Fundamental and clinical studies on ceftazidime in the perinatal period

Fundamental and clinical studies were carried out on ceftazidime (CAZ) in the perinatal period, and the results obtained were summarized below. Following bolus intravenous injection of CAZ 2 g, maternal serum concentrations of CAZ were as high as 145.3 +/- 17.2 micrograms/ml (mean +/- S.D.) at about 10 minutes, and then gradually decreased to 46.7 micrograms/ml at 2 hours, 5.31 micrograms/ml at 5 hours and 4 minutes, and 1.54 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in umbilical cord serum immediately after the administration, and concentrations were 31.0 +/- 1.54 micrograms/ml at about 10 minutes. Although the concentrations gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and later and was 3.00 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in amniotic fluid a little later than in umbilical cord serum, and concentrations of CAZ in amniotic fluid were as low as 1.50 +/- 0.67 micrograms/ml at about 10 minutes after the administration. Concentrations then gradually increased to 12.8 micrograms/ml at 2 hours and 26.5 micrograms/ml at 5 hours and 4 minutes, and even at 11 hours and 10 minutes, they were as high as 14.2 micrograms/ml. The above results demonstrated that the transfer of CAZ through placental barrier was very rapid and satisfactory. Also, CAZ showed good transfer into amniotic fluid, as well as sufficient retention, and was considered to be an effective antibiotic for prophylaxis of both fetal infections and amniotic fluid infections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and clinical studies of ceftazidime in perinatal period

Pharmacokinetic studies and clinical evaluations of ceftazidime (CAZ) were carried out in perinatal mothers and infants, and following results were obtained. The CAZ was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus was good. After intravenous injection or intravenous drip infusion of 1.0-2.0 g of CAZ, drug concentration in umbilical serum and amniotic fluid exceeded MICs of CAZ against main pathogenic organisms. Levels of CAZ in umbilical serum ranged 0.2-15.6 micrograms/ml after 1.0 g intravenous injection or intravenous drip infusion, and 0.7-27.2 micrograms/ml after 2.0 g intravenous injection, and those in amniotic fluid were 1.4-21.3 micrograms/ml after 1.0 g administration and 2.0-27.0 micrograms/ml after 2.0 g administration. According to the above results, it is possible to successfully prevent or treat perinatal infections by twice a day administration of CAZ at 1.0-2.0 g/dose. Clinically, CAZ was effective in the treatment of perinatal infections and the prophylaxis of intrauterine amniotic infection without any side effect. Moreover, newborn infants delivered from mothers receiving CAZ treatment did not have any abnormalities in laboratory test. The penetration of CAZ into mother's milk was low, thus the transfer of CAZ from milk to newborn infants should be low. The above results demonstrated that CAZ is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.     

Fundamental and clinical evaluation of ceftazidime in perinatal studies

In a chemotherapy of perinatal infections, the safety of mothers and their neonates and the transfer of a drug to amniotic fluid and fetus as well as its bacteriological efficacy are some of the important factors. In the present study, the authors have carried out a pharmacokinetic evaluation on the transfer of ceftazidime (CAZ), a new cephalosporin, to amniotic fluid and umbilical cord serum, and also a clinical study on its efficacy and safety in 3 cases of perinatal infections. Transfer ratios of CAZ to umbilical serum and to amniotic fluid were 25.3-46.5% and 0.6-17.5% (of maternal serum), respectively, after 1 g of CAZ was administered by bolus intravenous injection, and 24.3-85.8% and 1.6-17.5% (of maternal serum), respectively, after 2 g of CAZ was administered by bolus intravenous injection. These levels were high enough to expect that CAZ is an effective antibiotic both for treatment and prophylaxis of intrauterine fetal infections. Out of the 3 cases treated with CAZ, clinical efficacy was good in 2 cases which did not respond to other antibiotics. CAZ was considered to be clinically effective, although the number of cases treated was small. No abnormalities were observed at all either in subjective symptoms or objective findings in laboratory findings such as hepatic and renal functions of mothers, or neonates. This confirmed the high safety of CAZ. As earlier reports indicate, CAZ has a broad-spectrum of antibacterial activity against various bacteria including Gram-negative organisms and anaerobes, and shows a good transfer into intrauterine tissues, and high clinical efficacy in the field of obstetrics and gynecology.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel pharmacokinetic method for analysis of placental transfer of latamoxef in humans

A novel pharmacokinetic method was developed for analysing the behaviour of a drug in tissues. The absolute transfer ratio of a drug to a tissue was defined using the pharmacokinetic parameters obtained by this method. Composite data of latamoxef (moxalactam) concentration in maternal blood, umbilical cord blood and amniotic fluid following a 2g intravenous injection to pregnant women at delivery were analysed by this method to study the drug behaviour in pregnant women, fetuses and amniotic fluid. Latamoxef kinetics in pregnant women at full term were generally similar to that in previously reported healthy subjects. The concentration of latamoxef in umbilical cord blood peaked about 2 hours after dosing then decreased in parallel with the maternal blood concentration. The amniotic fluid concentration peaked about 7 hours after administration, then decreased slowly. The absolute transfer ratios to fetus and amniotic fluid were calculated to be about 2.5 and 0.37% respectively.     

