Clinical studies on cefoperazone in otorhinolaryngological field (author's transl)

Cefoperazone (CPZ) was administered to 23 patients of various infections in otorhinolaryngological field. These 23 cases included acute suppurative otitis media (11), acute exacerbation of chronic suppurative otitis media (11) and perichondritis of the auricle (1). Clinical response obtained in these cases was excellent in 11 cases (47.8%), good in 7 cases (30.4%), fair in 5 cases (21.7%) and none of poor case. The efficacy rate was 78.3%. Five cases of chronic suppurative otitis media and perichondritis of the auricle infected by Pseudomonas were over good effective in 4 cases. No side effect was observed in these 23 cases.     

Clinical studies on cefoperazone in the pediatric field (author's transl)

Cefoperazone (CPZ) at dose levels of 80 approximately 100 mg/kg/day, divided 3 approximately 4 times, was drip-infused or intravenously injected for a period of 2 approximately 6 days to 10 patients. All 10 cases, 4 cases of bronchopneumonia from which H. influenzae was detected (Group A S. pyogenes and S. pneumoniae were also detected in each 1 case). 2 cases of coli urinary tract infection, 1 case of acute colitis from which pathogenic E. coli was detected, 1 case of E. coli carrier, 1 case of acute bronchitis (bacteria were not detected), and 1 case of urinary tract infection (bacteria were not detected) showed rapid improvement of clinical symptoms with rapid eradication of the pathogenic bacteria. In one case of urinary tract infection where S. epidermidis and S. faecalis were simultaneously detected, S. epidermidis was removed but S. faecalis was merely decreased. The effective antibacterial concentration after intravenous injection of CPZ in the feces was determined and found to be present in sufficient concentrations to prevent colon infection. No particular side effects were observed during CPZ therapy.     

In vitro studies on antacids/Third communication (author's transl)

With an automated method, four antacid gel formulations were tested for antacid in vitro activity. In addition, some elements involved in the buffer effect were assayed in the solution parallel to the in vitro test. Of the four formulations, one showed only insufficient buffer effect. Compared with the common proton/metal ion exchange of antacid buffering, experimental data of another formulation suggest a partially different proton binding mechanism.     

Laboratory and clinical studies on cefoperazone in pediatrics treatment (author's transl)

Laboratory and clinical studies of cefoperazone (CPZ), a new semisynthetic cephalosporin, were investigated and following results were obtained. (1) Blood level: CPZ was given intravenous dose of 25 mg/kg and 50 mg/kg to each 3 children. In the former, the blood level of 15 minutes after injection was 194.2 mcg/ml on average and the half life was 106.2 minutes. In the latter, the blood level was 320.0 mcg/ml on average and half life was 102.2 minutes. (2) Urinary concentration: In the cases of the dose of 25 mg/kg, 35.9% of CPZ was recovered on average from the urine within 6 hours after injection, and the urinary concentration reached to 2,148.6 mcg/ml (0 approximately 2 hours). And in the cases of the dose of 50 mcg/kg, the recovery rate in urine was 43.6%, and the urinary concentration was 3,008.3 mcg/ml. (3) Cerebrospinal fluid level: CSF level was determined in a patient with bacterial meningitis by S. pneumoniae. Ninety mg/kg of CPZ were given intravenous injection. After 60 minutes CSF level was 3.35 mcg/ml, and after 80 minutes the blood level was 192.0 mcg/ml. (4) Bacteriological evaluation: Against 164 strains isolated clinical specimens, the bacteriological evaluation on CPZ was performed in comparison with cefotaxime (CTX), cefazolin (CEZ) and piperacillin (PIPC) by inoculum size of 10(8) cells/ml. CPZ showed antibacterial activity against Gram-negative bacteria almost similar to CTX and PIPC. (5) Clinical results: CPZ was given 48.3 approximately 360 mg/kg/day (average 146.1 mg/kg/day) by intravenous route to 46 patients with various infection. The overall efficacy rate was 80.4%. The rate of bacteriological effectiveness was 78.9% in 19 cases. (6) Side effects: As side effects, diarrhea, fever, rash, urticaria, leukopenia, eosinophilia, elevation of GOT, GPT, and LDH were observed, but not seriously.     

