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Antimicrobial Agents and Chemotherapy Feb 1984The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance,...
The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.
Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Proteins; Dibekacin; Gentamicins; Kidney Diseases; Kidney Tubules; Male; Netilmicin; Protein Binding; Rabbits
PubMed: 6712201
DOI: 10.1128/AAC.25.2.168 -
Clinical Pharmacology : Advances and... 2014Arbekacin sulfate (ABK), an aminoglycoside antibiotic, was discovered in 1972 and was derived from dibekacin to stabilize many common aminoglycoside modifying enzymes.... (Review)
Review
Arbekacin sulfate (ABK), an aminoglycoside antibiotic, was discovered in 1972 and was derived from dibekacin to stabilize many common aminoglycoside modifying enzymes. ABK shows broad antimicrobial activities against not only Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) but also Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. ABK has been approved as an injectable formulation in Japan since 1990, under the trade name Habekacin, for the treatment of patients with pneumonia and sepsis caused by MRSA. The drug has been used in more than 250,000 patients, and its clinical benefit and safety have been proven over two decades. ABK currently shows promise for the application for the treatment of multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant strains of P. aeruginosa and Acinetobacter baumannii because of its synergistic effect in combination with beta-lactams.
PubMed: 25298740
DOI: 10.2147/CPAA.S44377 -
Antimicrobial Agents and Chemotherapy Dec 1980The nephrotoxicity of dibekacin was compared with those of gentamicin and amikacin in a rat model. The doses used were 3, 10, and 30 times the suggested human... (Comparative Study)
Comparative Study
The nephrotoxicity of dibekacin was compared with those of gentamicin and amikacin in a rat model. The doses used were 3, 10, and 30 times the suggested human therapeutic dose on a weight basis. Indices of glomerular and tubular function failed to clearly differentiate the drugs. Dibekacin and gentamicin produced equally severe injury to the renal tissue. Slightly less damage occurred with amikacin.
Topics: Amikacin; Animals; Dibekacin; Gentamicins; Kanamycin; Kidney; Male; Rats
PubMed: 7235685
DOI: 10.1128/AAC.18.6.983 -
Antimicrobial Agents and Chemotherapy Sep 2015Corynebacterium striatum BM4687 was resistant to gentamicin and tobramycin but susceptible to kanamycin A and amikacin, a phenotype distinct among Gram-positive...
Corynebacterium striatum BM4687 was resistant to gentamicin and tobramycin but susceptible to kanamycin A and amikacin, a phenotype distinct among Gram-positive bacteria. Analysis of the entire genome of this strain did not detect any genes for known aminoglycoside resistance enzymes. Yet, annotation of the coding sequences identified 12 putative acetyltransferases or GCN5-related N-acetyltransferases. A total of 11 of these coding sequences were also present in the genomes of other Corynebacterium spp. The 12th coding sequence had 55 to 60% amino acid identity with acetyltransferases in Actinomycetales. The gene was cloned in Escherichia coli, where it conferred resistance to aminoglycosides by acetylation. The protein was purified to homogeneity, and its steady-state kinetic parameters were determined for dibekacin and kanamycin B. The product of the turnover of dibekacin was purified, and its structure was elucidated by high-field nuclear magnetic resonance (NMR), indicating transfer of the acetyl group to the amine at the C-3 position. Due to the unique profile of the reaction, it was designated aminoglycoside 3-N-acetyltransferase type XI.
Topics: Acetyltransferases; Anti-Bacterial Agents; Corynebacterium; Dibekacin; Kanamycin; Microbial Sensitivity Tests; Molecular Structure
PubMed: 26149994
DOI: 10.1128/AAC.01203-15 -
Antimicrobial Agents and Chemotherapy Mar 1978Against sulbenicillin- and gentamicin-susceptible strains of Pseudomonas aeruginosa, SCE-129 was about 10 times more active than sulbenicillin and had a similar activity... (Comparative Study)
Comparative Study
Against sulbenicillin- and gentamicin-susceptible strains of Pseudomonas aeruginosa, SCE-129 was about 10 times more active than sulbenicillin and had a similar activity to gentamicin and dibekacin. Sulbenicillin-resistant strains of P. aeruginosa were moderately resistant to SCE-129, whether these strains were gentamicin-resistant or not. Gentamicin-resistant strains of P. aeruginosa were resistant to dibekacin but not to SCE-129. Against P. maltophilia, the minimum inhibitory concentration of SCE-129 resembled those of sulbenicillin, gentamicin, and dibekacin. Most strains of P. cepacia were moderately resistant to SCE-129 and sulbenicillin and highly resistant to gentamicin and dibekacin.