Transplacental transfer and clinical application of aztreonam

Preclinical and clinical studies on aztreonam (AZT) in the perinatal period were carried out and the results are summarized below. 1. Concentrations of AZT in maternal serum, umbilical cord serum and amniotic fluid were measured after intravenous injection of AZT 1 g and 2 g, and intravenous drip infusion of AZT 1 g. As results, the transfer of AZT into umbilical cord serum started to increase in 1 to 2 hours, and the transfer of AZT into amniotic fluid started to increase after an elapse of 2 hours. Upon the intravenous injection of 2 g, AZT concentration in amniotic fluid was as high as 27.1 micrograms/ml even at 10 hours 30 minutes after the injection, and it was still 6.9 micrograms/ml at 20 hours or more after the injection. 2. AZT 2 g/day (b.i.d.) was administered by intravenous drip infusion to 1 perinatal infection case with pyelonephritis. It was clinically effective and neither side effect nor abnormal laboratory test value was observed.     

Fundamental and clinical studies on ceftazidime in neonates and premature infants

Ceftazidime (CAZ) was administered to 34 full-term and premature infants aged 0-27 days with various bacterial infections in a dose of 10 or 20 mg/kg by intravenous bolus injection, and plasma concentrations and urinary recovery rates in these subjects during recovery periods were studied. Because of the small number of the cases recruited, neonates were not divided into the full-term and the premature group, but into 3 groups based on day-age: 0-3 days, 4-7 days, and 8 days or older. Concentrations and rates of transfer of CAZ into cerebrospinal fluid (CSF) were determined in 2 cases, and biliary concentrations in another case. A clinical evaluation of CAZ was performed in 12 male and 6 female infants aged 1 day to 4 months and 19 days, including 2 each with purulent meningitis, pneumonia and pyelonephritis, 3 with septicemia, 1 each with septicemia suspected, cholangitis, osteomyelitis, bronchopneumonia, staphylococcal scaled skin syndrome, and acute enterocolitis and 3 for prophylactic use. Plasma concentrations and urinary recovery rates of CAZ The intravenous bolus injection at 10 mg/kg. Peak plasma concentrations of CAZ were obtained at the first collection (30 minutes) of blood samples or 1 hour in all 3 groups, ranging from 23.3 to 26.9 micrograms/ml with no significant variations, plasma concentrations then slowly decreased, and were still 6.04-9.88 micrograms/ml even at 6 hours after the administration. The half-lives of CAZ in plasma tended to be shorter in older day-age neonates, with mean half-lives being 3.59, 2.50 and 2.50 hours for the youngest. The intravenous bolus injection at 20 mg/kg. Peak concentrations were obtained at the first collection of blood samples in all 3 groups (0-3 days: 15 minutes, the others: 30 minutes), being 54.8, 39.9 and 43.8 micrograms/ml, respectively, then slowly decreased and were still 10.4-15.7 micrograms/ml even at 6 hours after the administration. Inter-age differences in half-lives were marked, i.e., 3.6 hours in 0-3-day group, 3.48 hours in 4-7-day group and 2.75 hours in 8-day or older group. Urinary recovery rates were about 40-60% without reference to day-age neonates. CSF concentrations About 50 mg/kg of CAZ was given to each of 2 cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Fundamental and clinical evaluation of ceftazidime in the perinatal period

Following an intravenous injection of ceftazidime (CAZ) 1 g, the ratio of transfer of the drug into a fetus was 59.9%, and umbilical serum concentrations of the drug reached the peak of 18.2 micrograms/ml at 1.5 hours, and were slightly higher than maternal serum concentrations at 2.93 hours and after, with half-life of 1.37 hours, the same as in maternal serum. Following an intravenous injection of CAZ 1 g, concentrations of CAZ in mother's milk at 2 hours after injection were 1.16 micrograms/ml on the 4th day of the treatment of CAZ, and 0.86 micrograms/ml on the 7th day. The CAZ was administered to cases of premature rupture of membrane. The prophylactic efficacy against puerperal infections in mothers was 92%, and that against fetal infections in neonates was 96.7%. The CAZ was also administered after cesarean section, and the prophylactic efficacy against postoperative infections was 93.3%. Neither subjective/objective adverse effects nor abnormal laboratory findings for which CAZ was suspected were observed in any mothers or neonates. From the above results demonstrating satisfactory maternal transfer into fetuses and the high degree of safety in fetuses and neonates, as well as its high antibacterial activity, CAZ is considered to be a useful drug for the treatment of perinatal infections.     

