A transplantable mouse T cell leukemia, DL 812, is characterized by high sensitivity to 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-l-chloroethyl)-l-nitrosourea hydrochloride (ACNU) and intensive systemic infiltration. When subcutaneously inoculated, DL812 cells invade many organs and cause marked splenomegaly without forming local tumors. Disseminated DL812 leukemias are clinically completely cured by a single intraperitoneal injection of l mg ACNU, but more ACNU resistant leukemias relapse immediately. A novel antitumor antibiotic, spergualin, is effective against various mouse leukemias. The effects of its analog with stronger anti-leukemia activity, 15-deoxyspergualin (DSG), on the relapse of DL812 leukemias after ACNU treatment were investigated. DDD mice were subcutaneously inoculated with 10⁶ DL812 cells and intraperitoneally injected with l mg ACNU once on day 11 and with 100μg DSG daily from day 12 on. The relapses were clinically completely suppressed for at least 30 days.WINN assays with spleen cells revealed that host immunity did not play a major role in maintenance of the clinical cure.Thus, when DSG treatment was discontinued after 15 or 30 daily injections, leukemias relapsed immediately. When it was extended to 50 daily injections, permanent cure was attained in 1 of 15 mice but relapses occurred under DSG treatment in the others. DSG is available for combined treatment of the leukemia. The current and previous results suggest that DL812 leukemias may serve as a model in study on immunochemotherapy of the disease.

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We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at hospital laboratories throughout Japan from September to December of 1989. The susceptibility testing was carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: (+++),(++),(+) and (-). IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Acinetobacter calcoaceticus, Bacteroides fragilis and had rather strong activities against Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and Achromobacter xylosoxidans, but was less active to Staphylococcus aureus, coagulasenegative staphylococci and Xanthomonas maltophilia. IPM has been found to have activities superior to those of other antibiotics tested against E. faecalis, E. cloacae, C. freundii, S. marcescens, P. aeruginosa and B. fragilis. No antibiotics tested showed good activities against MRSA except minocycline.

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[in Japanese]

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We evaluated the clinicale fficacya nd safety of intramuscular (as a new route of administration) imipenem/cilastatins odium (IPM/CS) in patientsw ith intrauterinien fectionsw hich are typical in the fieldo f obstetricsa nd gynecology. The obtained resultsa re summarized as follows.
1. Twenty-seven patientsw ere treated with IPM/CS, 250mg/250mg b.i.d.(3 patients), 5 00 mg/500mg b.i.d.(22) and other dosages (a change in dosing regimen, 2). The duration of treatment ranged from 3 to 11 days and the total dosage during an entire course of treatment varied from 1.5 to 9.0g. The drug was suspended in a lidocaine solution and administered in the gluteal muscle of the patients.
2. Clinicale fficaciewse re excellenti n 7 patients (26%), good in 19 (70%) and poor in 1 (4%) and the overa lle fncacy rate was 96.3%. All of the 8 patientsw ho had not previouslys howed improvements with treatment by other antibioticrse sponded well to this drug.
3. Bacteriologicalltyh, e clinicaelf ficacyr ate was 95.8% (23/24) and the eradicationr ate was 76.2% (16/21).
4. No adverse effectsd ue to the drug were observed. As abnormal laboratory test results, transiente levationso f GOT and GPT were noted in one patient.

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The ethcacy and the safety of intramuscular imipenem/cilastatin sodium (IPM/CS) were evaluated in 22 patients with obstetric and gynecologic infections. 0.5g/0.5g of IPM/CS was suspended in a lidocaine solution and administered in the gluteal muscle twice a day for 3-7 days. Nineteen patients with intrauterine infections were evaluable for the clinicale Mcacy and 22 for the safety.
1. Clinical efficacies were excellent in 6 patients, good in ll and poor in 2, and the efficacy rate was 89.5%. Thirteell out of 14 parients who had not responded to treatments with other previously administered antibiotics showed excellent or good responses to IPM/CS.
2. Causative bacteria were eradicated in 5 patients, decreased in 2, unchanged in 3 and replaced in 3, with an eradication rate of 61.5%.
3.Among 22 patients treated with IPM/CS, an eruption and general itching were observed in 1 patient, but no abnomal laboratory test values were observed.

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An investigation was made on the efficacy and the safety of miconazole (MCZ) in the treatment of deep seated mycosis. The drug was administered through intravenous drip infusion at dose levels of 800 to 2,000 mg/day to 21 cases of confirmed mycosis for which causative organisms was identified and to 32 cases to which other antibiotics considered to be appropriate had been administered at febrile stages but had failed to take effect, hence mycoses were strongly suspected.
The overall clinical efficacy rate was 84.3% (43/51). Treatments were “remarkably effective” in 6 cases, “effective” in 37, “not effective” in 8 and “indeterminable” in 2. The efficacy rates were 100% (21/21) in the confirmed mycosis cases and 73.3% (22/30) in the suspected mycosis cases.
The mycological efficacies in the cases for which causative strains were identified were: disappeared in 14 (66.7%), decreased in 4 (19%), unchanged in 2 (9.5%) and unknown in 1 (4.8%), thus the overall disappearance ratio was 70% (14/20).
Chest X-ray showed the disappearance of shadow in 1 patient and improvements in 14 of 23 patients examined.
Adverse reactions were observed in 5 of the 53 cases (9.4%).
From these results, MCZ may be considered as a highly useful drug not only in the treatment of deep mycosis but also in cases for which mycosis is strongly suspected.

