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The Journal of Antibiotics Feb 1993Only a limited number of strains of methicillin-resistant Staphylococcus aureus (MRSA) moderately resistant to arbekacin (ABK) have been isolated clinically. Three...
Only a limited number of strains of methicillin-resistant Staphylococcus aureus (MRSA) moderately resistant to arbekacin (ABK) have been isolated clinically. Three inactivated products of ABK have been obtained by reaction with excess amounts of a crude enzyme preparation extracted from an ABK-resistant MRSA strain (MIC, 25 micrograms/ml). The 2"-O-phosphate was the major product together with small amounts of the 6'-N-acetate and the double modification product. The structures of these modification products were determined by MS and NMR spectral analyses.
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Inactivation, Metabolic; Magnetic Resonance Spectroscopy; Methicillin Resistance; Staphylococcus aureus
PubMed: 8468247
DOI: 10.7164/antibiotics.46.310 -
Microbiology and Immunology 1992A conjugative aminoglycoside resistance plasmid pST2 has been isolated from Escherichia coli K-12 14R525, which was mated with a clinical isolate of Salmonella...
A conjugative aminoglycoside resistance plasmid pST2 has been isolated from Escherichia coli K-12 14R525, which was mated with a clinical isolate of Salmonella typhimurium S24. A novel resistance gene of aminoglycoside 6'-N-acetyltransferase[AAC(6')] was cloned from plasmid pST2 on a 1,393 kilobase (kb) of SphI-SalI fragment into vector pACYC184 and pUC18. This novel AAC(6') gene in plasmid pST2 acetylated kanamycin, amikacin, dibekacin, tobramycin, gentamicin, netilmicin, and sisomicin. The complete nucleotide sequence of the novel AAC(6') gene and its neighboring sequences were also determined. Minicell experiments detected only one protein of 24.7 kilodaltons (kDa) translated from an open reading frame of the 618 base pairs (bp) gene.
Topics: Acetyltransferases; Amino Acid Sequence; Aminoglycosides; Base Sequence; Cloning, Molecular; Disease Outbreaks; Drug Resistance, Microbial; Molecular Sequence Data; Phenotype; R Factors; Salmonella Infections; Salmonella typhimurium; Taiwan
PubMed: 1406363
DOI: 10.1111/j.1348-0421.1992.tb02033.x -
Antimicrobial Agents and Chemotherapy Dec 1990Following the use of amikacin as the principal aminoglycoside at a Denver hospital, amikacin resistance appeared first in Pseudomonas aeruginosa and then in Escherichia...
Following the use of amikacin as the principal aminoglycoside at a Denver hospital, amikacin resistance appeared first in Pseudomonas aeruginosa and then in Escherichia coli, Klebsiella pneumoniae, and other enteric organisms from debilitated and compromised patients who had spent time in intensive care units and who had been treated with multiple antibiotics, usually including amikacin. In a P. aeruginosa isolate, resistance to amikacin and tobramycin was transferable by the IncP-2 plasmid pMG77, while in E. coli and K. pneumoniae resistance was carried by the transmissible plasmids pMG220, pMG221, and pMG222 belonging to the IncM group. Isolates and transconjugants produced an enzyme with adenyltransferase activity with substrates having a 4'-hydroxyl group, such as amikacin, kanamycin, neomycin, Sch 21768, isepamicin (Sch 21420), or tobramycin, but not with aminoglycosides lacking this target, such as dibekacin, netilmicin, sisomicin, or gentamicin C components. Genes encoding the 4'-aminoglycoside nucleotidyltransferase [ANT(4')] activity were cloned from pMG77, pMG221, and pMG222. A DNA probe prepared from the ANT(4') found in P. aeruginosa hybridized with the ANT(4') determinant found in E. coli. A probe for the ANT(4') from Staphylococcal spp., which differs in its modification of substrates, like dibekacin, that have a 4"- but not a 4'-hydroxyl group, failed to hybridize with the gram-negative ANT(4') determinant, which consequently has been termed ANT(4')-II.
