Fundamental and clinical studies on aztreonam in pediatrics

Fundamental and clinical results of AZT in pediatrics were as follows. Pharmacokinetics of AZT was studied for 1 case with resulting high serum concentration and a half-life of approximate 1 hour. AZT was administered to 10 patients with bacterial infections with 100% clinical efficacy and 62.5% bacterial elimination. Side effect was 1 case of diarrhea. There were no abnormal laboratory or coagulation test findings nor vitamin K deficiency, platelet hypofunction or effects on intestinal bacterial flora. AZT was considered to be high in safety. The administration of 20 mg/kg AZT 3 times a day was considered to be an effective treatment for pediatric Gram-negative infections.     

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.     

Fundamental and clinical studies on aztreonam in the gynecological field

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic was studied on clinical efficacy for infectious disease in gynecological field. At about 80 minutes following intravenous injection of 1 g dose of AZT, it penetrated well into internal genital organs at therapeutic levels. Moreover it transferred very fast and enough into intrapelvic dead space exudate, and its level was kept still as high at 12 hours after administration. AZT was given to 20 women affected with gynecological infectious disease. The outcome of AZT therapy was as follows: effective in 5 out of 6 patients (83.3%) administered intravenously and in all of 14 patients (100%) received intramuscularly. Notable adverse effects or abnormal laboratory findings were not observed except 1 case of diarrhea and 2 cases of transient and slight elevation of serum CPK and transaminases. Based on these results, we may conclude that AZT is a highly effective and a very safe antibiotic for the treatment of infectious disease in gynecological field.     

Fundamental and clinical studies on aztreonam in the pediatric field

Fundamental and clinical studies on aztreonam (AZT), a new monobactam antibiotic, were performed in the pediatric field. The MICs of AZT were assessed against the clinically isolated strains in the pediatric infections. AZT showed an excellent antibacterial activity against Gram-negative bacteria, i.e., against E. coli (20 strains), K. pneumoniae (9), P. mirabilis (16), P. vulgaris (5), P. aeruginosa (10), S. typhimurium (4) and H. influenzae (11); the MICs of AZT against the above strains were less than 0.39 microgram/ml, 0.10 microgram/ml, 0.024 microgram/ml, 0.024 microgram/ml, 6.25 micrograms/ml, 0.10 microgram/ml and 0.10 microgram/ml, respectively. However, antibacterial activity of AZT against Gram-positive bacteria was inferior to that against Gram-negative bacteria, i.e., against the strains of S. aureus (16) and S. pyogenes (4), those MICs were more than 400 micrograms/ml and 3.13 micrograms/ml, respectively. Serum concentrations and urinary excretion of AZT were measured in 2 children aged 7 and 11 years after a single intravenous injection at the dose of 20 mg/kg. The mean serum concentration of AZT followed by the injection 62.5 micrograms/ml at 1/4 hour, 28.5 micrograms/ml at 1/2 hour, 16.5 micrograms/ml at 1 hour, 12.0 micrograms/ml at 2 hours, 3.6 micrograms/ml at 4 hours and 1.1 micrograms/ml at 6 hours, respectively. The mean half-life (beta-phase) was 1.24 hours. The mean urinary concentrations after the injection were 5,000 micrograms/ml in 0-2 hours, 1,650 micrograms/ml in 2-4 hours and 611 micrograms/ml in 4-6 hours and the mean urinary recovery rate up to 6 hours was 61.2%. These results in our studies were considered to be comparable with those reported in adults. In our clinical studies, AZT was administered to a total of 14 cases, i.e., acute pneumonia (4 cases), acute pyelonephritis (4), acute enteritis (5) and acute sppurative cholangitis (1). Clinical effect of AZT was excellent or good in 13 cases except fair in 1 case with acute enteritis and the efficacy rate (excellent and good) was 92.9%. With regard to bacteriological effect, all the strains of H. influenzae (3), E. coli (2), P. mirabilis (1) and P. vulgaris (1) were eradicated, but, S. typhimurium (4) was not eradicated. Neither side effect nor abnormal laboratory findings were observed during the study.     

