[in Japanese]

View full abstract

Concentrations of cefpiramide (CPM) in human lung tissues were determined after 1 g intravenous bolus injection in 6 patients with lung tumors and pyothorax. Concentrations of the CPM in blood and lung tissues were determined and analyzed pharmacokinetically.
Levels of CPM in the lung tissues reached 38.4 μg/g at 2 hours and declined to 27.7 μg/g in 6 hours. Levels of CPM in the lung tissues were higher than 50% of those in the serum between 100 minutes and 360 minutes after the administration of CPM.

View full abstract

Clinical studies were conducted on BRL 28500 (a formulation containing 15 parts ticarcillin plus 1 part clavulanic acid). BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i. d., generally for 10 days by drip infusion to patients with pelvioperitonitis or DOUGLAS' abscess.
The results obtained were summarized as follows.
1. Clinical efficacy was evaluated in 18 patients (pelvioperitonitis 14, DOUGLAS' abscess 4), but 8 patients out of a total of 26 patients were excluded.
2. In the evaluation of clinical improvement by doctors in charge, clinical improvement rates were 44.4% on day 3, 88.2% on day 5.
3. On the basis of committee judgement, the clinical efficacy rate was 100%.
4. The bacteriological eradication rate of causative organisms was 100% in 11 patients (15 strains). Five strains out of a total of 15 strains produced β-lactamase.
5. As a side effect, nausea was observed in 1 case. In laboratory examination, liver function abnormalities were observed in 1 case.
6. Regarding usefulness as judged by doctors in charge, the satisfactory rate was 83.3%.
From the above results, it has been concluded that BRL 28500 is very useful in the treatment of pelvioperitonitis and DOUGLAS' abscess.

View full abstract

The in vitro activity of cefpirome (HR 810), a new cephalosporin antibiotic having a 2, 3-cyclopentenopyridine group in the 3-position side chain, was compared with in vitro activities of 5 other cephalosporins. HR 810 showed a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria when tested using 71 standard strains and 876 clinical isolates. HR 810 inhibited 70% of the clinically isolated Staphyloco ccus aureus and Staphylococcus epidermidis strains when used at 0.59-0.84 μg/ml, 2-to 25-fold lower than values of reference antibiotics, and the compound was also highly effective against Enterococcus faecalis which is relatively resistant to most of the existing cephem antibiotics. The activity of HR 810 against Enterobacteriaceae members (11 species), based on its minimal inhibitory concentrations inhibiting 90% of bacterial growth (MIC₉₀s), was the highest among the cephalosporins used. Especially against Enterobacter species andCitrobacter freundii, the MIC₉₀s of the compound were 4-to 64-fold lower than the values of the other antibiotics. Against Pseudomonas aeruginosa, HR 810 was as active as cefoperazone, an antipseudomonal agent. The minimal bactericidal concentrations (MBCs) of HR 810 were equal to or only 2-fold greater than the MICs for most of 12 standard strains tested. The compound markedly decreased viable bacterial counts at its MICs, thus showing strong bactericidal activities. The in vitro activity of HR 810 was not affected by pH or human serum content of agar media, but the activity against Gram-negative bacteria was lowered as the inoculum size increased.

View full abstract

Sixty-six patients with tonsillitis or pharyngolaryngitis received oral norfloxacin (NFLX) 200 mg b.i.d. or 300 mg b.i.d. for not less than 3 days in general at School of Medicine, Yokohama City University, and 6 related hospitals.
The results are summarized as follows:
1. Ten patients were excluded from the study because 4 patients did not present at the follow-up visits, 4 patients did not follow the protocol and 2 patients had unclear infections. Thus, 56 patients were evaluated.
2. The fifty-six evaluable patients were classified as follows: Twenty patients were with tonsillitis and 36 were with pharyngolaryngitis. Thirty-eight patients were treated with 200 mg b.i.d. while 18 patients received 300 mg b.i.d. Thirty-two patients were male and 24 patients were female. Three patients were inpatients and 53 patients were outpatients. Most of patients were light or moderate cases, and the 26 patients had mild underlying disorders.
3. Clinical improvements were observed in 11 of 15 patients (73.3%) with tonsillitis and 25 of 30 patients (83.3%) with pharyngolaryngitis (80.0% overall) within 7 days administration.
4. Clinical improvements were observed in 15 of all 20 patients (75.0%) with tonsillitis and 30 of all 36 patients (83.3%) with pharyngolaryngitis (80.4% overall).
5. Bacteriologically, “eradication”, “decrease” and “replacement” were observed in 6, 2 and 1 patients, respectively.
6. As for adverse effects, nausea and headache were observed in 1 patient and abnormal changes in laboratory findings were noted in 1 patient (slight elevations of GOT and GPT).
7. Oral NFLX 200 mg b.i.d. or 300 mg b.i.d. was as almost equally effective as 200 mg t.i.d. in tonsillitis or pharyngolaryngitis. Thus NFLX 200 mg b.i.d. or 300 mg b.i.d. appears to give sufficient clinical efficiency.
8. When antibacterial activity and serum half-life of NFLX are considered, twice daily administration was confirmed to be sufficiently effective in the clinical application.

