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Antimicrobial Agents and Chemotherapy Aug 1985The resistance mechanisms of more than 2,000 aminoglycoside-resistant gram-negative aerobic bacteria were estimated by a method that assigned a biochemical mechanism...
The resistance mechanisms of more than 2,000 aminoglycoside-resistant gram-negative aerobic bacteria were estimated by a method that assigned a biochemical mechanism based on susceptibility to selected aminoglycosides. Strains from hospitals in Japan, Formosa, and Korea (the Far East) were compared with strains from Chile and the United States. Of the strains from Chile, 90% had an aminoglycoside resistance pattern indicative of the 3-N-acetyltransferase [AAC(3)-V] enzyme. Of the strains from the Far East, 78% had susceptibility patterns suggesting the presence of AAC(6') enzymes. In contrast, strains from the United States had a wider variety of resistance mechanisms including 2''-O-adenylyltidyltransferase [ANT(2'')], AAC(3), AAC(6'), and AAC(2'). Reflecting these differences in resistance patterns, the frequencies of resistance to gentamicin, tobramycin, dibekacin, and amikacin in strains from the United States were different from those in strains from the Far East. These differences seem to be correlated with different aminoglycoside usage in the two regions. In the United States, where gentamicin was the most widely used aminoglycoside, 92% of the strains were resistant to gentamicin, 81% were resistant to dibekacin, and 8.8% were resistant to amikacin. In the Far East, dibekacin and kanamycin were widely used in the past and more recently amikacin has been frequently used. Of the strains from this region, 99% were resistant to dibekacin, 85% were resistant to gentamicin, and 35% were resistant to amikacin.
Topics: Aminoglycosides; Anti-Bacterial Agents; Chile; Drug Resistance, Microbial; Gram-Negative Bacteria; Humans; Japan; Korea; Microbial Sensitivity Tests; Proteus vulgaris; Providencia; Pseudomonas; Serratia; Taiwan; United States
PubMed: 3914858
DOI: 10.1128/AAC.28.2.282 -
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 -
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 Jan 2013Pseudomonas aeruginosa NCGM1588 has a novel chromosomal class 1 integron, In151, which includes the aac(6')-Iaj gene. The encoded protein, AAC(6')-Iaj, was found to...
Pseudomonas aeruginosa NCGM1588 has a novel chromosomal class 1 integron, In151, which includes the aac(6')-Iaj gene. The encoded protein, AAC(6')-Iaj, was found to consist of 184 amino acids, with 70% identity to AAC(6')-Ia. Escherichia coli transformed with a plasmid containing the aac(6')-Iaj gene acquired resistance to all aminoglycosides tested except gentamicin. Of note, aac(6')-Iaj contributed to the resistance to arbekacin. Thin-layer chromatography revealed that AAC(6')-Iaj acetylated all aminoglycosides tested except gentamicin. These findings indicated that AAC(6')-Iaj is a functional acetyltransferase that modifies the amino groups at the 6' positions of aminoglycosides and contributes to aminoglycoside resistance of P. aeruginosa NCGM1588, including arbekacin.
Topics: Acetylation; Acetyltransferases; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Chromatography, Thin Layer; Dibekacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gentamicins; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Pseudomonas Infections; Pseudomonas aeruginosa; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Substrate Specificity
PubMed: 23070167
DOI: 10.1128/AAC.01105-12 -
Hinyokika Kiyo. Acta Urologica Japonica Dec 1987Changes of bacterial isolates from urine specimens of outpatients with urinary tract infections (UTI) from 1977 through 1984 were studied. Organisms which were isolated...
