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The Japanese Journal of Antibiotics Aug 1980Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle...
Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of 2.5, 5.0, 10.0 or 25.0 mg/kg/day for 13 weeks. Physiological saline was given as a control. Some dogs given 5.0 or 10.0 mg/kg/day were retained undosed for a further 5 weeks in order to assess recovery. Premature deaths from acute renal tubular nephrosis occurred in dogs given 25.0 and 10.0 mg/kg/day. Dogs which survived treatment at 10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after 4 weeks' treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after 13 weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined 5 weeks after the last dose of DKB at 5.0 mg/kg/day. All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.
Topics: Animals; Blood Chemical Analysis; Body Weight; Dibekacin; Dogs; Drinking; Eating; Female; Injections, Intravenous; Kanamycin; Kidney; Kidney Tubular Necrosis, Acute; Organ Size
PubMed: 7206221
DOI: No ID Found -
The American Journal of Medicine Jun 1986Following the development of amikacin, pharmaceutical companies made intensive efforts to find even more potent and broader-spectrum aminoglycosides. This effort was... (Comparative Study)
Comparative Study Review
Following the development of amikacin, pharmaceutical companies made intensive efforts to find even more potent and broader-spectrum aminoglycosides. This effort was justifiable in view of the fact that over the preceding decade, these agents, because of their unique properties, had proven to be the primary weapons in the therapeutic armamentarium for the treatment of seriously ill patients. Since the toxicities associated with the aminoglycosides were beginning to limit their use in general medicine, researchers ultimately shifted their emphasis from probing for higher-potency, broader-spectrum agents to finding those with a reduced potential for toxicity. This article addresses the issue of whether superior aminoglycoside derivatives will reach the marketplace in the future. A comparison is made of several key properties of virtually all aminoglycosides that have reached an advanced preclinical development stage, gone into the clinic, or been registered for commercial use over the past 10 years. The following parameters are used for comparisons with already marketed aminoglycosides: antibacterial potency, as measured by relative minimum inhibitory concentrations for 50 percent of the strains tested, against wild-type Pseudomonas aeruginosa; degree of resistance to inactivation by microbial enzymes; and potential for toxicity utilizing comparative acute intravenous lethal doses for 50 percent of the population in mice, values that appear to predict the maximum recommended daily doses in man. An assessment of a number of compounds, including three structurally related to gentamicin, two to sisomicin, two to kanamycin A, three to kanamycin B, and two to fortimicin, revealed that none had overall properties superior to those already being utilized commercially. In no case did a compound prove to be less toxic, and in many instances, the antibacterial potency of the newer agents was lower than that exhibited by the older aminoglycosides. Some increase in resistance to inactivating enzymes was seen, but only BB-K 311 proved refractory to more enzymes than did amikacin. In view of this and the fact that no new agents of promise have moved into the development stage during the past five years, it seems safe to say that the current armamentarium of aminoglycosides is all that will be available for use in the foreseeable future.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Microbial; Gentamicins; Humans; Kanamycin; Lethal Dose 50; Mice; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Sisomicin; Tobramycin
PubMed: 3089002
DOI: 10.1016/0002-9343(86)90499-7 -
Journal of Infection and Chemotherapy :... Dec 2011In an analysis of methicillin-resistant Staphylococcus aureus (MRSA) infected patients treated with arbekacin (ABK) only, Gram-negative bacteria (GNB) that were...
