A patient with rheumatoid arthritis-associated interstitial pneumonitis, treated with prednisolone, developed mild colitis due to Clostridium difficile in association with the use of cefotaxime (CTX). Diarrhea was successfully treated with the discontinuation of CTX and initiation of oral vancomycin.

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Clinical effect of cefadroxil (CDX) against urinary tract infections was reported herein. CDX, a daily dose of 0.75g t.i.d., has been applied for the treatment of (I) 40 cases with simple UTI for average 6.4 days and (II) 47 cases withthe complicated UTI for average 8.9 days. Rates of effectiveness were obtained 95% in (I) and 57% in (II). Side effects were noted in 10 cases (9.3%) out of total 107 cases.

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Cefaclor (CCL) was administered to 27 patients with acute pneumonia and the following results were obtained.
1. CCL was given 500mg t.i.d. for 6 to 23 days. The clinical effects of CCL were excellent in 2 cases, good in 14 cases, fair in 6 cases and poor in 5 cases, the efficacy rate was 59.3%.
2. No adverse reaction was observed.
3. We conclude that CCL is considerably useful in the treatment of acute pneumonia of outpatients.

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Biological effect of bestatin in combination with bleomycin against rat ascites hepatoma AH 66 was investigated. The combined use of bestatin and bleomycin both at a dose of 0.5mg/kg was found to have a strong inhibition of the tumor growth. The combined effect was also confirmed histologically as follows. In combination group, increase of necrobiosis area in the tumor lesion, augmentation of infiltration of lymphocytes and macrophages around the solid tumors, and marked replacement of necrotic area by fibrous granular lesion were stronger and more rapidly than that in the other group.

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Biological effect of bestatin against rat ascites hepatomas was investigated. Bestatin administration inhibited effectively growth of AH 130, AH 44 and AH 66, and prolonged survival days of the tumor-bearing rats. In addition bestatin slightly exhibited interferon production in spleen cells from ddY mice in vitro.

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Mezlocillin (MZPC), a new broad spectrum penicillin, was studied for its biliary excretion and levels in gallbladder tissues.
1. The mean serum concentration immediately after intravenous administration of 2g of MZPC in 6 cholecystectomised patients was found to be 535.5±43.5μg/ml, while its concentration in their gallbladerd bile was 1,500-6,500μg/ml at 30 minutes-1.5 hours and its concentration in their common duct bile was 6,500 and 4,000μg/ml at 2 hours and 2.5 hours, respectively. Besides, its gallbladder tissue level around 2 hours was 37.5-500μg/g, averaging as high as 215.6±79.5μg/g.
2. Crossover method was made to compare the biliary excretion of MZPC and PIPC in 4 patients inserted with a T-tube in their common bile duct. Each patient received 2g each of 2 antibiotics intravenously. In case 1 with normal liver function, both drugs revealed the peak concentration of 3,500μg/ml or more. In case 2, the peak concentration was 3,625μg/ml for MZPC but 2, 125μg/ml for PIPC. In case 3 with slight hepatic dysfunction, the peak concentration for MZPC and PIPC was 906.4μg/ml and 375.2μg/ml, respectively. In case 4 with moderate hepatic dysfunction, the peak concentration for MZPC and PIPC was 27.6μg/ml and 14.7μg/ml, respectively.
3. Simultaneous intravenous administration of MZPC and PIPC was made to compare the biliary excretion of these 2 antibiotics in 1 patient with T-tube drain in common bile duct. The bile concentration was measured by HPLC method which was developed by our laboratory. The concentration of MZPC was 2-fold higher than the concentration of PIPC. The peak concentration or biliary recovery (0-6 hours) of both antibiotics after single oral administration of chènodeoxycholic acid (CDCA) 600mg was 2-fold higher than before administration of CDCA in this patients.
4. The trace element such as manganese and zinc in the bile were measured in case 2 and 3 after administration of MZPC. The antibiotic was proved to have no effect of promoting excretion of manganese and zinc into bile as seen with APPC.
These results indicate that the biliary excretion of MZPC is twice as high as that of PIPC. It is also confirmed that the antibiotic distributes sufficiently into gallbladder tissues. It may thus be concluded that the antibiotic is a very useful drug for treatment of biliary tract infections.

