-
Antimicrobial Agents and Chemotherapy Dec 2013We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a...
We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (∼30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2″)], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2″) and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2″) and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2″) and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETBTY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.
Topics: Anti-Bacterial Agents; Base Sequence; Dibekacin; Drug Resistance, Multiple, Bacterial; Erythromycin; Exfoliatins; Gentamicins; Humans; Impetigo; Japan; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Retrospective Studies; Staphylococcal Scalded Skin Syndrome; Staphylococcus aureus
PubMed: 24080652
DOI: 10.1128/AAC.01062-13 -
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 -
Antimicrobial Agents and Chemotherapy Mar 1983Aminoglycoside antibiotics induce an early and characteristic lysosomal phospholipidosis in cultured fibroblasts and in kidney tubular cells. We have recently... (Comparative Study)
Comparative Study
Aminoglycoside antibiotics induce an early and characteristic lysosomal phospholipidosis in cultured fibroblasts and in kidney tubular cells. We have recently demonstrated an inhibition of lysosomal phospholipases A1 and A2 by gentamicin and amikacin in vitro. In vivo, gentamicin decreases the activity of phospholipase A1 (Laurent et al., Biochem. Pharmacol. 31:3861-3870, 1982). In the present study, we examined 14 aminoglycosides for in vitro inhibition of phospholipases. To mimic the situation prevailing in lysosomes, the enzymatic activities were assayed with phospholipid vesicles (liposomes) with a composition similar to that of lysosomal phospholipids (phosphatidylcholine, sphingomyelin, phosphatidylinositol, cholesterol; 4:4:3:5.5, molar ratio). We measured the hydrolysis of 1-palmitoyl-2-[1-14C]oleoyl phosphatidylcholine contained in the liposomes by a soluble fraction of highly purified lysosomes isolated from rat liver. Similar IC50S (concentrations causing 50% inhibition of enzymatic activity) were observed for dibekacin, gentamicin (with no major difference between C1, C1a, or C2), netilmicin, tobramycin, and kanamycin B. Sisomicin was slightly more inhibitory. Kanamycin A, N1-(L-4-amino-2-hydroxy-1-oxobutyl)dibekacin, and amikacin showed increasing IC50S. Streptomycin caused the least inhibition. Octa- and tetramethylkanamycin A are much less inhibitory than the parent drug. These results point to the number, the nature, and the respective positions of the cationic groups as essential determinants in causing inhibition of phospholipid breakdown. The binding of three aminoglycosides (gentamicin, amikacin, streptomycin) to the liposomes at pH 5.4 was also measured by gel permeation and was found to be related to the respective inhibitory potency of each drug. Insofar as lysosomal phospholipidosis is an early sign of intoxication by aminoglycosides, these results may serve as a basis for the development or screening of less toxic compounds in this class of antimicrobial agents.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; In Vitro Techniques; Kidney; Liposomes; Lysophosphatidylcholines; Lysosomes; Phosphatidylcholines; Phospholipases; Rats; Structure-Activity Relationship
PubMed: 6847172
DOI: 10.1128/AAC.23.3.440 -
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 -
Antimicrobial Agents and Chemotherapy Dec 2003We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination....
Efficacies of vancomycin, arbekacin, and gentamicin alone or in combination against methicillin-resistant Staphylococcus aureus in an in vitro infective endocarditis model.
We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination. Using two strains of clinically isolated methicillin-resistant Staphylococcus aureus, one GEN susceptible (GS171) and one GEN resistant (GR153), fibrin clots were prepared and suspended in the IVIEM. Antibiotics were given as boluses every 6 h (q6h), q12h, or q24h or by continuous infusion with VAN, q12h or q24h with ABK, and q8h or q24h with GEN. For combination treatment, VAN q12h plus ABK q24h and VAN q12h plus GEN q24h were given. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities were determined. The number of colonies within the fibrin clot was significantly decreased in all study groups compared with control groups (P<0.001). When VAN and ABK were administered alone, the number of colonies was significantly lower in GS171 than in GR153 by 8 h after administration (P=0.02) and was lowest in GS171 when ABK was administered q12h (P=0.01). At 72 h, ABK or VAN alone produced equivalent bacterial reductions regardless of dosing frequency and GEN resistance. In GR153, VAN plus ABK showed an additive effect till 24 h, although VAN plus GEN showed indifference. Our data suggest that ABK could be used as an alternative to VAN in GEN-resistant staphylococcal endocarditis. An additive effect was seen when VAN and ABK were used together in GEN-resistant strains until 24 h; however, further studies are warranted for the clinical application of this combination.
Topics: Aminoglycosides; Anti-Bacterial Agents; Area Under Curve; Blood Coagulation; Colony Count, Microbial; Dibekacin; Drug Therapy, Combination; Endocarditis, Bacterial; Fibrin; Gentamicins; Methicillin Resistance; Microbial Sensitivity Tests; Models, Biological; Staphylococcal Infections; Staphylococcus aureus; Vancomycin
PubMed: 14638480
DOI: 10.1128/AAC.47.12.3768-3773.2003 -
The Journal of Antibiotics Mar 1984A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to...