Clinical studies on cefoperazone in gynecological and obstetrical field (author's transl)

Fourteen patients suffering from female genital organ infections including mastitis and urinary tract infections were treated with cefoperazone (CPZ). CPZ was administered intravenously or by drip infusion at a dose of 2.0-4.0 g/day for 3-7 days. Clinical results obtained were as follows: Of 8 patients with genital organ infections, excellent responses were seen in 2 patients, good responses in 5 patients. Of 3 patients with mastitis, good responses were seen in all the patients. Of 3 patients with pyelonephritis, excellent and good responses were seen in all the patients. No adverse effects and abnormal laboratory findings were observed. From the above results, we concluded that CPZ was an effective and safe antibiotic against infections in the field of obstetrics and gynecology.     

Laboratory and clinical studies of cefoperazone in children (author's transl)

Experimental and clinical studies on cefoperazone (CPZ), a new synthetic cephalosporin, were performed in the field of pediatrics. 1) The MICs of CPZ against 26 strains of S. aureus, 21 strains of E. coli, 20 strains of K. pneumoniae and 15 strains of H. influenzae which were clinically isolated were estimated and compared with those of CEZ and ABPC. Some strains were found to be high in the MIC of CPZ against S. aureus, E. coli and K. pneumoniae by original inoculation but 88% of S. aureus, 95% of E. coli, 95% of K. pneumoniae and 100% of H. influenzae were under 6.25 mcg/ml by 100 times dilution inoculation. The MIC of CPZ against S. aureus was inferior to CEZ and superior to ABPC, and that against E. coli, K. pneumoniae and H. influenzae was superior to CEZ and ABPC. 2) The serum concentration, urinary concentration and recovery rate from urine were measured in two healthy infants and one infant in the stage of convalescence from cholangiohepatitis after a single intravenous administration of 25 mg/kg of CPZ. The mean serum concentration in the two healthy infants was 88.0 mcg/ml at 30 minutes, 63.0 at 1 hour, 31.4 at 2 hours, 12.2 at 4 hours and 4.2 at 6 hours; the half-life was 1.29 hours, and the recovery rate from urine was 14.5%. 3) The clinical effect of CPZ was examined in 16 cases of acute lobar pneumonia or acute bronchopneumonia, 1 case of acute bronchitis and 4 cases of acute urinary tract infections. All of the cases responded effectively or markedly effectively. Among the causative bacteria in those cases, 2 strains of S. pneumoniae, 1 strain of S. faecalis, 1 strain of H. influenzae and 2 strains of E. coli and 1 strain of K. pneumoniae disappeared following the administration of CPZ. The bacteriological effect against 1 strain of P. aeruginosa was unknown, but clinical effectiveness was observed in this case. No clinical side effects were observed. Laboratory examination carried out before and after the administration revealed a rise of GOT and eosinophilia in each one case, but in both abnormality returned to normal after termination of therapy.     

Fundamental and clinical studies of cefoperazone in children (author's transl)