A study on ceftazidime in the perinatal period

Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below. Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates. The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.     

Clinical evaluation of ceftazidime in infections in neonates and premature infants

Ceftazidime (CAZ) was evaluated in the treatment of infections in neonates and premature infants. In 1 mature neonate (age: 14 days) administered with 30.3 mg/kg of CAZ by a single bolus intravenous injection, the serum concentration of CAZ was 50 micrograms/ml at 30 minutes after the dosing, and the elimination half-life was 1.38 hours. The urinary recovery rate of administered CAZ during the first 6 hours was 52.9%. In 6 neonates (mean gestational period: 37.8 weeks, mean birth weight: 2,508 g, mean age: 3.7 days) administered with ca. 20 mg/kg of CAZ by single bolus intravenous injections, the mean serum concentration of CAZ was 63.6 micrograms/ml at 30 minutes after the dosing, and the half-life was 3.78 hours. In 3 out of the above 6 neonates, the mean urinary recovery rate of CAZ during the first 6 hours was 59.8%. Five neonates and 2 infants with infections were given 18.4-65.9 mg/kg of CAZ b.i.d.-q.i.d. by intravenous injections. One of these cases was excluded from an evaluation for clinical efficacy, because CAZ was given only for 2 days. In the remaining 6 cases, clinical efficacy was excellent in 1 case of urinary tract infection (E. coli + E. faecalis), good in 3 cases of pneumonia (P. aeruginosa + K. pneumoniae: 1, P. aeruginosa: 1, and causative organism unknown: 1), and poor in 1 case of sepsis (S. aureus). In 1 case of asphyxia neonatorum contaminated with meconium, CAZ was used prophylactically, resulting with no infection. No clinically adverse effect was observed. Also no abnormality was observed in laboratory analyses in the 6 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basic and clinical studies on ceftazidime in the pediatric field

Basic and clinical studies were made on ceftazidime (CAZ) in pediatric field, and the following results were obtained. The antibacterial activity of CAZ against clinically isolated and maintained strains was examined. CAZ was unequivocally more active than CEZ and CMZ against Gram-negative rods, with MIC distribution similar to that of CTX, except for that for P. aeruginosa. The MIC of CAZ was lower than that of CTX for P. aeruginosa. Compared with the MICs of CEZ, CMZ and CTX, CAZ showed slightly higher MICs for Gram-positive bacteria. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ were 64.9, 36.9, 28.3, 14.7, 4.92 and 2.42 micrograms/ml, respectively, with the half-life of 1.27 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 10 mg/kg of CAZ were 16.6, 24.5, 41.4, 17.1, 5.38 and 2.62 micrograms/ml, respectively, with the half-life of 1.28 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 20 mg/kg of CAZ were 73.1, 60.8, 39.3, 17.3, 8.23 and 4.45 micrograms/ml, respectively, with the half-life of 1.42 hours. The blood concentrations of CAZ, at 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 20 mg/kg of CAZ were 55.1, 69.0, 32.1, 11.4 and 4.56 micrograms/ml, respectively, with the half-life of 1.27 hours. Urinary recovery rate of CAZ during the first 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ was 86.7%. CAZ was administered to 17 children with infections, and the clinical response was excellent or good in 94%. CAZ was bacteriologically effective in 14 patients, all bacteria having been eradicated in them. The bacteria were E. coli in 10 patients, H. influenzae in 2, P. aeruginosa in 1 and S. pneumoniae in 1. As for side effects, slight elevation in GOT was observed in 1 case and eosinophilia, in another case.     

Clinical and laboratory evaluations of ceftazidime in perinatal use. A study of ceftazidime in the perinatal co-research group

Efficacy and safety of ceftazidime (CAZ) in women during the perinatal period and their neonates were evaluated by a perinatal co-research group, and the results obtained were summarized as follows. Following an intravenous bolus injection or a drip infusion of CAZ from 1 g to 2 g, CAZ was transferred to maternal serum, umbilical cord serum and amniotic fluid rapidly and effectively. In 31 cases of perinatal infections, clinical efficacy was excellent in 10 cases, good in 18 and poor in 3, with an efficacy rate of 90.3%. In 85 cases given CAZ for prophylaxis of infections accompanying premature rupture of the membrane or following cesarean section, prophylactic effects were noted in 81 cases (efficacy rate: 95.3%). Neither adverse effects, nor abnormal laboratory findings were observed in any case. Also, no abnormalities in total serum bilirubin were observed in any neonates. From the above results, CAZ is considered to be a safe and useful drug for infections in women in perinatal period, usually in a unit dose of 1 g twice daily, or if necessary, 2 g twice daily.     

