Tissue penetration of aztreonam in obstetrics and gynecology

The following results were obtained by measuring serum and tissue concentrations of aztreonam, a new monobactam antibiotic. Penetration into each tissue was favorable, particularly, to the portio vaginalis, but there was no conspicuous difference of the penetration among other tissues. Serum concentration tended to decrease with the lapse of time, but the concentration in each tissue did not show a specific pattern of change due to a considerable irregularity of the measured concentrations. No specific side effect was noted.     

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.     

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.     

Tissue penetration and clinical effects of ceftazidime in the field of obstetrics and gynecology

To study concentrations in the gynecological organs, ceftazidime (CAZ) was given intravenously by one shot of 0.5 g to 1 patient and of 1.0 g to 10 patients who underwent simple hysterectomy because of uterine myoma. Also, clinical effect of the drug was studied in 3 cases. The levels of CAZ in sera in uterine artery and elbow vein, and tissue concentrations in various sites of the gynecological organs obtained during 50 to 425 minutes after administration were determined by the paper-disc method with P. mirabilis ATCC 21100 strain. Concentrations of CAZ at 92 minutes after administration of 1.0 g i.v. were 39.8 mcg/ml in serum of uterine artery, 47.6 mcg/ml in serum of elbow vein, 20.5 mcg/g (tissue/serum ratio 0.43) in the ovary, 18.0 mcg/g (0.38) in the fallopian tube, 16.1 mcg/g (0.34) in the endometrium, 34.5 mcg/g (0.72) in the myometrium, 30.8 mcg/g (0.65) in the uterine cervix, 36.4 mcg/g (0.76) in the portio vaginalis and then gradually decreased time-dependently. Tissue concentrations were higher than those in serum in the endometrium, uterine cervix and portio vaginalis at 147 minutes after administration. CAZ concentrations of adipose tissue between 353 and 365 minutes after injection of 1.0 g were lower than 0.8 mcg/g. The clinical responses to CAZ in intrapelvic infections were good in all cases. Slight elevation of total bilirubin, to 1.5 mg/dl, was observed in a case. In the light of these clinical findings, CAZ appears to be a potent antibiotic effective in the clinical application.     

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.     

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.     

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

Penetration of aztreonam (AZT) into the uterus and the adnexal tissues and usefulness and safety of AZT for obstetric and gynecologic infections were studied with the following results. By one shot intravenous injection of AZT 1 g, the uterus and the adnexal tissues showed favorable penetration with Cmax 27.0-48.5 micrograms/g, AUC 29.4-84.9 micrograms X hr/g and Tmax 0.10-0.44 hours. MIC50, MIC80 and MIC90 of AZT for Gram-negative bacteria measured prior to administration were very low being 0.10 micrograms/ml, 0.20 micrograms/ml and 1.56 micrograms/ml, respectively. Clinical effect of AZT for 30 infection cases in obstetrics and gynecology was evaluated according to an overall efficacy criteria resulting in "good" for all the cases. With regard to microbiological effect, 90.9% of the pathogens isolated prior to the administration were eliminated by AZT. During and after the administration of AZT, side effect due seemingly to AZT was not observed in subjective and objective symptoms and laboratory values.     

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

Aztreonam (AZT), a new monobactam antibiotic, was basically and clinically applied to the field of obstetrics and gynecology, obtaining the following results. The pelvic dead space exudate level of AZT after 30 minutes-intravenous drip infusion of 1 g attained the peak of 22.66 micrograms/ml at 1 hour from initiation of infusion and thereafter declined gradually, contrasting the peak of 34.38 micrograms/ml of the cubital vein at 30 minutes. Total of 13 cases comprising 4 with intrauterine infection, 5 with adnexitis and 4 with pelveoperitonitis were intravenously treated with AZT at a dose of 1 g twice daily. The overall clinical results were excellent in 3 cases and good in 10 cases. No side effects were observed in any of the cases treated with AZT.     

