To investigate annual changes in the susceptibility of clinical isolates to midecamycin acetate (MDM-AC), minimum inhibitory concentrations (MICs) of MDM-AC were determined for clinical isolates obtained from outpatients since 1985. MDM-AC-resistant strains of Staphylococcus spp. andStreptococcus spp. have shown similar degrees of resistance to midecamycin and josamycin. Regarding this as macrolide resistance, proportions of macrolide-resistant strains tended to increase for Staphylococcusaureus and Streptococcus pneumoniae but to decrease for Streptococcus pyogenes.
1. For S. aureus, 8% of the strains isolated in 1985, 20% in 1987 and 20% in 1989 were macrolide-resistant. Of these macrolide-resistant strains, 70% or more in 1987 and 80% or more in 1989 were methicillin-resistant S. aureus (MRSA).
2. For S. pneumoniae, 8% of the strains isolated in 1985, 12% in 1987 and 12% in 1989 were macrolide-resistant, indicating a tendency for resistant strains to increase annually.
3. For S. pyogenes, 8% of the strains isolated in 1985, 4% in 1987 and 0% in 1989 were macrolide-resistant, showing a decreasing tendency.
4. MDM-AC is still thought to be a clinically useful antibacterial agent because it still shows antibacterial activity against 80% or more of Gram-positive cocci clinically isolated in recent years and a low degree of induction of macrolide resistance in Staphylococcus spp.

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Effects of various antacids (sodium bicarbonate, aluminium hydroxide gel) and an H2-blocker (cimetidine) on the absorption and excretion of a new cephem drug for oral use, cefteram pivoxil (CFTM-PI), were studied in healthy adult volunteers.
1. No significant differences were found in serum levels of CFTM and CFTM-A (an inactive isomer of cefteram (CFTM)) or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with sodium bicarbonate and that given CFTM-PI alone.
2. There were no significant differences in serum levels of CFTM and CFTM-A or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with aluminium hydroxide gel and that given CFTM-PI alone.
3. In contrast, serum levels of CFTM and its urinary recovery rate were significantly less in the group given the drug in combination with cimetidine than in that given a single administration 2-3.5 hours and 2-4 hours after administration, respectively. Clinical considerations may remain.

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Imipenem/cilastatin sodium (IPM/CS), a newly developed carbapenem antibiotic, was administered to a total of 152 patients with severe infections complicating hematological disorders, of whom 138 patients are included in the present analysis of efficacy and 152 in that of safety.
Most of the underlying diseases were acute leukemia (76/138), and most patients suffered from sepsis or suspicion of sepsis (84/138).
Out of 138 patients in whom efficacy was evaluable, responses were excellent in 41 patients, good in 55, fair in 19, and poor in 23.
The overall clinical efficacy rate was 69.6% (96/138).
Prior antibiotic treatment and peripheral neutrophil count had significant effects on the clinical response.
The overall eradication rate of bacteria was 76.2%.
Adverse reactions were observed in 15 patients (9.9%) and abnormal laboratory test results in 19 patients (12.5%).
From the above findings, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections accompanying hematopoietic disorders.

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Cefuzonam (CZON) which has a broad spectrum on both Gram-negative and Gram-positive bacteria including methicillin-resistant Staphylococcus aureus was evaluated in severe infections associated with hematological disorders.
Sixty five patients were treated with CZON. Among them, 56 patients were evaluable for effectiveness. Nine patients were not evaluable because 3 patients were treated with combination of other antibiotics such as ceftizoxime, norfloxacin, ofloxacin, 1 patient was subjected to additional herapy of G-CSF and γ-globulin, 4 were the patients with other disease than hematologic disorder (3 malignant methotheliomas, 1 ovarian cancer), and the remaining one was prophylactically treated.
Excellent responses were observed in 21 (37.5%) patients, good responses in 11 (19.6%) patients, with an overall efficacy rate of 57.1%. The efficacy rate in septic patients was 80% (4/5), and that in patient whose peripheral granulocytes were continuously below 100/μl was 60% (3/5).
Three patients who suffered from malignant methothelioma, one patient who suffered from ovarian cancer, one patient who was treated prophylactically were included in the final evaluation of side effects.
Side effects were observed in 2 patients (2/61, 3.3%). In a patient of 7 years, mild liver disfunction (GOT/GPT, 46/55) was found in 10 days after CZON treatment was started. In a patient of 65 years, mild appetite loss was identified in 2 days after CZON administration was begun. The liver disfunction was improved soon after the cessation of the treatment. The mild appetite loss disappeared while the treatment was continued.
These results showed that CZON was an effective and safe antibiotic for the treatment of severe infections in patients with hematological disorders.

