Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and the penetration of CMNX into pelvic dead space exudate were good. The mean peak serum level after single intravenous injection was 190.8 micrograms/ml. The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time. CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained. No side effect was observed. From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.     

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

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

Fundamental and clinical study on cefuzonam in the field of obstetrics and gynecology

Cefuzonam (L-105, CZON), a new beta-lactam antibiotic, was studied for its transfer into intrapelvic tissues and for clinical efficacy in the treatment of obstetrical and gynecological infection. 1. Following an intravenous 1 hour drip infusion of 1 g, the transferred CZON into uterine tissues reached and was maintained at effective concentrations which were defined as levels exceeding MICs against clinical isolates frequently obtained from patients in the field of obstetrics and gynecology. The peak concentration of CZON in the pelvic dead space exudate was estimated to be 20 micrograms/ml at 0.5-1 hour after infusion. 2. Subjects studied were 5 patients with the following infections: pyometra (3 cases), puerperal intrauterine infection (1 case), vaginal cuff infection (1 case). Clinical efficacies were good in 4 cases and poor in 1 case. No notable side effects or abnormal laboratory test results were noted.     

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.     

Pharmacokinetics and clinical studies on ceftriaxone in the field of obstetrics and gynecology

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

Fundamental and clinical studies of ceftizoxime in obstetrical and gynecological field

This paper, is concerned with fundamental and clinical studies of ceftizoxime, a newly developed cephalosporin derivative, in the field of obstetrics and gynecology. 1. Concentrations of ceftizoxime after administration 1 g of ceftizoxime by 1 hour drip infusion were determined in genital organs in 17 patients and the exudate of pelvic dead space in 6 patients. Simulated maximal concentrations with the ratios to the simulated peak serum levels were as follows: 27.9 micrograms/g for fundal myometrium with the ratio of 48%, 36.0 micrograms/g for portio vaginalis with 62%, 17.1 micrograms/g for ovary with 29%, 15.0 micrograms/g for oviduct with 26% and 16.2 micrograms/ml for the exudate of pelvic dead space with 30%. 2. Minimal inhibitory concentrations of ceftizoxime were determined against clinically isolated organisms from female genital infectious diseases. Ceftizoxime was found to have a potent in vitro activity against Gram negative bacilli; for example, 0.1 microgram/mg or low against E. coli and K. pneumoniae. Against P. aeruginosa, P. cepacia and b. fragilis, ceftizoxime had an activity which expected to be effective in the clinical use. 3. We gave ceftizoxime to 6 patients comprising 4 patients with puerperal fever, 1 with septic abortion and 1 with tubo-ovarian abscess in daily doses of 2 to 3 g by b.i.d or t.i.d intravenous drip infusion for 4--12 days. The results of the treatment were 'excellent' in 3 patients, 'good' in 2, and 'unevaluatable' in 1. 4. Adverse reactions occurred in 2 patients who showed eruption during the medication with ceftizoxime. These patients had allergic histories due to penicillin derivatives. From the above results it is concluded that ceftizoxime is a useful drug for infections in obstetrical and gynecological field.     

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

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

Fundamental studies of cefoxitin in the field of obstetrics and gynecology

The concentration of cefoxitin (CFX, Merxin) in dead space exudate was studied in 14 patients following total extirpation of diffuse uterine cervical cancer. A two-compartment model was used for the analysis. The results obtained were as follows: Calculated maximum concentrations of CFX in the pelvic dead space exudate were 26.55 micrograms/ml at 2.11 hours, 31.07 micrograms/mg at 2.01 hours and 51.51 micrograms/ml at 2.10 hours after 1 hour intravenous drip infusions of CFX 2, 3 and 4 g, respectively. These concentrations were higher than the MIC80 of 12.5 micrograms/ml against E. coli and B. fragilis and were maintained for a sufficient period of time. Based on the results of this study, CFX is considered to be an important and valuable drug in the field of obstetrics and gynecology.     