Fundamental and clinical studies of aztreonam in pediatric infections

Fundamental and clinical studies were carried out with aztreonam (AZT), a new monocyclic beta-lactam antibiotic, in pediatric infections. Results were as follows. The mean half-lives in the vein blood were 1.09 hours, 1.18 hours, 1.22 hours after injection, when the doses were 10, 20 and 40 mg/kg, respectively. Dose response was observed. The average recovery rates in the urine between 0 and 6 hours were 40.2%, 42.3%, 50.8% when the doses were 10, 20 and 40 mg/kg, respectively. The antibacterial activity of AZT against 16 clinical isolates were determined in comparison with those of ABPC, CPZ, LMOX and CTX. Against 8 clinical isolates of E. coli and 3 of H. influenzae, the activity of AZT was equal or superior to that of CPZ, LMOX and CTX, and way by far superior to that of ABPC. Twenty-three pediatric patients received AZT in doses ranging from 48 to 79 mg/kg divided 3 times a day; 12 cases of urinary tract infection, 9 cases of respiratory tract infection and 2 cases of bacterial enterocolitis. The rate of clinical effectiveness was 100%. No side effect was observed. Slight elevation of GOT and GPT were observed in 2 cases, increase of platelet count in 2. All were considered to be transient and mild.     

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

Fundamental and clinical studies on aztreonam (AZT), a new synthetic monobactam antibiotic, were performed and following results were obtained. Concentration of AZT was examined in serum, internal genital tissues and retroperitoneal fluid after a single intravenous administration of 1 g dose. The venous serum level of AZT was 114.0 micrograms/ml at 10 minutes after the administration, then decreased to 7.0 micrograms/ml at 3 hours. Since concentration of AZT in examined tissues showed wide variation, it was irrelevant to calculate transfer ratio. Concentration in retroperitoneal fluid made the peak of 40.0 +/- 22.6 micrograms/ml at 1 hour after the administration, then slowly decreased to 13.4 +/- 3.2 micrograms/ml at 6 hours. Judging from above data, the transfer of AZT to retroperitoneal fluid was favorable. In clinical trial, AZT was given to 17 cases with obstetrical and gynecological infections such as endometritis, uterine adnexitis, pelvic peritonitis, parametritis and lymphocystitis. The efficacy was evaluated as excellent in 2 cases, good in 12 and poor in 3, and efficacy rate was 82.4%. No side effects were observed in any of the cases. In laboratory findings, transient elevation of liver function in 2 cases and eosinophilia in 1 case were noticed.     

Fundamental and clinical studies of aztreonam in the field of pediatric

The fundamental and clinical studies of aztreonam (AZT) were performed. The results were as follows: The MICs of AZT for E. coli and Salmonella sp. which were recently isolated in the pediatric field were less than 0.78 micrograms/ml. AZT also was effective against ABPC/PIPC-resistant bacteria. The MIC of AZT for V. parahaemolyticus was less than 1.56 micrograms/ml. The peak serum levels of AZT which were occurred just after the 1 hour drip infusion of 10-30 mg/kg were 60.5-136.8 micrograms/ml, and at 6 hours after infusion the serum levels were 1.3-6.1 micrograms/ml; therefore, the dose response was proved. The mean half-lives (T 1/2) were between 1.21 and 1.36 hours. The excretion rates in urine up to 6 hours after intravenous drip infusion were between 32.7 and 77.5%. The ratio of the cerebrospinal fluid concentration to serum in the child with purulent meningitis was 3.5% at 1 hour after the intravenous injection at the dose of 69 mg/kg, and the ratios of the subdural fluid levels to serum were 31.3-37.5%. The levels of AZT into the feces by the multiple dosage were 0-840 micrograms/g. Twenty-five pediatric patients with acute infections had been treated by intravenous injection or drip infusion at the doses of 49-120 mg/kg/day (almost 50-100 mg/kg/day) for 4 to 13 days. The efficacy rate of excellent + good was 84% and that of excellent + good + fair was 96%. The efficacy rate of excellent + good was 100% in all cases with upper/lower respiratory tract infection, bronchopneumonia, and acute urinary tract infection caused by Gram-negative rods. The clinical efficacy was observed in all cases with acute bacterial enteritis. Although AZT was clinically effective against Salmonella enteritis, bacteriological efficacy on the causative organisms was not observed in some cases. Although AZT was bacteriologically effective in 1 patient with typhoid, it did not alleviated fever. AZT showed activity to 9 strains isolated from the culture of throat swab, urine and feces. No side effects were clinically observed in all cases, while slight elevations of laboratory findings were observed in 4 cases.     

