Severe infections accompanied by hematopathy under granulocytopenic conditions were treated with cefmetazole (CMZ).
Subject diseases mainly consisted of acute leukemia, agranulocytosis and aplastic anemia; combined infections were septicemia, pneumonia, fever of an undetermined origin, etc. As for causative organisms found in cases that could be examined, Gram-negative bacilli such as Klebsiellapneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa and Enterobacter cloacae were isolated, as was Staphylococcus aureus. In general, 4 g of CMZ divided into 2 administrations was given per day through intravenous injection or intravenous drip infusion.
On the basis of the judgement criteria for effectiveness established by TAKAKU et al., the efficacy rate in this study was found to be 68%, including 2 cases that showed excellent responses to treatment of infections caused by S. aureus. Cases that showed pyretolysis within 4 days had over 1,000/μl of neutrophils, while cases with less than 1,000/μl showed no pyretolysis. No hepatorenal dysfunctions related to the treatment with CMZ were seen as side effects except increases of transaminase in 1 case.
These results indicate that CMZ is a useful drug for the treatment of infections accompanied by hematopathy under granulocytopenic condition.

View full abstract

Cefroxadine (CXD) was administered to patients with acute uncomplicated cystitis (AUC) in a dose of 250 mg t.i.d. for 3-7 days. The patients were divided into 2 groups (<70and>70 years old) and clinical efficacy and incidents of recurrence were assessed.
1. Out of 83 patients treated, clinical efficacy was evaluated in 62 patients including 10 elder patients on the 3rd day and in 47 patients including 9 elder patients on the 7th day. In both groups clinical efficacy rates were 100% on the 3rd and 7th day.
2. Among 24 patients including 7 elder patients, who showed excellent response on the 7th day, recurrence was examined on the 14th day. The recurrence rate was 0% by the criteria proposed by the UTI committee in Japan. However, two patients (under 70 years of age) among them were considered as positive for recurrence by doctors in charge.
Consequently, in both aged groups CXD showed excellent results in the treatment of AUC.

View full abstract

Clinical evaluation of forphenicinol, a low molecular weight immunomodulator, in patients with Mycobacterium avium, Mycobacterium intracellulare complex pulmonary infections has been conducted in a multicenter trial participated by 9 institutions in Kyushu during a period of 12 months from July 1982 to August 1983. Forphenicinol was administered for 6 months without changing the regimen of antituberculous drugs used previously. The following results were obtained.
1. Ten out of 33 eligible patients were evaluated as showing good responses; In 5 of them, elimination of M. avium, M. intracellulare complex from sputum was observed. In the other 5 patients, number of bacilli excreted was decreased significantly after treatment.
2. All of the cases with good responses were those which were simultaneously administered with antituberculous drugs.
3. Patients with thick-walled cavities, following cured tuberculosis, which was superimposed with M. avium, M. intracellulare complex, were poorly responded to forphenicinol.
4. Side effects were observed in 3 out of 41 patients; 1 case each with fever, abdominal distension and anorexia. No abnormalities in laboratory test values were observed.

View full abstract

We treated pneumonia due to anaerobic bacteria, Mycoplasma pneumonia, and other type of pneumonia with clindamycin-2-phosphate (CLDM-P) and studied the distribution of the drug into pleural effusion. The obtained results are summarized as follows.
1. CLDM-P showed excellent effects in all the treated cases of pneumonia due to anaerobic bacteria and Mycoplasma pneumonia. But the success rate was 50% in cases of other type of pneumonia. We suggest that the drug must be used in due consideration of the types of causative bacteria.
2. Five cases which had developed pleural effusions were treated with intravenous drip of CLDM-P 1,200 mg in 200 ml electrolytic solution to see the distribution into pleural effusions. The results showed hat the distribution ratio was 9.0% on the average. Peak levels were 1.86-6.07 μg/ml and the concentration was as high as 1.28 μg/ml on the average 24 hours after administration.