Pharmacokinetic and clinical studies on cefodizime in obstetrics and gynecology

Cefodizime (CDZM), a new cephem antibiotic, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results are summarized as follows: Concentrations of CDZM in serum and genital tissues following 1 g drip infusion (30 min.) were determined and good penetration of CDZM into tissues was recognized. The maximum level in uterine arterial serum was 56.25 micrograms/ml and maximum tissue levels ranged 23.56-40.64 micrograms/g which were above its MIC80's for main pathogenic organisms. Peak concentrations of CDZM in pelvic dead space exudates following 1 g intravenous bolus injection or drip infusion ranged 6.25-6.52 micrograms/ml. The clinical efficacy of CDZM in 17 cases of obstetrical and gynecological infections was investigated using a dose of 1-3 g daily. The clinical efficacy rate was 88.2% (15/17 cases). Bacteriologically, the eradication rate was 83.3%. No side effects or abnormal laboratory test values were observed.     

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.     

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

Fundamental and clinical studies were made on piperacillin (PIPC) and the results were obtained as follows. Serum and uterine tissue concentrations of PIPC were obtained from 36 to 215 minutes after intravenous single shot of 2 g of PIPC. The cervix uteri, endometrium and corpus uteri showed the highest antibiotic levels of 38.0, 43.0 and 33.0 mcg/g, respectively, at 65 minutes after injection, and oviduct and ovary showed the highest level of 31.5 and 28.5 mcg/g at 36 minutes. Its concentrations were sufficiently effective against the major pathogens (Gram-negative bacilli and anaerobes) demonstrated in the field of obstetrics and gynecology. PIPC was administered 6 patients, including 3 of pelvic peritonitis (isolated organism was E. coli 1), 2 of acute endometritis (Klebsiella sp. 1, Peptococcus sp. + Bacteroides sp. 1) and 1 of acute adnexitis, in a dosage of 1 or 2 g twice or 3 times a day for a period of 5 to 8 days by intravenous administration or intravenous drip infusion. Clinical response was obtained excellent in 1 and good in 5. No adverse reaction as observed in any of the cases treated with PIPC, nor was there any marked changes in the laboratory findings.     

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

Basic and clinical studies on ceftazidime ( CAZ ) were carried out in the field of obstetrics and gynecology. The following results were obtained. The CAZ levels in the pelvic dead space exudate and serum were measured with passage of time in patients undergoing radical hysterectomy with pelvic lymphadenectomy for uterine cervical cancer after intravenous drip infusion of 1 g for 30 minutes. The serum level attained the peak of 87.0 micrograms/ml immediately after completion of the drip infusion and rapidly decreased thereafter. On the other hand, the pelvic dead space exudate level reached the peak of 27.9 micrograms/ml at 1 hour after completion of the drip infusion and gradually decreased thereafter, keeping higher levels than the serum levels. A total of 10 cases comprising 2 of adnexitis, 1 of pelvioperitonitis , 2 of pyometra and 5 of BARTHOLIN's abscess was treated with CAZ intravenous injection at a dose of 1 g twice daily for 5 approximately 6 days. The clinical efficacy was excellent in 1 case and good in 9 cases. Neither adverse reactions nor abnormal laboratory findings were observed in any of the cases.     