As a result of conducting experimental and clinical tests with the newly developed cephalosporin, cefoperazone (CPZ), the following conclusions were obtained: (1) When tested against 10 strains of Staphylococcus aureus and 16 strains of Staphylococcus epidermidis, the antibacterial activity of CPZ was found to be weaker than that of CEZ. Against 5 strains of A-beta-Streptococcus and 4 strains of Streptococcus pneumoniae, both CPZ and CEZ exhibited similar excellent antibacterial activity. CPZ was effective against 18 strains of Escherichia coli though its activity was influenced by the amount of inoculated bacteria present. Against 15 strains of Haemophilus influenzae and 10 strains of Haemophilus parahaemolyticus, CPZ was found to be more effective than CEZ though several high-resistant strains were noted. CPZ also showed more excellent antibacterial activity than CEZ against 4 strains of Haemophilus parainfluenzae, 5 strains of Klebsiella pneumoniae, 8 strains of Salmonella sp., 4 strains of Pseudomonas aeruginosa and 4 strains of Proteus sp. (2) The mean half-life in the blood following intravenous injections of 25 mg/kg and 10 mg/kg of CPZ to three children was 70 minutes. (3) One hour after intravenous injection of 25 mg/kg of CPZ to 3 cases of aseptic meningitis, drug concentration in the cerebrospinal fluid (CSF) was 1.20 mcg/ml, less than 0.39 mcg/ml and 1.55 mcg/ml. In one case, the CSF/serum ratio was 2.7%. (4) The average recovery rate in the urine of children who had received intravenous administrations of 25 mg/kg (3 children) and 10 mg/kg (1 child) was 17.8% between 0 and 6 hours. (5) Eighteen pediatric patients received CPZ in doses ranging from 48 to 170 mg/kg divided three-four times a day. They were RTI in 7, URI in 5, UTI in 5, SSSS in 1 and enteritis in 1 children. The clinical effectiveness of CPZ was judged to be remarkedly effective in 11 children, effective in 5 children and ineffective in 3 children, with an overall effective rate of 84.2%. One patient of tonsillitis combined sinusitis was considered 2 cases. The three cases in which the drug was found to e ineffective were 2 cases of pyothorax and 1 case of sinusitis. (6) Side effects were 1 case of eosinophilia, 2 cases of elevation of GOT and GPT, and 1 case of mild elevation of GOT. All were considered to be minor.     

Muscle irritation study on cefoperazone (author's transl)

Muscular injury caused by cefoperazone (CPZ) was compared with that of cefazolin (CEZ), cephaloridine (CER) or cephalothin (CET) in adult and juvenile male rabbits. These drugs were dissolved by the way of clinical use and were injected singly into the muscular vastus lateralis. Then, the degree of muscular injury at the time of 48 hours and 7 days after the injection was judged from muscle ratio, gross local observation and histological observations. The degree of muscular injury caused by these drugs was compared also with that of saline 075% or 6% acetic acid. The following results were obtained: There was no difference among CPZ, CEZ and CER on the degree of muscular injury and these changes were almost equal to those of 0.75% acetic acid, however severer than that of saline. While, muscular injury caused by CET was severer than that of CPZ, CEZ, CER or 0.75% acetic acid, but milder than 6% acetic acid. The inflammatory reaction against these drugs was almost similar in adult and juvenile rabbits.     

Clinical studies of cefoperazone in the treatment of pyoderma (author's transl)

Cefoperazone (CPZ), a new semisynthetic cephalosporin derivative, was administered in the treatment of pyoderma. The results are shown as follows. CPZ was given to 21 patients with pyoderma. In 21 patients, marked improvement was seen in 7, effectiveness in 10, slight improvement in 1 and ineffective in 3. Total clinical effectiveness rate was 81.0%. No serious side effects were observed.     

Fundamental and clinical studies of cefoperazone in pediatric patients (author's transl)

1. Susceptibility, concentrations in serum and spinal fluid, and clinical effect of cefoperazone (CPZ), a newly developed cephalosporin in Japan, were examined in 28 infants from 2 days to 12 years of ages with various infections. 2. The overall clinical evaluation in 22 cases received CPZ alone was found to be markedly effective in 11 cases and effective in 6 cases; the efficacy rate was as good as 85.0%. 3. The mean half-life following a single intravenous injection of 25 mg/kg to 3 infants was 80.7 minutes. 4. The side effects observed during the therapy were 2 cases of rash and 1 case of vascular pain and these symptoms improved after interruption of therapy. The side effects of CPZ seemed to be not more noticeable than other cephalosporins.     

