Bb-K8, a New Semisynthetic Aminoglycoside Antibiotic

Kawaguchi, Hiroshi; Naitô, Takayuki; Nakagawa, Susumu; Fujisawa, Kei-Ichi

doi:10.7164/antibiotics.25.695

Cited by 297 publications

(121 citation statements)

References 14 publications

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“…They have been largely replaced by semi-synthetic analogs (for example, amikacin, dibekacin and arbekacin) that are chemically modified in the 2-4-O-(6-amino-6-deoxy-a-D-glucopyranosyl)-2-deoxystreptamine and ring I aminosugar moieties and now broadly used clinically. [15][16][17][18] Earlier attempts to improve antibiotic efficacy with modifications in the ring III moiety were limited to chemical variations at the C6 00 position. 19,20 Recently, we developed protocols to stereoselectively attach aglycosyl donors to an 'optimized' disaccharide neamine core to produce novel kanamycin class aminoglycosides.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

et al. 2010

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Many Actinomycetes aminoglycosides are widely used antibiotics. Although mainly antibacterials, a few known aminoglycosides also inhibit yeasts, protozoans and important crop pathogenic fungal oomycetes. Here we show that attachment of a C8 alkyl chain to ring III of a neamine-based aminoglycoside specifically at the 4 00 -O position yields a broad-spectrum fungicide (FG08) without the antibacterial properties typical for aminoglycosides. Leaf infection assays and greenhouse studies show that FG08 is capable of suppressing wheat fungal infections by Fusarium graminearum-the causative agent of Fusarium head blight-at concentrations that are minimally phytotoxic. Unlike typical aminoglycoside action of ribosomal protein translation miscoding, FG08's antifungal action involves perturbation of the plasma membrane. This antibacterial to antifungal transformation could pave the way for the development of a new class of aminoglycoside-based fungicides suitable for use in crop disease applications. In addition, this strategy is an example of reviving a clinically obsolete drug by simple chemical modification to yield a new application.

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Section: Introductionmentioning

confidence: 99%

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

et al. 2010

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“…Amikacin is a new aminoglycoside antibiotic with an antibacterial spectrum comparable to gentamicin and tobramycin (3,4). Since aminoglycosides are excreted mainly through the kidney and not metabolized in the body, their toxic effects are increased in renal failure.…”

mentioning

confidence: 99%

Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Madhavan

Yaremchuk²,

Levin³

et al. 1976

Antimicrob Agents Chemother

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Serum and dialysate levels of amikacin were determined at appropriate intervals after a 300-mg intravenous dose as a continuous infusion in six patients with end-stage renal failure undergoing hemodialysis and in three patients on peritoneal dialysis. The mean serum half-life of amikacin was 3.75 h during (or after) hemodialysis and 29 h during (or after) peritoneal dialysis. Although not on hemodialysis in the same six patients, the serum half-life was 28 h. The results indicate that the maintenance dose of amikacin should be markedly decreased in patients with severe renal failure even ifthey are treated with peritoneal dialysis, and that serial serum antibiotic concentrations are essential to prevent cumulative toxicity of the drug.Amikacin is a new aminoglycoside antibiotic with an antibacterial spectrum comparable to gentamicin and tobramycin (3, 4). Since aminoglycosides are excreted mainly through the kidney and not metabolized in the body, their toxic effects are increased in renal failure. However, these antibiotics may be the only available agents to treat life-threatening infections. It, therefore, is important to know how renal failure and renal dialysis effect the pharmacology of amikacin. We accordingly determined the serum concentration, half-life, and dialysate concentration of amikacin in patients with renal failure who were being dialyzed, and the results are the subject of this report.MATERIALS AND METHODS Patient selection. Studies were performed in six patients undergoing a 4-h hemodialysis using two Cordis-Dow model no. 4 hollow fiber kidneys. Blood flow during dialysis was approximately 200 ml/min, and dialysate flow was 500 ml/min. Three patients who were being treated with peritoneal dialysis using Impersol solution run at 2 liters/h for 48 h were studied. The patients had stable creatinine clearance values below 10 mg/min.Patients with congestive heart failure, concurrent hepatic disease, and acute blood loss were excluded from this study. The age, sex, body weight, serum creatinine, total protein, and serum albumin levels in six patients with end-stage renal disease on hemodialysis are summarized in Table 1. All patients were evaluated before and 1 week after amikacin administration for adverse effects, and no changes were found in the histories and physical examinations, blood count, urinalysis, bilirubin, serum glutamic oxalacetic transaminase, alkaline phosphatase, serum protein, serum albumin, creatinine, blood urea nitrogen, and serum electrolytes.Collection of specimens. Patients on hemodialysis. A single dose of 300 mg of amikacin was administered intravenously (i.v.) over a period of 60 min starting 75 min before the onset of dialysis. Blood samples were drawn at the beginning of dialysis and thereafter at 5, 30, 90, 210, and 270 min and 12 and 24 h. The dialysate was collected and pooled. Volumes were measured, and a 20-ml sample was taken for antibiotic assay and then frozen immediately. The same dose of amikacin was given 10 to 14 days later to the same six patients on a day...

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“…Amikacin is a semisynthetic aminoglycoside antibiotic produced by acylation of kanamycin A (14). It is effective in the treatment of patients with serious infections due to gram-negative bacilli and is particularly useful in therapy of infections involving organisms that are resistant to other aminoglycoside antibiotics (1,21).…”

mentioning

confidence: 99%

Amikacin pharmacokinetics in pediatric patients with malignancy

Cleary¹,

Pickering²,

Kramer³

et al. 1979

Antimicrob Agents Chemother

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The pharmacokinetics of anmikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and nonnal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 mim produced concentrations in serum of 29.3 ± 5.7 jig/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 ± 1.7 jsg/ml and at 6 h of 1.2 ± 0.3 ,ug/ml. The serum half-life was 1.24 ± 0.09 h, volume of distribution was 0.26 ± 0.02 liter/kg, and total body clearance rate was 131 ± 10 ml/min per 1.73 m2. No accumulation of amnikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

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Bb-K8, a New Semisynthetic Aminoglycoside Antibiotic

Cited by 297 publications

References 14 publications

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Amikacin pharmacokinetics in pediatric patients with malignancy

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