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

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied both fundamentally and clinically with following results. In 33 cases undergone total hysterectomy and adnexectomy, 1 g of CMNX was administered intravenously by the drip infusion route over 1 hour and changes in drug concentration in the venous blood and uterine arterial blood as well as in various uterine tissues including endometrium, myometrium, cervix uteri, portio vaginalis, oviduct and ovary were studied. In addition, in 3 cases also received 1 g of CMNX over 1 hour by the drip infusion route, changes in the concentration of CMNX in the pelvic dead space exudate were investigated. In each tissue studied, the drug concentration higher than 40 micrograms/g was attained at 20 minutes after completion of drip infusion, showing good transfer of CMNX. In the pelvic dead space exudate, the peak concentration of 24.7 micrograms/ml appeared at 4 hours after completion of drip infusion and at 12 hours still a concentration of 4.5 micrograms/ml was maintained. In the treatment of 15 cases of obstetrical and gynecological infections, CMNX was used. In all of the cases treated, clinical results better than good were obtained, with excellent results in 2 cases and good results in 13 cases. In none of the cases side effects or laboratory abnormalities were observed. From these results CMNX is considered to be a useful drug for the treatment of various infections in the field of obstetrics and gynecology.     

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

Fundamental and clinical studies on cefminox (CMNX, MT-141), a new cephamycin antibiotic, were performed and the following results were obtained. Concentration of CMNX was examined in serum, internal genital organs and retroperitoneal fluid after a single intravenous administration of 1.0 g dose. The venous serum level of CMNX was 62.8 +/- 7.02 microgram/ml (Mean +/- S.D.) at 30 minutes after the administration. The sufficient transfer of CMNX to internal genital organs and retroperitoneal fluid was demonstrated. In clinical trial, CMNX was given to 10 cases with obstetrical and gynecological infections. The efficacy was evaluated as excellent in 1 case, good in 8 cases and poor in 1 case. No side effects were observed in any of the cases treated with CMNX.     

Clinical studies on cefminox in the field of obstetrics and gynecology

Clinical and laboratory studies on cefminox (CMNX, MT-141), a new injectable cephamycin antibiotic, were made in the field of obstetrics and gynecology, and following results were obtained. In the clinical trial, 12 cases were treated with CMNX given by intravenous drip infusion. The results were excellent in 2 cases, good in 8 cases and poor in 2 cases. The effectiveness rate was 83.3%. No side effect was recognized. No significant changes of laboratory findings were noticed.     

Basic and clinical studies on cefminox in obstetrics and gynecology

Fundamental and clinical studies on cefminox (CMNX, MT-141), a new cephamycin antibiotic, were carried out and the results were as follows. After the intravenous one shot administration of 1 g CMNX to 17 cases, serum concentrations, tissue concentrations in pelvic organs and protein binding capacities in serum were measured. Blood concentrations ranged between 100-200 micrograms/immediately after the injection and declined gradually. Half-life (T1/2) was 75 minutes. Tissue concentrations were 30-70 micrograms/g (tissue weight) 10 minutes after injection and declined. Half-life was 90 minutes. The average serum protein binding rate was 66.3 +/- 8.4%. Correlation between tissue concentration (Y) and free serum concentration (X) was expressed as Y = 0.42 + 7.14X. Correlation coefficient (r) was 0.80 (r = 0.80). Correlation coefficient in serum concentrations between HPLC and bioassay was 0.83 and that in free concentration was 0.97. In clinical studies, CMNX was administered to 19 cases of obstetric and gynecological infections. The patients were constituted of 3 with puerperal endometritis, 3 with pyometra, 3 with pelvic peritonitis, 3 with parametritis, 3 with adnexitis, 2 with BARTHOLIN's abscess and 1 with retroperitoneal abscess and vulva abscess. Overall clinical efficacy was 89.5% (17/19). Bacteriologically 26 strains were isolated, 6 strains of E. coli, 4 strains of B. fragilis, 2 strains of P. anaerobius and P. asaccharolyticus and each one of E. faecalis, S. epidermidis, N. gonorrhoeae, S. marcescens, P. maltophilia, A. calcoaceticus, K. pneumoniae, P. mirabilis, H. influenzae, S. intermedius, E. lentum and F. varium. Twenty of these 24 strains were eliminated after the administration, K. pneumoniae was decreased, E. faecalis, S. marcescens and P. maltophilia remained unaffected. No side effects were observed but 1 case showed mild elevation of transaminases which normalized 1 week after CMNX was stopped.     

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.     

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.     