View full abstract

We examined if superoxide anions would be produced when bleomycin-Cu (II) were incubated with cysteine under an aerobic condition. Strong reductions of cytochrome c and nitroblue tetrazolium chloride were observed when 0.065 mM bleomycin-Cu (II) and 0.1 mM cysteine were incubated. Neocuproine, which binds specifically with Cu (I), inhibited the reduction of both agents, while superoxide dismutase inhibited only the reduction of nitroblue tetrazolium chloride. These results suggest that cytochrome c is directly reduced by the cuprous ion released from bleomycin-Cu (II) in a reducing reaction with cysteine and nitroblue tetrazolium chloride is reduced by the superoxide anion formed in the reaction of the cuprous ion with oxygen.

View full abstract

When a drug is instilled into the bladder provided with experimental cystitis, the drug could be transferred into the serum. We studied the transfer of mecillinam into the serum, and found that the extent of transfer varied with the method to cause experimental cystitis and also occurredeven in the normal bladder. It was suspected that in the inflamed bladder, a part of mecillinam excreted into the urine would possibly be transferred again into the serum through bladder wall.

View full abstract

single intravenous dose of 2g of cefpiramide (CPM) was administered prophylactically to 11 patients at 30, 60, 120, or 180 minutes before hip surgery.
Peak concentrations in different tissues of CPM were observed in 30 minutes after intravenous injection. Mean concentrations of CPM were 246.0 μg/ml in peripheral blood, 298.5μ g/ml in bone marrow blood and 77.5 μg/g in cancellous bone at 30 minutes after administration. Half-lives of CPM were 152 minutes in peripheral blood and 105 minutes in bone marrow blood.
The concentrations of CPM observed in the above study were higher and its retention longer than expected values.

View full abstract

Clavulanic acid/ticarcillin (BRL 28500) was administerd to 36 patients with severe infections accompanying various hematological diseases. The rate of efficacy was 52% on the whole. Adverse reactions were minimal.

View full abstract

(TIPC) plus 1 part clavulanic acid (CVA). 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 intraperitoneal infections or biliary tract infections. Drug concentrations in the ascites were determined.
A total of 76 cases was treated with BRL 28500. These cases included 49 intraperitoneal infections (suppurative peritonitis 29, postoperative peritonitis 20) and 18 biliary tract infections (cholecystitis 5, cholangitis 13). Nine cases were excluded from evaluation according to the committee's assessment.
The clinical improvement as assessed by surgeons in charge increased with the duration of continued treatment and efficacies were assessed as 57.1% on day 5, 63.0% on day 7 and 77.8% on day 10 in intraperitoneal infections. Corresponding results in biliary tract infections were 38.9%, 40.0% and 42.9%, respectively. From these results it is clear that the degree of improvement is related to the duration of treatment.
The clinical usefulness as assessed by surgeons in charge of the study was 63.8% in intraperitoneal infections (suppurativeperitonitis75.0%, postoperative peritonitis 47.4%) and 58.8% in biliary tract infections (cholecystitis 100%, cholangitis 41.7%). The overall rate of usefulness was 62.5%.
The clinical efficacy rates as assessed by the committee were 81.6% in intraperitoneal infections (suppurative peritonitis 93.1%, postoperative peritonitis 65.0%) and 66.7% in biliary tract infections (cholecystitis 100%, cholangitis 53.8%). In cases where causative organisms were isolated, the efficacies were 92.9% in suppurative peritonitis, 58.8% in postoperative peritonitis, 50.0% in cholangitis and overall, 69.2%. In cases from which TIPC-resistant organisms were isolated, the overall efficacy rate was 65.4% (suppurative peritonitis 88.9%, postoperative peritonitis 58.3% and cholangitis 40.0%).
Regarding bacteriological effect as assessed by the committee, the eradication rate was 76.9% in intraperitoneal infections and 40.0% in biliary tract infections (71.0% overall). In cases from whom ticarcillin-resistant organisms were isolated the corresponding rates were 68.4% and 33.3%respectively,(63.6% overall).
In 4 patients with peritonitis drug levels in the ascites were determined following adminis-tration of BRL 28500 by drip infusion. Good levels of both TIPC and CVA were detected 1 to 3. 5 hours after administration.
Considering side effects, mild nausea and vomiting were observed in 1 case (1.3% incidence).In laboratory findings, slight eosinophilia was seen in 2 cases and liver function abnormalities including transaminase elevation in 6 cases (8/75, 10.7%). These abnormalities returned to nor-mal after the cessation of the treatment.
On the basis of these results it was concluded that both components of BRL 28500, TIPC and CVA, are well distributed to the ascites and the product is considered to be very useful in the treatment of peritonitis and biliary tract infections even where these infections are caused by TIPC-resistant organisms.

