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Canadian Journal of Ophthalmology.... Oct 2015
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Conjunctivitis; Cross-Sectional Studies; Dacryocystitis; Dibekacin; Eye Infections, Bacterial; Female; Humans; Infant; Keratitis, Herpetic; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin
PubMed: 26455994
DOI: 10.1016/j.jcjo.2015.05.006 -
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 -
Journal of Korean Medical Science Jun 2015Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ear infections. We attempted to evaluate the clinical usefulness of arbekacin in treating chronic...
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ear infections. We attempted to evaluate the clinical usefulness of arbekacin in treating chronic suppurative otitis media (CSOM) by comparing its clinical efficacy and toxicity with those of vancomycin. Efficacy was classified according to bacterial elimination or bacteriologic failure and improved or failed clinical efficacy response. Ninety-five subjects were diagnosed with CSOM caused by MRSA. Twenty of these subjects were treated with arbekacin, and 36 with vancomycin. The bacteriological efficacy (bacterial elimination, arbekacin vs. vancomycin: 85.0% vs. 97.2%) and improved clinical efficacy (arbekacin vs. vancomycin; 90.0% vs. 97.2%) were not different between the two groups. However, the rate of complications was higher in the vancomycin group (33.3%) than in the arbekacin group (5.0%) (P=0.020). In addition, a total of 12 adverse reactions were observed in the vancomycin group; two for hepatotoxicity, one for nephrotoxicity, eight for leukopenia, two for skin rash, and one for drug fever. It is suggested that arbekacin be a good alternative drug to vancomycin in treatment of CSOM caused by MRSA.
Topics: Adult; Aged; Anti-Bacterial Agents; Chronic Disease; Dibekacin; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Otitis Media, Suppurative; Staphylococcal Infections; Treatment Outcome; Vancomycin; Young Adult
PubMed: 26028918
DOI: 10.3346/jkms.2015.30.6.688 -
The Journal of Antibiotics Dec 2015Arbekacin, an aminoglycoside antibiotic, is an important drug because it shows a potent efficacy against methicillin-resistant Staphylococcus aureus. However, resistance... (Comparative Study)
Comparative Study
Arbekacin, an aminoglycoside antibiotic, is an important drug because it shows a potent efficacy against methicillin-resistant Staphylococcus aureus. However, resistance to arbekacin, which is caused mainly by the bifunctional aminoglycoside-modifying enzyme, has been observed, becoming a serious problem in medical practice. To create new arbekacin derivatives active against resistant bacteria, we modified the C-4″ and 6″ positions of its 3-aminosugar portion. Regioselective amination of the 6″-position gave 6″-amino-6″-deoxyarbekacin (1), and it was converted to a variety of 6″-N-alkanoyl derivatives (6a-z). Furthermore, regioselective modifications of the 4″-hydroxyl group were performed to give 4″-deoxy-4″-epiaminoarbekacin (2) and its 4″-N-alkanoyl derivatives (12 and 13). Their antibacterial activity against S. aureus, including arbekacin-resistant bacteria, was evaluated. It was observed that 6″-amino-6″-N-[(S)-4-amino-2-hydroxybutyryl]-6″-deoxyarbekacin (6o) showed excellent antibacterial activity, even better than arbekacin.
Topics: Anti-Bacterial Agents; Dibekacin; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus
PubMed: 25990952
DOI: 10.1038/ja.2015.61 -
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 Jun 2015
Comparative Study
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Design; Escherichia coli; Gentamicins; Kanamycin; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Solubility; Staphylococcus aureus
PubMed: 25712399
DOI: 10.1038/ja.2015.6 -
Antibiotics (Basel, Switzerland) May 2015Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify...
Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine, clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin), which had high anti-persister activity. Among them, tosufloxacin and colistin had the highest anti-persister activity and could completely eradicate E. coli persisters in 3 days in vitro while the current UTI antibiotics failed to do so. Our findings may have implications for the development of a more effective treatment for UTIs.
PubMed: 27025620
DOI: 10.3390/antibiotics4020179 -
The Japanese Journal of Antibiotics Aug 2014Arbekacin (ABK) is one of aminoglycosides which has indications for septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan. ABK...
Arbekacin (ABK) is one of aminoglycosides which has indications for septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan. ABK shows good clinical and microbiological efficacies also against Gram-negative bacteria (GNB), including Pseudomonas aeruginosa. In addition, furthermore, ABK would be sometimes effective also against antimicrobial-resistant GNB. We investigated ABK inhalation, which showed good pulmonary drug delivery, for the treatment of pneumonia caused by multidrug-resistant Gram-negative organisms and MRSA. Six patients with pneumonia were treated with ABK inhalation therapy (50 mg x three times/day). We observed clinical effect for multidrug-resistant organisms in 6/6 patients. Although routine use of aerosolized antibiotics might not be able to be recommended for multidrug-resistant organisms, we might be able to adopt the ABK inhalation therapy for pneumonia especially caused by multidrug-resistant Gram-negative organisms in some situations where systemic therapy alone might be failure or inadequate, or where intravenous access is not available because of systemic toxicity. Further studies would be needed for ABK inhalation therapy for pneumonia.
Topics: Adult; Aged; Anti-Bacterial Agents; Child; Dibekacin; Female; Humans; Infant; Male; Pneumonia
PubMed: 25420319
DOI: No ID Found -
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 Oct 2014Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153...
Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6')-Iz. Escherichia coli transformed with a plasmid containing aac(6')-Iak exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6')-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.
Topics: Acetyltransferases; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Neomycin; Netilmicin; Sisomicin; Stenotrophomonas maltophilia; Tobramycin
PubMed: 25092711
DOI: 10.1128/AAC.03354-14