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

Aztreonam (AZT, E-0734), a new beta-lactam antibiotic, was fundamentally and clinically studied. The following results were obtained. The serum and internal genital tissue levels for AZT after 1 g intravenous injection had been kept at more than about 20 micrograms/ml and 3.0 micrograms/g, respectively, during 1 hour. AZT was administered at 1-2 g of daily dose by intravenous injection or intravenous drip infusion to 5 patients with obstetric and gynecological infections, comprising 1 of pyometra, parametritis, Bartholin's abscess, puerperal endometritis and diffuse peritonitis. Clinical efficacy was; excellent in 1 puerperal endometritis case, good in 2 cases and poor in 2 cases. Neither side effect nor abnormal laboratory finding was observed.     

Pharmacokinetics and clinical studies on aztreonam in neonates

Pharmacokinetic and clinical studies on aztreonam (AZT) were performed in neonates. Serum concentrations and urinary excretion of AZT were determined in 12 neonates with ages between 0 and 7 days (birth weights were between 1,260 and 3,500 g) upon intravenous injection or 1 hour drip intravenous infusion of AZT at 20 mg/kg. Serum concentrations of AZT at 1 hour after i.v. administration were 54.0 +/- 12.5 micrograms/ml, and half-lives were 6.01 +/- 0.70 hours. Serum concentrations of AZT reached their peaks at the end of drip infusion with levels of 42.1 +/- 17.6 micrograms/ml in the d.i.v. group and half-lives were 6.40 +/- 1.88 hours. Urinary recovery rates in the first 12 hours after administration were 28.5 +/- 6.4% for the i.v. group and 32.3 +/- 13.9% for the d.i.v. group. AZT was administered to 12 neonatal patients (2 cases of sepsis, 2 cases of suspected sepsis, 3 cases of pneumonia, 2 cases of urinary tract infection and 3 cases for prophylaxis), and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. Clinical efficacies in 9 cases except 3 cases with prophylactic use were excellent in 1 case, good in 5 cases, fair in 1 case, poor in 1 case and unknown in 1 case, thus the efficacy rate was 75%. Bacteriological effects in 3 strains with Gram-negative bacilli were eradicated in 2 strains and unchanged in 1 strain, hence the bacteriological eradication rate was 66.7%. Increased GOT and GPT were observed in 1 cases as abnormal laboratory test results, but the abnormality was not serious.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in neonates

Pharmacokinetic and clinical studies on aztreonam (AZT) in mature and premature neonates were carried out. The results are summarized as follows. The mean serum peak level of AZT after intravenous administration at a single dose of 20 mg/kg in 3 to 4 day-old-neonates was 36.6 +/- 2.39 micrograms/ml at 1 hour after dosage. The mean serum level at 6 hours after dosage was 13.5 +/- 2.03 micrograms/ml. The mean half-life time was 3.86 +/- 0.92 hours. The mean urinary excretion rate was 25.1 +/- 5.18% in the first 6 hours after intravenous administration. AZT was administered in 4 cases, but the effects could not be evaluated. No side effect was observed except an elevation of GOT.     