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We evaluated the therapeutic efficacy of miconazole (MCZ, Florid-F inj.®), a new antifungal agent for parenteral use, in deep-seated fungal infections of respiratory tract system. A daily dose of 400-1,800 mg of MCZ was given intravenously for 12-38 days (mean: 23.4 days) to 7 patients: 2 patients with pulmonary aspergillosis, 1 patient with bronchial aspergillosis, 1 patient with pulmonary candidiasis and 3 patients with candidemia. One additional patient with pulmonary aspergillosis received three instillations of 20 mg of MCZ into the thoracic cavity. The clinical effects were excellent in 1, good in 4 and poor in 3 patients. The efficacy rate was 100% in 5 cases with respiratory fungal infections but 3 cases with candidemia did not respond well to the treatment. Four strains each of Aspergillus sp. and Candida sp. were identified as causative organisms. Seven of the 8 strains were eradicated by administration of MCZ. Side effects observed were irritation and heat in a leg in 1 patient, hyperlipoidemia in 2 patients and eosinophilia in 1 patient. The adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that MCZ is one of the most useful antifungal agents for parenteral use as a first choice on deep-seated fungal infections in the respiratory tract.

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We evaluated the efficacy of a combination therapy with carumonam (CRMN) and clindamycin (CLDM) on severe infections in patients with hematologic malignancies. Fifty three patients were included in this study. The efficacy of the combination therapy was evaluated according to the criteria by TAKAKU et al. Fourteen cases were evaluated as excellent, and 24 cases were as good, with a total rate of effectiveness of 71.7% (38/53). It should be noted that the rate of effectiveness in patients having less than 100/μ1 neutrophiles was 77.3% (17/22). Adverse effects were observed in 2 patients (3.7%). One case was hepatotoxicity and the other was nephrotoxicity. Both were mild and transient, however. These observations suggested that the combination therapy with CRMN and CLDM was effective and safe for the treatment of severe infections in patients with hematologic malignancies.

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Thirty children were treated with cefdinir (CFDN) for the evaluation of its clinical efficacy and side effects. Their ages ranged from 1 to 9 years. The dosage of CFDN ranged from 8.1 to 15.9 mg/kg/day with the treatment continued for 2 to 10 days. Twenty-eight of the 30 patients were evaluated for clinical efficacy; 10 patients with tonsillitis, 3 with scarlet fever, 4 with lower respiratory infections, 2 with otitis media, 2 with cervical lymphadenitis, 3 with urinary tract infections and 4 with skin and soft tissue infections. The remaining 2 patients who had viral diseases were included in the evaluation for side effects. Clinical responses were excellent in 14 patients, good in 12, fair in 1 and poor in 1 with an efficacy rate of 92.9%. Diarrhea was noted in one of the 30 patients.
A pharmacokinetic study on CFDN was performed in 8 fasting patients whose ages ranged from 3 to 7 years. Serum concentrations of CFDN peaked at 0.59 to 1.76 μg/ml (mean 1.13 μg/ml) at 2 hours after dosing of 3 mg/kg in 4 patients, and 0.89 to 2.49 μg/ml (mean 1.49 μg/ml) 2 or 3 hours after dosing of 6 mg/kg in the other 4 patients. The 8-hour urinary excretion rates were 16.0% to 21.3% (mean 17.4%) in 4 patients given a dose of 3 mg/kg and 10.9 to 21.1% (mean 15.5%) in 4 patients given a dose of 6 mg/kg.