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Biologicals tudiesw ere done on numbers of methicillin-resistant strains of Staphylococcus aureus (MRSA) eitherc linicallyi solateda t medical institutensa tionwide and sent to us or isolateda nd identifiebdy us from samples obtained in the year 1990 from patientsw ith various infections. The resultso f the studiesa re summarized as follows.
1. The origins of the 1,047 strains used in our studies included arterial and venous blood samples (6.9%), samples from the respiratoryt ract (43.3%), surgicala nd dermatologicals amples (30.2%), otorhinoiaryngologicaaln d ophthalmologicals amples (3.8%), urological samples (7.2%), fecal samples (5.1%) and others (3.6%), thus samples from the respiratoryt ract were the most frequent.
2. The strainsw ere classifieadc cording to coagulase types into type II (76.4%), type III (2.1%), type IV (15.4%), type VII (5.3%) and other types (0.8%), thus type II strainsw ere the most numerous.
When classifieadc cording to their origins, t ype II strainsw ere found in a significantlhyi gh frequency in respiratoryt racts amples, and type IV strainsa ppeared to be present at relativelhyi gh frequencies in the surgical, dermatological, otorhinolaryngological and ophthalmological samples. Some coaguiase types were found more frequently in samples from some institutes than in others, but coagulase type distributions were similar in different localities.
3. The strains were classified according to their enterotoxin types into type A (22.8%), type B (10.5%), type C (54.9%) and other types (11.7%), thus type C strains were the most frequgnt. Significant correlations were observed between enterotoxin type C and coagulase type II, and type A and type IV.
4. Defining strains with minimum inhibitory concentrations (MICs) of ≥100μg/ml as high MRSA and≤50μg/ml as moderate MRSA, 94.8% of coagulase type II strains were high MRSA and 78.9% of coagulase type IV strains were moderate MRSA, thus coagulase type II strains tended to be high in methicillin resistance.
5. MIC₅₀ and MIC₉₀ of vancomycin (VCM) against many of these strains of MRSA were 0.78 and 1.56μg/ml, respectively, suggesting that VCM has also a potent antibacterial activity against recent isolates of MRSA in Japan.

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Since cefodizime (CDZM) shows a broad antimicrobials pectrum and relativellyo ng half lifein blood, we examined itss ynergistiac ction with minocycline (MINO) in vitroa gainst staphylococcus aureus.
1. CDZM in the presence of MINO, most of cases at 1 MIC showed FIC index>0.5-≤2 against methicillin-susceptible S. aureus (MSSA), thus the results suggested a synergistic action against S. aureus.
2. CDZM in combination with MINO at 1 MIC or sub MIC where therapeutically a favorable efficacy is expected on MINO-susceptible strains exhibited FIC index ≤0.5-≤1, Methicillin-resistant S. aureus (MRSA), thus suggesting a synergistic action against MINOsusceptible MRSA strains.
Synergism was hardly recognized against MINO-resistant MRSA strains, however.
3. Synergism by both drugs was produced in MINO-susceptible strains of S. aureus including MRSA where MIC by CDZM was high or moderate, but no synergism was demonstrated against MINO-resistant strains. That is, synergistic action by both drugs was thought to depend on antimicrobial activity of MINO.

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The object of this study was to establish the most effective regimen of cefodizime (CDZM) for patients with chronic renal failure undergoing hemodialysis (HD).
T1/2β of CDZM upon 1g intravenous administration was 3.50±0.72 hours in an on-HD group, and it was 11.26±3.89 hours in an off-HD group.
When CDZM was administered consecutively at a dose of 1g or 2g only after HD, the serum concentration of CDZM was maintained at levels sumcient to exert antibacterial activity, and no tendency for accumulation was observed.
The most effective regimen of CDZM to HD patients, therefore, has been that in which conc1uded to administration was done only after completion of HD, in a dose of 1g for mild infections and that of 2g for severe infections.

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Susceptibilities of 232 strains of 40 bacterial groups to cefpirome (CPR) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zones by thesingle-disc method under the experimental conditions established by KANAZAWA.
The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional assay of over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), and the rapid assay (about 3-4 or 5-6 hours incubation), thus confirming the applicability of thesingle-disc assay for CPR.
Analysis of the data obtained by using CPR disc containing 30μg revealed the primary regression equation to be: D (diameter, mm) =26.7-9.2 log MIC (μg/ml) in the conventional assay, D=33.8-12.7 log MIC (μg/ml) in the delayed assay, D=21.2-6.7 log MIC (μg/ml) in 5-6 hours rapid assay, and D=14.8-4.1 log MIC (μg/ml) in 3-4 hours rapid assay.
The range of variations in MICs estimated from the diameter of inhibition zone by thedisc test was then calculated in comparison with that in MIC determined by the 2-fbld agar dilution test, as a refbrence for the experimental errors which may be involved in the estimation of MIC of CPR by the single-disc assay.

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