Clinical effect of aztreonam in infections in obstetrics and gynecology

Aztreonam (SQ 26,776, AZT), a new monobactam antibiotic, was studied in obstetrics and gynecology with the following results. For the study of tissue penetration, 1 g AZT was administered by intravenous drip infusion for 1 hour. The concentration was high in elbow venous blood and uterine arterial blood 60 minutes after the administration. Each uterine tissue concentration other than the endometrium was as high as 26.7-31.7% of the blood level and salpinx and ovary concentration were 25.9% and 5.2%, respectively. Each tissue concentration decreased to less than 0.6 microgram/g in the uterine, the ovary and the salpinx 280 minutes thereafter. In the review of obstetric and gynecologic genital infections, clinical efficacy of AZT was "poor" for 1-endometritis, "poor" for 1-pyometra, "excellent" for 1-puerperal fever, "excellent" (1) and "good" (2) for 3-pelvioperitonitis, "excellent" for 1-parametritis and "good" for 2-infectious lymphocele with overall effective rate of 77.8% (7/9). AZT was microbiologically effective for Gram-negative bacteria, such as E. coli, K. pneumoniae, etc. As for safety, neither side effects nor abnormal laboratory findings in the examination of blood, hepatic function, renal function and urine due to AZT were reported.     

Pharmacokinetic and clinical studies on aztreonam in the perinatal period in obstetrics and gynecology

Pharmacokinetic and clinical studies on aztreonam (AZT) in the perinatal period in obstetrics and gynecology were performed with the following results. 1. Concentrations of AZT in maternal serum, umbilical cord serum, amniotic fluid and neonatal serum were determined after 1 hour intravenous drip infusion of 1 g. The maternal serum concentration was 32.2 micrograms/ml at 26 minutes after administration, gradually decreasing thereafter to 13.2 micrograms/ml at 2 hours 33 minutes, 4.9 micrograms/ml at 3 hours 21 minutes and 2.9 micrograms/ml at 5 hours 3 minutes. Umbilical cord serum concentration was 17.0 micrograms/ml at 36 minutes after drip infusion and still remained at 4.0-16.1 micrograms/ml at 5 hours after administration. Amniotic fluid concentration was 9.9 micrograms/ml at 3 hours 21 minutes after drip infusion and showed 3.3 micrograms/ml at 16 hours 26 minutes after administration. Most of the maximum serum concentrations of newborns between 3 to 24 hours after delivery were not detectable, with only one case with 2.2 micrograms/ml at 9 hours after delivery. 2. AZT 1 or 2 g x 2/day was given by intravenous drip infusion to 12 cases of perinatal infections in obstetrics and gynecology for 5 to 8 days. Clinical efficacies were evaluated as excellent in 8 cases, effective in 2 and not effective in 2 with 83.3% efficacy rate. With respect to side effects, minor degree of urticaria was observed in 1 case. Another case showed a transient elevations of GOT, GPT and Al-P in laboratory tests.     

Clinical studies on aztreonam in infections in obstetrics and gynecology

Clinical effect was studied for aztreonam (AZT) on 2 patients being treated for malignant tumors. One-two grams of AZT was administered b.i.d. by intravenous drip infusion for 6-7 days. In case 1 with pyometra, there were excellent improvements in WBC, CRP and fever pattern. Unfavorable BUN and S-Cr. values were found, but these were considered to be side effects due to cisplatin. These improved finally, and clinical effect was also excellent. Case 2, a urinary tract infection + prophylactic postoperative administration case, was treated in combination with another drug presuming mixed infection and AZT was shown to be effective clinically and overall. No side effects in cases 1 or 2 were considered to be due to AZT.     

In vitro activity and clinical evaluation of aztreonam in the field of obstetrics and gynecology

Antimicrobial activity of aztreonam (AZT) against 231 clinical isolates in the field of obstetrics and gynecology was determined by agar-plates dilution method. Almost of all strains of E. coli (108 strains) tested were susceptible to the concentration of 0.20 micrograms/ml of AZT. Anaerobic bacteria, however, were less susceptible to this antibiotic than to cefazolin. The concentrations of AZT were determined in serum and pelvic tissue samples obtained at various intervals after 1 hour intravenous drip infusion with 1 g. The concentrations of AZT in pelvic tissues were maximal 9.3 micrograms/g at 57 minutes but less than 0.6 micrograms/g at 3 hours or more after injection. Clinical efficacy of AZT was evaluated in 6 cases consisted of two each with Bartholin's abscess and intrauterine infection and one each with post partum endometritis and acute adnexitis. Clinical efficacies were seen in 5 cases.     

