Using 9 strains of Candida albicans mutants resistant to either a triazole-antifungal vibunazole, an imidazole-antifungal ketoconazole or a morpholine-antifungal amorolfine, experiments were conducted to see whether cross-resistance was developed to any of these 3 different famililies, as well as to an allylamine-antifungal terbinafine. All four compounds are known to selectively inhibit fungal ergosterol biosynthesis. All the mutant strains were found to be more or less resistant to other families of ergosterol biosynthesis inhibitors but not to terbinafine.

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To investigate the antibiotic activity of cefteram (CFTM), the minimum inhibitory concentrations (MICs) of CFTM and of the control drugs were determined against clinically isolated strains received from November 1991 to April 1993 from 19 dental facilities throughout the country, as well as against clinically isolated strains from samples obtained at this center from patients with dental infectious diseases, and the following results were obtained.
1. 430 strains were detected in 198 cases but identified strains amounted to 425. They are comprised of 204 strains of oral streptococci (48.0%), 81 strains of Peptostreptococcus spp.(19.1%), 10 strains of Bacteroides spp.(2.4%), 23 strains of Prevotella spp.(5.4%), and 9 strains of Porphyromonas spp.(2.1%). The ratios of Gram-positive bacteria v.s. Gram-negative bacteria were 78.4% and 21.6%, respectively, and the Gram-positive bacteria were isolated at higher frequency than Gram-negative bacteria.
2. The MIC₉₀'s of CFTM against oral streptococci and Peptostreptococcus spp. were 0.10μg/ml and 0.05 μg/ml, and year to year increases of incidences of resistance against CFTM were not observed. Some strains, however, appeared to have obtained resistance to CFTM.
3. Among Bacteroides spp., Prevotella spp., Porphyromonas spp. which used to belong to genus Bacteroides, there were some strains resistant to CFTM. As a whole, however, no year to year increases in the incidence of CFTM resistance among these strains also.
4. Two strains of 6 Staphylococcus aureus subsp. aureus were methicillin-resistant.
5. The above observations indicate that CFTM still shows strong antimicrobial activity against clinically isolated strains that may be involved in dental infections.

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Using multiple drug-resistant clinical isolates isolated since September 1992, minimum inhibitory concentrations (MICs) of cefpirome (CPR) were determined. Several control drugs were also used, and these MIC-determinations were made to determine the antibiotic activity of CPR.
The obtained rusults are summarized as follows:
1. Antibiotic activities of CPR against methicillin-resistant Staphylococcus spp., Enterococcus faecalis, and benzylpenicillin-insensitive or resistant Streptococcus pneumoniae showed that expanded antibacterial spectrum of CPR and its enhanced antibiotic action against Gram-positive bacteria. We suggest that among the existing fourth-generation cephem antibiotics, CPR is “characteristically strong against Gram-positive bacteria”.
2. Strong antibiotic activities of CPR were recognized against bacteria of family Enterobacteriaceae that were resistant to the third-generation cephems. The strong antibiotic activities appeared to be due to CPR's stability and decreased affinity for β-lactamase.
3. Antibacterial spectrum of CPR was expanded against non-glucose fermented Gram-negative bacilli including Pseudomonas aeruginosa. It appears that this expansion of antibacterial spectrum is due to CPR's affinities for a wide range of penicillin-binding proteins as well as its improved permeability into tissues.

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β-Lactamase production and activities in sputa of patients with community-acquired lower respiratory tract infections (LRTI) were determined and following results were obtained:
1) Suspected causative organisms frequently isolated were H. influenzae and Streptococcus pneumoniae. Similar results were previously reported.
2) Various β-lactamase producing indigenous bacteria were detected. In many cases these indigenous β-lactamase producing strains were isolated even when suspected causative bacteria were not β-lactamase producers.
3) β-Lactamase activities were detected from 61.5% of the sputa tested. Remaining activities of antibiotics added to the sputa were highly correlated with detection of β-lactamases produced by suspectedly causative and indigenous strains and with presence of β-lactamase activities in the sputa. Sulbactam/cefoperazone was stable in sputa than other antibiotics tested.
4) We concluded that the ig-lactamase produced by indigenous strains can be one of the factors of indirect pathogenicity in the community-acquired LRTI.

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We compared clinical efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) with those ofSBT/CPZ combined with aminoglycoside (amikacin (AMK), tobramycin (TOB), etc.) in treatmentof respiratory tract infections in patients with underlying respiratory diseases, with cancer, or withacute exacerbation of chronic respiratory infections.
Clinical evaluations of monotherapy with SBT/CPZ in a total of 30 patients showed excellentresults in 5, good results in 17. Clinical effects of combined therapy of SBT/CPZ plus differentaminoglycosides in a total of 33 patients were excellent in 18, good in 5. The efficacy rates(excellent plus good) were 73.3% in the monotherapy and 69.7% in the combined therapy.
AMK was used concomitantly with SBT/CPZ in 16 of 33 patients. Clinical effects of SBT/CPZ plus AMK were excellent in 10, good in 3, and the efficacy rate was 81.3%.
Bacteriological effects were evaluable against 11 strains in the monotherapy group, and against 17 strains in the combined therapy group. The eradication rates were 54.5% in the monotherapygroup, and 81.3% in the combination therapy group.
Diarrhea was observed in a patient who received the monotherapy. Abnomal laboratory test results were observed on in 5 patients who received the monotherapy, and in 4 patients who received one of the combined therapies. All abnormalities disappeared after the completion or discontinuation of therapies.
We considered SBT/CPZ combined with an aminoglycoside is a useful chemotherapy for respiratory tract infections in patients with underlying diseases and acute exacerbation of chronic respiratory tract infections.