Topics: Amikacin; Anti-Bacterial Agents; Bacteriophage Typing; Culture Media; DNA, Recombinant; Drug Resistance, Microbial; Escherichia coli; Gram-Negative Bacteria; Klebsiella pneumoniae; Nucleic Acid Hybridization; Nucleotidyltransferases; Plasmids; Pseudomonas aeruginosa; Pyocins; Tobramycin
PubMed: 1965106
DOI: 10.1128/AAC.34.12.2381 -
Antimicrobial Agents and Chemotherapy Aug 1990Enterococcus faecium BM4102 was resistant to macrolide-lincosamide-streptogramin B-type (MLS) antibiotics; tetracycline-minocycline; and high levels of kanamycin,...
Enterococcus faecium BM4102 was resistant to macrolide-lincosamide-streptogramin B-type (MLS) antibiotics; tetracycline-minocycline; and high levels of kanamycin, neomycin, tobramycin, and dibekacin but not gentamicin. This aminoglycoside resistance phenotype is new in enterococci. The genes conferring resistance to aminoglycosides and MLS antibiotics in this strain were carried on a plasmid, pIP810, that was self-transferable to to other Enterococcus strains. Resistance to tobramycin and structurally related aminoglycosides, kanamycin, neomycin, and dibekacin, was due to synthesis of a 4',4"-aminoglycoside nucleotidyltransferase. Homology was detected by hybridization between pIP810 DNA and a probe specific for a gene encoding an enzyme with identical site specificity in staphylococci. The bacteriostatic activity of amikacin apparently was not affected by the presence of the enzyme, although it was modified in vitro. However, the bactericidal activity of amikacin and the synergism of this aminoglycoside with penicillin were abolished.
Topics: Anti-Bacterial Agents; Culture Media; DNA, Bacterial; Drug Resistance, Microbial; Gene Expression Regulation, Bacterial; Gentamicins; Lactams; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Nucleotidyltransferases; Penicillins; Phenotype; Plasmids; Streptococcus; Tobramycin
PubMed: 2171424
DOI: 10.1128/AAC.34.8.1565 -
Hinyokika Kiyo. Acta Urologica Japonica Apr 1989In vitro studies of elimination of arbekacin (HBK), a new aminoglycoside antibiotic, from blood by means of hemodialysis or adsorption with charcoal, and pharmacokinetic...
In vitro studies of elimination of arbekacin (HBK), a new aminoglycoside antibiotic, from blood by means of hemodialysis or adsorption with charcoal, and pharmacokinetic studies in patients with renal dysfunction were examined. HBK was well eliminated by hollow fiber type artificial kidney (HFAK) with a half-life of 0.13 hr. HBK was also well eliminated by an adsorption tube containing charcoal with even shorter half-life of 0.03 hr. As to pharmacokinetics of HBK in patients with renal dysfunction, blood levels became higher with a greater reduction in 24 hr endogenous creatinine clearance (Ccr). A decreasing tendency was also seen in urinary recovery rate. These results indicated that hemodialysis and adsorption with charcoal are useful for elimination of HBK from blood. It is recommendable in patients with renal dysfunction to take some measures such as prolongation of administration interval of HBK according to the extent of decrease in Ccr.
Topics: Adsorption; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Charcoal; Dibekacin; Female; Humans; Kanamycin; Kidney Diseases; Male; Middle Aged; Renal Dialysis
PubMed: 2735273
DOI: No ID Found -
The Journal of Antibiotics Jan 1988The genetic and biochemical basis of a 200-fold increase in kanamycin (KM)-resistance shown in Streptomyces griseus SS-1198PR generated by protoplast regeneration was...
Mechanism of increased kanamycin-resistance generated by protoplast regeneration of Streptomyces griseus. I. Cloning of a gene segment directing a high level of an aminoglycoside 3-N-acetyltransferase activity.
