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.     

Clinical studies on cefpiramide in the field of obstetrics and gynecology

Cefpiramide (CPM) was evaluated for clinical effects in the treatment of obstetrical and gynecological infections. The following results were obtained. CPM was given to 11 cases. Clinical efficacy was good in 8 cases and poor in 3 cases. The poor cases were parametritis and pyometra from those Serratia sp., K. pneumoniae, P. magnus, E. faecalis and B. ovatus were isolated. Other 1 case was external genital abscess with no isolated bacteria. There was a slight transaminase elevation in 1 case but no other appreciable side effects or abnormal laboratory findings were observed.     

Clinical studies of cefpiramide in obstetrics and gynecology

In vivo transfer and therapeutic efficiency of a new cephalosporin derivative, cefpiramide (CPM) have studied in perinatal and gynecologic field. The following results have been obtained. The level of CPM transferred to uterus and adnexa was higher than its MIC against majority of Gram-negative bacilli, such as E. coli. This drug as demonstrated its efficiency, in treating 3 infection cases refractory to cephalothin, ampicillin and cephalexin, out of which 1 had "excellent" and 2 had "good" results. No side effect was evidenced in any of our patients. In conclusion, this drug has satisfactory tissue transfer as well as sufficient safety and excellent efficiency in treatment of perinatal infection cases.     

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 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 studies of ceftazidime in the field of obstetrics and gynecology

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

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 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.     

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.     

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.     

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

Fundamental and clinical studies on cefuzonam (CZON, L-105), a new cephem antibiotic, were carried out. The results obtained are summarized as follows: 1. Upon drip infusion of 1 g CZON, a good transfer of the drug into female genital organ was observed. The transfer of CZON into exudates of the pelvic dead space was also good. 2. Clinical efficacy of CZON was good in 1 case we tested. No side effect was observed.     

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

Fundamental and clinical studies on cefpimizole (AC-1370), a new cephalosporin derivative, in the field of obstetrics and gynecology have been investigated, and the following results were obtained. High concentrations of AC-1370 in internal genital organs were detected after intravenous administration of 1.0 g of AC-1370. In the treatment of 14 cases of infection, the therapeutic effects were excellent or good in 11 cases and overall efficiency rate excluding 1 case with side effects was 84.6% (11/13). No serious side effect was observed except 1 case of nausea and vomiting.     

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 on fosfomycin sodium in the field of obstetrics and gynecology

Fosfomycin sodium (FOM-Na) was studied both fundamentally and clinically in the field of obstetrics and gynecology with following results. It showed good transference into the uterine tissues when given intravenously. The peak concentrations achieved in the uterine tissues following intravenous administration of 2 g of FOM-Na were 26.56 to 53.48 micrograms/g when given as one shot injection and 20.16 to 39.47 micrograms/g as drip infusion. In the serum of vein and uterine artery, peak concentrations of 163.6 to 143.40 micrograms/ml and 120 to 113.12 micrograms/ml were reached following one shot injection and drip infusion, respectively. In general, FOM-Na concentrations in the uterine tissues showed similar changes as those observed for serum concentrations. Clinically, FOM-Na was used in the treatment of 17 cases of obstetrical and gynecological infections at 2 g per dose twice daily as intravenous drip infusions. In all of these cases, good clinical efficacy was obtained. No side effects were observed.     

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.     

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

Fundamental and clinical studies on sulbactam/cefoperazone (SBT/CPZ), a combination drug of sulbactam and cefoperazone, were carried out in the field of obstetrics and gynecology. The following results were obtained: Transfer into female genital organ tissues Following 1 hour intravenous drip infusion of SBT/CPZ, favourable transfers of both of SBT and CPZ to female genital organ tissues and pelvic dead space exudate were observed. Clinical evaluation A total of 12 cases comprising 6 with intrauterine infection, 1 with pyometra, 1 with abscess of portio vaginalis, 2 with parametritis, 1 with pelvioperitonitis and 1 with purulent lymphocyst was treated with SBT/CPZ. Clinical efficacy was excellent in 6 cases, good in 5 cases and poor in 1 case, with overall efficacy rate of 92%. The bacteriological efficacy was judged as eradicated in 3, and as decreased in 2 out of 5 evaluable cases. In all of the 5 cases, isolated organisms were beta-lactamase producing organisms. No notable side effects or abnormal laboratory findings were observed except 1 case with elevations of GOT and GPT.     

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.