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Journal of Clinical Microbiology Jan 201616S rRNA methyltransferases confer resistance to most aminoglycosides, but discriminating their activity from that of aminoglycoside-modifying enzymes (AMEs) is...
16S rRNA methyltransferases confer resistance to most aminoglycosides, but discriminating their activity from that of aminoglycoside-modifying enzymes (AMEs) is challenging using phenotypic methods. We demonstrate that arbekacin, an aminoglycoside refractory to most AMEs, can rapidly detect 16S methyltransferase activity in Enterobacteriaceae with high specificity using the standard disk susceptibility test.
Topics: Anti-Infective Agents; Dibekacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Enterobacteriaceae; Genotype; Humans; Phenotype; RNA, Ribosomal, 16S; tRNA Methyltransferases
PubMed: 26537447
DOI: 10.1128/JCM.02642-15 -
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 -
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 -
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 -
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 -
PloS One 2014To determine the in vitro activity of antibiotics, including arbekacin, cefminox, fosfomycin and biapenem which are all still unavailable in India, against Gram-negative...
Determination of MIC distribution of arbekacin, cefminox, fosfomycin, biapenem and other antibiotics against gram-negative clinical isolates in South India: a prospective study.
OBJECTIVES
To determine the in vitro activity of antibiotics, including arbekacin, cefminox, fosfomycin and biapenem which are all still unavailable in India, against Gram-negative clinical isolates.
METHODS
We prospectively collected and tested all consecutive isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. from blood, urine and sputum samples between March and November 2012. The minimum inhibition concentration (MIC) of 16 antibiotics was determined by the broth micro-dilution method.
RESULTS
Overall 925 isolates were included; 211 E. coli, 207 Klebsiella spp., 153 P. aeruginosa, and 354 Acinetobacter spp. The MIC50 and MIC90 were high for cefminox, biapenem and arbekacin for all pathogens but interpretative criteria were not available. The MIC50 was categorized as susceptible for a couple of antibiotics, including piperacillin/tazobactam, carbapenems and amikacin, for E. coli, Klebsiella spp. and P. aeruginosa. However, for Acinetobacter spp., the MIC50 was categorized as susceptible only for colistin. On the other hand, fosfomycin was the only antibiotic that inhibited 90% of E. coli and Klebsiella spp. isolates, while 90% of P. aeruginosa isolates were inhibited only by colistin. Finally, 90% of Acinetobacter spp. isolates were not inhibited by any antibiotic tested.
CONCLUSION
Fosfomycin and colistin might be promising antibiotics for the treatment of infections due to E. coli or Klebsiella spp. and P. aeruginosa, respectively, in India; however, clinical trials should first corroborate the in vitro findings. The activity of tigecycline should be evaluated, as this is commonly used as last-resort option for the treatment of multidrug-resistant Acinetobacter infections.
Topics: Acinetobacter; Anti-Bacterial Agents; Cephamycins; Dibekacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; India; Klebsiella; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas aeruginosa; Thienamycins
PubMed: 25068396
DOI: 10.1371/journal.pone.0103253 -
BMC Genomics Jul 2014With the development of space science, it is important to analyze the relationship between the space environment and genome variations that might cause phenotypic...
BACKGROUND
With the development of space science, it is important to analyze the relationship between the space environment and genome variations that might cause phenotypic changes in microbes. Klebsiella pneumoniae is commonly found on the human body and is resistant to multiple drugs. To study space-environment-induced genome variations and drug resistance changes, K. pneumoniae was carried into outer space by the Shenzhou VIII spacecraft.
RESULTS
The K. pneumoniae strain LCT-KP289 was selected after spaceflight based on its phenotypic differences compared to the ground-control strain. Analysis of genomic structural variations revealed one inversion, 25 deletions, fifty-nine insertions, two translocations and six translocations with inversions. In addition, 155 and 400 unique genes were observed in LCT-KP214 and LCT-KP289, respectively, including the gene encoding dihydroxyacetone kinase, which generates the ATP and NADH required for microbial growth. Furthermore, a large number of mutant genes were related to transport and metabolism. Phylogenetic analysis revealed that most genes in these two strains had a dN/dS value greater than 1, indicating that the strain diversity increased after spaceflight. Analysis of drug-resistance phenotypes revealed that the K. pneumoniae strain LCT-KP289 was resistant to sulfamethoxazole, whereas the control strain, LCT-KP214, was not; both strains were resistant to benzylpenicillin, ampicillin, lincomycin, vancomycin, chloramphenicol and streptomycin. The sulfamethoxazole resistance may be associated with sequences in Scaffold7 in LCT-KP289, which were not observed in LCT-K214; this scaffold contained the gene sul1. In the strain LCT-KP289, we also observed a drug-resistance integron containing emrE (confers multidrug resistance) and ant (confers resistance to spectinomycin, streptomycin, tobramycin, kanamycin, sisomicin, dibekacin, and gentamicin). The gene ampC (confers resistance to penicillin, cephalosporin-ii and cephalosporin-i) was present near the integron. In addition, 30 and 26 drug-resistance genes were observed in LCT-KP289 and LCT-KP214, respectively.
CONCLUSIONS
Comparison of a K. pneumoniae strain obtained after spaceflight with the ground-control strain revealed genome variations and phenotypic changes and elucidated the genomic basis of the acquired drug resistance. These data pave the way for future studies on the effects of spaceflight.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Comparative Genomic Hybridization; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Integrons; Klebsiella pneumoniae; Mutation; Phylogeny; Sequence Analysis, DNA; Space Flight; Virulence
PubMed: 25015528
DOI: 10.1186/1471-2164-15-589