The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered “intensive” chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens.
1. Bacteriological effects
Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized.
2. Clinical effects
1) Staggered chemotherapy:
Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%).
2) Staggered “intensive” chemotherapy:
Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total:excellent 60.0%, efficacy rate 90.0%.

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Bactericidal activities of isepamicin and ofloxacin against Pseudomonas aeruginosa E7 were examined using an in vitro computer programmed pharmacokinetic simulation system. Concentration of the drugs simulated the pharmacokinetic data obtained in healthy human adult subjects after 200 mg or 400 mg I. M. administration of isepamicin (ISP), and 300 mg P. O. administration of ofloxacin (OFLX). P. aeruginosa cell counts were depressed by ISP or OFLX to-4log-5log levels of magnitude below the initial cell counts. The time required in recovery of cell counts to the initial level after treatment with ISP (200mg) was longer than that after OFLX (300mg) treatment. An excellent synergistic effect was observed between ISP and OFLX.

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The Antibacterial activity of minocycline (MINO) and that of cefuzonam (CZON) were assessed with clinical isolates of 19 species, and compared with that of other antibiotics.
MINO was highly active against methicillin-sensitive Staphylococcus aureus (MSSA), Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Helicobacter pylori, Flavobacterium meningosepticum, Acinetobacter calcoaceticus, Peptostreptococcus spp. and Propionibacterium acnes, but not as effective against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas cepacia and Alcaligenes xylosoxidans.
CZON was highly active against MSSA, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, N. gonorrhoeae, M (B). catarrhalis, H. influenzae, H. pylori, P. mirabilis, Peptostreptococcus ssp. and P. acnes, but not effective against MRSA. It was minimally active against Gram-negative rods (E. coli, K. pneumoniae, etc.) and bacteria that do not ferment glucose.

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Glucose non-fermentative Gram-negative bacilliare important nosocomial pathogens. This study concerned with susceptibilities toantibacterial agents of strains of Glucosenon-fermentative Gram-negative bacilli that were isolated from cultures of clinical materials at 123 hospital labora tories throughout Japan from September to December of 1991. The tests for susceptibilities were performed according to the disk dilution method recommended by NCCLS
The following bacteria were tested: Pseudomonas aeruginosa, Pseudomonas cepacia, Acinetobacter calcoaceticus, Alcaligenes spp., Alcaligenes xylosoxidans, Flavobacterium spp. and Xanthomonas maltophilia. The antibacterial agents tested were as follows: piperacillin (PIPC), ceftazidime (CAZ), aztreonam (AZT), imipenem (IPM), minocycline (MINO), gentamicin, amikacin (AMK) and ofloxacin (OFLX).
1. Eighty percent of the strains of P. aeruginosa and P. cepacia were sensitive to CAZ. More than ninety percent of the strains of A. calcoaceticus were sensitive to IPM, MINO, OFLX. To PIPC and IPM, about eighty percent of the strains of Alcaligenes spp. and A. xylosoxidans were sensitive. The strains of Flavobacterium spp. and X. maltophilia showed high sensitivities to MINO.
2. Annual changes in antimicrobial susceptibility patterns over 4 years (1988-1991) show that there has been a gradual increse in sensitive strains of P. aeruginosa to PIPC, CAZ and AMK. Sensitive strains of P. cepacia to AZT, IPM and MINO, and A. calcoaceticus to CAZ and MINO also have gradually increased. No yearly changes were observed in high sensitivity to MINO of the strains of Flavobacterium spp. and X. maltophilia.

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Antimicrobial activities of arbekacin (ABK) against various clinical isolates, 335 strains obtained in 1991, were determined and the reliability of the ABK disk susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of two different systems for the interpretation of the disk tests was evaluated as to which system would be more useful for the evaluation of clinical efficacy of ABK. The 4 category system used in Japan, and the system proposed by the Japanese Society for Antimicrobial Chemotherapy were studied.
In this study, MICs were determined using the Mueller-Hinton agar containing 50mg/L of Ca and 25mg/L of Mg at an inoculum level of 10⁶ CFU/ml. MIC₉₀ values of ABK against Staphylococcus aureus (MSSA and MRSA) and Staphylococcus epidermidis were both 3.13μg/ml. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris, Enterobacter spp., and Citrobacter spp., were also≤3.13μg/ml. MIC₉₀values against Pseudomonas aeruginosa and Serratia spp. were both 50μg/ml.
The disk susceptibility test was carried out according to the instruction in the Showa disk manual. The inhibition zones obtained with the disk method were compared with MICs. Results of ABK disk susceptibility test with 30, 10, 5 or 2μg disks were well correlated with MICs, showing the reliability of the disk method in estimating approximate values of MICs (r=-0.627-0.724, P<0.01).
In the 4 category classification system currently used, break points in MIC values of ABK proposed are (+++) MIC<3μg/ml,(++) MIC>3-10μg/ml,(+) MIC>10-50μug/ml and (-) MIC>50μg/ml. The results obtained with Showa 30μg disks showed false positive in 13.4%, and false negative in 3.9% of the samples. With 10μg disks, false positive and false negative were 8.1%, and 3.9%, respectively. Similarly, those with 5μg and 2μg disks were 6.9% and 7.2%, and 3.0% and 14.6%, respectively.
In the break point classification system of Japanese Society for Antimicrobial Chemotherapy, the MIC break point for ABK proposed is 2μg/ml. It appeared to be difficult to make out this break point on the inhibition zone diameters obtained with various disks used, since there were nosignificant difference in the inhibition zone diameters against strains with MIC values ranging 0.39-3.13μg/ml.
A pharmacokinetic examination with the recommended dose schedule for ABK (100mg IM or IV) showed that plasma levels of ABK reached 3.7-11.3μg/ml. Based on the pharmacokinetic data and recommended dose schedule for ABK, MIC break points of 3μg/ml presently used in the 4 category systems and 2μg/ml proposed by Japanese Society for Antimicrobial Chemotherapy are reasonable. This suggestion is further supported by the clinical findings of MOORE et al.(J. Infect. Dis. 155: 93-99, 1987). An increse in positive responses to aminoglycoside therapy was demonstrated when ratio of peak concentration in plasma/in vitro MIC was increased and a significant clinical response was obtained at a ratio of about 2 and a maximal response was achieved at a ratio of about 8.