Basic study on cefminox in the field of obstetrics and gynecology

In patients with carcinoma of the uterine cervix, cefminox (CMNX, MT-141) was given intravenously after panhysterectomy and the pelvic dead space exudate and serum levels of the drug were determined at various periods. The pelvic dead space exudate level reached its peak of 67.21 +/- 39.81 micrograms/ml at 2 hours, which decreased gradually to 26.04 +/- 6.66 micrograms/ml at 6 hours. In the serum, the drug level attained the peak of 152.98 +/- 85.37 of 7.26 +/- 1.66 micrograms/ml was still detected. The pelvic dead space exudate level was much higher than its MIC or 3h-MBC at all periods studied. From these results it was considered that CMNX achieves levels high enough to be expected of clinical efficacy in the pelvic dead space exudate and serum.     

Results of the clinical use of cefminox in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141) was used in the treatment of obstetrical and gynecological infections with following results. In the treatment of a total of 8 cases including 4 cases of intrauterine infections, 2 cases of pyosalpinx and 2 cases of pelvioperitonitis, clinical results obtained were rated as excellent in 4 cases (50%) and good in 2 cases (25%). When good and excellent results were combined as representing effectiveness, the effective rate was 75% (6/8 cases). The 2 cases, which gave poor results, were under treatment for ovarian carcinoma. CMNX was found effective for intrauterine infections (postpartal) and pyosalpinx, especially those caused by E. coli. None of the cases experienced side effects.     

Bacteriological study of cefminox in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141), a new cephem antibiotic, was determined of its antibacterial activity against 304 clinical isolates with following results. CMNX was inferior to CEZ or CMZ in the activity against 78 isolates of Staphylococcus sp., but it was superior to these antibiotics in the activity against 104 isolates of E. coli. Against 53 isolates of Bacteroides sp., CMNX showed higher activity than CEZ or CMZ. In the activity against 69 isolates of Peptococcus sp. and Peptostreptococcus sp., CMNX was almost equal to CEZ.     

Use of cefminox in infections in the field of obstetrics and gynecology

A total of 15 cases of obstetrical and gynecological infections was treated with cefminox (CMNX, MT-141), a new cephamycin antibiotic, with following results. The subjects consisted of 3 cases of salpingitis, 2 cases of parametritis, 5 cases of endometritis, and 1 case each of puerperal fever, inflammation of the pelvic dead space, Bartholin's pyocele, vulvar abscess and suppurative mastitis. In 2 cases of endometritis, pelveoperitonitis and adnexitis were complicated, respectively. As a rule, CMNX was administered intravenously at a dosage of 1 g each twice a day by drip infusion route. The clinical results were rated as excellent in 8 cases, good in 6 cases and poor in 1 case, with an efficacy rate of 93.3%. No subjective or objective side effects were seen nor any abnormal laboratory test results were found.     

Transfer of cefminox to tissues in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141), a new cephamycin, was studied of its transfer into the serum and tissues with following results: After an intravenous injection of 1 g of CMNX, the serum concentration of the drug achieved in the uterine artery was almost equal to that in the elbow vein, showing good transfer of the drug. After an intravenous injection of 1 g of CMNX, favorable results were also obtained for concentrations achieved in all of the adnexal and uterine tissues studied. From the results obtained, it is expected that CMNX is highly effective in particular for infections caused by E. coli, Klebsiella sp. and B. fragilis.     

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 studies on ceftriaxone in the field of obstetrics and gynecology

Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904) were performed in the field of obstetrics and gynecology and the following results were obtained. The serum concentration was maintained at a high level to remain 22 micrograms/ml about 24 hours after intravenous injection with 1 g CTRX. The level in each tissue except myometrium reached a peak of 50 micrograms/g or higher at 54 minutes after intravenous injection with 1 g CTRX. The peak level in the dead space exudate, obtained 4 to 6 hours after intravenous injection was 77 micrograms/ml with 1 g, and 125 micrograms/ml and 115 micrograms/ml with 2 g. The clinical efficacy was observed in all the cases (excellent in 1 and good in 3) consisting of 1 with Bartholin's abscess, 2 with adnexitis and 1 with pelvioperitonitis. Neither adverse reaction nor posttreatment laboratory test abnormality was observed in any case.     

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

Cefpiramide (SM-1652, CPM), a new cephem antibiotic was studied for the transfer into intrapelvic tissues and clinical efficacy in the field of obstetrics and gynecology. The results were obtained as follows. Clinical results of 17 patients with obstetrical and gynecological infection were excellent in 10 cases, good in 6, and poor in 1 with the efficacy rate of 94.1%. Following a single intravenous 30 minutes-drip infusion of 1 g dose of CPM, the peak of serum level and intrapelvic tissues were obtained at 30-60 minutes after completion of the administration. No adverse reaction or abnormal laboratory findings were observed.     