Changes of bacterial isolates from urine specimens of outpatients with urinary tract infections (UTI) from 1977 through 1984 were studied. Organisms which were isolated from patients with bacteriuria of over 10(3) bacteria per ml of urine regardless of grade of pyuria were studied. The incidence of UTI, especially that of acute cystitis was decreased during the recent 8 years. E. coli was the most predominant isolate in acute UTI with an isolation frequency of over 70% every year, followed by S. epidermidis nearly every year. Citrobacter spp., Klebsiella spp., P. mirabilis and S. aureus were also isolated steadily every year. Bacterial isolates in acute UTI were generally composed of these six species of bacteria. Although many kinds of bacteria were isolated in chronic UTI, E. coli was the most frequent species with an isolation frequency of 17-37%, followed by E. faecalis except in 1981 and 1982. The tendency of gram-negative rods to increase in acute and chronic UTI was observed except in 1981 and 1982. A slight decrease in sensitivity of E. coli and P. mirabilis against ampicillin (ABPC) and sulbenicillin (SBPC) was observed in acute UTI. In chronic UTI, the tendency of the sensitivity of E. coli against ABPC, SBPC and nalidixic acid to recover and the tendency of the sensitivity of P. aeruginosa against dibekacin to decrease were observed. E. faecalis was estimated to be sensitive to gentamicin, cefazolin, minocycline and fosfomycin. However, unlike those species mentioned above, many strains of E. faecalis showed a positive disc sensitivity to these drugs.
Topics: Acute Disease; Anti-Bacterial Agents; Bacteria; Chronic Disease; Drug Resistance, Microbial; Female; Humans; Japan; Male; Outpatients; Urinary Tract Infections; Urine
PubMed: 3448922
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Feb 2004Serratia marcescens S-95, which displayed an unusually high degree of resistance to aminoglycosides, including kanamycins and gentamicins, was isolated in 2002 from a...
Serratia marcescens S-95, which displayed an unusually high degree of resistance to aminoglycosides, including kanamycins and gentamicins, was isolated in 2002 from a patient in Japan. The resistance was mediated by a large plasmid which was nonconjugative but transferable to an Escherichia coli recipient by transformation. The gene responsible for the aminoglycoside resistance was cloned and sequenced. The deduced amino acid sequence of the resistance gene shared 82% identity with RmtA, which was recently identified as 16S rRNA methylase conferring high-level aminoglycoside resistance in Pseudomonas aeruginosa. Histidine-tagged recombinant protein showed methylation activity against E. coli 16S rRNA. The novel aminoglycoside resistance gene was therefore designated rmtB. The genetic environment of rmtB was further investigated. The sequence immediately upstream of rmtB contained the right end of transposon Tn3, including bla(TEM), while an open reading frame possibly encoding a transposase was identified downstream of the gene. This is the first report describing 16S rRNA methylase production in S. marcescens. The aminoglycoside resistance mechanism mediated by production of 16S rRNA methylase and subsequent ribosomal protection used to be confined to aminoglycoside-producing actinomycetes. However, it is now identified among pathogenic bacteria, including Enterobacteriaceae and P. aeruginosa in Japan. This is a cause for concern since other treatment options are often limited in patients requiring highly potent aminoglycosides such as amikacin and tobramycin.
Topics: Aged; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Cloning, Molecular; DNA, Bacterial; Dibekacin; Drug Resistance, Bacterial; Escherichia coli; Histidine; Humans; Male; Methylation; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; RNA, Ribosomal, 16S; Ribosomes; Serratia Infections; Serratia marcescens; tRNA Methyltransferases
PubMed: 14742200
DOI: 10.1128/AAC.48.2.491-496.2004 -
Antimicrobial Agents and Chemotherapy Nov 2006Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant...
Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CL(CR)), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CL(CR) + (26.5/age) (CL(CR) < 80 ml/min) and CL (liter/h) = 0.0130 CL(CR) + 0.0342WT + (26.5/age) (CL(CR) >/= 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Aminoglycosides; Anti-Bacterial Agents; Child; Dibekacin; Dose-Response Relationship, Drug; Female; Humans; Male; Methicillin Resistance; Middle Aged; Models, Statistical; Population; Reproducibility of Results; Sepsis; Staphylococcal Infections
PubMed: 17065621
DOI: 10.1128/AAC.00420-05 -
Antimicrobial Agents and Chemotherapy Feb 1984The relationship between plasmid-coded aminoglycoside 2"-O-nucleotidyltransferase [ANT(2")] activity and the minimum inhibitory concentration for aminoglycosides was...
