A well controlled comparative study of KW-1070, a new aminoglycoside antibiotics, and amikacin was carried out in the treatment of complicated urinary tract infections. Patients received 200mg of either KW-1070 or amikacin twice a day for 5 days by intramuscular injection. All patients had pyuria of over 5 WBCs per high power field, bacteriuria of over 104 bacteria per ml of urine and underlying urinary disease. The overall clinical efficacy of treatment was evaluated by the criteria proposed by the UTI Committee in Japan as excellent, moderate or poor.
Of the 230 patients admitted to the study, 117 received KW-1070 and 113 received amikacin. Excellent and moderate responses were obtained in 70.1% of the 117 patients receiving KW-1070 and 53.1% of the 113 patients receiving amikacin. This difference was statistically significant (P<0.01). When clinical efficacies of both drugs were compared in relation to the type of infection which was classified into 6 categories according to the criteria of UTI Committee, significantly higher efficacies of treatment were obtained in Group 3 in KW-1070 group.
The overall bacteriological responses were obtained in 82.5% of 183 strains in KW-1070 group and in 70.0% of 180 strains in amikacin group. This difference was again statistically significant (P<0.01). When bacteriological responses to treatment were compared between two groups according to the bacterial species, eradication rate of Serratia spp. was significantly higher but that of Pseudomonas aeruginosa was significantly lower in KW-1070 group.
Drug related subjective side effects were observed in two patients in amikacin group but none in KW-1070 group. Drug related aggravations in laboratory test results were observed in 21 cases from 9 patients receiving KW-1070 and 21 cases from 11 patients receiving amikacin. There were no significant differences between the two treatment groups regarding the incidence of side effects and KW-1070 appeared to be as well tolerated as amikacin.
From these results, we concluded that KW-1070 was very useful in the treatment of complicated urinary tract infections except for those due to Pseudomonas aeruginosa.

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Branhamella catarrhalis has long been considered to be a harmless upper respiratory tract commensal of humans.Its recent recognition as a significant of pathogen lower respiratory tract infection in patients with conpromized pulmonary function underscores the needs for prompt and reliable isolation and identification of Branhamella catarrhalis.
Minimum inhibitory concentration (MIC) values for 29 antibiotics against 31 strains of Branhamella catarrhalis and 34 strains of non-pathogenic Neisseria species, isolated from patients with respiratory tract infection, were measured with an inoculum size of 10⁶/ml. In the MICs of 29 antibiotics (6 penicillins, 12 cephalosporins, 3 aminoglycosides, 2 macrolides, minocycline, chloramphenicol, sulfamethoxazole-trimethoprim and nalidixic acid), the geometric mean MICs for the clinical isolates of Branhamella catarrhalis were almost uniformly lower than the MICs of the corresponding antibiotics for the clinical isolates of non-pathogenic Neisseria species.
50 % of the Branhamella catarrhalis isolates produced β-lactamase. MICs of amoxicillin and cefoperazone for the 16 strains of Branhamella catarrhalis were significantly diminished by combination of clavulanic acid or CP 45899. But these MICs for the 34 strains of Neisseria species were not affected by clavulanic acid or CP 45899.

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In the clinical studies on josamycin (JM) against mycoplasmal pneumonia, the following results were obtained.
1. JM was administered orally to 20 cases in a daily dose of 0.8-1.6g and good responses (8 excellent cases and 12 good cases) were obtained. The elevated body temperature dropped in 1.5 days and chest X-ray shadows disappeared in 11.1 days after administration of JM on average respectively.
2. As to the side effects, there was only a slight rise of GOT and GPT in one case among 20 cases, though this patient returned to normal after discontinuation of the drug. No other side effects were found.
3. Judging from our clinical results, JM is considered to be one of the useful antibiotics in the treatment of mycoplasmal pneumonia.

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A new imidazole-containing antimycotic isoconazole showed following biological activities toward C. albicans cells when it was applied at a fungistatic level (20μg/ml) or fungicidal levels (≥40μg/ml):(1) inhibition of syntheses of proteins, RNA, DNA, mannalis and alkali-insoluble glucans as measured by incorporation of appropriate radiolabeled substrates;(2) suppression of influx and stimulation of efflux of 2-deoxyglucose;(3) inhibition of intracellular retention of sorbose;(4) release of intracellular K⁺, 260nm-absorbing materials and proteins; and (5) degradation of cellular macromolecules such as RNA, DNA and proteins. On the other hand, the respiratory activity of C. albicans cells was affected by the drug to much lesser extents, although the respiration with exogenous glucose was more profoundly impaired than the endogenous respiration. The results of experiments which were conducted to seek any relationship between the respiratory activity and isoconazole-sensitivity of C. albicans cells revealed that they were apparently irrelevant.
On the basis of all these data, it is reasonably suggested that isoconazole may primarily interact with fungal cell membranes, causing inhibition of transmembrane transport of exogenous substrates and damage of permeability barrier, with resultant inhibition of syntheses of macromolecules and degradation of macromolecules, as well as suppression of respiration with exogenous substrates. This may be considered as the biochemical basis of the antifungal action of isoconazole.