The genetic and biochemical basis of a 200-fold increase in kanamycin (KM)-resistance shown in Streptomyces griseus SS-1198PR generated by protoplast regeneration was investigated. A 15-kb Bcl I-DNA segment responsible for the KM-resistance was cloned into pIJ61 with Streptomyces lividans TK21 as host. The KM-resistance segment was then subcloned into pIJ702 as a 1.8-kb BamH I-Bgl II fragment with a BamH I site essential for the KM-resistance. Both S. lividans TK21 containing the cloned segments and S. griseus SS-1198PR showed multiple resistance to KM, dibekacin and gentamicin C complex. Cell free extracts from these strains inactivated the antibiotics in the presence of acetyl CoA in agreement with their resistance pattern. The structure of the inactivated KM-A was determined as 3-N-acetyl-KM-A indicating acetylation by an aminoglycoside acetyltransferase, AAC(3). The substrate range of the enzyme was unique and was designated AAC(3)-V. No genetic linkage was found between the cloned 15 kb Bcl I segment and the separately cloned streptomycin resistance gene (str) segment (3.8 kb Sph I fragment). The str genes cloned from both the parent (SS-1198) and the strain SS-1198PR were identical in their size, restriction site and function. In addition, these strains showed no significant difference in the total DNA digestion pattern. These results indicate that protoplast regeneration may cause a critical change in a specific region of DNA resulting in a high activity of an AAC(3) with a novel substrate range.
Topics: Acetylation; Acetyltransferases; Cloning, Molecular; Drug Resistance, Microbial; Genes, Bacterial; Kanamycin; Protoplasts; Regeneration; Streptomyces griseus; Streptomycin
PubMed: 3126171
DOI: 10.7164/antibiotics.41.94 -
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 -
Journal of Dairy Science Aug 1987Ribonucleic acid synthesis continues at a low rate within 1 h of germinal vesicle breakdown. To determine if this newly synthesized mRNA is required for the resumption...
Ribonucleic acid synthesis continues at a low rate within 1 h of germinal vesicle breakdown. To determine if this newly synthesized mRNA is required for the resumption of meiosis in cattle oocytes, cumulus-enclosed oocytes were removed from 2 to 4-mm antral follicles directly into Dulbecco's medium with or without the RNA inhibitor, alpha-amanitin, or the protein synthesis inhibitor, cycloheximide (10 micrograms/ml). They were washed twice and matured for 28 or 48 h in medium 199, with Earle's salts, 2.2 g/L NaHCO3 and L-glutamine supplemented with 20% heated fetal calf serum to which were added gonadotropins (10 micrograms/ml NIH-LH-S18; 10 micrograms/ml NIH-FSH-S8; 20 ng/ml NIH-P-S9), estradiol-17 beta (1.5 micrograms/ml), solcoseryl (30 microliter/ml), and Dibekacin sulfate (100 micrograms/ml) with or without the inhibitors. After 28 h of maturation, 95.8% of control oocytes had undergone germinal vesicle breakdown and formation of a metaphase plate compared with only 1.3% of those continuously exposed to cycloheximide and 38% of those continuously exposed to amanitin. Exposure to cycloheximide or amanitin for only the first 16 h of culture followed by 12 h of inhibitor free culture resulted in 96.6% germinal vesicle breakdown with cycloheximide but only 56.5% germinal vesicle breakdown with amanatin. We conclude newly synthesized mRNA and protein synthesis is required for both full cumulus cell expansion and germinal vesicle breakdown.
Topics: Amanitins; Animals; Cattle; Cycloheximide; Female; In Vitro Techniques; Meiosis; Oocytes; Protein Biosynthesis; RNA
PubMed: 2444633
DOI: 10.3168/jds.S0022-0302(87)80192-3 -
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 1987The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on... (Comparative Study)
Comparative Study
The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on hemodialysis) after administration of a single 3-mg/kg dose. Six healthy subjects received the 3-mg/kg dose both intramuscularly (i.m.) and intravenously (i.v.) (1-h infusion). Uremic patients were given the 3-mg/kg dose as an i.m. injection, except for the hemodialysis patients, who received the dose as a 1-h i.v. infusion. After the i.m. injection, the peak concentrations in serum were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. The elimination half-life in serum increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearances of less than 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After the same 3-mg/kg dose as a 1-h i.v. infusion in six hemodialysis patients, the elimination half-life averaged 48 and 5 h off and on a 4- to 5-h hemodialysis session, respectively. The habekacin pharmacokinetic data appeared to be similar to those of the other available aminoglycoside antibiotics.
Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Uremia
PubMed: 3606062
DOI: 10.1128/AAC.31.4.575