In an analysis of methicillin-resistant Staphylococcus aureus (MRSA) infected patients treated with arbekacin (ABK) only, Gram-negative bacteria (GNB) that were inhibited by low minimal inhibitory concentrations (MICs) of amikacin (AMK) or gentamycin (GM) were eradicated by the end of the ABK treatment. On the other hand, GNB that were only inhibited by high MICs of AMK or GM persisted until the end of treatment with ABK only. Thus, ABK can be expected to be effective even in cases of mixed infection with GNB and MRSA.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Coinfection; Dibekacin; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections
PubMed: 21667069
DOI: 10.1007/s10156-011-0262-x -
Hinyokika Kiyo. Acta Urologica Japonica Jan 1984Dibekacin (DKB) was administered to patients with complicated urinary tract infections without any indwelling catheter to evaluate objectively and comparatively the... (Clinical Trial)
Clinical Trial Comparative Study
Dibekacin (DKB) was administered to patients with complicated urinary tract infections without any indwelling catheter to evaluate objectively and comparatively the efficacy, safety and usefulness of intravenous drip infusion once daily and twice daily in a well-controlled study. A 50 mg dose of DKB was administered twice a day to group A, and a 100 mg dose was given once a day to group B. In both groups the drug was given by 1-hr i.v. infusion for 5 consecutive days. Drug efficacy was evaluated in 72 (group A: 36, group B: 36) of the 83 patients treated, and the safety was evaluated on 81 patients (group A: 41, group B: 40). There were no significant differences in the background characteristics between the two groups. The overall clinical efficacy judged by the Committee for Evaluation of Clinical Efficacy was "excellent" in 14% and "moderate" in 50% of group A, and "excellent" in 17% and "moderate" in 64% of group B, the efficacy being higher for group B than group A, but the difference was not statistically significant. The overall drug efficacy rate for each type of infection excluding group 2, was slightly higher in group B, but this difference was not significant either. The overall clinical efficacy for each site of infection, was higher for group B but the differences were not significant. The overall clinical efficacy as judged by the attending physicians was "excellent" in 17% and "moderate" in 58% of group A, and "excellent" in 25% and "moderate" in 61% of group B. The intergroup difference was thus smaller than that judged by the Committee. The elimination rates against bacteriuria were 58% for both groups A and B, and the decrease rates including "cleared" were 42% against pyuria for both groups A and B. Bacteriological evaluation, showed that there was no significant difference in the eradication rates, between group A (65%) and group B (70%). But the eradication rate for gram-positive bacteria was 40% in group A and 81% in group B, there being a significant difference (P less than 0.05) between them. The evaluation of usefulness gave 44% and 53% "satisfactory" rates, respectively, for groups A and B. The results for the "average score" were also the same in both groups. There were no side effects in any of the 81 patients examined. Abnormal laboratory test values attributed to the drug were seen only in 3 and 2 patients in groups A and B, respectively, there being no difference between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria; Clinical Trials as Topic; Dibekacin; Drug Administration Schedule; Drug Resistance, Microbial; Female; Humans; Infusions, Parenteral; Kanamycin; Male; Middle Aged; Urinary Tract Infections
PubMed: 6375317
DOI: No ID Found -
The Japanese Journal of Antibiotics Feb 1977
Topics: Bacteria; Dibekacin; Drug Resistance, Microbial; Gentamicins; Kanamycin
PubMed: 853578
DOI: No ID Found -
The Japanese Journal of Antibiotics Dec 1983Serum concentrations of dibekacin (DKB), sisomicin (SISO) and gentamicin (GM) were measured in 3 rabbits after intratracheal administration through the transtracheal...
Serum concentrations of dibekacin (DKB), sisomicin (SISO) and gentamicin (GM) were measured in 3 rabbits after intratracheal administration through the transtracheal teflon tube. The peak serum levels (average) were 106 micrograms/ml (administrated 100 mg DKB for injection), 148 micrograms/ml (administrated 100 mg DKB solution), 166 micrograms/ml (administrated 100 mg SISO solution) and 80 micrograms/ml (administrated 80 mg GM solution). Serum concentrations and urine excretions of DKB were measured in 3 volunteers after aerosol administration using ultrasonic nebulizer. The peak serum levels (average) were 4.6 micrograms/ml (administrated 100 mg DKB for injection) and 3.1 micrograms/ml (administrated 100 mg DKB solution). The urine excretions (average) were 3.7 mg and 4.3 mg respectively during 6 hours. Before and after administration of DKB aerosol the spirogram and flow-volume curve were examined in the volunteers. But the examinations showed no changes. Sputum concentrations were measured in 1 patient with chronic bronchobronchiolitis after administration of DKB aerosols using the ultrasonic nebulizer. The highest sputum concentration was acquired immediately after nebulization and the sputum levels decreased gradually while time passed. Six patients with the lower respiratory tract infections were treated with DKB aerosol therapy and the utility rate was 80%.