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Pharmacokinetic, bacteriological, and clinical studies were performed in pediatrics on cefditoren pivoxil (CDTR-PI, ME1207) in granules.
1. Serum concentrations and urinary excretions of CDTR after administration of CDTR-PI to children (ages between 1 and 10) were investigated.
Five cases were administrated with CDTR-PI at a dose level of 3 mg/kg 30 minutes after meal.Serum concentrations in these cases reached their peaks at 2 hours after administration with an average level of 1.23±0.34μg/ml and diminished to 0.04±0.04μg/ml at 8 hours after administration with a half-life of 1.60±0.38 hours.
Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 14.9±0.9%.
Five cases were administrated with CDTR-PI at a dose level of 6 mg/kg 30 minutes after meal.
Serum concentrations with the drug after meal reached their peaks at 1 hour after administration with an average level of 2.62±0.42 μg/ml and diminished to 0.21±0.11μg/ml at 8 hours after administration with a half-life of 1.58±0.31 hours.
Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 17.0±0.7%.
These data also showed that serum and urinary concentrations of the drug depended on dose levels.
2. CDTR-PI was administered to 31 pediatric patients (their ages ranged between 1 year and 10 years) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Clinical effects were evaluable in 24 cases including 2 cases of scarlet fever, 1 case of acute pharyngitis, 12 cases of acute purulent tonsillitis, 4 cases of acute bronchitis, 5 cases of acute pneumonia. Clinical responses were excellent in 16 cases, effective in 8 cases, with an efficacy rate of 100%.
Antimicrobial effects against a total of 16 strains identified or assumed to be pathogenic bacteria were evaluated. The 16 strains of bacteria included 4 strains of Staphylococcus aureus, 6 strains of Streptococcus pyogenes, 2 strains of 13-Streptococcus, 4 strains of Haemophilus influenzae. All the bacteria listed here were judged to have been eradicated except 2 strains of H. influenzae (1 was decresed and _1 was unchanged) thus, the eradication rate was 87.5%. Two strains of bacteria replaced infection causing bacteria. Streptococcus pneumoniae replaced S. pyogenes and S. aureus replaced H. influenzae.
No adverse side reactions were observed. As an abnormal laboratory test result, a moderate elevation of GPT was observed. This abnormality was only slight, and the elevetion of GPT was found to be normal on a reinspection.
Bases on these results, CDTR-PI was considered to be effective and safe in the treatment of pediatric infections.

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The efficacy, safety and usefulness of S6472 capsules (cefaclor, long-acting preparation) were investigated in non-catheterized patients with complicated cystitis using the double blind method with S6472 granules as a control. Each of the patients was orally administrated with 375 mg of the drug twice a day for 7 days, and clinical effectiveness was evaluated according to the Criteria of Drug Efficacy of UTI (the Third Edition). The following results were obtained.
1. There was no significant bias between the capsule-administrated group (A) and the granule-administrated group (B) in background factors.
2. The overall clinical efficacy rates were 78.7% in Group A and 80.5% in Group B, which showed no significant difference. No significant difference was observed also between groups IV and VI in the efficacy for any of the UTI groups.
3. Eradication rates in bacteriological response were 85.9% and 86.0% in Group A and B, respectively.
4. Clinical efficacy rates evaluated according to doctors in charge of patients were 78.7% and 74.7% in Group A and B, respectively, showing no significant difference between the two groups.
5. The incidences of adverse reactions were 3.0% in Group A (3 out of 101 cases) and 7.1% in Group B (7 out of 98), thus no significant difference was found between the two groups.
Abnormal test values in laboratory examinations included 5 cases (in 4 among 75 patients) in Group A, but were not detected in any of the 76 patients in Group B. No statistically significant difference were observed between the two groups, however.
6. No significant difference between the two groups was observed in the usefulness evaluation including efficacy and safety profiles on an analog scale by the doctors in charge of patients.
These results indicate that S6472 capsules have the same efficacy, safety and usefulness as S6472 granules, suggesting that both drugs are equally excellent for non-catheterized patients with complicated cystitis.

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Nineteen patients who underwent pulmonary resection due to lung diseases were administered with 2g of cefminox (CMNX) by intravenous drip infusion just before surgery. CMNX levels in the serum and lung tissue were determined and pharmacokinetic parameters were derived. The obtained results are summarized as follows:
1. Pharmacokinetic parameter (K₁/K₂) derived from serum and lung tissue concentrations using deconvolution method was 0.46.
2. CMNX was useful for prophylaxis of postoperative infections with lung resection.

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To evaluate the usefulness of aspoxicillin (ASPC) in the field of plastic ana reconstructive surgery, we examined its transfer to the skin.
1. After intravenous drip infusion of ASPC for 1 hour at a dose of 2 g in 13 adults and at 1g in 2 children, the mean serum ASPC concentration 1 hour after termination of the infusion was 70.46±28.05,μg/ml. The mean concentration in the skin tissue 1 hour after infusion in 15 patients was 32.45±118.47μg/g. The rate of transfer to the skin 1 hour after infusion in the 15 patients was 52.9±29.7%.
2. The ASPC concentrations in skin tissues and the rates of its transfer to the skin did not differ significantly between 5 patients with facial surgery and 10 with surgery in the trunk or limbs.
3. To prevent postoperative infections, ASPC was intravenously drip infused twice daily for 2-3 days after operation at a dose of 2 g in adults and 1 g in children. No postoperative infection occurred in any patient, suggesting the effectiveness of this drug. In addition, no side effects or abnormalities in clinical examination values were observed.

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