Clinical trial of aztreonam in the field of obstetrics and gynecology

Clinical effect and safety of aztreonam (AZT) in the obstetrics and gynecology were studied in 17 cases of obstetric and gynecological infections. AZT was administered at a dose of 2 g per day by intravenous drip infusion, for 4-8 days depending on severity of the disease. The results showed that AZT was effective in 14 out of 17 cases and the overall efficacy rate was 82.4%. E. coli, Enterobacter, E. faecalis, etc. were detected in 8 out of 17 cases, and after AZT treatment other strains appeared in 3 clinically effective cases. There was a slight elevation of GOT and GPT in 1 case but no other appreciable side effect or abnormal laboratory value was observed.     

Clinical evaluation of aztreonam in the field of obstetrics and gynecology

Aztreonam (AZT), a new monobactam antibiotic was evaluated on clinical efficacy and bacteriological response in gynecological and obstetrical infections, and the following results were obtained. AZT was given to 22 cases with obstetrical and gynecological infections at a dose of 1 g X 2 times daily and 86.4% of clinical efficacy, 45.5% of eradicated rate on diagnosis, 52.5% of bacteriological response on isolated organisms and 83.3% of bacteriological effect on cases isolated Gram-negative bacteria were assessed. Side effect incidence was very low.     

Clinical experience with aztreonam in the field of obstetrics and gynecology

Aztreoman (SQ 26,776, AZT), a synthetic monobactam antibiotic, was applied clinically in the field of obstetrics and gynecology. AZT was administered by intravenous drip infusion for 6 to 8 days at a daily dose of 2 g divided in 2 times to 5 cases. Klebsiella in 1 case with puerperal endometritis, Enterococcus, Propionibacterium and Bacteroides in each 1 case with pyometra was isolated. The clinical effect of Klebsiella was excellent. Bacteroides in 1 not-examined case was good. Enterococcus and Bacteroides with pyometra was not effective. Side effects were observed in 2 cases. One case with eclampsia arised LDH and A1-P in serum and 1 case with hepatitis arised GOT and GPT in serum.     

Clinical studies on aztreonam in various infections in obstetrics and gynecology

Aztreonam (AZT) was administered to 10 patients with obstetric and gynecologic infections to evaluate its clinical effect. Two-four grams of AZT per day (b.i.d.) were administered for the treatment for 4-15 days by intravenous drip infusion or intravenous injection. AZT was effective for 3 cases of pelvic peritonitis, 1 case of pyoovarium and 2 cases of Bartholin's abscess. For 2 cases of intrauterine infection, AZT was effective for 1 case, and the other case could not be judged. For 2 cases of local infection, AZT was effective for 1 case and ineffective for 1 case. Efficacy rate was 89% for the 9 cases excluding the 1 unevaluable case. Microbiological effect was determined for 4 out of 10 cases. Two strains of Haemophilus influenzae and one each of Escherichia coli, Bacteroides fragilis and Streptococcus intermedius were isolated, but all of them were eliminated for a elimination rate of 100%. Neither abnormal laboratory findings in hepatic or renal functions, etc. nor side effects were recognized.     

Pharmacokinetics and clinical evaluations on aztreonam in perinatal infections in obstetrics and gynecology. A study of aztreonam in the perinatal co-research group