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Pharmacokinetic, bacteriological and clinical studies on cefdinir (CFDN), a newly developed oralcephalosporin, were performed on children with infections.
The pharmacokinetics was examined in 3 patients. The peak plasma concentrations were 1.97 μg/ml, 0.84 μg/ml and 1.67 μg/ml in the 3 patients. The 0 to 6 or 8-hour urinary excretion rates were 22.2%, 18.1%, and 32.7%, respectively. These results were similar to those in adult patients.
Clinical response to CFDN was evaluated in 21 patients, 4 patients with pharyngitis (an efficacy rate of 100%), 7 with tonsillitis (85.7%), 1 with bronchitis (excellent), 1 with pneumonia (fair), 6 with scarlet fever (100%), 1 with staphylococcal scaled skin syndrome (good) and 1 with urinary tract infection (good). Thus, an overall efficacy rate of 90.5% was achieved.
With regard to microbiological effect on pathogens, 14 of the 15 strains identified as pathogens were eradicated, with an eradication rate of 93.3%.
The safety was evaluated in a total of 23 cases. Diarrhea, elevated eosinophile count and elevated S-GPT were observed in one patient each. The side effect and abnormalities in laboratory tests were not serious, however.
It was concluded that CFDN, with its excellent antibacterial effect, was an efficacious and safe drug for the treatment of pediatric infections.

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Pharmacokinetic and clinical studies on cefdinir (CFDN) capsule and fine granules in children were performed and the following results were obtained.
1. Plasma level and urinary excretion of CFDN were determined in 10 children with ages 7 to 13 years given single doses of 2.3 to 7.5 mg/kg. Six of the 10 children received the drug orally before meal and the other 4 after meal. Plasma concentration peaked at 2 to 4 hours in the children administered the drug before meal, and at 3 to 4 hours in those given the drug after meal. The 8-hour urinary recovery rate was 18.8%.
2. Clinical efficacies were evaluated in 23 children with bacterial infections. The children were given the drug orally at dose levels of 3.3 to 6.3 mg/kg 3 times a day. Clinical effects of CFDN were excellent in 7 and good in others, hence the overall clinical efficacy rate was 100%.
3. Bacteriologically, 18 of the 19 strains of causative organisms identified were eradicated, with an overall bacteriological eradication rate of 94.7%.
4. As for side effects, loose stool was observed in 1 case, but it disappeared in a few days. In laboratory tests a slight elevation of GOT and GPT were observed in 1 case, but no additional treatment was needed.
5. CFDN is a useful oral antibiotic for the treatment of bacterial infections in pediatric field.

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Cefdinir (CFDN), a new oral cephalosporin, was administered to10patients with various infections and the following results were obtained.
1.Clinical responses in 10 patients (1patient with rhinitis, 2with sinusitis, 1with pharyngitis, 1 with tonsillitis, 4with scarlet fever and1with abscess) were excellent in6and good in4with an efficacy rate of100%.
2.Eleven species of bacteria were isolated (3of Staphylococcus aureus, 6 of Streptococcus pyogenesand 2of Haemophilus influenzae) and all of them were eradicated by the treatment with CFDN.
3.No side effects or abnormal laboratory test values were noted.None of the patients refused to take the drug.

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Cefdinir (CFDN, FK482) was evaluated for its safety, efficacy and pharmacokinetics in28children. CFDN was effective in100%of22evaluable cases with respiratory, middle ear, urinary or soft tissue infections.From the clinical response, adverse effects and the pharmacokinetic results, daily dose of9-18mg/kg, administered in3divided portions is suggested.Increase of dose will be associated withincrease of gastrointestinal side effects.The data suggest that CFDN is safe and effective when used in children with infections caused by susceptible bacteria including Staphylococcus aureus.