Topics: Cefsulodin; Dibekacin; Gentamicins; Kanamycin; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Pseudomonas aeruginosa; Sulbenicillin
PubMed: 122528
DOI: 10.1128/AAC.13.3.536 -
The Tohoku Journal of Experimental... Jun 1987A possible mechanism responsible for the combined effects of sulbenicillin and dibekacin on Pseudomonas aeruginosa IAM 1007 was investigated. The bactericidal activity... (Comparative Study)
Comparative Study
A possible mechanism responsible for the combined effects of sulbenicillin and dibekacin on Pseudomonas aeruginosa IAM 1007 was investigated. The bactericidal activity of the above two drugs in combination was very strong. The regrowth of test strains after removal of the drugs was suppressed markedly, even when they were exposed to sulbenicillin plus dibekacin at a subinhibitory concentration of individual drugs. Sulbenicillin caused elongation of the bacterial cells. At the early stage of elongation, no demonstrable changes of ultrastructure of the cell wall were observed. At the late stage, lysis of the peptidoglycan layer occurred and spheroplast was formed. However, most of the outer membrane of the cell wall remained intact. Sulbenicillin acts upon the peptidoglycan layer, but not on the outer membrane. Thus it is difficult for sulbenicillin alone to cause cell lysis. On the other hand, dibekacin caused destruction of ribosomes and lysis of the outer membrane of the cell wall. Both sulbenicillin and dibekacin act on the cell wall, the former on the peptidoglycan layer (the inner membrane) and the latter on the outer membrane. The combined use of sulbenicillin and dibekacin caused elongation of bacilli and severe destruction of the inner and outer membranes of the cell wall. These morphological changes occurred even when the concentration of the individual drug was lower than its minimum inhibitory concentration (MIC). Furthermore, the cells elongated by sulbenicillin were ruptured easily when treated with dibekacin subsequently. The bacilli treated with dibekacin at a concentration lower than MIC and then treated with sulbenicillin at a concentration lower than MIC showed a marked elongation of the cells, which indicated that the effects of sulbenicillin was enhanced by dibekacin. These findings suggested strongly that sulbenicillin and dibekacin act on cell wall constituents and that their effects were complementary and synergistic.
Topics: Cell Wall; Dibekacin; Drug Synergism; Kanamycin; Microscopy, Electron; Penicillin G; Pseudomonas aeruginosa; Sulbenicillin
PubMed: 3114912
DOI: 10.1620/tjem.152.119 -
Antimicrobial Agents and Chemotherapy Apr 1985The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has... (Comparative Study)
Comparative Study
The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has been described in the literature. Thirty-three healthy male volunteers received a continuous intravenous infusion of isotonic saline with inulin, followed 1 h later by inulin plus gentamicin, dibekacin, tobramycin, netilmicin, or amikacin (1 mg/kg per h) or amikacin (4 mg/kg per h) over a period of 2 h. Brain-stem-evoked response audiometry was performed both before and at the end of each infusion. The latency of wave V remained constant whichever antibiotic was considered. The glomerular filtration rate did not vary significantly during the infusion of each drug. The percent fractional excretion was 79 +/- 6, 81 +/- 22, 85 +/- 5, and 99 +/- 9 for gentamicin, dibekacin, tobramycin, and netilmicin, respectively, and 83 +/- 4 and 124 +/- 13 for amikacin at concentrations of 1 and 4 mg/kg per h, respectively. Net balance and renal clearance were similar for the five aminoglycosides when administered at a rate of 1 mg/kg per h. With gentamicin only, fractional excretion was correlated with the urinary flow rate. We can conclude that (i) gentamicin, generally considered the most nephrotoxic agent, had the highest degree of net reabsorption; (ii) netilmicin exhibited a net zero tubular balance; (iii) amikacin had different patterns of tubular disposition according to the dose, i.e., reabsorption at 1 mg/kg per h and secretion at 4 mg/kg per h, raising the hypothesis of a saturable process of reabsorption; and (iv) these differences in tubular reabsorption could account at least in part for the known different nephrotoxic potentials of these five aminoglycosides in humans.