Pharmacokinetics and clinical studies on an injectable monobactam antibiotic aztreonam (AZT), were carried out in perinatal infections in obstetrics and gynecology and the obtained results are summarized as follows. 1. Pharmacokinetic study (1) Upon one-shot intravenous injection of AZT 1 g before delivery, maternal serum concentration of AZT was 89.0 micrograms/ml immediately after the injection and a half-life (T 1/2) of 0.96 hour was observed. Umbilical-cord serum concentration showed a peak value of 16.5 micrograms/ml at 1.26 hours after the injection and gradually decreased with a T 1/2 of 1.91 hours. The transfer into amniotic fluid was observed and the peak value of AZT in amniotic fluid reached 12.9 micrograms/ml at 5.57 hours after the injection and slowly decreased thereafter with a T 1/2 of 4.42 hours. Transfer and disappearance in one-shot 2 g intravenous injection and 1 g intravenous drip infusion (1 hour) of AZT were very similar to the results obtained with the one-shot 1 g intravenous injection. (2) The residual serum concentration in neonates after one-shot 1 g intravenous injection of AZT to the mother was almost below the detectable limit. Transfer of AZT into milk was scarcely recognized. 2. Clinical studies (1) AZT was injected to 47 cases with various perinatal infections and it was more than "effective" in 45 cases with an efficacy rate of 95.7%. Also, all the 12 cases to which AZT was administered for prophylaxis of infections showed prophylactic effect. Bacterial eradication was obtained with 25 strains out of 29 aerobic Gram-negative bacteria, but 1 strain "persisted" and for 3 strains results were "unknown", hence an eradication rate of 96.2% was obtained. However, AZT treatment resulted in a little lower eradication rate against Gram-positive bacteria. (2) One case (1.3%) of minor degree of urticaria was found as a side effect, and one case each of eosinophilia and elevation of GOT, GPT and Al-P was observed as abnormal laboratory value. From the above results of pharmacokinetics and clinical evaluation, it has been concluded that AZT is a useful and highly safe drug in various perinatal infections and prophylaxis.     

Clinical review and antibacterial effect of aztreonam in infections in obstetrics and gynecology

Clinical effect in obstetrics and gynecology was studied on aztreonam (AZT), a potent monobactam antibiotic for Gram-negative bacteria. AZT was tested for 7 cases and effective for all of them with quite a high effective rate of 100%. Neither side effect nor abnormal laboratory findings were noted and it sufficiently proves the property of AZT, a totally chemical-synthesized product with lower incidence of allergic reaction. The above results suggest that AZT is useful for obstetrics and gynecologic infections in view of its high stability to beta-lactamase and dehydropeptidase and high potency against Gram-negative bacteria.     

Tissue distribution of cefotetan in the field of obstetrics and gynecology

The concentrations of cefotetan (CTT) in serum, uterus, ovary and oviduct tissues were determined in 30 patients after single intravenous drip infusion of 1 g over 1 hour. 1. Peripheral blood level of CTT was determined from 3 to 24 hours after injection. The maximum level was observed at 3 hours after injection and the concentration went down gradually with time. 2. The tissue concentrations of CTT in intrapelvic organs also tended to decrease with time and hardly detected 24 hours after injection. 3. From 3 to 12 hours after injection, mean penetration rate of CTT into intrapelvic organs was 40% and more. 4. Among intrapelvic organs, penetration rate into portio was highest, and others were ovary, uterine cervix, oviduct, endometrium, myometrium and uterine myoma in order of lowering penetration rate. 5. The penetration rate into uterine myoma was approximately half that into normal tissue. Considering above results, CTT is expected to show sufficient effects against Gram-negative bacilli and Bacteroides sp. when reasonably dosed.     

Fundamental and clinical evaluation of cefodizime in obstetrics and gynecology

Cefodizime (CDZM, THR-221), a newly developed injectable cephem antibiotic agent, was evaluated for its distribution in intrapelvic genital organ tissues, penetration into exudate of retroperitoneal space and breast milk and therapeutical effects on some infections in obstetrics and gynecology. The results obtained are summarized as follows. 1. When 1 g of CDZM was administered by drip infusion over a 60 minutes period, its serum concentration reached 53.51 micrograms/ml at the completion of drip infusion, then declined rapidly. Peak concentrations of CDZM in intrapelvic genital organ tissues were higher than 20 micrograms/g at different times. CDZM was transferred to the exudate of retroperitoneal space and its concentration reached a peak of 7.01 micrograms/ml at 2.67 hours after initiation of 60 minutes drip infusion at a dose of 1 g, then declined slowly but stood at 4.93 micrograms/ml even at 8 hours. The transfer of CDZM to breast milk was similar to other cephem antibiotic agents and peak levels of CDZM in milk were 0.13-0.36 microgram/ml at 2 or 3 hours after administration of a dose of 1 g. 2. In the clinical study, CDZM was administered by drip infusion over 60 minutes to 6 patients with obstetrical and gynecological infections at a daily dose of 2-6 g. Clinical results were good in 5, poor in 1, and the efficacy rate was 83.3%. No side effects nor abnormal laboratory test results were observed.