Fundamental and clinical studies of ceftazidime in the field of obstetrics and gynecology

Ceftazidime ( CAZ ), a new cephalosporin antibiotic, was fundamentally and clinically studied. The following results were obtained. Serum and internal genital tissue levels of CAZ were measured following intravenous drip infusion of 1 g for 30 minutes. Serum levels of more than 10 micrograms/ml and tissue levels of more than about 7 micrograms/ml were maintained after 2 hours to 2 hours and 30 minutes, respectively. Favourable transfer of CAZ into the pelvic dead space exudate was observed. The exudate level attained its peak of 31.54 micrograms/ml on average at 2 hours and was 16.8 micrograms/ml on average even at 8 hours after intravenous drip infusion. A total of 6 cases comprising 1 of adnexitis, 2 of pyometra, 1 of endometritis and 2 of parametritis was treated with CAZ at a dose of 0.5 approximately 2.0 g twice daily by intravenous injection or intravenous drip infusion. The clinical response was excellent in 1 case, good in 4 cases and poor in 1 case. Abnormal laboratory findings and side effects due to the drug were not noted.     

Laboratory and clinical studies on ceftazidime in the field of pediatrics

Laboratory and clinical studies on ceftazidime ( CAZ ), a new cephem antibiotic, were carried out in the field of pediatrics. The results were as follows: Antibacterial activities of CAZ against clinically isolated strains of S. pneumoniae, H. influenzae, E. coli and P. aeruginosa were compared with those of cefotaxime (CTX), ceftizoxime (CZX), latamoxef ( LMOX ), cefoperazone (CPZ) and cefmetazole (CMZ), and also with cefsulodin (CFS) and gentamicin (GM) against P. aeruginosa. Against S. pneumoniae and H. influenzae, CAZ was almost as active as CTX, CZX and CPZ. Against E. coli, it was almost as active as CTX, CZX and LMOX . Against P. aeruginosa, it was almost as active as CFS and GM. Serum concentrations and urinary excretion rates after intravenous bolus injection of CAZ at doses of 20 mg/kg and 10 mg/kg for 5 minutes in each 2 cases (4 cases in total) were determined. The mean serum concentrations of CAZ were 78.9 and 52.0 micrograms/ml at 15 minutes, 38.5 and 27.4 micrograms/ml at 1 hour, and 6.5 and 4.8 micrograms/ml at 4 hours, with serum half-lives (T 1/2) of 1.39 and 1.80 hours respectively. Mean cumulative urinary excretion rate within 6 hours after administration was 84.6%. In a patient with chronic renal failure, serum half-life was 3.22 hours and urinary excretion rate within 6 hours was 22.8% (after intravenous bolus injection of CAZ at a dose of 10 mg/kg). CAZ was administered at a dose of 55.5 mg/kg by intravenous bolus injection to a child with purulent meningitis. The levels of CAZ in the cerebrospinal fluid (CSF) at 1 hour after administration were 2.7-38.9 micrograms/ml with CSF/Serum ratios of 3.2-28.8%. Forty-two pediatric patients with various bacterial infections (pyelonephritis 14, tonsillitis 1, bronchopneumonia 3, pneumonia 17, purulent meningitis 1, bacteremia 2, SSSS 1, enterocolitis 3) were treated with CAZ at a daily dose of 49-222 mg/kg t.i.d. or q.i.d. (as a rule 60 mg/kg t.i.d.). The efficacy rate was 97.6% clinically and 97.8% bacteriologically. No adverse reactions were observed except 1 case with mild diarrhea. Abnormal laboratory findings were also only mild; eosinophilia in 1, slight elevation of GOT in 5 and that of GOT & GPT in 3 cases. These results indicate the usefulness of CAZ in the treatment of bacterial infections in children.     