Topics: Adult; Aerosols; Aged; Animals; Bronchitis; Dibekacin; Drug Evaluation; Gentamicins; Humans; Kanamycin; Male; Middle Aged; Rabbits; Respiratory Therapy; Sisomicin; Sputum
PubMed: 6674552
DOI: No ID Found -
Emerging Infectious Diseases Jun 2005Emergence of the newly identified 16S rRNA methylases RmtA, RmtB, and ArmA in pathogenic gram-negative bacilli has been a growing concern. ArmA, which had been...
Emergence of the newly identified 16S rRNA methylases RmtA, RmtB, and ArmA in pathogenic gram-negative bacilli has been a growing concern. ArmA, which had been identified exclusively in Europe, was also found in several gram-negative pathogenic bacilli isolated in Japan, suggesting global dissemination of hazardous multiple aminoglycoside resistance genes.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Dibekacin; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Global Health; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Methyltransferases; Microbial Sensitivity Tests; RNA, Ribosomal, 16S
PubMed: 15963295
DOI: 10.3201/eid1106.040924 -
Acta Pharmacologica Et Toxicologica Sep 1983The cochleo- and vestibulotoxicity of dibekacin and netilmicin were compared in a guinea pig model. Both aminoglycosides were administered subcutaneously for 21 days at... (Comparative Study)
Comparative Study
The cochleo- and vestibulotoxicity of dibekacin and netilmicin were compared in a guinea pig model. Both aminoglycosides were administered subcutaneously for 21 days at the dose level of 150 mg/kg/day. Control animals were injected with saline. Dibekacin-treated animals showed a significant (P less than 0.05) increase in the thresholds of the Preyer pinna reflex and the VIIIth nerve compound action potential in response to sound click stimulation. Moreover, a deterioration of the electrophysiologic auditory response and an almost complete suppression of the post-rotatory nystagmus were detected. In contrast, netilmicin did not induce any significant change in auditory and vestibular functions as compared to the control group. Our results demonstrated that netilmicin was devoid of ototoxicity in the guinea pig, while dibekacin provoked mild cochlear and severe vestibulotoxicity.
Topics: Action Potentials; Animals; Auditory Threshold; Cochlea; Dibekacin; Evoked Potentials, Auditory; Female; Gentamicins; Guinea Pigs; Kanamycin; Labyrinth Diseases; Male; Netilmicin; Nystagmus, Pathologic
PubMed: 6637512
DOI: 10.1111/j.1600-0773.1983.tb01130.x -
The Japanese Journal of Antibiotics Oct 1979
Comparative Study
Topics: Animals; Anti-Bacterial Agents; Cochlea; Dibekacin; Ear; Electric Stimulation; Hair Cells, Auditory; Infusions, Parenteral; Kanamycin; Kidney Diseases; Rabbits; Tobramycin; Vestibulocochlear Nerve
PubMed: 513289
DOI: No ID Found -
The Journal of Pharmacology and... Jul 1983Among presently available aminoglycosides, dibekacin has the least toxic effect on the functions of the cochlea and the vestibule. We investigated the potential...
Among presently available aminoglycosides, dibekacin has the least toxic effect on the functions of the cochlea and the vestibule. We investigated the potential nephrotoxicity of dibekacin at various dose levels and durations of treatment. In the rat, the injection of high doses (50 mg/kg for 8 days) produced: 1) a reduction in renal function and the onset of cellular necrosis; 2) the appearance of myeloid bodies in the cells of the proximal tubule; 3) accumulation of the drug in the renal cortex at a concentration of 4.4 micrograms/mg of protein; 4) a reduction in the lysosomal latency of N-acetyl-beta-D-glucosaminidase; and 5) disorders of the activity of cortical enzymes cathepsin B and sphingomyelinase. The effect of dibekacin is similar to that of the other aminoglycosides, but it would seem to be less nephrotoxic than gentamicin.
Topics: Acetylglucosaminidase; Animals; Cathepsin B; Cathepsins; Dibekacin; Dose-Response Relationship, Drug; Female; Kanamycin; Kidney; Kidney Cortex; Kidney Tubules, Proximal; Lysosomes; Rats; Rats, Inbred Strains; Sphingomyelin Phosphodiesterase; Time Factors; Vacuoles
PubMed: 6864541
DOI: No ID Found