Pharmacokinetic and clinical studies on aztreonam in perinatal period

Pharmacokinetic and clinical studies were carried out on aztreonam (AZT), a monobactam antibiotic with a high activity against Gram-negative bacteria. The results obtained are summarized as follows: 1. Following 2 g bolus intravenous injection, transfers of AZT to umbilical cord serum and amniotic fluid were found to be satisfactory. AZT level in amniotic fluid was higher than 1 micrograms/ml at 40 minutes after administration and it was at 3.7 micrograms/ml in 23.5 hours. 2. In the treatment of 9 patients with perinatal infections, clinical efficacies of AZT were judged excellent in 3 cases and good in 6 cases. 3. No side effects and abnormal laboratory findings due to the drug were observed in any case. These results indicate that AZT may be a useful antibiotic for the treatment of perinatal infections.     

Preclinical and clinical studies on aztreonam in pediatric surgery

Aztreonam (AZT) was administered to immature infants, neonates and infants for preclinical and clinical studies. 1. Sufficient serum concentrations were obtained upon 1-hour intravenous drip infusion of AZT 40 mg/kg to infants with biliary atresia. The average T1/2 was about 1 hour and urinary recovery rates were in a range between 35.2 and 61.3%. Biliary recovery rates were 0.03-0.4%. 2. AZT was given to 5 cases for prophylaxis and the results showed its prophylactic effect in 3 cases. 3. AZT is effective against Gram-negative bacteria and its efficacies in the treatment of 4 infection-cases were "excellent" in 2 cases and "effective" and "somewhat effective" in 1 case each. 4. Neither side effects nor abnormal laboratory test values were observed in any of the 9 cases given AZT.     

Preclinical and clinical studies on aztreonam in obstetrics and gynecology

Aztreonam (AZT), a new monobactam antibiotic, was studied in obstetrics and gynecology with the following results. The tissue concentration of AZT in the female genital organs was relatively high at the portio vaginalis and the cervix uteri followed by at the ovary and the myometrium, but the distribution to the endometrium and the oviduct was a little poor. The concentration of AZT in the pelvic dead space exudate was highest at 2 hours after intravenous injection whereas it was highest at 5 hours after intravenous drip infusion. However, there was no significant difference in the concentration between intravenous injection and intravenous drip infusion and the distribution to the pelvic dead space exudate was relatively good. AZT was clinically administered to pyometra (3 cases), puerperal endometritis (3), adnexitis and endometritis (3), pelvioperitonitis (1), Bartholin's abscess (4) and purulent vulvitis (1), a total of 15 cases with an overall effective rate of 93.3%. AZT was microbiologically effective for Gram-negative bacteria such as E. coli and K. pneumoniae, but also effective for anaerobes and some Gram-positive bacteria, etc., for which MIC of AZT is high. With regard to safety of AZT, neither side effects nor abnormal laboratory findings were reported.     

Fundamental and clinical studies on ceftazidime

Ceftazidime ( CAZ ) was evaluated for its pharmacokinetics and clinical effects in the treatment of obstetrical and gynecological infections. The following results were obtained: Transfer of CAZ into various parts in the uterus and the uterine adnexa was found to be satisfactory, and relatively high concentration of the drug was maintained in the pelvic dead space exudate. Infections in the obstetrics and gynecology: 2 approximately 4 g of CAZ was given to 12 patients for 4 approximately 11 days and satisfactory clinical effect was obtained in 9 patients. There was a slight GOT elevation in 1 case but no other appreciable side effect or abnormal laboratory value was observed.     

Fundamental and clinical studies on cefminox

Cefminox (CMNX, MT-141) was tried in children with various infection and the following results were obtained. Serum levels and urinary recovery of CMNX were studied in 2 patients aged with 9 and 11 years. After intravenous injection of 20 mg/kg, the mean serum concentrations at 15, 30 minutes, 1, 2, 4, and 6 hours after the administration were 178.7, 122.2, 73.9, 41.0, 14.0 and 5.3 micrograms/ml, respectively. The half-life in serum was 1.36 hours. The average urinary recovery rate of CMNX was 86.5% at 6 hours after the administration. The therapeutic efficacy was excellent in 18, good in 1 and poor in 1 patient, the efficacy rate being 95%. As for the side effects, slight elevation of S-GOT and drug fever were observed in 2 cases.     

