ceftriaxone (CTRX) in pediatric surgery were performed and the results obtained are summarized below.
1. In neonates, serum and urinary levels of CTRX were measured in 4 patients following injection (CTRX 20mg/kg, intravenous bolus injection). Highest levels in serum were observed at 15 or 30 minutes, 59.4-212.5μg/ml. Serum levels of CTRX then decreased very slowly, and serum half-lives (T1/2) were 7.9-27.1 hours. Urinary recovery rates were 17.0-54.7% in 12 hours.
2. Bile levels of CTRX were also measured in 8 patients with congenital biliary atresia and a patient with congenital biliary dilatation (CBD). Highest levels of CTRX in bile, 10.2 and 13.2μg/ml, were noted in 2 hours following injection to 2 patients. But in other patients, CTRX was undetectable in bile. Recovery rate in bile in 12 hours in a CBD patient was 0.19%.
3. The CTRX was administrated to 7 patients (a case of infected lung cyst, 2 cases of peritonitis and 4 cases as prophylaxis to postoperative infection). Clinical results were good in all cases. No clinical and laboratory adverse reaction due to the administration of CTRX was observed.
It is concluded that CTRX is a safe and effective antibiotic in pediatric surgery. However, care has to be practiced in determining dosage and interval of CTRX administration because of its pharmacokinetical characteristics.

View full abstract

Basic and clinical investigations were conducted on ceftriaxone (CTRX), a cephem antibiotic with a wide antibacterial spectrum and with especially high activity against Gram-negative bacteria. The results obtained are summarized as follows:
1. CTRX, following intravenous drip infusion of 1g, had a serum half-life of 5.8 hours, which is longer than that of any other existing cephem antibiotics.
2. The level of CTRX in the umbilical cord serum 6 hours after intravenous drip infusion of 1g was at a satisfactory level, 15μg/ml.
3. The CTRX was remarkably effective or effective in 9 cases, and the activity was high even in cases where penicillin or other third-generation cephems were ineffective.
These results seem to indicate that CTRX may be effective in perinatal and intrauterine fetal infections.

View full abstract

Laboratory studies and clinical evaluation of ceftriaxone (CTRX) were carried out with mothers and infants in perinatal period.
The presence of synergistic effect between CTRX and amniotic fluid were studied using a broth dilution method. Stronger effects were recognized when both agents were present together compared to each agent alone by the fact that values of MIC and MBC became closer together for Escherichia coli as well as for Streptococcus agalactiae. Against the growth of E. coli, a synergism was observed, but for S. agalactiae, only an additive effect was found.
The placental transmission of CTRX upon the administration was rapid, and the blood CTRX level reached its peak shortly after the intravenous administration of the drug. The transport of the drug into the fetus through placenta was excellent and one dose of 1g of CTRX gave drug concentrations in the umbilical cord serum and amniotic fluid higher than MIC's against main pathogenic organisms. According to these results, it should be possible to treat or prevent perinatal infections by a dose of one gram per day of CTRX, once or twice daily.
Cases of perinatal infections were treated with CTRX. An effective treatment without side effects was obtained. No physical abnormalities nor unusual laboratory test results were recognized in neonates delivered from mothers who received CTRX administration. The penetration of CTRX into mothers' milk was low, thus the drug transfer into neonates through the breast-feeding should not be a problem. It appears, from the above study, that CTRX is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

View full abstract

1. Ceftriaxone (CTRX) was not transferred well into cerebrospinal fluid in healthy individuals.
2. The transplacental passage and the transfer of CTRX into amniotic fluid were very good, and CTRX seems useful for the treatment of perinatal infections.
3. Clinically, CTRX was very effective against amniotic infections and infections of the puerperal uterus: Clinical efficacies were excellent in 1 case and good in 3 out of 4 cases (efficacy rate: 100%).
4. No side effects or laboratory abnormalities were observed.

View full abstract

The pharmacokinetics of ceftriaxone (CTRX) and its clinical efficacy in perinatal infections were studied. The obtained results are summarized as follows.
1. Concentrations of CTRX in maternal serum, umbilical cord serum and amniotic fluid were determined following intravenous injection with 1g of CTRX.
Maternal serum levels were not lower than 100μg/ml immediately after administration, and gradually decreased to about 10μg/ml in 12 hours, and to 4μg/ml in 24 hours. The half-life of CTRX in maternal serum was 5.6 hours.
CTRX levels in umbilical cord serum were about 7μg/ml at 10 minutes after injection, increasing to 12 to 13μg/ml in 12 hours and decreasing to 5μg/ml in 24 hours.
CTRX levels in amniotic fluid were slightly lower than those in the umbilical cord serum, and about 2μg/ml at 10 minutes after injection, and they remained at 4 to 8μg/ml thereafter for 28 hours.
2. CTRX (1g) was intravenously administered twice daily to 9 patients with perinatal infections for 3 to 7 days. Clinical efficacies of CTRX were judged excellent in 2 cases and good in 7, suggesting that CTRX was effective in all cases.
No side effects or laboratory abnormalities were observed in any case.
As a result of these findings, CTRX may be considered a very useful antibiotic in perinatal infections.

View full abstract

Ceftriaxone (CTRX), a new cephem antibiotic with high activity against Grampositive and Gramnegative bacteria, was investigated pharmacokinetically in 30 mothers in the perinatal period. The obtained results are summarized below.
1. The maximum CTRX level in the maternal serum was 135 μg/ml between 20 and 25 minutes after an intravenous administration of 1g of CTRX.
2. The transfer of CTRX into the umbilical cord serum and the amniotic fluid was very good. CTRX levels in these fluids were about 20% and 10% of the maternal serum level, respectively.
3. No side effect was observed in mothers or neonates.
4. CTRX is a useful antibiotic for perinatal infections.

View full abstract

Ceftriaxone (CTRX), a new cephalosporin antibiotic, was studied for its pharmacokinetic features and clinical efficacy in the perinatal period and the obtained results are summarized below.
1. Following a one shot intravenous injection of 1g of CTRX into each of 29 parturient women, CTRX levels were between 4.5 and 19.5μg/ml at 6 hours postdose and between 4.5 and 4.7μg/ml at 24 hours postdose in the amniotic fluid and between 11.7 and 22.7μg/ml at 6 hours postdose and between 4.5 and 4.7μg/ml at 24 hours postdose in the umbilical cord serum. It was shown that CTRX was maintained there at high levels for a long time and the transfer of CTRX into the umbilical cord serum was better than that of other antibiotics.
2. Following a one shot intravenous injection of 1g of CTRX into each of 12 cases of puerpera, CTRX was detected in the mother's milk until 10hours postdose, though at a very low level averaging 0.32 to 0.79μg/ml. It was considered, however, that CTRX affected little infants through the mother's milk.
3. CTRX was evaluated to be very effective in 2, effective in 5 and ineffective in 1, of 8 cases of infections during the perinatal period. From the above results, CTRX appeared to be effective against infections during the perinatal period.

View full abstract