View full abstract

Nine hundred seventy cases of childhood bacterial meningitis treated at 107 institutions in Japan from 1979 through 1984 were studied using questionnaire.
The number of cases that underwent antimicrobial monotherapy remained nearly constant during the study period, but cases of therapies with B-lactam combined with aminoglycosides (AGs) decreased in number and a gradual increase in the use of B-lactam combined with non-AGs antibiotics including β-lactam (Non AGs) was observed.
A trend showing decrease in case fatality rate (CFR) was observed except that CFR for Gram-positive bacterial infections treated with B-lactam+AGs remained at a same level.
Cases treated with antibiotics were classified into 3 groups according to major etiological pathogens.
Cases with Staphylococcus aureus gave a poor prognosis, among 27 total cases, CFR was 28.6% (2/7) with monotherapy, 50. OM (6/12) with, 9-lactam+ AGs and 37.5% (3/8) with B-lactam+NonAGs (P <0.1).
Among 100 cases of group B Streptococcus (GBS), CFR was 20. OM as a whole, 17.3% (9/52) for monotherapy and 34.5% (10/29) for B-lactam+ AGs (P < 0.1).
Among 198 cases of Streptococcus pneumoniae, CFR was 12.1% as a whole, and was 12.3% (18/146) with monotherapy. CFR for the cases treated with β-lactam+ AGs was 20.8% (5/24) and with j3-lactam+Non AGs was 3.6% (1/28)(P<0. 1).
CFR for 292 cases of Haemophilus influenzae meningitis was fairly low, and was 6.1% (9/148) with monotherapy, 7.4% (5/68) with β-lactam+ AGs and 3.9% (3/76) with B-lactam+Non AGs, thus very slight differences were observed among the 3 groups of treatment.
Among 111 cases of Escherichia coli, monotherapy and B-lactam+Non AGs gave 6.5% (2β1) CFR, and 5.6% (1/18) CFR, respectively, whereas 13-lactam+ AGs showed CFR of 19.4% (12/62), demonstrating a significant difference tendency (P <0.1). Similar tendencies were observed in the cases of Listeria monocytogenes, Proteus mirabilis, Pseudomonas aeruginosa and Enterococcus faecalis. Contrary to the high CFR observed with the β-lactam+AGs treatment, significantly low CFR was frequently obtained in cases treated with a combination of penicillins with cephalosporins including latamoxef or B-lactam with chloramphenicol.
Infections with GBS, E. coli, and P. mirabilis occurred largely in the age between 0 to 6 months and CFR was especially high in the very young. CFR for cases treated with B-lactam+AGs was higher than CFR for cases with monotherapy. This was particularly true for GBS (P<0.05). These facts point out that ampicillin+AGs treatment may have a problem in the treatment of neonates.