A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to rabbits using different infusion times. The peak serum level (Cmax) was seen to decrease progressively on increasing infusion time. The maximum value of Cmax was obtained after administration of the antibiotic by single bolus injection with an average value of 18.297 +/- 9.694 micrograms/ml, while the minimum value was obtained after intravenous infusion over 1 hour, with an average value of 6.597 +/- 1.250 micrograms/ml. A series of linear relationships was established between different pharmacokinetic parameters and the infusion time and a decrease was observed in the pharmacokinetic parameters alpha, K12, K21 and K13 when the infusion time was increased. Changes were also observed in the distribution kinetics of dibekacin in the rabbit on varying the infusion conditions, suggesting alterations in the access and permanence of the antibiotic in tissues.
Topics: Animals; Dibekacin; Infusions, Parenteral; Kanamycin; Kinetics; Male; Models, Biological; Rabbits; Time Factors
PubMed: 6725142
DOI: 10.7164/antibiotics.37.285 -
Antimicrobial Agents and Chemotherapy Mar 1981The in vitro activities of four new beta-lactam antibiotics and dibekacin against aerobic bacteria were compared. The new cephalosporins were more broadly active against... (Comparative Study)
Comparative Study
The in vitro activities of four new beta-lactam antibiotics and dibekacin against aerobic bacteria were compared. The new cephalosporins were more broadly active against gram-negative bacteria than were presently available cephalosporins, but were less active against staphylococci.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Cephalosporins; Dibekacin; Kanamycin; Microbial Sensitivity Tests; Penicillins; Piperacillin
PubMed: 6454384
DOI: 10.1128/AAC.19.3.490 -
Antimicrobial Agents and Chemotherapy Oct 1985A rapid, simple, and accurate method for the determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography is described. The serum...
A rapid, simple, and accurate method for the determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography is described. The serum proteins were precipitated with 3.5% perchloric acid containing sodium octanesulfonate. After centrifugation, a sample of the supernatant was directly injected into the chromatograph. The determination of kanamycin and dibekacin was performed by a combination of reverse-phase, ion-pair chromatography, postcolumn derivatization with o-phthalaldehyde, and fluorescence detection. The correlation coefficients with fluorescence polarization immunoassay were 0.996 for kanamycin and 0.957 for dibekacin.
Topics: Chromatography, High Pressure Liquid; Dibekacin; Humans; Kanamycin; Spectrometry, Fluorescence
PubMed: 4073874
DOI: 10.1128/AAC.28.4.521 -
The Journal of Antibiotics Jul 1981The effects of habekacin on corneal ulceration, caused by Pseudomonas aeruginosa IFO 3455, were studied in mice, in comparison with gentamicin and tobramycin. The...
The effects of habekacin on corneal ulceration, caused by Pseudomonas aeruginosa IFO 3455, were studied in mice, in comparison with gentamicin and tobramycin. The minimal inhibitory concentrations of the antibiotics for the organism were: habekacin 2 microgram/ml, gentamicin 2 microgram/ml, and tobramycin 1 microgram/ml. Habekacin showed protective and therapeutic effects on Pseudomonas keratitis. The 50% effective dose was approximately 1 microgram per mouse, when the drug was topically applied three hours after the infection, and about 0.2 mg per mouse, when the antibiotic was intramuscularly injected one hour after the bacterial challenge to the cornea. Significant therapeutic and protective activities of habekacin were observed even by starting the topical and/or intramuscular treatment after the corneal ulcers were formed: i.e. 15 hours after the bacterial infection. Complete cure of Pseudomonas keratitis was found within a week in a number of the infected mice by both topical and systemic administrations of the drug. The protective and therapeutic effects of habekacin were comparable to those of gentamicin and tobramycin.
Topics: Administration, Topical; Aminoglycosides; Animals; Anti-Bacterial Agents; Corneal Ulcer; Dibekacin; Injections, Intramuscular; Keratitis; Male; Mice; Pseudomonas Infections
PubMed: 7287591
DOI: 10.7164/antibiotics.34.892 -
PloS One 2013In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at the...
In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at the Hiroshima University Hospital, Japan. Pulsed-field gel electrophoresis of SpeI-digested genomic DNAs from the isolates suggested the clonal expansion of a single strain; however, only one strain, NK0009, was found to produce metallo-β-lactamase. PCR and subsequent sequencing analysis indicated NK0009 possessed a novel class 1 integron, designated as In124, that carries an array of four gene cassettes: a novel aminoglycoside (AG) resistance gene, aac(6')-Iag, blaIMP-1, a truncated form of blaIMP-1, and a truncated form of aac(6')-Iag. The aac(6')-Iag encoded a 167-amino-acid protein that shows 40% identity with AAC(6')-Iz. Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin. A conjugation experiment and subsequent Southern hybridization with the gene probes for blaIMP-1 and aac(6')-Ig strongly suggested In124 is on a conjugal plasmid. Transconjugants acquired resistance to gentamicin and were resistant to virtually all AGs, suggesting that the In124 conjugal plasmid also possesses a gene conferring resistance to gentamicin.
Topics: Acetylation; Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Base Sequence; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Gene Order; Humans; Integrons; Kinetics; Molecular Sequence Data; Phylogeny; Pseudomonas Infections; Pseudomonas aeruginosa; Sequence Alignment; beta-Lactamases
PubMed: 23950962
DOI: 10.1371/journal.pone.0070557