Laboratory and clinical studies of cefoperazone in pediatric field (author's transl)

The authors have carried out the laboratory and clinical studies of cefoperazone (CPZ). The results were as follows: The sensitivity was estimated by plate dilution method on 26 strains of S. aureus, E. coli and K. pneumoniae, 25 strains of P. aeruginosa, 14 strains of Salmonella sp. and 9 strains of GM resistant P. aeruginosa isolated from patients. The distribution of sensitivity of S. aureus was 1.56 approximately 25 mcg/ml and the peak of distribution was 3.13 mcg/ml. The growth of 96.2% of E. coli was inhibited at concentration of less than 12.5 mcg/ml. The growth of 50.0% of K. pneumoniae was inhibited at concentration of less than 6.25 mcg/ml. The peak of distribution of P. aeruginosa was 12.5 approximately 25 mcg/ml (GM sensitive) and 12.5 mcg/ml (GM resistant). CPZ was given by drip infusion for 30 minutes at a single dose of 25 mg/kg to 2 children, and by drip infusion for 60 minutes at a single dose of 46.9 mg/kg to a child. The serum mean level of CPZ was 127.5 +/- 8.5 mcg/ml at 30 minutes, 30.5 +/- 7.5 mcg/ml at 1 hour, 23.5 +/- 3.5 mcg/ml at 2 hours, 10.5 +/- 1.5 mcg/ml at 4 hours and 6.8 +/- 2.4 mcg/ml at 6 hours after administration at a single dose of 25 mg/kg, respectively. The serum level was 102.0 mcg/ml at 1 hour, 32 mcg/ml at 2 hours, 14.5 mcg/ml at 5 hours and 12.5 mcg/ml at 7 hours after administration at a single dose of 46.9 mg/kg. Half-life time was 92 minutes. The mean urinary excretion rate was 32.0 +/- 7.3% in the drip infusion for 30 minutes up to 8 hours after administration. CPZ was effective in 6 of 8 cases with pediatric bacterial infections. No side effects were observed except for 1 case with elevation of GOT.     

Treatment of pertussis with cefoperazone (author's transl)

Clinical trial of cefoperazone (CPZ) for the treatment of 15 cases suffering from pertussis was performed and the results were as follows. The method of administration, as a rule intravenous infusion was performed at 100 approximately 200 mg/kg/day. (1) Seventeen strains of Bordetella pertussis showed under 0.006 mcg/ml of MIC. It was similar to PIPC. (2) Any effect to hepatic or renal function was not observed. (3) Clinical response obtained in these cases was excellent in 13 cases (86.7%), good in 2 cases (13.3%) and none of poor case.     

Clinical evaluation of cefoperazone in children (author's transl)

Clinical evaluation was made on cefoperazone (CPZ) and the following conclusions were obtained. (1) Serum concentrations of the drug after a one-shot intravenous injection of 22.2 mg/kg were 77 mcg/ml (30 minutes), 50 mcg/ml (1 hour) and 8.9 mcg/ml (4 hours) and T 1/2 of serum concentration was 68.5 minutes. A 35-day-old female with obstructive jaundice associated with choledochal cyst was given by a 30-minute drip infusion of 26.8 mg/kg of the drug. Serum concentration was 90 mcg/ml at the end of infusion, slowly declined thereafter, and was 47.5 mcg/ml at 6 hours. Its T 1/2 was 395 minutes. A patient with pyelonephritis complicated with right hydronephrosis was similarly treated with 24.4 mg/kg. T 1/2 of serum concentration was not prolonged, i.e., 82.1 minutes, but urinary recovery rate up to 6 hours was decreased to 15.9%. (2) Five patients, including three with pyelonephritis (causative organism: K. pneumoniae 2 and P. aeruginosa 1) and each one patient with pneumonia (unknown) and with postoperative infection (S. faecalis), respectively, were treated with 66.7 approximately 96.8 mg/kg/day of CPZ in 3 divided doses for 5 approximately 12 days either by one-shot intravenous or by 30 approximately 60-minute drip infusion. An overall efficacy rate was excellent in 3 and good in 2, and there was no failure. Causative organisms disappeared in all cases. (3) Although one patient was excluded from the study because the diagnosis was supposed to be viral pneumonia, all six patients who were given CPZ did not exhibit any adverse reactions except for mild eosinophilia in two instances. (4) The foregoing results as well as the review of the literature clearly indicate the effectiveness of CPZ in the treatment of bacterial infections in children.     