View full abstract

We discussed the antimicrobial susceptibilities of Proteus group isolated in 1983 and 1984 and also the annual changes of the susceptibilities from 1980 to 1984. The tested strains were isolated in 103 hospitals in Japan. Antibiotics tested for this study were ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ), and gentamicin (GM). The MIC's were determined by the standard method of the Japan Society of Chemotherapy.
Susceptibilities of the bacterial strains to the 4 antibiotics were described below;
1. Proteus mirabilis had good susceptibilities to all the antibiotics tested.
2. Susceptibilities of Proteus vulgaris were low to ABPC and CEZ, but high to CMZ and GM.
3. Proteus morganii showed low susceptibilities to ABPC and CEZ, and moderate to CMZ and GM.
4. Susceptibilities of Proteus rettgeri were low to ABPC and CEZ, and 25-40% of the strains were resistant to CMZ and GM.
5. Proteus inconstance had low susceptibilities to ABPC and CEZ, but fairly good to CMZ. About 55% of the strains showed resistance to GM.
6. There were no significant annual changes in susceptibilities of P. mirabilis, P. vulgaris and P. morganii to ABPC, CEZ and CMZ during the period from 1980 to 1984, but decreased susceptibilities to GM were noted in 1982.
7. There was no evidence of changes in susceptibilities of strains of P. rettgeri to ABPC and CMZ, but a tendency of decreasing susceptibilities to CEZ was shown from 1981.
8. P. inconstance showed no major changes in susceptibilities to ABPC, CMZ and GM.
9. Frequencies of resistant strains with MIC of 25 pg per ml or more in P. mirabilis, P. morganii and P. rettgeri were higher in 1982 and/or 1983 than the other years.

View full abstract

Cefuzonam (CZON) one of the aminothiazolyloxyiminoacetamido cephalosporins, was studied for its antibacterial activity, absorption and excretion, concentration in the cerebrospinal fluid (CSF) and the penetration, and clinical efficacy. The following are a summary of the results:
1. Antibacterial activity
The antibacterial activity of CZON was studied on clinically isolated Staphylococcus aureus (cefazolin (CEZ)-susceptible and CEZ-tolerant strains), Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. Compared with CZON were cefmenoxime (CMX), latamoxef (LMOX), cefoperazone, cefmetazol (CMZ), cefotiam and CEZ, but for S. aureus cefamandole (CMD) was replaced for CPZ.
Activities of CZON against S. aureus, both CEZ-susceptible and CEZ-tolerant strains, were superior to those of 6 control drugs. The distribution of MICs for the CEZ-susceptible strains was 0.10-12.5 μg/ml, and for the CEZ-tolerant strains 0.20->100 μg/ml. MIC peaks were 0.39 μg /ml and 0.78-1.56 μg/ml for CEZ-susceptible and CEZ-tolerant strains, respectively. Against both susceptible and tolerant strains, CZON showed superiority to CMZ and CMD, which are used prevalently and used for Methicillin-resistant S. aureus also. Distributions of MICs of CZON (and the peak of MICs) on E. coli, K. pneumoniae, and P. mirabilis were <0.025-1.56 (<0.025), <0.025-25 (6_0.025-0.05), 6.0.025-25 (<0.025) μg/ml, respectively, showing CZON's similar antibacterial activity to those of cephalosporins, CMX and LMOX, which are 5th group.
2. Absorption and excretion
Eight patients, aged 10 months to 15 years, were administered with CZON 20 mg/kg, one shot intravenously. Serum concentrations somewhat varied from patient to patient, but the mean value was 48.7 μg/ml after 30 minutes of administration which decreased rapidly to 13.3 μg/ml after 1 hour, to 3.4 μg/ml after 2 hours, to 1.14 μg/ml after 4 hours, and to 0.15 μg/ml after 6 hours. Half-lives were 0.67-1.47 hours, with the mean of 0.87 hour. Urinary recovery rates were 24.7-55.9%, with the mean of 45.1%, in 6 hours after administration.
3. CSF concentration and penetration rate
To 4 pediatric patients with purulent meningitis, CZON 25 mg/kg or 50 mg/kg was administered and the concentration in CSF was measured. In only one case the concentration was close to those of 5th group cephalosporins, and CZON concentrations in CSF at around 2-2.5 hours after injection were 1.0-5.0 μg/ml, and rates of penetration were estimated to be 8.0-23.3%.
4. Clinical results
Treated with this compound were 2 cases of purulent meningitis complicated with septicemia, 3 cases of purulent meningitis, 5 cases of septicemia/bacteremia, 11 cases of bronchialpneumonia, 3 cases of bronchitis, 5 cases of purulent lymphadenitis, 6 cases of urinary tract infection, 1 case each of septicemia and osteomyelitis, cellulitis, abscess, and Salmonella infection, comprised 39 cases in total. Except one unevaluable death case of purulent meningitis, 38 cases were clinically evaluated and in all cases CZON was efficacious. Pathogens were detected in 33 cases and in 31 cases the erradication of pathogens was observed during the course of treatment. Considerably large dosage of 90. 9 mg to 300 mg/kg/day was used for purulent meningitis and septicemia cases, but for other infections 60 mg/kg/day was administered as a rule. Side effect was observed in 1 case each of fever, petechia and diarrhea, with no severe symptoms of special note. No abnormality in laboratory test values was found except one case of GOT/GPT elevation for which the CZON therapy was continued.