Pharmacokinetic and clinical studies on latamoxef in the field of obstetrics and gynecology

Latamoxef (LMOX) 1 g was administered twice daily for 5 days to patients undergoing operation for myoma uteri and the time course of tissue concentrations of the drug and the prophylactic effect of the treatment on postoperative infection were studied. 1. Area under concentration-time curve (AUC) of LMOX was the highest in the perimetrium (45.3%), followed by the cervix uteri (39.2%), endometrium (35.9%), oviduct (35.1%), myometrium (29.5%), and ovary (24.4%). 2. Cmax was the highest in oviduct (46.9 micrograms/g), followed by Cmax's in perimetrium (44.2 micrograms/g), cervix uteri (35.8 micrograms/g), myometrium (26.9 micrograms/g), endometrium (25.6 micrograms/g), and ovary (24.3 micrograms/g). 3. Serum half-lives were T1/2(alpha) = 0.27 hour and T1/2(beta) = 1.81 hours. 4. Prophylactic efficacy against postoperative infections was 94.3%, and febrile morbidity was 5.7%. The preoperative and postoperative laboratory tests did not show appreciable changes, no adverse reaction was observed. In the present study, LMOX showed good transfer into gynecological tissues, suggesting its very high usefulness in the treatment of infection and in the postoperative management.     

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

Ceftazidime (CAZ), a new cephalosporin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CAZ into intrapelvic genital organs were good after a single drip infusion of 1.0 g for 30--60 minutes. The maximum level of 76.4 micrograms/ml was obtained in uterine artery serum at 8 minutes after administration. The high concentrations were also obtained in genital tissues; the maximum concentrations ranged from 46.8--62.1 micrograms/g at 20 minutes after administration and the levels were as high as 2.1--7.7 micrograms/g at 5 hours and 40 minutes after administration. The concentration curves in tissues were consistent with those of serum levels. The concentrations of CAZ in retroperitoneal dead space exudate were determined after intravenous drip infusion of 1 g. The peak levels ranged from 26 to 32 micrograms/ml after 30 minutes of administration and the level of 8.53 micrograms/ml was sustained even 6 hours later. Good response was obtained in cases of gyneco-obstetric infections such as intrauterine infection, intrapelvic infection and external genital infection with daily dose of 2--4 g. CAZ was effective in 13 out of 14 cases (the efficacy ratio; 92.9%). As to side effects, gastric discomfort and vomiting were observed in 1 case.     

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.     

Pharmacokinetic and clinical studies on cefodizime in the field of obstetrics and gynecology

Pharmacokinetic and clinical studies on cefodizime (THR-221, CDZM) were carried out and the following results were obtained. Concentrations of CDZM in serum and uterine tissues were determined from 38 to 282 minutes after drip infusion of 1 g CDZM. CDZM reached peak level of 25.0 micrograms/g or higher in each tissue during a period of 38 to 83 minutes. Concentrations of CDZM in the dead space exudate after drip infusion of 2 g CDZM were also studied. At 240 minutes after injection, CDZM concentration in exudate reached a peak of 46.88 micrograms/ml. These levels far exceeded MICs of CDZM against major pathogens most often isolated in the field of obstetrics and gynecology. CDZM was administered to 7 patients with their diseases diagnosed as pelvic peritonitis (4 cases) or acute adnexitis (3 cases) at a dose of 2-4 g per day for 6-14. days. Clinical response was good in all cases. Transient elevation of liver function was noticed in 2 cases. No other adverse reactions were noted during the study.     

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

Fundamental and clinical studies on cefuzonam (CZON, L-105), a new oxime type cephalosporin, were performed and the results obtained are summarized below: 1. Concentrations of CZON were determined in serum, internal genital organs and retroperitoneal fluid after a single intravenous administration of 1 g dose. The peripheral serum level of CZON was 74.0 micrograms/ml at 15 minutes after the administration. A sufficient transfer of CZON into internal genital organs and retroperitoneal fluid was demonstrated. 2. In clinical trial, CZON was given to 11 cases with obstetrical and gynecological infections. Efficacies were evaluated as good in 9 cases and poor in 2 cases. No side effects were observed in any of the cases treated with CZON. In laboratory examinations, transient elevation of serum GOT, GPT and alkaline phosphatase was noted in 1 case.     

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.