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Fundamental and clinical efficacy evaluation has been made in the study on the therapy with intravenous drip infusion of tobramycin (TOE) which is one of the aminoglycoside antibiotics and which has been recently approved of intravenous administration.
The fundamental evaluations were made with intravenous drip infusion of 60mg of TOB for 1 hour and that of 120mg of TOB for 2 hours to 4 healthy adult volunteers on crossover method. Follow-up determinations were made for comparison on its concentrations in blood and urine samples which were collected both at intervals thereafter, using 2 assay methods of the bioassay and the EMIT methods.
The maximum blood level of TOB based on the intravenous drip infusion of 60mg for 1 hour was 5.9μg/ml and 4.6μg/ml by the bioassay and the EMIT methods at the end of intravenous drip infusion, respectively, and 0.3μg/ml and 0.4μg/ml, respectively, at 6 hours after the drip infusion. The T 1/2 value was 1.81 hours with bioassay and 2.41 hours with the EMIT method.
The maximum blood level of TOB through drip infusion method of 120mg of TOB for 2 hours was 7.5μg/ml by bioassay and 5.8μg/ml by EMIT method. The T 1/2 value was 1.87 hours and 1.99 hours, respectively.
The recovery rate of TOB from urine until 24 hours after the administration was 83.0% and 94.4% with the doses of 60mg and 120mg, respectively, which were determined only with the bioassay.
The correlation coefficient between the agar well method and the EMIT method was 0.963 and 0.972 in the groups of intravenous drip infusion of 60mg for 1 hour and 120mg for 2 hours, respectively, showing proximity to each other.
TOB was kept administered with a daily dose of 120mg at a time to 11 cases and at 2 times to 1 case with chronic complicated infections of urinary tracts (comprising 9 cases with chronic complicated cystitis, 2 with chronic complicated pyelonephritis, and 1 with acute epididymitis). Of the 12 patients, 8 could meet the criteria for evaluation of drug efficacy and 6 of them proved to be effective, while 2 were ineffective.
The efficacy rate was so high as 75%.
The rate of disappearance of bacteria was 80.0%, which was very high. No side effect was specifically found out, except 1 case showing slight rise in S-GOT.

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[in Japanese]

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We administered miconazole to patients with deep-seated fungal infections, to nvestigate into the linical and mycological responses to the drug and also into its clinical safety. We also looked into the responses of amphotericin B (AMPH), flucytosine (5-FC) and the combination of the 2 drugs to deep mycoses in the past 10 years, for retrospective comparison of the findings achieved in the treatment with miconazole.
1. A clinical response rate of 85% (29/34 patients) was achieved in the treatment of deep-seated fungal infections with miconazole.
2. Mycologically, a fungus eradication rate of 79% (22/28 patients) and a fungus decrease rate of 11% (3/28) were achieved with the miconazole treatment, comparison of the response to miconazole alone and that to AMPH alone revealed that the former was significantly preferable.
3. Side effects of miconazole were observed in 23% of the treated patients (15/66). Statistical analysis of the incidence of side effects of miconazole and that of AMPH showed that the former was significantly lower.

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The pharmacokinetics of ampicillin (ABPC) during and following intravenous drip infusion in 3 healthy volunteers weighing 63.0kg to 75.0kg. ABPC was administered 1.0g by intravenous drip infusion for 1 hour.
1. Serum concentrations were measured, and simulation curve were obtained by using one-com-partment model and two-compartment model. The simulation curve by two-compartment model was more applicable to every founds than the simulation curve by one-compartment model.
2. Most appropriated administration rate of intravenous drip infusion was discussed due to calculated serum levels, therapeutic AUC and effective time.

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A comparative study of the serum, atrial muscle, and pericardial fluid concentrations of latamoxef (LMOX) and cephalothin (CET) was performed in 18 adult patients having cardiac surgery. Patients were randamly assigned to recieve either a single dose of CET 30mg/kg, LMOX 30mg/kg, or LMOX 20mg/kg. Each drug was administered intravenously soon after anesthetic maintenance was achieved.
After each drug administration, serum samples were obtained at various time intervals before, during, and after extracorporeal circulation (ECC), and assayed for CET and LMOX concentration. A sample of pericardial fluid was collected immediately after the pericardium was opened. The right atrial appendage tissue samples were obtained at the time of heart cannulation. The pharmacokinetics and penetration characteristics of each drug were analysed by the method of two-compartment model.
Serum concentrations of CET following a single intravenous injection of 30mg/kg were the high values, 172.4±35.6μg/ml at 5 minutes, and 92.9±33.8μg/ml at 15 minutes after injection. The initial (before bypass) half-life was 0.22±0.11 hour (13.1 minutes) while half-lives during and after ECC were prolonged significantly. In the cases of CET group, the myocardial tissue concentration value of 4.86μg/g was obtained in only 1 case. The mean pericardial fluid concentration was 4.69±3.35μg/ml at 5 to 30 minutes after injection.
Serum concentration of LMOX following a injection of 30mg/kg were 253.6±67.4μg/ml at 5 minutes, and 176.3±64.1μg/ml at 15 minutes after injection. On the other hand, following a injection of 20 mg/kg of LMOX, serum concentrations were 158.6±26.2μg/ml, 108.8±11.3μg/ml at 5 and 15 minutes after injection, respectively. The initial half-lives at the dosage of 30 and 20mg/kg of LMOX were identical, namely, each values were 0.62±0.17 and 0.61±0.25 hour. During and after ECC, the half-lives of LMOX were prolonged. The concentration-time profiles of LMOX in atrial appendage and pericardial fluid were higher than that of CET and the penetration values were obtained in all cases. These data support the prophylactic effect of each drug to reach tissue concentrations greater than the MIC of the antibiologic for the suspected pathogen, but also suggest, if the operation is prolonged, the need to administer a second dose of these drugs.