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To investigate antibacterial activities of isepamicin (ISP), MICs of ISP as well as other aminoglycosides (AGs) were determined against many strains of Gram-negative bacilli that were clinically isolated in 1993.
1. No ISP-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella spp., Enterobacter spp. or Proteus mirabilis.
2. ISP-resistant strains were observed among isolates of Citrobacter freundii, Serratia spp., Proteus vulgaris, Morganella morganii, Providencia spp. and Pseudomonas aeruginosa. The frequency of resistant strains in each species, however, was lower for ISP than other AGs.
3. When MIC₉₀s were compared, antibacterial activities of ISP determined in this study were quite similar to those determined during the drug's development period (1980's) in Japan, suggesting no increase in the number of ISP-resistant strains over the years.
4. The number of clinically isolated Gram-negative bacilli resistant to multiple drugs are increasing in from year to year Japan. Our results in this study suggest that antibacterial activities of ISP may be potent enough against such Gram-negative bacilli resistant to multiple drugs.

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We performed a randamized clinical trial in granulocytopenic patients with carcinoma or leukemia.
Patients with persistent fever for more than 2 days despite antibiotic therapy were randomized to antibiotic plus fluconazole therapy group (FLCZ group) or antibiotic therapy only group (antibiotic group) by the envelope method.
It was possible to evaluate clinical efficacies in 62 patients (37 patients in FLCZ group and 25 patients in antibiotics group).
In patients whose neutrophil counts were less than 100/μl on the initial day of therapy, clinical efficacy rates were 72.0% (18/25) in FLCZ group and 57.1% (8/14) in antibiotics group. In patients whose neutrophil counts continued to be less than 100/μl during therapy, clinical efficacy rates were 64.3% (9/14) and 50.0% (3/6), respectively. Further, in patients whose neutrophil counts continued to be less than 500/μl during therapy, they were 76.9% (20/26) and 53.3% (8/15), respectively. No severe side effects nor severe case of abnormal change in laboratory test values due to fluconazole were observed in this trial.
These data suggest that empiric antifungal therapy with fluconazole is effective for fungal infections in granulocytopenic patients with carcinoma and leukemia.

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We administrated cefodizime (40mg/kg) to 13 patients with simple herniorrhaphy in the pediatric field and determined its concentrations in tissues and serums.
The mean serum and tissue levels of cefodizime after administration were 43.1±13.3μg/ml, and 23.1±6.4μg/g, respectively, at 3 hours. Cefodizime concentrations of the tissue and serum were maintained at relatively high levels for many hours. The ratio of cefodizime concentrations in tissue to serum became high at 3 hours after administration, and this suggests that tissue concentrations decreased more slowly than serum levels, and cefodizime concentrations in tissue were maintained at fairly high levels over a long period.
No side effects caused by cefodizime were observed.
From pharmacokinetic and clinical observations, cefodizime appears to be a safe and effective injectable antibiotic for the treatment of infections in children.

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We administered imipenem/cilastatin sodium (IPM/CS) to patients with gynecological infections as initial treatment and evaluated changes in blood interleukin 6 (IL-6) as an infection marker.
1. The subjects consisted of 7 patients with chorioamnionitis, 4 with intrauterine infections, and 1 with subcutaneous abscess. IPM/CS (1-2g/day) was intravenously drip infused. This therapy was markedly effective in 1 patient and effective in 11; the response rate was 100%.
2. IL-6 generally began to decrease earlier than CRP. Before drug administration, correlations were observed between IL-6 and CRP (r=0.946) between IL-6 and elastase (r=0.355), and between elastase and CRP (r=0.579). During the entire course, correlations were observed between IL-6 and CRP (r=0.581), between IL-6 and elastase (r=0.303), and between elastase and CRP (r=0.776).
These results suggest that blood IL-6 reflects early the pathologic state and treatment effects, and is a useful infection marker in gynecological infections.

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We evaluated the effectiveness and safety of imipenem/cilastatin sodium (IPM/CS) in gynecological infections at gynecological departments at multiple institutions in Yamagata Prefecture.
The subjects consisted of 64 patients with gynecological infections, 9 with urinary tract infections, and 21 with other infections. IPM/CS was intravenously drip infused at a dose of 1-2g/day. The overall response rate was 97.9% (92/94); 96.9% (62/64) for gynecological infections, 100% (9/9) for urinary tract infections, and 100% (21/21) for other infections.
Bacteriologically the response rate was 97.3% (36/37), and the eradication rate was 97% (32/33). As for subjective and objective side effects, only diarrhea was observed in 1 patient. Clinical laboratory examinations showed no abnormal values.
These results suggest the usefulness of IPM/CS for gynecological infections.

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