View full abstract

Clinical studies of cefuzonam (CZON, L-105) were performed in patients of obstetrics and gynecology, and the results obtained are summarized below.
1. CZON was intravenously administered at a daily dose of 1 g to 11 cases including 3cases with intrauterine infection (pyometra), 2 cases of intrapelvic infection (1 case of pelvic dead space infection and 1 case of pelvic peritonitis), 1 case of adnexitis, and others (2 cases of vaginal cuff infection, and 1 case each of vaginal abscess, BALTHOLIN'S abscess, and vulvar abscess).
Clinical efficacy was excellent in 1 case and good in 10 cases.
2. CZON showed a good antibacterial effect in single and mixed infections.
3. Neither side effects nor abnormal values in clinical laboratory findings attributable to the drug were observed.

View full abstract

Cefuzonam (CZON, L-105), a new semisynthetic cephem antibiotic, was studied in the field of obstetrics and gynecology, pharmacokinetically and clinically. Following is a summary of the results.
1. Concentrations of CZON in serum and genital organs following intravenous drip infusion of 1 g of the drug over 60 minutes were measured. Samples were taken during 40 to 190 minutes after the end of the infusion. Ratios of concentrations of the drug transferred into genital organs to the concentration in the cubital venous serum were 0.5 to 1.5 in many cases.Levels of the drug in the genital organs examined well exceeded MICs for common causative organisms in obstetric and gynecologic infections.
2. Therapeutic effects of 1 g or 2 g of CZON by drip infusion twice daily were evaluated in 8 patients. Overall clinical efficacy was 62.5% (5/8). No side effects or abnormal laboratory findings due to the drug were noted.
The results suggest that CZON is a useful antibiotic for obstetric and gynecologic infections.

View full abstract

Cefuzonam (CZON), a new cephem antibiotic agent, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results were summarized as follows.
1. The absorption and the tissue penetration of CZON into intrapelvic genital organs were good. The peak serum level in uterine artery after an intravenous drip infusion of 1.0 g was 49.0 μg/ml, and the highest peak level of 23.0 μg/g in tissues was obtained. After drip infusion of 2.0 g, the peak serum level in uterine artery was 137 μg/ml and the highest peak tissue concentration was 54.6 μg/g. Tissue concentrations of the drug changed in a similarpattern to serum levels and a dose-dependent response was recognized.
2. The penetration of CZON into intrapelvic dead space exudate was good. The level reached a peak of 8.17 μg/ml 4 hours after and intravenous drip infusion of 1.0 g and diminished slowly.
3. The clinical efficacy of CZON at a daily dose of 2 g was evaluated in 21 cases of obstetrics and gynecologic infections. The efficacy rate was 85.7% (18/21 cases). Bacteriologically, the eradication rate obtained was 93.3%. No side effects or abnormal laboratory values were observed.

View full abstract

Cefuzonam (CZON, L-105) was studied clinically in the field of obstetrics and gynecology, and the results obtained are summarized below:
1. The concentration of the drug in blood decreased rapidly after drip infusion was completed, and the concentration diminished after 1 hour to one tenth of the level detected at 5-9 minutes, and to an almost undetectable level after 3 hours. The rapid decrease of blood concentrations appears to indicate that the excretion of CZON was much faster than other antibiotics.No conclusive data were obtained on changes of concentrations with time in tissues due to the small number of cases analyzed and scattering of the data obtained.
2. The concentration in the pelvic dead space exudate reached a peak of 18.5 μg/ml at 30 minutes after the end of infusion and decreased to 0.092 μg/ml after 10 hours.
3. CZON was administered to 5 cases of obstetric and gynecological infections. The efficacy was good in 4 cases and poor in 1 case. No side effects or laboratory test abnormalities were observed.

View full abstract

Seventeen patients with gynecological infections (5 cases each of BARTHOLIN'S abscess and adnexitis, 4 cases of endometritis and 1 case each of bartholinitis, pyosalpinx and vulvar abscess) were treated with cefuzonam (CZON, L-105) administered by intravenous drip infusion, 1-2 g twice daily, for 4 to 12 days (6 g to 23 g in total).
The clinical effectiveness reached 94.1%, including 1 excellent case, 15 cases good, and a poor case. Bacteria were detected in 9 cases, and with CZON treatment, bacterial eradications were obtained in 6 case, but, in 3 cases, bacterial replacements were observed.
No abnormal laboratory findings were noted.
From the above results, CZON seemed to be a highly effective and useful agent for gynecological infections.