Topics: Adult; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Blood Proteins; Dibekacin; Electrolytes; Gentamicins; Glomerular Filtration Rate; Humans; Kidney Tubules; L-Lactate Dehydrogenase; Male; Netilmicin; Protein Binding; Tobramycin
PubMed: 4004192
DOI: 10.1128/AAC.27.4.520 -
Antimicrobial Agents and Chemotherapy 2015Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We...
Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp., and Enterobacter spp. The highest arbekacin MIC among S. aureus isolates from PHP (43% methicillin-resistant S. aureus [MRSA]) was 4 μg/ml. Among P. aeruginosa isolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50 and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested against Acinetobacter baumannii. Against Enterobacteriaceae from PHP, arbekacin and gentamicin (MIC50 and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50 and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50 and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potent in vitro activity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.
Topics: Amikacin; Anti-Bacterial Agents; Dibekacin; Enterobacter; Humans; Klebsiella; Microbial Sensitivity Tests; Pneumonia; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Staphylococcus aureus; Tobramycin
PubMed: 25801559
DOI: 10.1128/AAC.04839-14 -
The Journal of Antibiotics Oct 2000Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their...
Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKB also retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM, paromomycin], NM retained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTM and istamycin B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others. Streptomyces lividans TK21 containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.
Topics: Acetylation; Acetyltransferases; Actinomycetales; Aminoglycosides; Anti-Bacterial Agents; Bacillus subtilis; Carbohydrate Sequence; Chromatography, Thin Layer; Drug Resistance, Microbial; Microbial Sensitivity Tests; Molecular Sequence Data; Streptomyces
PubMed: 11132963
DOI: 10.7164/antibiotics.53.1168 -
MicrobiologyOpen Jun 2019Kanamycin B as the secondary metabolite of wild-type Streptomyces kanamyceticus (S. kanamyceticus) ATCC12853 is often used for the synthesis of dibekacin and arbekacin....
Kanamycin B as the secondary metabolite of wild-type Streptomyces kanamyceticus (S. kanamyceticus) ATCC12853 is often used for the synthesis of dibekacin and arbekacin. To construct the strain has the ability for kanamycin B production; the pSET152 derivatives from Escherichia coli ET12567 were introduced to S. kanamyceticus by intergeneric conjugal transfer. In this study, we established a reliable genetic manipulation system for S. kanamyceticus. The key factors of conjugal transfer were evaluated, including donor-to-recipient ratio, heat-shock, and the overlaying time of antibiotics. When spores were used as recipient, the optimal conjugation frequency was up to 6.7 × 10 . And mycelia were used as an alternative recipient for conjugation instead of spores; the most suitable donor-to-recipient ratio is 1:1 (10 :10 ). After incubated for only 10-12 hr and overlaid with antibiotics subsequently, the conjugation frequency can reach to 6.2 × 10 which is sufficient for gene knockout and other genetic operation. Based on the optimized conjugal transfer condition, kanJ was knocked out successfully. The kanamycin B yield of kanJ-disruption strain can reach to 543.18 ± 42 mg/L while the kanamycin B yield of wild-type strain was only 46.57 ± 12 mg/L. The current work helps improve the content of kanamycin B in the fermentation broth of S. kanamyceticus effectively to ensure the supply for the synthesis of several critical semisynthetic antibiotics.
Topics: Anti-Bacterial Agents; Conjugation, Genetic; Escherichia coli; Fermentation; Gene Transfer Techniques; Kanamycin; Plasmids; Streptomyces
PubMed: 30449069
DOI: 10.1002/mbo3.747