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In vitro activities of antimicrobial agents against causative organisms isolated from patients withurinary tract infections were investigated by dilution method using MIC 2000 (Dynatec) during July to October in 1982.
The summarized results are as follows:
1. PMPC and CCL have showed potent activities against E. coli among the oral antimicrobial agents. PMPC and CCL at 3.13μg/ml inhibited 90% of E. coli tested.
CTM, CTX, CZX, CMX and LMOX at concentrations of 0.39μg/ml or less among the parenteral antimicrobial agents inhibited 90% of E. coli tested.
2. The value of MIC₉₀ (concentration at which 90% of isolates are inhibited) against K. pneumoniae results in the resistant range for ABPC, NA, CEX, CCL and ST. Among the parenteral cephems, CMX seemed most effective against K. pneumoniae tested.
3. C. freundii seemed generally low susceptible to antimicrobial agents tested. Among the oral agents, PMPC, PPA and ST have showed moderate activity against C. freundii. Among the parenteral agents, CMX and LMOX also showed moderate activity against C. freundii, inhibiting 50% of the strains tested at 6.25μg/ml.
4. Among the oral agents, PMPC showed the most potent activity against E. cloacae. E. cloacae tested were highly resistant to the first and second generation cephems. Among the third generation, CMX seemed the most potent activity against E. cloacae isolated. However, CMX concentration of 1.56μg/ml was necessary to inhibit 50% of tested E. cloacae.
5. P. mirabilis tested was resistant to all oral antimicrobial agents except CCL and ST. The value of MIC₉₀ of the first and second generation cephems against P. mirabilis results in the moderately susceptible range (6.25-25μg/ml). The third generation seemed most effective against P. mirabilis tested.
6. PMPC, NA, PPA and ST concentrations of 0.78-1.56μg/ml were necessary to inhibit 50% of tested P. vulgaris. CEZ and CTM seemed less potent activity than CFX and CMZ against P. vulgaris. CTX, CZX, CMX and LMOX except CPZ have showed potent activities against P. vulgaris, these at 0.1μg/ml or less inhibited 50% of P. vulgaris tested.
7. P. aeruginosa has been resistant to the third generation cephems except CPZ, but TOB, GM, AMK, CFS, PIPC and CPZ have showed high activities against P. aeruginosa, inhibiting 50% of the strains tested at 0.39-6.25μg/ml.
8. The oral antimicrobial agents, and first and second generation cephems had not showed significant activity against S. marcescens. And strains of S. marcescens were relatively susceptible to the third generation cephems.
9. We have compared the relative in vitro potency of CZX and LMOX with CMX against Serratia spp., Citrobacter spp. and Enterobacter spp. which were fully resistant to the first and second generation cephems. The activity of CMX and CZX against Serratia spp. was similar, inhibiting 50% of the strains at 1.56-3.13μg/ml. The activity of CMX and LMOX against Citrobacter spp. was similar, inhibiting 50% of the strains at 6.25μg/ml. The activity of CMX, CZX and LMOX against Enterobacter spp. was similar, inhibiting 50% of the strains at 3.13-6.25μg/ml.

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The frequency of the causative strains in urinary tract infections was investigated from the point of view of the patient's background such as age, sex administration of antibiotics and so on. Especially, the frequency of the causative strains isolated from patients within 3 days after the administration of antibiotics has markedly decreased. However, the frequency of the resistant strains such as P. aeruginosa, Enterobacter spp., Citrobacter spp. and Serratia spp. has increased after 8 days' administration of antibiotics.

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In vitro susceptibilities have been investigated against several species isolated from patients with simple and complicated urinary tract infections (UTI) during 1980-1982. Antimicrobial activities of the third generation cephems against E. coli isolated from patients with complicated UTI were found to decrease slightly in 1982. And those against Klebsiella spp. isolated from patients with simple and complicated UTI were also found to decrease similarly. Against P. mirabilis, all the drugs tested have showed relatively potent activities and slight changes in the susceptibility. The marked decrease of susceptibility against Citrobacter spp. isolated from UTI have been found even in the third generation cephems. Especially, Citrobacter spp. exhibited a greater degree of resistant to CZX and CPZ. Strains of P. aeruginosa were on the whole susceptible to the drugs tested, CFS, GM, TOB and AMK, inhibiting 50-80% of the strains tested at 1.56μg/ml. CTX, CZX and CMX seemed most effective against S. marcescens among the third generation cephems, inhibiting 50-90% of the strains tested at 3.13mu;g/ml.

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