Laboratory and clinical studies on aztreonam in the pediatric field

Laboratory and clinical studies were performed as follows on aztreonam (AZT), a new monobactam antibiotic. Pharmacokinetics Serum concentrations of AZT were measured in 1 patient given 20 mg/kg by intravenous bolus injection. The peak concentration was 100 micrograms/ml at 15 minutes, and T 1/2 was 1.85 hours. Clinical efficacy AZT was administrated intravenously to 10 patients in doses of 59.2-170.7 mg/kg (average 76.1 mg/kg) t.i.d. for 3-8 days (average 5.3 days); 5 with pneumonia, 1 with bronchitis, 1 with lymphadenitis, 1 with sepsis (suspected) and 2 with urinary tract infections. The overall efficacy rate was 80%, i.e., efficacy was excellent in 5, good in 3, fair in 1 and poor in 1. Bacteriological efficacy was excellent, i.e., 4 of 4 Gram-negative strains disappeared. Any clinical side effects and laboratory abnormalities were not observed. The above results suggest that AZT is a useful antibiotic for treating pediatric bacterial infections, especially due to Gram-negative bacteria.     

Pharmacokinetic, bacteriological and clinical studies on aztreonam in neonates

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of AZT were determined in 18 neonates with ages between 1 and 30 days (gestation periods were 36 to 40 weeks and birth weights were 1,890 to 4,300 g) and in 2 infants with 54 and 60 days of age (gestation periods were 36 and 40 weeks, and birth weights were 2,300 and 3,300 g, respectively) upon one-shot intravenous injection of AZT 10 mg/kg (7 cases) or 20 mg/kg (11 cases) to the 18 neonates and 20 mg/kg to the 2 infants. Ampicillin (ABPC) 25 mg/kg was simultaneously injected to 5 cases of the neonates given AZT 20 mg/kg by one-shot intravenous injection and plasma concentrations of ABPC in these 5 cases were also studied. Plasma concentrations in neonates at 0.5 hour after intravenous injection of AZT 10 mg/kg were 11.5 to 27.6 micrograms/ml (average 20.3 +/- 5.5 micrograms/ml) and decreased with half-lives of 2.72 to 5.70 hours (average 3.81 +/- 1.28 hours), and the plasma levels at 8 hours after administration were 3.3 to 8.7 micrograms/ml (average 5.8 +/- 2.5 micrograms/ml). In the cases given AZT at 20 mg/kg, plasma levels at 0.5 hour were 12.4 to 48.8 micrograms/ml (average 35.9 +/- 11.6 micrograms/ml) and decreased with half-lives of 1.69 to 4.14 hours (average 2.94 +/- 0.76 hours) and AZT levels at 8 hours were 1.1 to 10.6 micrograms/ml (average 5.6 +/- 3.6 micrograms/ml). Urinary recovery rates in the first 8 hours after intravenous injection of the 10 mg/kg group were 15.5 to 61.9% (average 37.8 +/- 21.8%) and 16.3 to 62.2% (average 43.5 +/- 16.2%) for the 20 mg/kg group. Plasma concentrations in infants after administration of AZT 20 mg/kg were 33.0 to 35.6 micrograms/ml (average 34.3 +/- 1.8 micrograms/ml) at 0.5 hour and decreased with half-lives of 1.76 to 3.77 hours (average 2.77 +/- 1.42 hours) and AZT plasma levels at 8 hours were 1.4 to 5.8 micrograms/ml (average 3.6 +/- 3.1 micrograms/ml). Urinary recovery rates were 35.4 to 64.8% (average 50.1 +/- 20.8%). These results suggested that AZT shows a dose-dependent, high plasma concentration even in the neonatal period, as well as good urinary excretion from an early stage of the administration.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in the perinatal period