View full abstract

To evaluate the usefulness and the safety of cefuzonam (CZON, L-105) against obstetric and gynecological infections, we conducted clinical trials and obtained the results summarized as follows.
1. Thirteen patients with obstetric and gynecological infections (intrauterine infection 2 cases, adnexitis 7, 1 case each of abscess of adnexa uteri, abscess of the vaginal wall, pyelonephritis, and mammitis) were treated with CZON. The CZON was administered by intravenous injection or intravenous drip infusion, 1 g twice daily for 4 to 7 days (8 g to 14 g in total).The clinical effect was good in 12 and poor in 1.
2. Four cases, on which other antimicrobial agents were ineffective, responded well to CZON.
3. The CZON displayed excellent effects on anaerobic bacteria (Peptostreptococcus anaerobius, Bacteroides fragilis) and Gram negative rods (Escherichia coli, Klebsiella pneumoniae).
4. No side effects or laboratory abnormalities were observed.
5. From the above results, CZON appeared to be an effective and useful drug for obstetric and gynecological infections.

View full abstract

The distribution of cefuzonam (CZON, L-105) into the uterus and uterine adnexa was investigated and the usefulness and the safety of CZON in obstetric and gynecological infections were studied. The results are summarized as follows:
1. Following one shot intravenous injection of CZON 1 g, a good distribution of the drug into tissues of uterus and uterine adnexa was observed, with C_max values of 15.7-33.9 μg/g, T_maxof 7.3-34.0 minutes and AUC values of 18.7-35.3 μg·hr/g.
2. In all of the 30 cases of obstetric and gynecological infections treated, CZON was evaluated effective.
3. Bacteriologically, 93.9% of total bacteria that had been isolated were eliminated by the administration of the drug.
4. Against all the strains of bacteria isolated before the treatment and replaced bacteria, MIC₅₀, MIC₈₀ and MIC₉₀ of CZON were 0.20 μg/ml, 12.5 μg/ml and 25 μg/ml, respectively, showing low values.
5. Subjective and objective findings and clinical laboratory test values during and after the trial showed no side effects associated with CZON.

View full abstract

To study the transfer of cefuzonam (CZON, L-105) into female genital organs, concentrations of the compound in pelvic dead space exudate were measured in cases of radical hysterectomy due to cervical cancer and analyzed by the two-compartment model.
When CZON 1 g was drip-infused intravenously, the concentration in the cubital vein blood was 46.95 μg/ml at 1 hour after the start of infusion. Concentrations in the pelvic dead space exudate reached the peak of 11.29 μg/ml at 2.44 hours after the start, were higher than 4 μg/ml after 8 hours and were higher than 1.7 μg/ml after 12 hours.
The area under the concentration-time curve in the pelvic dead space exudate was 77.85 μg·hr/ml. From these results CZON was considered to be effective when administered at 1 g against infections of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Haemophilus influenzae, but increased dose levels seemed necessary against infections of Staphylococcus epidermidis and Bacteroides fragilis.
In 3 cases of obstetric and gynecological infections the efficacy of CZON was good in 2 cases and unknown in the other case.

View full abstract

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 μg/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.

View full abstract

In gynecological infections, especially intrapelvic infections, it is sometimes difficult to identify causal microorganisms. In those cases, it becomes a hard task to select most effective antibiotics, hence the use of wide-spectrum antibiotics becomes necessary.
We recently had opportunities to clinically use cefuzonam (CZON, L-105) which has a wide range of spectrum against various bacteria including Staphylococcus aureus, Escherichia coli, Grampositive and Gram-negative anaerobes, etc. The following is a summary of the clinical results:
1. In 7 cases of gynecological infections CZON was evaluated “excellent” in 1 case and “good” in 6 cases, thus the efficacy rate was 100%.
2. Against intrauterine infection caused by S. aureus, “excellent” effect was observed.
3. No sign of side effects was noted in any of the cases.
4. In 1 case, slight elevations of S-GOT and S-GPT were recorded but the elevations were transient.

View full abstract

Concentrations of cefuzonam (CZON) in peripheral venous serum, uterine arterial serum and intrapelvic female organs of 29 women undergone simple total hysterectomy were determined by bioassay, using the cylinder-plate diffusion method.
With an intravenous injection of CZON 1 g, the concentration at time 0 (C, O) of peripheral venous serum and uterine arterial serum were 148.1 μg/ml and 155.4 μg/ml, respectively.
Biological half-lives (T 1/2) of CZON were 1.07 hours in peripheral venous serum and 1.02 hours in uterine arterial serum. Concentrations in peripheral arterial serum were higher than 1.0 μg/ml at 4 hours after injection and remained at higher levels than minimal inhibitory concentrations necessary for most Escherichia coli strain for at least 4 hours.
Concentrations of CZON in female organs were kept as high as peripheral venous serum, and ratios of CZON concentrations in uterine tube and endometrium to that in peripheral venous serum were 0.74±0.34 and 0.44±0.25, respectively.
Since CZON is characterized by potent antibacterial activity and broad spectrum, it should be effective for infectious diseases of the female uro-genital tract.

View full abstract