Fundamental and clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology

A combination of sulbactam, a beta-lactamase inhibitor, plus cefoperazone (SBT/CPZ = 1/1) was studied in the field of obstetrics and gynecology, and the results were following: Absorption and transfer into genital organ tissues were good. With the 1g intravenous injection the maximum serum concentrations in the uterine artery were 88.6 micrograms/ml for CPZ and 50.0 micrograms/ml for SBT, and the maximum tissue concentrations were 12.2-17.4 micrograms/g for CPZ and 9.8-21.4 micrograms/g for SBT. When the 2 g was administered, the maximum tissue concentrations were 11.9-26.7 micrograms/g for CPZ and 6.0-8.0 micrograms/g for SBT. These elimination showed the similar trend as their serum levels, and their tissue levels were higher than MIC80 for the main organisms. Their penetration into the intrapelvic dead space exudate was also good and showed that the peak levels were 30.1 micrograms/ml for CPZ and 17.4 micrograms/ml for SBT at 2 hours after the 2 g intravenous injection. The peak levels of 34.4 micrograms/ml for CPZ and 8.8 micrograms/ml for SBT at 6 hours after 2 g intravenous drip infusion were obtained. Their elimination was slow, and the concentration higher than MIC80 for main organisms was maintained for a long period of time. For gyneco-obstetrical infections such as adnexitis, intrauterine, intrapelvic and external genital organ infections, a daily dose of 2-4 g of SBT/CPZ produced a 100% clinical efficacy in 10 patients and a 88.9% bacteriological effect. The eradication ratio was more than 80% against beta-lactamase producing organisms. Side effects were few. The above results indicated that SBT/CPZ was useful in the field of obstetrics and gynecology.     

Fundamental and clinical studies of cefpimizole in obstetrics and gynecology

The findings from recent fundamental and clinical studies of the efficacy of cefpimizole (AC-1370) in obstetrics and gynecology are reported in this paper. The AC-1370 concentrations in genital tissues sampled 30 to 56 minutes (a mean of 41.4 minutes) after intravenous injection of 1 g of the drug were 14 to 76 micrograms/g (a mean of 32.4 micrograms/g). The mean transfer ratios of the drug into the genital tissues to the concentration in the uterine arterial blood were such that the transfer ratio into the portio vaginalis was the highest, followed by the uterine cervix and the myometrium, and that into the oviduct was the lowest with about 1/2 that into the portio vaginalis. The concentration in the antecubital venous blood and that in the uterine arterial blood remained similar for all patients. The transfer of AC-1370 into the pelvic dead space exudate reached a peak (49.5 micrograms/ml) 1 hour, and also a peak (49.8 micrograms/ml) 2 hours after the intravenous injection. It then decreased gradually, but remained high, being higher than that in the antecubital venous blood about 50 minutes after the intravenous injection. Ten patients with infections in gynecology were treated with 1.0 to 4.0 g daily of AC-1370, to a total dose of 6 to 52 g, over a period of 3 to 13 days. One of them showed excellent response, 8 showed moderate response, and another showed poor response to the treatment: in other words, a response rate of 90% was achieved. Bacteriologically, pathogens were eradicated from 3 and decreased in 3, and microbial substitution occurred in another patient. No side effects of the drug were observed except for eruption in 1 patient. None of the 10 patients showed any abnormalities in laboratory findings. From the present fundamental and clinical studies of AC-1370, we have drawn the conclusion that the drug is one of extremely useful antibiotics in the treatment of infections in obstetrics and gynecology.     

A fundamental study on T-1982 (cefbuperazone) in the field of obstetrics a gynecology

T-1982 (cefbuperazone) concentrations in antecubital venous blood and pelvic dead space exudate were examined in 4 patients who had received radical hysterectomy due to uterocervical cancer. Data analysis for the transfer of T-1982 into pelvic dead space exudate was performed with the stimulation curves prepared from pharmacokinetic parameters by the three-compartment model. When T-1982 was given at a dose of 1 g, the peak level in the venous blood was 83.7 micrograms/ml at 1 hour after the start of administration. With regards to T-1982 concentration in pelvic dead space exudate, the peak level of 19.3 micrograms/ml was observed at 2.24 hours after the start of administration and relatively high concentration of about 6.1 micrograms/ml was observed even at 8 hours after the start of administration. From the above results, it is concluded that T-1982 is a useful drug for the treatment of infections in the field of obstetrics and gynecology.     