Pharmacokinetic and clinical studies of aztreonam (AZT) in perinatal infections in the field of obstetrics and gynecology were performed with the following results. 1. At one shot intravenous injection, 1 g AZT showed rapid distribution to the umbilical-cord serum with concentrations higher than 15 micrograms/ml in 1 hour 36 minutes after injection and higher 10 micrograms/ml even in 4 hours 30 minutes after injection. Significant difference in concentrations was not observed between arterial serum sample and venous serum sample of the umbilical-cord in a single subject. The concentration in the amniotic fluid reached a level higher 10 micrograms/ml in 3 hours 37 minutes after injection. 2. Distribution into milk reached a concentration between less than 0.4 micrograms/ml to 1.0 micrograms/ml by 6 hours after administration. 3. AZT 1 g x 2/day was given by intravenous drip infusion to 4 cases of perinatal infection in obstetrics and gynecology for 5 to 9 days. Clinically, AZT was effective for all the cases. Neither side effect nor abnormal laboratory value was observed. Consequently, AZT was considered to be highly effective and safe for its clinical use in the parturition and the puerperium.     

Pharmacokinetic and clinical studies on aztreonam in neonates and premature infants

Aztreonam (AZT) was studied for its pharmacokinetics, clinical effect and effect on intestinal bacterial flora in neonates, and the results obtained are summarized as follows: 1. Serum concentrations of AZT upon intravenous administration of 20 mg/kg were 38.6 micrograms/ml in 30 minutes, 30.6 micrograms/ml in 1 hour and 13.6 micrograms/ml in 6 hours. The T 1/2 was 3.73 hours. Ampicillin (ABPC) 25 mg/kg was concurrently used with AZT in 2 cases and serum concentrations of AZT in these 2 cases were 40.3 and 36.9 micrograms/ml in 30 minutes, 35.7 and 32.6 micrograms/ml in 1 hour, and 13.1 and 10.2 micrograms/ml in 6 hours, respectively. T 1/2's were 3.32 and 2.91 hours, respectively, and no interaction between the 2 drugs was observed. 2. AZT was administered to 21 neonates between 0 and 83 days of age and ABPC was concurrently administered to 18 of the cases. Clinical evaluation was made in 14 cases, where AZT was remarkably effective in 7 cases, effective in 6 cases and not effective in 1 case. Of the 21 cases, 1 case of diarrhea, 1 case each of eosinophilia, an increase in platelets, an increase in platelets and an elevation of GOT and a decrease in platelets were recorded. 3. With respect to effects of AZT on intestinal bacterial flora, fecal concentrations of AZT upon its single administration to 2 cases were low suggesting, there was little effect on the intestinal flora. Some effect on anaerobes, however, was recognized in 4 cases in which ABPC was concurrently used.     

Laboratory and clinical studies of aztreonam in the pediatric field

The authors have carried out the laboratory and clinical studies of aztreonam (AZT) and obtained the following results. The antibacterial activities of AZT against the clinical isolates of E. coli, K. pneumoniae and P. aeruginosa were measured by the agar dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of E. coli to AZT ranged from 0.025 or lower to 1.56 microgram/ml, and the peak of distribution was 0.05 microgram/ml. The peak of susceptibility distribution of K. pneumoniae was 0.025 microgram/ml or lower, and the distribution of P. aeruginosa ranged from 0.1 to 100 micrograms/ml higher and the peak of distribution was 3.13 micrograms/ml. After intravenous bolus injection of 20 mg of AZT in 4 children, the mean peak serum level was 117 +/- 35.1 micrograms/ml at 15 minutes after injection, and half-life time was 1.42 hours. The mean urinary excretion rates was 63.2 +/- 30.6% up to 6 hours after bolus injection of 20 mg/kg of AZT. AZT was given 11 cases with bacterial injection. Daily doses of AZT were from 41.7 to 94.9 mg/kg. Clinical results obtained were excellent and good responses in 8 of 11 cases (72.7%). No side effect was observed.