View full abstract

Cefuzonam (CZON) was administered to 50 pediatric patients with infections, and the efficacy was investigated in 49 patients. The efficacy rate was 83.7% and the drug was evaluated to be highly effective for diseases in the pediatric field.
The activity of CZON was especially good against Staphylococcus aureus, and the efficacy rate for 13 clinical isolates was 69.2%, which was comparable to that of cefotiam or cefazolin.
CZON appeared to be useable alone in Gram-positive infections. It might be very powerful in the control of infections in secondary immunodeficiency.

View full abstract

Newly developed cefuzonam (CZON) was tested in 21 children and serum and urinary concentration and urinary recovery rates were determined. To 9 cases, 3 groups of 3 cases each, CZON was given at 10, 20 or 40 mg/kg one shot intravenously, and to 12 cases, 3 groups of 5, 3, 4 cases each, 10, 20 or 40 mg/kg was drip-infused over 1 hour. To 1 case of purulent meningitis 55.6 mg/kg was given one shot intravenously and concentrations in cerebrospinal fluid (CSF) and serum were measured. In 37 pediatric patients comprising 1 with tonsillitis, 24 with pneumonia, 1 with purulent meningitis and bacteremia, 7 with urinary tract infection, and 1 each with staphylococcal scalded skin syndrome, purulent lymphadenitis, periarthritis of jaw joint, maxillary sinusitis and orbital abscess, CZON was tried at 21.6 mg/kg (mean) per dose, 3 or 4 doses daily, one shot intravenously, for 7 days (mean).
The clinical efficacy and antibacterial effectiveness were investigated. Also, the side effects were investigated and clinical laboratory tests done in the 37 pediatric cases plus 6 cases in which CZON was used but which were excluded from the efficacy analysis because they did not involve infections. The following is a summary of the results:
1. To 3 groups of 3 children each, 10, 20 or 40 mg/kg of CZON was given one shot intravenously. In each case the maximum serum concentration was observed at 5 min. after injection, and mean values of 3 groups with 10, 20 and 40 mg/kg dosing were 57.1, 147.2 and 316.7 mcg/ml respectively, indicating a dose-dependent response among the 3 groups. Mean half-lives were 0.83, 1.10 and 0.79 hours for 10, 20 and 40 mg/kg groups, respectively. The 10 mg/kg and the 40 mg/kg groups showed similar half-lives but the half-life of the 20 mg/kg group was a little longer than those of the other 2.
2. CZON was drip-infused over 1 hour to a total of 12 children divided into 3 groups of 5, 3 and 4 children at dose levels of 10, 20 and 40 mg/kg, respectively. In all cases maximumserum concentrations were observed at 1 hour after the start of infusion, that is, at the end ofinfusion, with mean values of 22.3, 50.3 and 76.6 mcg/ml for 10, 20 and 40 mg/kg groups, respectively. In all of the 3 groups, serum concentrations of CZON changed with time, were lower than those of one shot administration in same dose levels, but a dose-dependent response was observed among the 3 groups. Mean serum half-lives were 0.73, 0.69 and 0.91 hour for 10, 20 and 40 mg/kg groups, respectively. The 10 mg/kg and the 20 mg/kg groups showed parallel halflives, which were a little shorter than that of 40 mg/kg group.
3. In the 3 groups of 3 cases administered with 10, 20 and 40 mg/kg one shot intravenously, mean maximum urinary concentrations attained at 0 2 hours after the one shot injection were 1,283.3, 2, 123.3 and 7, 116.7 mcg/ml, respectively. Mean urinary recovery rates within 6 hours after administration were 55.0, 57.78 and 51.9% for 10, 20 and 40 mg/kg groups, respectively.
4. For the 3 drip infusion groups, urinary concentrations were determined in 4, 3 and 4 cases of 10, 20 and 40 mg/kg dosing, respectively, but 3 of the 4 cases of 40 mg/kg dosing group had no urination within 2-4 hours after the start of drip infusion, hence they were excluded from averaging. In all the 3 groups, maximum concentrations of CZON in urine were observed at 0-2 hours after the start of drip infusion, with mean values of 872.3, 2,955.7 and 1,479.5 mcg/ml for 10, 20 and 40 mg/kg dosing groups, respectively. Mean urinary recovery rates within 6 hours after the start of drip infusion were 45.5, 50.0 and 43.1% for dosing groups of 10, 20 and 40 mg/kg, respectively, with the 20 mg/kg group showing a little higher recovery rate than the other 2.
5. To 1 case of purulent meningitis CZON 55.6 mg/kg was given one shot intravenously on day 3.