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Cefdinir (CFDN, FK482) granules, a new oral antibiotic for children, were given to children withinfections. The results obtained are summarized as follows.
1. The plasma level of CFDN peaked at 0.38-0.88 μg/ml in 2-3 hours after administration of the drug at a dose of 3 mg/kg. Meanwhile, the plasma level peaked at 1.85 μg/ml in 3 hours after administration of 6 mg/kg. The plasma level was higher in the 6 mg/kg group than that in the 3 mg/kg group, thus a dose response was clearly observed.
2. The 8 hour urinary excretion accounted for 10.3-17.4% of administered amount of the drug in children with 3-6 mg/kg dosage.
3. CFDN granules were administered to a total of 42 children with upper or lower airway infections or with urinary tract infections at daily doses of 9.0-20.7 mg/kg in 3 divided portions.
The clinical efficacy was “excellent” in 28 patients, “good” in 13, and “fair” in 1, hence an efficacy rate of 97.6% was obtained.
4. Bacteria identified from various diseases were 29 strains of 9 species, and the eradication rate was 82.8%.
5. No.side effects were noted in any of the children.
Laboratory test results showed an abnormality in 1 case each with a rise of platelet count and eosinophilia.

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We studied the clinical efficacy of cefdinir (CFDN), a new oral cephalosporin, in 18 children withages 2 years and 4 months to 11 years and 4 months with pediatric infections. The diagnoses consistedof respiratory tract infections in 15 cases, impetigo in 2 and balanoposthitis in 1. Clinical efficacies wereexcellent in 11 patients and good in 7, with an efficacy rate of 100%. Bacteriologically, 9 (64.3%) of the14 strains of clinical isolates were eradicated. No side effects nor abnormal laboratory findings wereobserved.
We have concluded that CFDN is a useful antibiotic for the treatment of mild to moderate pediatricinfections.

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We studied pharmacokinetics and clinical effects of cefdinir (CFDN), a newly developed oral cephalosporin, and the following results were obtained.
1. Pharmacokinetics of CFDN in 2 patients were investigated. The 2 patients with ages of 8 years (36.5 kg, body weight) and 6 years (26.5 kg, body weight) were administered with 3 mg/kg of fine granules of CFDN on empty stomachs. Peak plasma levels of CFDN were 0.85 μg/ml in one patient and 0.56 μg/ml in the other. The 8-hour urinary recovery rate was 21.6% of the administered dose in one and was not calculable in the other.
2. Clinical effects of CFDN were studied in 25 children with various infectious diseases: 11 with acute pharyngitis, 1 with acute tonsillitis, 2 with acute laryngitis, 3 with acute bronchitis, 2 with acute bronchopneumonia, 4 with scarlet fever, 1 with acute otitis media, 1 with acute lymphadenitis. The efficacy rate was 96% (24/25), and the bacteriological eradication rate was 83.3% (10/12).
3. No side effects were noted. Clinical laboratory test values were investigated in 14 patients. There were no seriously abnormal laboratory test findings except a slight elevation of eosinophile and GPT.

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Clinical trials of cefdinir (CFDN) in pediatric infections were carried out. Results are summarized as follows.
1. Mean half-lives of CFDN in serum in children when administered on an empty stomach were 1.24 hours (3 mg/kg per os) and 1.85 hours (6 mg/kg per os).
2. Mean 8 hour urinary excretion rates of CFDN were 19.0% (3 mg/kg/per os) and 10.5% (6 mg/kg per os).
3. CFDN was administered to 28 children with various infections: 12 patients with tonsillitis, 8 with bronchitis, 2 with pneumonia, 4 with urinary tract infections, 1 staphylococcal scalded skin syndrome and 1 with impetigo. The overall efficacy rate was 89.3%.
4. Diarrhea was noted in 1 patient. Abnormal laboratory test values encountered were eosinophilia in 2 patients, thrombocytosis in 1.

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[in Japanese]

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