Experience with imipenem/cilastatin sodium in the field of obstetrics and gynecology

Fundamental and clinical studies on a new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), were carried out in the field of obstetrics and gynecology. The following results were obtained. The concentration of MK-0787 in uterine tissue was 3.5 approximately 8.2 micrograms/g at about 30 minutes after an administration of 0.5 g/0.5 g of MK-0787/MK-0791 by a 30-minute intravenous drip infusion. The concentration decreased to less than 0.5 microgram/g by approximately 3 hours. The level of MK-0787 in the pelvic dead space exudate reached a peak of 24.0 +/- 4.4 micrograms/ml at 1 hour after an administration of MK-0787/MK-0791 0.5 g/0.5 g and was higher than the plasma level at 1 hour. The level in the pelvic dead space exudate was 2.0 +/- 0.8 microgram/ml at about 6 hours. The MK-0787/MK-0791 was administered to 4 patients with gynecologic infections (2 patients with pelvic peritonitis, 1 patient with salpingitis, 1 patient with a vulvar abscess). The clinical efficacy was good in all 4 patients. Neither adverse effects nor abnormal laboratory findings were observed. It appears that MK-0787/MK-0791 is a safe and useful antibiotic for the treatment of obstetrical and gynecological infections.     

Pharmacokinetics and clinical studies on cefpimizole in the field of obstetrics and gynecology

Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good. The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0 micrograms/ml. High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4 approximately 39.0 micrograms/g after an intravenous drip infusion. The changing patterns of the tissue concentrations were similar to those in the serum. The penetration of AC-1370 into intrapelvic dead space exudate was good. The level reached a peak of 35 micrograms/ml at 2 approximately 4 hours after an intravenous drip infusion with 1 g and 3.7 micrograms/ml after 12 hours. AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1 approximately 2 g twice a day. Few side effects were observed.     

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.     

Clinical trial and basic study on the tissue transfer of cefminox

Cefminox (CMNX, MT-141) was studied both fundamentally and clinically with following results: In the treatment of 3 cases of Bartholin's abscess, 2 cases of pyometra, and 1 case each of bartholinitis, inflammation of the pelvic dead space, retroperitoneal abscess and pelvic peritonitis, CMNX was administered at a dosage of 1 g. The global clinical results were rated as good in 9 cases. From these findings it is considered that CMNX is promising as an antibiotic with extremely high efficacy for infections of the field of obstetrics and gynecology. Furthermore, since in none of our cases side effects or laboratory abnormalities were observed, CMNX is considered to be a drug with high efficacy and safety. In 5 cases received 1 g of CMNX intravenously, concentrations of the drug in the serum and tissues of internal genital organs were determined. CMNX was maintained at concentrations higher than 20 micrograms/ml for the serum and 10 micrograms/g for each tissue studied. In the pelvic dead space exudate 10 to 20 micrograms/ml of the drug was still detected even at 8 hours after the administration. These results obtained by our fundamental study support the efficacy of CMNX demonstrated in the clinical part of our study.     

Fundamental and clinical studies on aztreonam

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic, was studied on the transfer into intrapelvic tissues and on the clinical efficacy in the treatment of 19 cases of obstetrical and gynecological infections. The AZT levels were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer. The simulation curves for AZT were well performed after the decision of the pharmacokinetic parameters using the two-compartment model. Following 1-hour intravenous drip infusion of 1 g of AZT, the peak concentration of AZT in cubital venous blood was estimated 73.3 micrograms/ml at the end of infusion. The peak concentration of AZT in the pelvic dead exudate was estimated 18.6 micrograms/ml at 2.31 hours after infusion. Following intravenous 1-hour drip infusion of 1 g, the transferred level of AZT into uterine tissues was maintained at the effective concentration which means the excess level of the MIC against clinical isolates often observed in the field of obstetrics and gynecology. AZT was administered 2-4 g/day in 2 times a day by intravenous drip infusion for 60-90 minutes. The subjects were 19 patients with the following infections; pyometra (1), puerperal intrauterine infection (4), postoperative parametritis (4), pelvioperitonitis (2), purulent lymphocyst (1), acute salpingoophoritis (1), vaginal stump abscess (1), Douglas abscess (2), pelvioperitonitis + pyosalpinx (2), vulval abscess (1). Clinical efficacy was; excellent in 2 cases, good in 11 cases and poor in 6 cases. No notable side effect or abnormal laboratory finding was noted.