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The properties of clinical isolates of Acinetobacter calcoaceticus were studied by growth, susceptibility to antimicrobial agents and mixed culture tests in vitro in an attempt to analyse the infectiousness of this organism. A. calcoaceticus was found to grow in an extremely wide range of temperature with a short division time. Studies assessing the influence of the culture medium pH and the time course of viable organisms in urine revealed that survival was possible even under relatively poor conditions, suggesting that A. calcoaceticus is a hardy organism. From the viewpoint of the response to the hosts' defense mechanism, the susceptibility to human serum was studied. An interstrain difference in susceptibility was found, some strains were susceptible while others were not. In susceptibility tests to antimicrobial agents, A. calcoaceticus was found to be highly sensitive to tetracyclines, aminoglycosides and colistin. The bacterial colonization readily occured in the presence of ineffective antibiotics in vitro.

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In vitro combined activity of cephalothin (CET) and amikacin (AMK), cefazolin (CEZ) and dibekacin (DKB), cefmetazole (CMZ) and DKB against K.pneumoniue PCI 602 was examined. Bactericidal activity against K.pneumoniae PCI 602 was enhanced by combination of cephems.(CEPs) and aminoglycosides (AGs). When bacilli were treated for two hours with CEPs (1.2 MIC) plus AGs (1/2MIC), the viable cell count decreased markedly and the colony-forming unit was found to be 1/1, 000 of the initial inoculum.
Morphological changes of K.pneumoniae PCI 602 were observed by electron microscopy, when bacilli were treated with CEZ and DKB alone and in combination. Combination of CEZ (1/2 MIC) and DKB (1/2 MIC) caused marked destruction of the bacilli.

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Tobramycin nomogram for the aged people which will be easy to use by clinicians as a guide of dosage regimen was prepared.
Adjustment of daily dosage in the aged people is done by a variable frequency dosage regimen. The dose at one time was fixed at 1.5mg/kg for i. m. injection and 1.0mg/kg for i. v. d.(30min.) from the monitored serum levels. The average half-life of tobrdmycin was estimated using both calculated creatinine clearance from serum creatinine level and pharmacokinetic parameters with renal impaired patients that taken from literatures. The dose vs. body weight, the frequency of daily dosage vs. age and serum creatinine level were designed to this nomogram. We selected as the kinetic parameters, that is the value of relationship between creatinine clearance and elimination rate constant which was reported by Bechtol and Black.
Tobramycin nomogram which we have deviced using factors easy to obtain clinically and easy to establish a dosage regimen based upon the decrease of renal function by aging would be very useful in performing tobramycin therapy in the geriatric patients.

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Ampicillin, cephalothin, minocycline, and kanamycin were injected intraperitoneally at dose of 100mg/kg into male Wistar rats weighing 200-250 gm. The drugs were chosen representatives of penicillins, cephalosporins, tetracyclines, and aminoglycosides resp ively. Kidney homogenates were separated into a supernatant fraction consisting primarily of cytoplasm and microsomes, and a sediment fraction consisting primarily of lysosomes and mitochondria. Antibiotic concentrations were measured in both fractions. Minocycline and kanamycin showed a tendency to accumulate in the sediment fraction for a long time, whereas ampicillin and cephalothin did not. This pharmacokinetic study on subcellular fractions may provide an interesting and valuable approach to predicting functional and morphological kidney changes caused by antibiotics.

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Pharmacokinetics of amikacin were examined in five patients undergoing hemodialysis whose mean creatinine clearance was 3.0ml/min, after intravenous 1-hour continuous infusion of 4mg/kg in the on-and off dialysis state.
In the off-dialysis state, individual pharmacokinetic parameters were widely distributed, reflecting the residual renal functions of patients, and significant linear relationships between K_el and C_er were noted: K_el=0.00488+0.00621×C_er (γ=0.974).
Pharmacokinetic parameters in the off-dialysis state, calculated by the mean serum concentrations were: C_max=18.0μg/ml, T_1/2 (β)=43.1hr., K_el=0.025hr.^-1, V_d=0.284l/kg.
During dialysis, these parameters were: C_max=17.7μg/ml, T_1/2 (β)=5.5hr., K_el=0.237hr.^-1, V_d=0.282l/kg.
T_1/2 (βA) was markedly shortened by the 6-hour hemodialysis, whereas C_max and V_d remained unchanged.
Pharmacokinetic data were used to make dosage regimen recommendations for the treatment of patients undergoing hemodialysis.
The administration of amikacin at a 4mg/kg dose at the end of every hemodialysis sessions may be effective and safe for the treatment of bacterial infections in these patients.

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