Clinical examination of cefoperazone in pediatrics (author's transl)

Clinical studies on cefoperazone (CPZ), a new cephalosporin, were carried out at our department. Seventeen children wih the following bacterial infections were treated with CPZ; pneumonia (7), bronchitis (6), tonsillitis (1), sepsis (2) and purulent meningitis (1). The dosage was 56 approximately 182 mg/kg/day, divided into 4 doses, and given intravenous injection. The duration of administration was from 4 to 15 days. Clinical results were excellent in 3 cases, good in 9 cases, moderate in 3 cases, poor in 1 case and uncertain in 1 case. The overall efficacy rate was 75.0%. No side effects were observed.     

Clinical results of cefoperazone in pediatric infections (author's transl)

In order to evaluate effectiveness of cefoperazone (CPZ) in the treatment of bacterial infections of children, the clinical studies were carried out. CPZ was administered by one-shot injection to 28 patients at daily dose of 50 approximately 160 (average 89.7) mg/kg in 3 approximately 4 divided dose for 2 approximately 10 (average 5.6) days. The overall efficacy rate in 28 cases was 92.9%, i.e., excellent in 16 (57.1%), good in 10 (35.7%), fair in 1 (3.6%) and poor in 1 case (3.6%). Temporary rise of GOT and GPT or only GOT was observed in each 1 case out of 28 cases (7.1%), but any other abnormality was not observed throughout this series. Based on the above results, CPZ was thus considered to be a useful antibiotic in treatment of pediatric infections caused by Gram-positive cocci and Gram-negative rods.     

In vitro studies on parsalmide / bioavailability and protein binding (author's transl)]

The values of the diffusion constants at the different pH-values obtained using Stricker's apparatus, demonstrate that 2-propargyloxy-5-amino-N-(n-butyl)-benzamide(parsalmide, My 46-1) is characterized by a good absorption rate at gastric level and by a high absorption rate in the intestinal tract. The per cent of parsalmide bound to serum proteins, mainly to serum albumin, decreases with increasing concentration of parsalmide. Human serum binds about 55--70%, whereas bovine and equine serum bind about 40--60% of parsalmide at the different concentrations tested. The binding between parsalmide and serum proteins is a weak one: bound parsalmide is therefore set free very easily.     

Results of application of cefoperazone to pediatric infections (author's transl)

Cefoperazone (CPZ) was studied clinically and the following results were obtained. The drug was administered to 21 cases of bacterial infections; respiratory tract infection (17), lymphadenitis (1), urinary tract infection (1), enterocolitis (1) and purulent meningitis (1). The daily dose was 50 approximately 125 mg/kg. The drug was given by one-shot intravenous injection, 3 approximately 4 times a day and the duration of administration was from 3 approximately 18 days. The overall efficacy rate was 81.0%, i.e., excellent in 11 cases, good in 6 cases, moderate in 2 cases and poor in 2 cases. CPZ was potent in the treatment of ampicillin-resistant Haemophilus influenzae meningitis. One patient developed exanthema. No other serious side effects were observed.     

Photochemical studies on N-acetyl-arylamides (author's transl)

Photochemical Studies on N-Acetyl-arylamides Acetanilide, p-ethoxyacetanilide, p-methoxyacetanilide and o-methoxyacetanilide have been irradiated in solution. In addition to ortho- and/or para-aminoacetophenones, which were partially formed by the elimination of an alkoxy-group, azobenzenes were also found.     

Clinical experience with cefoperazone in the pediatric field (author's transl)

Cefoperazone (CPZ) was given intravenously to 23 children with the following acute bacterial infections; 10 cases of pneumonia, 4 cases of urinary tract infection, 2 cases of purulent cervical lymphadenitis, 2 cases of pertussis pneumonia, 2 cases of septicemia, 1 case of osteomyelitis, 1 case of perforative peritonitis and 1 case of bacterial meningitis. Clinical effectiveness was obtained in 20 cases out of 23 cases and bacteriological effectiveness in 14 cases out of 17 cases. With CPZ, the following side effects developed; transient diarrhea in 1 case, asymptomatic eosinophilia in 2 cases. From the above clinical results, it is apparent that CPZ is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.