Pharmacokinetic studies on ceftazidime in the obstetrical and gynecological field

Concentrations of ceftazidime ( CAZ ) were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer. Data analysis was performed by the simulation curves prepared from pharmacokinetics parameters using the three-compartment model. Following 1-hour intravenous drip infusion of 1 g of CAZ , the mean drug concentration in venous blood was 75.54 micrograms/ml at 1 hour after start of the infusion. The mean CAZ level in the pelvic dead space exudate was as high as 23.87 micrograms/ml at 2.09 hours after start of the infusion, and the AUC was 149.11 micrograms . hr/ml. The above results suggest that CAZ is a useful drug clinically with good penetration into the pelvic dead space.     

Fundamental and clinical studies on ceftazidime in the field of obstetrics and gynecology

Fundamental and clinical studies were performed on ceftazidime ( CAZ ), a new cephem antibiotic. Following a single intravenous administration of 1 g dose of CAZ , the transfer of CAZ to the internal genital organs was good. The transfer of CAZ to retroperitoneal fluid was excellent. In a clinical trial, CAZ was given to 6 patients with obstetrical and gynecological infections. The efficacy was evaluated as excellent in 3 cases and good in the other 3 cases. No adverse effects were observed in any of the patients treated with CAZ .     

Fundamental and clinical study on cefminox in the obstetrical and gynecological field

In order to assess clinical utility of cefminox (CMNX, MT-141), its transference into internal genital organ tissues and pelvic dead space was determined. In addition, transference of CMNX from maternal blood into fetal umbilical cord blood as well as into amniotic fluid was evaluated. In the clinical study, CMNX was administered in 4 cases. The following results were obtained. Transference into internal genital organ tissues; The concentration ratio of each tissue against serum concentration ranged from 25.3 to 42.7%, showing favourable transference as compared to other cephems. Transference into pelvic dead space; At 6 hours after intravenous injection of 1 g CMNX, its concentration in the pelvic dead space reached its peak of 38.8 micrograms/ml of the serum concentration, followed by gradual decrease. Transference into umbilical cord blood and amniotic fluid; Following intravenous injection of 1 g CMNX, its concentration in umbilical cord blood became almost similar to that of maternal blood at about 3 hours later, being 20 micrograms/ml. After that, it tended to decrease in accordance with the concentration in maternal blood. It appears that the drug persists for a more prolonged period in amniotic fluid. Clinical results: Clinically, CMNX was used in the treatment of 4 cases including 2 cases of lymphocystitis, 1 case of intrapelvic cellulitis and 1 case of postoperative wound abscess, and the results obtained were rated as excellent in 1 case, good in 2 cases and poor in 1 case with an efficacy rate of 75%. None of the cases treated experienced adverse reactions nor any laboratory abnormalities were observed.     

Fundamental and clinical studies on ceftazidime in pediatric surgery

Fundamental and clinical studies of ceftazidime (CAZ) were performed in pediatric surgery. The results obtained were summarized below. Serum and urinary levels of CAZ were measured in 5 patients following injection (CAZ: 10 or 20 mg/kg, intravenous bolus injection). Highest levels in serum were observed within 30 minutes, 30.4 micrograms/ml and 49.5-62.9 micrograms/ml with 10 mg/kg and 20 mg/kg doses, respectively. Then serum levels of CAZ decreased gradually except in 1 case with a metabolic disease, and serum half-lives (T 1/2) were 1.19-1.88 hours for the high doses. The highest levels in urine were observed in 0-2 hours, and the urinary recovery rate was 59-100%. The bile levels were also measured in 3 patients who underwent radical operations of congenital biliary atresia (CBA). Highest levels of CAZ in bile, 4.47-9.66 micrograms/ml, were noted in 0-2 or 2-4 hours following injection. Recovery rates for 8 hours were 0.11, 0.17 and 0.20% for the 3 patients. The CAZ was administrated to 7 patients for prophylaxis of the postoperative infection (5 cases) or to treat ascending cholangitis in CBA (2 cases). Clinical results were good in 4, fair in 1, poor in 1 and unknown in 1. No clinical and laboratory side effect due to the administration of CAZ was observed. It is concluded that CAZ is a safe and effective antibiotic in pediatric surgery.     

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)     

Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.     

Fundamental and clinical studies on aztreonam in obstetrics and gynecology

Fundamental and clinical studies on gynecological use of aztreonam (AZT), a new monobactam, were performed with following results. Following the intravenous administration of 1 g dose of AZT, the transfer of AZT to pelvic dead space exudate was good, in which the concentration of that was 14.9 micrograms/ml (2 hours), 15.3 micrograms/ml (3 hours) after injection. The transfer of AZT to serum of umbilical cord and amniotic fluid was excellent. In a clinical trial, AZT was given to 5 patients with obstetric and gynecological infections. The clinical efficacy was evaluated as excellent in 1 case and good in the other 4 cases. No adverse effects were observed in any of the patients treated with AZT.