The relationship between plasmid-coded aminoglycoside 2"-O-nucleotidyltransferase [ANT(2")] activity and the minimum inhibitory concentration for aminoglycosides was studied. ANT(2") was very unstable, and therefore, procedures for handling this enzyme were optimized. Escherichia coli L58058.1 producing ANT(2") was resistant to gentamicin, sisomicin, kanamycin, tobramycin, and dibekacin but susceptible to netilmicin, amikacin, and neomycin. However, only amikacin and neomycin were not modified by ANT(2"). A correlation between the substrate profile of the enzyme tested at 0.15 mM and the minimum inhibitory concentrations of the aminoglycosides could not be demonstrated. The substrate concentration-dependent enzyme activity curves proved to be a better alternative than a substrate profile based on tests at one concentration. At concentrations of greater than 10(-2) mM, ANT(2") demonstrated substrate inhibition that explains the discrepancy between ANT(2") activity and the minimum inhibitory concentrations. A close correlation was found between the physiological efficiency (Vmax/Km ratio) of ANT(2") and the minimum inhibitory concentrations for the enzyme-producing strain.
Topics: Aminoglycosides; Anti-Bacterial Agents; Chromatography, Affinity; Conjugation, Genetic; Drug Resistance, Microbial; Escherichia coli; Kinetics; Nucleotidyltransferases
PubMed: 6324668
DOI: 10.1128/AAC.25.2.234 -
The Journal of Antibiotics Aug 1976The nephrotoxicity of rats caused by dibekacin (3',4'-dideoxykanamycin B) or kanamycin with or without dextran was effectively reduced by D-glucaro-delta-lactam...
The nephrotoxicity of rats caused by dibekacin (3',4'-dideoxykanamycin B) or kanamycin with or without dextran was effectively reduced by D-glucaro-delta-lactam potassium salt, as evidenced by lower levels of blood urea nitrogen and kidney edema rate, better excretion of antibiotics,and less morphological damage. Protection was dosage related, and potentiated with increasing doses, but only when the two drugs were given simultaneously. Among three alkali-metal salts examined, the potassium salt was almost equal to the lithium salt, but surpassed the sodium salt in effectiveness. Inorganic salts, in particular potassium chloride were found to be effective for the protection of normal rats, but their effect decreased for the dehydrated rats, especially in the presence of dextran.
Topics: Aminoglycosides; Animals; Dehydration; Glucaric Acid; Kanamycin; Kidney Diseases; Lactams; Male; Potassium; Rats; Sodium; Sugar Acids
PubMed: 993122
DOI: 10.7164/antibiotics.29.833 -
Proceedings of the National Academy of... Mar 1982Nephrotoxicity is an important side effect of aminoglycoside antibiotics, which are used to control infections caused by Gram-negative bacteria. Accumulation of...
Nephrotoxicity is an important side effect of aminoglycoside antibiotics, which are used to control infections caused by Gram-negative bacteria. Accumulation of aminoglycosides and phospholipids in the lysosomes is a prominent and early feature of aminoglycoside nephrotoxicity and is characterized histologically by the presence of numerous multilamellar bodies in kidney proximal tubule cells. Previous studies have shown that the drug-induced phospholipid fatty liver in man and animals is due to concentration of certain cationic amphiphilic drugs in lysosomes with inhibition of lysosomal phospholipases. It seemed possible that this mechanism might also explain the elevated levels of phospholipid and increased numbers of multilamellar bodies reported in the kidney cortex in aminoglycoside nephrotoxicity. In this study, subcellular localization of acid phospholipases A and C has been shown to be lysosomal in rat kidney cortex. A soluble lysosomal protein fraction was isolated and found to contain both phospholipase A and phospholipase C activity. Streptomycin did not inhibit the release of fatty acids from [3H]dioleoylphosphatidylcholine. However, amikacin, dibekacin, gentamicin, and tobramycin inhibited both phospholipase A and phospholipase C. Our results suggest that the accumulation of phospholipids in lysosomes of kidney cortex, an early and pervasive feature of acute aminoglycoside nephrotoxicity, is due to inhibition of lysosomal phospholipases.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Kidney; Lysosomes; Male; Phospholipases; Phospholipases A; Rats; Structure-Activity Relationship; Type C Phospholipases
PubMed: 6951205
DOI: 10.1073/pnas.79.5.1663