View full abstract

Cefuzonam (CZON, L-105) a newly developed cephalosporin, has broad spectrum on Grampositive or-negative bacteria and may also be effective against Staphylococcus aureus against which third generation cephalosporins are largely ineffective.
We studied the pharmacokinetics and clinical effects of CZON on infectious disease of children. The diseases we studied included 2 cases of bacterial meningitis and 1 case each of viral meningitis, enterocolitis, upper respiratory infection, pneumonia, and mycoplasmal pneumonia.
CZON was administered by drip infusion. Dose levels were 20-53 mg/kg/30-60 minutes, 3 times a day. For 5 cases, was studied time course of concentrations of CZON in plasma.Median T 1/2 was 0.96 hour. Concentrations in cerebrospinal fluid (CSF) were studied in cases of pneumonia and bacterial meningitis. In the case of pneumonia the CSF concentration of
CZON was 0.272 μg/ml after 45 minutes, in the case of meningitis they were 0.155 μg/ml after 5 hours. Both of these values were higher than MIC of 0.025 μg/ml against Haemophilus influenzae which was isolated from a case of bacterial meningitis. This MIC was lower than that of cefotiam and cefazolin, as well as of cefmenoxime.
Clinical effects were excellent on pneumonia, good on upper respiratory infection, fair on mycoplasmal pneumonia. CZON, however, was ineffective in the treatment of a case of bacterial meningitis from which a susceptible strain of H. influenzae was isolated. Clinical effect of the drug was not clear in the treatment of another case of bacterial meningitis, viral meningitis and a case of enterocolitis. There was no side effect.
From these results, it has been concluded that CZON is a useful antibiotic for treating various bacterial infections in children.

View full abstract

Cefuzonam (CZON), a new semisynthetic cephalospolin antibiotic, was administered intravenously at a dose of 1.0 g twice a day for 14 days to 20 patients with complicated urinary tract infections and the therapeutic efficacy of the drug and safety were evaluated.
The results obtained were summarized as follows.
1. After 5 days, clinical results were excellent in 7, moderate in 3 and poor in 9 cases. The overall effectiveness rate was 52.6%. Bacteriologically, 24 out of 32 isolated strains were susceptible to this drug, but 8 strains were found to be resistant.
2. After treatment, clinical results were excellent in 6, moderate in 3 and poor in 10 cases.The overall effectiveness was 47.4%. In bacteriological results of 32 isolated strains, 26 strains were eradicated and 6 strains persisted.
3. Among 20 cases treated none showed subjective or objective symptoms of side effects.Noted as clinical laboratory test abnormalities were eosinophilia in 1 case after 5 days, increase of S-GOT, r-GTP, and K in 1 case, and increase of S-creatinine in 1 case at the termination of treatment. All of these abnormalities were mild and normal values were restored soon after at the termination of the treatment.

View full abstract